Human Papillomavirus and Related Diseases Report WORLD

Human Papillomavirus and Related Diseases Report WORLD Version posted on www.hpvcentre.net in March 20 th, 2015

- ii - Rights ICO Information Centre on HPV and Cancer (HPV Information Centre) 2014 All rights reserved. Publications of the ICO Information Centre on HPV and Cancer (HPV Information Centre) can be obtained from HPV Information Centre Secretariat, Institut Català d Oncologia, Avda. Gran Via de l Hospitalet, 199-203 08908 L Hospitalet del Llobregat (Barcelona, Spain, e-mail: hpvcentre@iconcologia.net). Requests for permission to reproduce or translate HPV Information Centre publications - whether for sale or for noncommercial distribution- should be addressed to HPV Information Centre Secretariat, at the above address (e-mail: hpvcentre@iconcologia.net). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part the HPV Information Centre concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers products does not imply that they are endorsed or recommended the HPV Information Centre in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the HPV Information Centre to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the HPV Information Centre be liable for damages arising from its use. The development of this report has been supported by grants from the European Comission (7th Framework Programme grant HEALTH-F3-2010-242061, HEALTH-F2-2011-282562, HPV AHEAD). Recommended citation: Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, Brotons M, Mena M, Cosano R, Muñoz J, Bosch FX, de Sanjosé S, Castellsagué X. ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in the World. Summary Report 2015-04-08. [Data Accessed]

- iii - Abbreviations Abbreviation HPV PREHDICT Project Table 1: Abbreviations Full term Human papillomavirus infection health-economic modelling of PREvention strategies for Hpv-related Diseases in European CounTries ICO Information Centre on HPV and Cervical Cancer Genital Warts Recurrent respiratory papillomatosis Squamous Intraepithelial Lesions Low-grade cervical lesions High-grade cervical lesions Invasive cervical cancer Carcinoma in situ Cervical Intraepithelial Neoplasia HPV Information Centre GW RRP SIL LSIL HSIL ICC CIS CIN AIN2/3 Anal intraepithelial neoplasia of grade 2 and/or 3 VIN 2/3 Vulvar intraepithelial neoplasia of grade 2 and/or 3 VAIN 2/3 Vaginal intraepithelial neoplasia of grade 2 and/or 3 PeIN 2/3 Penile intraepithelial neoplasia of grade 2 and/or 3 95% CI 95% Confidence Interval N Number of cases tested HPV Prev HPV prevalence ASR Age-standardized rate MSM Men who have sex with men Non MSM Heterosexual men SCC Squamous cell carcinomas STI Sexually transmitted infections HIV/AIDS Human immunodeficiency virus/acquired immunodeficiency syndrome TS Type Specific EIA Enzyme ImmunoAssay RLBM Reverse Line Blotting Method RFLP Restriction Fragment Length Polymorphism RHA Reverse Hybridization Assay RLH Reverse Line Hybridisation LiPA Line Probe Assay SBH Southern Blot Hybridization ISH In Situ Hybridization MABA Micro Array-Based Assay LBA Line-Blot Assay HC2 Hybrid Capture 2 SAT Suspension Array Technology PCR Polymerase Chain Reaction SPF Short Primer Fragment q-pcr quantitative Polymerase Chain Reaction RLBH Reverse Line Blot Hybridization RT-PCR Real Time Polymerase Chain Reaction DBH Dot Blot Hybridization HR High Risk DSA Direct Sequence Analysis MAA Microchip Array Assay

- iv - Executive summary Human papillomavirus (HPV) infection is now a well-established cause of cervical cancer and there is growing evidence of HPV being a relevant factor in other anogenital cancers (anus, vulva, vagina and penis) and head and neck cancers. HPV types 16 and 18 are responsible for about 70% of all cervical cancer cases worldwide. HPV vaccines that prevent against HPV 16 and 18 infection are now available and have the potential to reduce the incidence of cervical and other anogenital cancers. This report provides key information for Less developed regions on cervical cancer, other anogenital cancers and head and neck cancers, HPV-related statistics, factors contributing to cervical cancer, cervical cancer screening practices, HPV vaccine introduction, and other relevant immunization indicators. The report is intended to strengthen the guidance for health policy implementation of primary and secondary cervical cancer prevention strategies in the region. Less developed regions has a population of 2,645 millions women aged 15 years and older who are at risk of developing cervical cancer. Current estimates indicate that every year 527,624 women are diagnosed with cervical cancer and 265,653 die from the disease. Cervical cancer ranks as the 3rd most frequent cancer among women in the World. Population Table 2: Key statistics in the World Women at risk for cervical cancer (Female population aged >=15 yrs) in millions 2645.080 2100.870 544.200 Burden of cervical cancer Annual number of new cervical cancer cases 527,624 444,546 83,078 Standardized incidence rates per 100,000 population in cervical cancer 14.0 15.7 9.9 Annual number of cervical cancer deaths 265,653 230,158 35,495 Standardized mortality rates per 100,000 population in cervical cancer 6.8 8.3 3.3 Burden of cervical HPV infection Prevalence (%) of HPV 16 and/or HPV 18 among women with: World Less developed regions More developed regions Normal cytology 3.9 3.8 3.8 Low-grade cervical lesions (LSIL/CIN-1) 25.5 24.5 25.9 High-grade cervical lesions (HSIL/ CIN-2 / CIN-3 / CIS) 51.5 46.1 53.6 LSIL, low-grade intraepithelial lesions; HSIL, high-grade intraepithelial lesions; CIN, cervical intraepithelial neoplasia; CIS, carcinoma in-situ. Cervical cancer 70.0 71.9 71.5

LIST OF CONTENTS - v - Contents Abbreviations Executive summary iii iv 1 Introduction 1 2 Demographic and socioeconomic factors (last update 25 Nov 2013) 3 3 Burden of HPV related cancers 7 3.1 Cervical cancer.............................................. 7 3.1.1 Incidence (last update 22 Jul 2014)............................. 7 3.1.2 Mortality (last update 14 Jul 2014)............................. 20 3.1.3 Comparison of incidence and mortality (last update 14 Jul 2014)........... 29 3.2 Anogenital cancers other than the cervix.............................. 30 3.2.1 Anal cancer (last update 22 Jul 2014)........................... 30 3.2.2 Vulvar cancer (last update 22 Jul 2014).......................... 37 3.2.3 Vaginal cancer (last update 22 Jul 2014).......................... 43 3.2.4 Penile cancer (last update 22 Jul 2014)........................... 49 3.3 Head and neck cancers......................................... 55 3.3.1 Pharyngeal cancer (excluding nasopharynx) (last update 15 Jan 2014)....... 55 4 HPV related statistics 62 4.1 HPV burden in women with normal cytology, precancerous cervical lesions or invasive cervical cancer.............................................. 62 4.1.1 HPV prevalence in women with normal cytology.................... 63 4.1.2 HPV type distribution among women with normal cytology, precancerous cervical lesions and cervical cancer.................................. 85 4.1.3 Terminology............................................ 126 4.2 HPV burden in anogenital cancers other than the cervix..................... 127 4.2.1 Anal cancer and precancerous anal lesions......................... 127 4.2.2 Vulvar cancer and precancerous vulvar lesions....................... 137 4.2.3 Vaginal cancer and precancerous vaginal lesions..................... 149 4.2.4 Penile cancer and precancerous penile lesions....................... 157 4.3 HPV burden in men........................................... 161 4.4 HPV burden in head and neck..................................... 173 4.4.1 Burden of oral HPV infection in healthy population.................... 173 4.4.2 HPV burden in head and neck cancers............................ 174 5 Factors contributing to cervical cancer (last update 08 Aug 2013) 191 6 Reproductive and sexual behaviour (last update 08 Aug 2013) 195 7 HPV preventive strategies 196 7.1 Cervical cancer screening practices (last update 30 Jul 2013)................. 196 7.2 HPV vaccination............................................. 204 7.2.1 HPV vaccine licensure and introduction (last update 26 Nov 2013).......... 204 8 Protective factors for cervical cancer (last update 30 Sep 2013) 208 9 References 210

LIST OF FIGURES - vi - List of Figures 1 World s geographical regions................................................... 1 2 Population pyramid estimates of the World compared to developing and developed regions for for 2013..... 3 3 Population trends of four selected age groups in the World compared to developing and developed regions for 2013 4 4 Age-standardized incidence rates of cervical cancer in World (estimations for 2012).................. 7 5 Ranking of cervical cancer to others cancers among all women and women ages 15-44 years, according to incidence rates in World (estimations for 2012).......................................... 9 6 World age-standarized incidence rates compared to regions and sub-regions (estimations for 2012)........ 10 7 Ten most frequent cancer in all women in the World compared to developing and developed regions (estimations for 2012)............................................................... 11 8 Ten most frequent cancer in all women in the World compared to the continents (estimations for 2012)..... 12 9 Ten most frequent cancers in women ages 15-44 yrs in the World compared to developing and developed regions (estimations for 2012)....................................................... 13 10 Ten most frequent cancers in women ages 15-44 yrs in the World compared to the continents (estimations for 2012)................................................................. 14 11 Age-specific incidence of cervical cancer in World and its regions (estimations for 2012)............... 15 12 Annual number of new cases of cervical cancer by age group in developed and developing regions and five continents (estimations for 2012)................................................ 16 13 Annual number of cases and age-specific incidence rates of cervical cancer in World and its regions (estimations for 2012)............................................................... 17 14 Annual number of cases and age-specific incidence rates of cervical cancer in World and its regions (estimations for 2012) (Continued)....................................................... 18 15 Age-standardized mortality rates of cervical cancer in World (estimations for 2012).................. 20 16 World age-standardized mortality rates of cervical cancer compared to regions and sub-regions (estimations for 2012)................................................................. 22 17 Ranking of cervical cancer to others cancers among all women and women ages 15-44 years, according to mortality rates in World (estimations for 2012).......................................... 23 18 Age-specific mortality of cervical cancer in World and its regions (estimations for 2012)............... 24 19 Annual number of deaths of cervical cancer by age group in developed and developing regions and five continents (estimations for 2012)....................................................... 25 20 Annual number of deaths and age-specific mortality rates of cervical cancer in World and its regions (estimations for 2012)............................................................... 26 21 Annual number of deaths and age-specific mortality rates of cervical cancer in World and its regions (estimations for 2012) (Continued)....................................................... 27 22 Age-specific incidence and mortality rates of cervical cancer in World and its regions (estimations for 2012).. 29 23 Comparison of incidence and mortality rates of cancer of pharyngeal cancer (excluding nasopharynx) by sex and age group in the World. Includes ICD-10 codes:c09-10,c12-14 (estimations for 2012)................ 57 24 Comparison of incidence and mortality rates of cancer of pharyngeal cancer (excluding nasopharynx) in male by age group in the World. Includes ICD-10 codes:c09-10,c12-14 (estimations for 2012)................ 58 25 Comparison of incidence and mortality rates of cancer of pharyngeal cancer (excluding nasopharynx) in female by age group in the World. Includes ICD-10 codes:c09-10,c12-14 (estimations for 2012).............. 60 26 Prevalence of HPV among women with normal cytology in the World.......................... 63 27 Crude age-specific HPV prevalence (%) and 95% confidence interval (grey shadow) in women with normal cytology in the World.......................................................... 64 28 Prevalence of HPV among women with normal cytology in Africa by country and study............... 65 29 Prevalence of HPV among women with normal cytology in Africa by country and study (continued)........ 66 30 Prevalence of HPV among women with normal cytology in Africa by country and study (continued)........ 67 31 Prevalence of HPV among women with normal cytology in Americas by country and study............. 68 32 Prevalence of HPV among women with normal cytology in Americas by country and study (continued)...... 69 33 Prevalence of HPV among women with normal cytology in Americas by country and study (continued)...... 70 34 Prevalence of HPV among women with normal cytology in Americas by country and study (continued)...... 71 35 Prevalence of HPV among women with normal cytology in Asia by country and study................ 72 36 Prevalence of HPV among women with normal cytology in Asia by country and study (continued)......... 73 37 Prevalence of HPV among women with normal cytology in Asia by country and study (continued)......... 74 38 Prevalence of HPV among women with normal cytology in Asia by country and study (continued)......... 75 39 Prevalence of HPV among women with normal cytology in Asia by country and study (continued)......... 76 40 Prevalence of HPV among women with normal cytology in Asia by country and study (continued)......... 77 41 Prevalence of HPV among women with normal cytology in Asia by country and study (continued)......... 78 42 Prevalence of HPV among women with normal cytology in Europe by country and study............... 79 43 Prevalence of HPV among women with normal cytology in Europe by country and study (continued)....... 80 44 Prevalence of HPV among women with normal cytology in Europe by country and study (continued)....... 81 45 Prevalence of HPV among women with normal cytology in Europe by country and study (continued)....... 82 46 Prevalence of HPV among women with normal cytology in Europe by country and study (continued)....... 83 47 Prevalence of HPV among women with normal cytology in Oceania by country and study.............. 84

LIST OF FIGURES - vii - 48 Prevalence of HPV 16 among women with normal cytology in Africa by country and study............. 86 49 Prevalence of HPV 16 among women with normal cytology in Americas by country and study........... 87 50 Prevalence of HPV 16 among women with normal cytology in Americas by country and study (continued).... 88 51 Prevalence of HPV 16 among women with normal cytology in Asia by country and study.............. 89 52 Prevalence of HPV 16 among women with normal cytology in Asia by country and study (continued)....... 90 53 Prevalence of HPV 16 among women with normal cytology in Europe by country and study............. 91 54 Prevalence of HPV 16 among women with normal cytology in Europe by country and study (continued)..... 92 55 Prevalence of HPV 16 among women with normal cytology in Oceania by country and study............ 93 56 Prevalence of HPV 16 among women with low-grade cervical lesions in Africa by country and study....... 94 57 Prevalence of HPV 16 among women with low-grade cervical lesions in Americas by country and study..... 95 58 Prevalence of HPV 16 among women with low-grade cervical lesions in Americas by country and study (continued) 96 59 Prevalence of HPV 16 among women with low-grade cervical lesions in Asia by country and study........ 97 60 Prevalence of HPV 16 among women with low-grade cervical lesions in Asia by country and study (continued). 98 61 Prevalence of HPV 16 among women with low-grade cervical lesions in Europe by country and study....... 99 62 Prevalence of HPV 16 among women with low-grade cervical lesions in Europe by country and study (continued) 100 63 Prevalence of HPV 16 among women with low-grade cervical lesions in Oceania by country and study...... 101 64 Prevalence of HPV 16 among women with High-grade cervical lesions in Africa by country and study....... 102 65 Prevalence of HPV 16 among women with High-grade cervical lesions in Americas by country and study.... 103 66 Prevalence of HPV 16 among women with High-grade cervical lesions in Americas by country and study (continued)................................................................ 104 67 Prevalence of HPV 16 among women with High-grade cervical lesions in Asia by country and study........ 105 68 Prevalence of HPV 16 among women with High-grade cervical lesions in Asia by country and study (continued) 106 69 Prevalence of HPV 16 among women with High-grade cervical lesions in Europe by country and study...... 107 70 Prevalence of HPV 16 among women with High-grade cervical lesions in Europe by country and study (continued)108 71 Prevalence of HPV 16 among women with High-grade cervical lesions in Oceania by country and study..... 109 72 Prevalence of HPV 16 among women with invasive cervical cancer in Africa by country and study......... 110 73 Prevalence of HPV 16 among women with invasive cervical cancer in Americas by country and study (continued) 111 74 Prevalence of HPV 16 among women with invasive cervical cancer in Americas by country and study (continued) 113 75 Prevalence of HPV 16 among women with invasive cervical cancer in Asia by country and study (continued).. 114 76 Prevalence of HPV 16 among women with invasive cervical cancer in Asia by country and study (continued).. 115 77 Prevalence of HPV 16 among women with invasive cervical cancer in Asia by country and study (continued).. 116 78 Prevalence of HPV 16 among women with invasive cervical cancer in Europe by country and study (continued). 117 79 Prevalence of HPV 16 among women with invasive cervical cancer in Europe by country and study (continued). 119 80 Prevalence of HPV 16 among women with invasive cervical cancer in Europe by country and study (continued). 120 81 Prevalence of HPV 16 among women with invasive cervical cancer in Oceania by country and study....... 121 82 Ten most frequent HPV oncogenic types among women with and without cervical lesions in World compared to developing and developed regions............................................... 122 83 Ten most frequent HPV types among women with invasive cervical cancer by histology in the World compared to developing and developed regions.............................................. 123 84 Ten most frequent HPV types among cases of anal cancer in Africa compared to the World............. 132 85 Ten most frequent HPV types among cases of anal cancer in Americas compared to the World........... 132 86 Ten most frequent HPV types among cases of anal cancer in Asia compared to the World.............. 133 87 Ten most frequent HPV types among cases of anal cancer in Europe compared to the World............ 133 88 Ten most frequent HPV types among cases of anal cancer in Oceania compared to the World............ 134 89 Ten most frequent HPV types among cases of AIN 2/3 in Africa compared to the World............... 134 90 Ten most frequent HPV types among cases of AIN 2/3 in Americas compared to the World............. 135 91 Ten most frequent HPV types among cases of AIN 2/3 in Asia compared to the World................ 135 92 Ten most frequent HPV types among cases of AIN 2/3 in Europe compared to the World............... 136 93 Ten most frequent HPV types among cases of AIN 2/3 in Oceania compared to the World.............. 136 94 Ten most frequent HPV types among cases of vulvar cancer in Africa compared to the World............ 144 95 Ten most frequent HPV types among cases of vulvar cancer in Americas compared to the World.......... 144 96 Ten most frequent HPV types among cases of vulvar cancer in Asia compared to the World............. 145 97 Ten most frequent HPV types among cases of vulvar cancer in Europe compared to the World........... 145 98 Ten most frequent HPV types among cases of vulvar cancer in Oceania compared to the World........... 146 99 Ten most frequent HPV types among cases of VIN 2/3 in Africa compared to the World............... 146 100 Ten most frequent HPV types among cases of VIN 2/3 in Americas compared to the World............. 147 101 Ten most frequent HPV types among cases of VIN 2/3 in Asia compared to the World................ 147 102 Ten most frequent HPV types among cases of VIN 2/3 in Europe compared to the World............... 148 103 Ten most frequent HPV types among cases of VIN 2/3 in Oceania compared to the World.............. 148 104 Ten most frequent HPV types among cases of vaginal cancer in Africa compared to the World........... 151 105 Ten most frequent HPV types among cases of vaginal cancer in Americas compared to the World......... 152 106 Ten most frequent HPV types among cases of vaginal cancer in Asia compared to the World............ 152 107 Ten most frequent HPV types among cases of vaginal cancer in Europe compared to the World........... 153 108 Ten most frequent HPV types among cases of vaginal cancer in Oceania compared to the World.......... 153 109 Ten most frequent HPV types among cases of VaIN 2/3 in Africa compared to the World............... 154

LIST OF FIGURES - viii - 110 Ten most frequent HPV types among cases of VaIN 2/3 in Americas compared to the World............. 154 111 Ten most frequent HPV types among cases of VaIN 2/3 in Asia compared to the World................ 155 112 Ten most frequent HPV types among cases of VaIN 2/3 in Europe compared to the World.............. 155 113 Ten most frequent HPV types among cases of VaIN 2/3 in Oceania compared to the World.............. 156 114 Prevalence of female tobacco smoking worldwide....................................... 191 115 Total fertility rates worldwide.................................................. 192 116 Prevalence of oral contraceptive use worldwide........................................ 193 117 Prevalence of HIV worldwide.................................................. 194 118 Proportion of young women (15-24 years) who have had sex before the age of 15 worldwide............. 195 119 Licensure status of current HPV vaccines worldwide.................................... 204 120 Status of HPV vaccination programs worldwide....................................... 205 121 Prevalence of male circumcision worldwide.......................................... 208 122 Prevalence of condom use worldwide.............................................. 209

LIST OF TABLES - ix - List of Tables 1 Abbreviations............................................................ iii 2 Key statistics in the World.................................................... iv 3 Population (in millions) estimates in the World for 2013.................................. 5 4 Sociodemographic indicators in the World for 2013..................................... 5 5 Incidence of cervical cancer by regions and sub-regions in the World (estimations for 2012)............. 8 6 Cervical cancer mortality in regions and sub-regions in the World (estimations for 2012).............. 21 7 Incidence of anal cancer by cancer registry and sex..................................... 30 8 Incidence of vulvar cancer by cancer registry......................................... 37 9 Incidence of vaginal cancer by cancer registry........................................ 43 10 Incidence of penile cancer by cancer registry......................................... 49 11 Incidence of cancer of pharyngeal cancer (excluding nasopharynx) by sex, world by regions and sub-regions. Includes ICD-10 codes:c09-10,c12-14 (estimations for 2012)............................... 55 12 Mortality of cancer of pharyngeal cancer (excluding nasopharynx) by sex, world regions and sub-regions. Includes ICD-10 codes:c09-10,c12-14 (estimations for 2012)................................. 55 13 Prevalence of HPV 16/18 in women with normal cytology, precancerous cervical lesions and invasive cervical cancer by regions and sub-regions in the World........................................ 85 14 Type-specific HPV prevalence in women with normal cytology, precancerous cervical lesions and invasive cervical cancer in the World........................................................ 124 15 Type-specific HPV prevalence among invasive cervical cancer cases by histology in the World........... 125 16 Studies on HPV prevalence among cases of anal cancer in the World........................... 127 17 Studies on HPV prevalence among cases of AIN 2/3 in the World............................. 129 18 Studies on HPV prevalence among cases of vulvar cancer in the World......................... 137 19 Studies on HPV prevalence among cases of VIN 2/3 in the World............................. 141 20 Studies on HPV prevalence among cases of vaginal cancer in the World......................... 149 21 Studies on HPV prevalence among cases of VAIN 2/3 in the World............................ 150 22 Studies on HPV prevalence among cases of penile cancer in the World.......................... 157 23 Studies on HPV prevalence among cases of PeIN 2/3 in the World............................ 160 24 Studies on anogenital HPV prevalence among men in the World............................. 162 25 Studies on anogenital HPV prevalence among men from special subgroups in the World............... 165 26 Studies on oral HPV prevalence among healthy populations in the World........................ 173 27 Studies on HPV prevalence among cases of oral cavity cancer in the World....................... 174 28 Studies on HPV prevalence among cases of oropharyngeal cancer in the World.................... 180 29 Studies on HPV prevalence among cases of hypopharyngeal or laryngeal cancer in the World............ 185 30 Cervical cancer screening policy in the World......................................... 196 31 HPV vaccination policy in female population in the World................................. 206 32 References of studies included.................................................. 210

1 INTRODUCTION - 1-1 Introduction Figure 1: World s geographical regions Northern Europe Eastern Europe Northern America Western Europe Central Asia Caribbean Southern Europe Northern Africa Western Asia Southern Asia Eastern Asia Central America Western Africa South Eastern Asia Micronesia Middle Africa Eastern Africa Polynesia Melanesia South America Australia and New Zealand Southern Africa Data sources: United Nations Statistics Division- Standard Country and Area Codes Classifications. The ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre) aims to compile and centralize updated data and statistics on human papillomavirus (HPV) and HPV-related cancers. This report aims to summarize the data available to fully evaluate the burden of disease in NA and to facilitate stakeholders and relevant bodies of decision makers to formulate recommendations on the prevention of cervical cancer and other HPV-related cancers. Data include relevant cancer statistic estimates, epidemiological determinants of cervical cancer such as demographics, socioeconomic factors, risk factors, burden of HPV infection in women and men, and cervical screening and immunization practices. The report is structured into the following sections: Section 2, Demographic and socioeconomic factors (last update 25 Nov 2013). This section summarizes the socio-demographic profile of NA. For analytical purposes, NA divided into five regions: NA, NA, NA, NA, (Figure). Section 3, Burden of HPV related cancers. This section describes the current burden of invasive cervical cancer and other HPV-related cancers in NA with estimates of prevalence, incidence and mortality rates. Section 4, HPV related statistics. This section summarizes reports on prevalence of HPV and HPV type-specific distribution in women with normal cytology, women with precancerous lesions and invasive cervical cancer. In addition, the burden of HPV in other anogenital cancers (anus, vulva, vagina, and penis) are presented. Section 5, Factors contributing to cervical cancer (last update 08 Aug 2013). This section describes factors that can modify the natural history of HPV and cervical carcinogenesis such as the use of smoking, parity, oral contraceptive use and co-infection with HIV. Section 6, Reproductive and sexual behaviour (last update 08 Aug 2013). This section presents sexual and reproductive behaviour indicators that may be used as proxy measures of risk for HPV infection and anogenital cancers. Section 7, HPV preventive strategies. This section presents preventive strategies that include ba-

1 INTRODUCTION - 2 - sic characteristics and performance of cervical cancer screening status, status of HPV vaccine licensure introduction, and recommendations in national immunization programs. Section 8, Protective factors for cervical cancer (last update 30 Sep 2013). This section presents the prevalence of male circumcision and condom use that have shown a protective effect against HPV transmission.

2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS (LAST UPDATE 25 NOV 2013) - 3-2 Demographic and socioeconomic factors (last update 25 Nov 2013) Figure 2: Population pyramid estimates of the World compared to developing and developed regions for for 2013 Males World Females 80+ 75 79 70 74 65 69 60 64 55 59 50 54 45 49 40 44 35 39 30 34 25 29 20 24 15 19 10 14 5 9 Under 5 44,862,128 73,318,461 47,910,524 61,545,144 67,885,516 79,626,349 92,674,149 102,444,160 131,858,674 138,594,304 162,112,959 165,137,606 189,877,994 190,866,407 219,770,330 217,271,067 239,972,087 235,301,305 248,485,956 242,427,713 269,036,313 260,933,166 304,560,610 292,586,581 314,471,945 297,981,962 306,020,988 287,040,787 308,160,349 288,073,431 322,123,886 300,574,309 340,685,824 317,926,471 Less developed regions Males Females 80+ 75 79 70 74 65 69 60 64 55 59 50 54 45 49 40 44 35 39 30 34 25 29 20 24 15 19 10 14 5 9 Under 5 25,381,703 36,238,908 30,537,994 36,942,931 45,663,506 51,399,344 63,956,538 69,080,503 96,065,750 98,275,706 122,043,410 121,447,173 146,378,758 145,166,054 175,939,967 172,611,606 196,493,577 191,600,719 205,448,352 199,482,809 225,577,735 218,108,661 260,505,473 249,830,491 273,275,359 258,522,980 269,435,089 252,164,123 273,798,200 255,331,738 287,037,815 267,145,904 304,701,833 283,723,888 More developed regions Males Females 80+ 75 79 70 74 65 69 60 64 55 59 50 54 45 49 40 44 35 39 30 34 25 29 20 24 15 19 10 14 5 9 Under 5 19,480,425 37,079,553 17,372,530 24,602,213 22,222,010 28,227,005 28,717,611 33,363,657 35,792,924 40,318,598 40,069,549 43,690,433 43,499,236 45,700,353 43,830,363 44,659,461 43,478,510 43,700,586 43,037,604 42,944,904 43,458,578 42,824,505 44,055,137 42,756,090 41,196,586 39,458,982 36,585,899 34,876,664 34,362,149 32,741,693 35,086,071 33,428,405 35,983,991 34,202,583 Population by sex and age group Estimated population in a country, area or region as of 1 July of the year indicated. Data sources: United Nations, Department of Economic and Social Affairs, Population Division (2013). World Population Prospects: The 2012 Revision, CD-ROM Edition. Available at: http://esa.un.org/wpp/unpp/panel_population.htm

2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS (LAST UPDATE 25 NOV 2013) - 4 - Figure 3: Population trends of four selected age groups in the World compared to developing and developed regions for 2013 Projections World Projections Number of women (in millions) 700 600 500 400 300 200 100 Women 15 24 yrs Girls 10 14 yrs Number of women (in millions) 5,200 4,200 3,200 2,200 1,200 200 All Women Women 25 64 yrs 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 2060 2070 2080 2090 2100 Less developed regions Projections Number of women (in millions) 700 600 500 400 300 200 100 0 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 2060 2070 2080 2090 2100 Women 15 24 yrs Girls 10 14 yrs More developed regions Projections 700 600 500 400 300 200 100 0 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 2060 2070 2080 2090 2100 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 2060 2070 2080 2090 2100 Projections Number of women (in millions) 5,200 4,200 3,200 2,200 1,200 200 All Women Women 25 64 yrs 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 2060 2070 2080 2090 2100 Projections Number of women (in millions) Women 15 24 yrs Girls 10 14 yrs Number of women (in millions) 5,200 4,200 3,200 2,200 1,200 200 All Women Women 25 64 yrs 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 2060 2070 2080 2090 2100 Female population trends Number of women by year and age group Estimated population in a country, area or region as of 1 July of the year indicated. Data sources: United Nations, Department of Economic and Social Affairs, Population Division (2013). World Population Prospects: The 2012 Revision, CD-ROM Edition. Available at: http://esa.un.org/wpp/unpp/panel_population.htm

2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS (LAST UPDATE 25 NOV 2013) - 5 - Table 3: Population (in millions) estimates in the World for 2013 Region / Country Male Female 10-14 years 15+ years Total 10-14 years 15+ years Total World 308.16 2639.50 2947.66 288.07 2645.08 2933.15 Less developed regions 273.80 2136.70 2410.50 255.33 2100.87 2356.20 More developed regions 34.36 502.80 537.16 32.74 544.20 576.94 Africa 66.10 325.58 391.68 64.57 331.40 395.97 Eastern Africa 23.91 103.62 127.53 23.66 106.08 129.74 Middle Africa 8.61 36.92 45.53 8.55 37.83 46.38 Northern Africa 10.03 71.66 81.69 9.63 72.60 82.23 Southern Africa 2.86 20.19 23.05 2.84 21.95 24.79 Western Africa 20.69 93.19 113.88 19.89 92.94 112.83 Americas 40.56 358.85 399.41 38.94 379.02 417.96 Caribbean 1.87 15.51 17.39 1.81 16.10 17.90 Central America 8.60 55.81 64.41 8.24 61.39 69.63 Northern America 11.70 140.10 151.80 11.20 146.92 158.13 South America 18.38 147.43 165.81 17.69 154.61 172.30 Asia 181.17 1642.36 1823.53 165.26 1591.28 1756.54 Central Asia 2.83 22.24 25.07 2.72 23.51 26.23 Eastern Asia 48.07 681.18 729.25 41.93 655.52 697.45 South-Eastern Asia 28.30 221.39 249.68 27.07 229.04 256.11 Southern Asia 90.10 626.94 717.04 82.34 601.45 683.79 Western Asia 11.87 90.60 102.48 11.18 81.77 92.95 Europe 18.84 298.25 317.09 17.90 328.65 346.55 Eastern Europe 6.89 114.86 121.75 6.55 134.38 140.93 Northern Europe 2.82 40.39 43.20 2.69 42.42 45.11 Southern Europe 3.94 64.35 68.29 3.72 68.24 71.96 Western Europe 5.19 78.66 83.85 4.94 83.61 88.56 Oceania 1.49 14.47 15.95 1.41 14.73 16.13 Australia & New Zealand 0.88 11.09 11.97 0.84 11.41 12.25 Melanesia 0.55 2.96 3.51 0.51 2.90 3.41 Micronesia 0.03 0.18 0.21 0.03 0.18 0.20 Polynesia 0.04 0.24 0.27 0.03 0.23 0.27 Estimated population in a country, area or region as of 1 July of the year indicated. Americas: Including Bermuda, Greenland, and Saint-Pierre-et-Miquelon. Caribbean: Including Anguilla, Antigua, Aruba, British Virgin Islands, Cayman Islands, Domi Including Saint Helena, Ascension, and Tristan da Cunha. Eastern Africa: Including Seychelles. Less developed regions: The less developed regions comprise all regions of Africa, Asia (excluding Japan Micronesia: Including Falkland Islands (Malvinas). Including Kiribati, Marshall Islands, Nauru, Northern Mariana Islands and Palau. More developed regions: The more developed regions comprise all regions of Europe plus Northern America Northern America: Including Bermuda, Greenland, and Saint-Pierre-et-Miquelon. Including Anguilla, British Virgin Islands, Caribbean Netherlands, Cayman Islands, Dominica, Montserrat, Saint Kitts and Nevis, Sint Maarten (Dutch part) and Turks and Caicos Islands. Northern Europe: Including Faeroe Islands, and Isle of Man. Polynesia: Including American Samoa, Cook Islands, Pitcairn, Tokelau, Tuvalu, and Wallis an Including Marshall Islands, Nauru, Northern Mariana Islands, and Palau. South America: Including Falkland Islands (Malvinas). Including Bermuda, Greenland, and Saint Pierre and Miquelon. Southern Europe: Including Andorra, Gibraltar, Holy See, and San Marino. Aggregated by the HPV Information Centre pooling its individual areas/countries. Western Africa: Including Liechtenstein, and Monaco. Including Saint Helena, Ascension and Tristan da Cunha. Western Europe: Including Andorra, Gibraltar, Holy See, and San Marino. Including Liechtenstein, and Monaco. Data sources: United Nations, Department of Economic and Social Affairs, Population Division (2013). World Population Prospects: The 2012 Revision, CD-ROM Edition. Available at: http://esa.un.org/wpp/unpp/panel_population.htm Table 4: Sociodemographic indicators in the World for 2013 Indicator Male Female Total Population in 1,000s 1,a 3,551,649.3 b 3,610,470.1 b 7,162,119.2 b Population growth rate (%) 1 - - 1.2 c Median age of the population (years) 1 - - 28.5 d Population living in urban areas (%) 2 - - 51.6 d Crude birth rate (births per 1,000 population) 1 - - 20.1 c Crude death rate (deaths per 1,000 population) 1 - - 8.1 c Life expectancy at birth (years) - - - Adult mortality rate (probability of dying between 15 and 60 - - - years per 1,000 population) Under-five mortality rate (per 1,000 live births) - - - Gross national income per capita (PPP int $) 3 - - 12,079 e Density of physicians (per 10,000 population) - - - (Continued)

2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS (LAST UPDATE 25 NOV 2013) - 6 - Table 4 Continued Indicator Male Female Total Adult (15 years and over) literacy rate (%) - - - Youth (15-24 years) literacy rate (%) - - - Net primary school enrollment ratio 4 87.8 d 89.7 d 88.8 d Net secondary school enrollment ratio 4 61.3 d 63.7 d 62.5 d PPP int. $: purchasing power parity at international dollar rate. a Estimated population in a country, area or region as of 1 July of the year indicated. Year of estimation: b 2013 ; c 2005-2010 ; d 2010 ; e 2012; Data sources: 1 United Nations, Department of Economic and Social Affairs, Population Division (2013). World Population Prospects: The 2012 Revision, CD-ROM Edition. Available at: http://esa.un.org/wpp/unpp/panel_population.htm 2 United Nations, Department of Economic and Social Affairs, Population Division (2012). World Urbanization Prospects : The 2011 Revision. CD-ROM Edition - Data in digital form (POP/ DB/WUP/Rev.2011). 3 World Development Indicators Database, 2013. Washington, DC, World Bank. Available at: http://databank.worldbank.org/data/download/gni.pdf [Accessed on July 2013] 4 UNESCO Institute for Statistics Data Centre [online database]. Montreal, UNESCO Institute for Statistics, 2013. Available at: http://stats.uis.unesco.org [Accessed on July 2013]

3 BURDEN OF HPV RELATED CANCERS - 7-3 Burden of HPV related cancers 3.1 Cervical cancer Cancer of the cervix uteri is the 4th most common cancer among women worldwide, with an estimated 527,624 new cases and 265,653 deaths in 2012. Worldwide, mortality rates of cervical cancer are substantially lower than incidence with a ratio of mortality to incidence to 50.3% (GLOBOCAN 2012). The majority of cases are squamous cell carcinoma followed by adenocarcinomas. (Vaccine 2006, Vol. 24, Suppl 3; Vaccine 2008, Vol. 26, Suppl 10; Vaccine 2012, Vol. 30, Suppl 5; IARC Monographs 2007, Vol. 90) This section describes the current burden of invasive cervical cancer in World and its regions with estimates of annual number of new cases, deaths, and incidence and mortality rates. 3.1.1 Incidence (last update 22 Jul 2014) KEY STATS. About 527,624 new cervical cancer cases are diagnosed annually in World (estimations for 2012). Cervical cancer ranks as the 4 th cause of female cancer in World. Cervical cancer is the 2 nd most common female cancer in women aged 15 to 44 years in World. Figure 4: Age-standardized incidence rates of cervical cancer in World (estimations for 2012) ASR, age-standardized incidence rates; Rates per 100,000 women per year. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 8 - Table 5: Incidence of cervical cancer by regions and sub-regions in the World (estimations for 2012) Cumulative risk (%) Ranking of CC Area N cases Crude rate a ASR a ages 0-74 yrs b All women Women 15-44 yrs World 527,624 15.1 14.0 1.4 4 2 Less developed 444,546 15.6 15.7 1.6 2 2 regions More developed 83,078 13.0 9.9 0.9 11 2 regions Africa 99,038 18.5 27.6 3.0 2 2 Eastern Africa 45,707 25.8 42.7 4.6 1 1 Middle Africa 11,540 17.2 30.6 3.4 1 2 Northern Africa 5,813 5.6 6.6 0.7 4 4 Southern Africa 8,652 29.3 31.5 3.1 2 1 Western Africa 27,326 17.2 29.3 3.2 2 2 Americas 83,195 17.2 14.9 1.4 4 2 Caribbean 5,018 23.6 21.0 2.0 2 2 Central America 18,792 23.1 23.5 2.3 2 1 Northern America 14,377 8.1 6.6 0.6 13 4 South America 45,008 22.2 20.3 2.0 2 2 Asia 284,823 13.7 12.7 1.3 3 2 Central Asia 5,850 18.5 18.6 1.8 2 1 Eastern Asia 78,006 10.1 7.9 0.7 7 2 South-Eastern 50,566 16.6 16.3 1.7 2 2 Asia Southern Asia 145,946 17.1 19.3 2.1 2 2 Western Asia 4,455 3.8 4.4 0.5 11 4 Europe 58,373 15.2 11.4 1.1 6 2 Eastern Europe 33,882 21.7 16.3 1.5 4 2 Northern Europe 5,382 10.6 8.7 0.8 10 3 Southern Europe 9,285 11.6 8.5 0.8 11 2 Western Europe 9,824 10.2 7.3 0.7 14 4 Oceania 2,195 11.7 10.2 0.9 8 3 Australia & New 938 6.8 5.5 0.5 12 4 Zealand Melanesia 1,198 26.8 33.3 3.2 2 1 Micronesia 23 8.5 8.7 0.9 6 4 Polynesia 36 10.8 11.0 1.1 5 3 ASR: Age-standardised rate. a Rates per 100,000 women per year. b Cumulative risk (incidence) is the probability or risk of individuals getting from the disease during ages 0-74 years. For cancer, it is expressed as the % of new born children who would be expected to develop from a particular cancer before the age of 75 if they had the rates of cancer observed in the period in the absence of competing causes. Western Asia estimates for Globocan 2012 do not include Cyprus. Cyprus accounts for Southern Europe estimates. Standardised rates have ben estimated using the direct method and the World population as the reference. Ranking of cervical cancer incidence to other cancers among all women ages 15-44 years according to highest incidence rates (ranking 1st). Ranking is based on crude incidence rates (actual number of cervical cancer cases). Ranking using ASR may differ. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 9 - Figure 5: Ranking of cervical cancer to others cancers among all women and women ages 15-44 years, according to incidence rates in World (estimations for 2012) Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014. Includes anal cancer (C21).

3 BURDEN OF HPV RELATED CANCERS - 10 - Figure 6: World age-standarized incidence rates compared to regions and sub-regions (estimations for 2012) World, developed and developing regions Continent's sub regions Less developed regions 15.7 Eastern Africa 42.7 Melanesia 33.3 Southern Africa 31.5 Middle Africa 30.6 World 14.0 Western Africa 29.3 Central America 23.5 Caribbean 21.0 South America 20.3 More developed regions 9.9 Southern Asia Central Asia 19.3 18.6 0 10 20 South Eastern Asia 16.3 Africa Five continents 27.6 Eastern Europe Polynesia Micronesia 16.3 11.0 8.7 Americas 14.9 Northern Europe Southern Europe 8.7 8.5 Eastern Asia 7.9 Asia 12.7 Western Europe 7.3 Northern America 6.6 Europe 11.4 Northern Africa Australia \& New Zealand 6.6 5.5 Oceania 10.2 Western Asia 4.4 0 10 20 30 0 10 20 30 40 50 Cervical cancer: Age standardized incidence rate per 100,000 women per year World Standard. Female (All ages) Rates per 100,000 women per year. Western Asia estimates for Globocan 2012 do not include Cyprus. Cyprus accounts for Southern Europe estimates. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 11 - Figure 7: Ten most frequent cancer in all women in the World compared to developing and developed regions (estimations for 2012) Less developed regions More developed regions World Breast 31.3 Breast 74.1 Breast 43.3 Cervix uteri 15.7 Colorectum 23.6 Colorectum 14.3 Lung 11.1 Lung 19.6 Cervix uteri 14.0 Colorectum 9.8 Corpus uteri 14.7 Lung 13.6 Stomach 7.8 Thyroid 11.1 Corpus uteri 8.2 Liver 6.6 Cervix uteri 9.9 Stomach 7.5 Corpus uteri 5.5 Melanoma of skin 9.3 Ovary 6.1 Ovary 5.0 Ovary 9.1 Thyroid 6.1 Thyroid 4.7 Non Hodgkin lymphoma 7.1 Liver 5.4 Oesophagus 4.1 Stomach 6.7 Non Hodgkin lymphoma 4.1 0 15 30 45 60 75 0 15 30 45 60 75 0 15 30 45 60 75 Age standardized incidence rate per 100,000 women per year Kaposi sarcoma estimates available for Sub-Saharan Africa countries only. Includes HIV disease resulting in Kaposi sarcoma Cancer of the colorectum: Includes anal cancer (C21). Kaposi Sarcoma: Includes B21.0 (HIV disease resulting in Kaposi sarcoma). Non-Hodgkin lymphoma: Includes HIV disease resulting in malignant neoplasms (B21). Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 12 - Figure 8: Ten most frequent cancer in all women in the World compared to the continents (estimations for 2012) Africa Europe Breast 36.2 Breast 71.1 Cervix uteri 27.6 Colorectum 23.6 Colorectum 5.8 Lung 15.1 Liver 5.8 Corpus uteri 13.9 Ovary 4.8 Cervix uteri 11.4 Non Hodgkin lymphoma 3.8 Ovary 9.9 Oesophagus 3.5 Melanoma of skin 8.9 Corpus uteri 3.5 Thyroid 7.8 Stomach 3.2 Stomach 6.4 Kaposi sarcoma 2.9 Non Hodgkin lymphoma 5.9 0 15 30 45 60 75 90 0 15 30 45 60 75 90 Americas Oceania Breast 67.6 Breast 79.2 Lung 21.6 Colorectum 29.2 Colorectum 17.6 Melanoma of skin 25.5 Cervix uteri 14.9 Lung 20.0 Corpus uteri 12.3 Corpus uteri 12.3 Thyroid 12.1 Thyroid 11.3 Non Hodgkin lymphoma 7.0 Cervix uteri 10.2 Ovary 6.8 Non Hodgkin lymphoma 9.4 Melanoma of skin 6.2 Ovary 8.0 Leukaemia 5.6 Leukaemia 6.4 0 15 30 45 60 75 90 0 15 30 45 60 75 90 Asia World Breast 29.1 Breast 43.3 Cervix uteri 12.7 Colorectum 14.3 Lung 12.7 Cervix uteri 14.0 Colorectum 11.1 Lung 13.6 Stomach 9.3 Corpus uteri 8.2 Liver 6.9 Stomach 7.5 Corpus uteri 5.9 Ovary 6.1 Ovary 5.0 Thyroid 6.1 Thyroid 5.0 Liver 5.4 Oesophagus 4.3 Non Hodgkin lymphoma 4.1 0 15 30 45 60 75 90 0 15 30 45 60 75 90 Age standardized incidence rate per 100,000 women per year Kaposi sarcoma estimates available for Sub-Saharan Africa countries only. Includes HIV disease resulting in Kaposi sarcoma Cancer of the colorectum: Includes anal cancer (C21). Kaposi Sarcoma: Includes B21.0 (HIV disease resulting in Kaposi sarcoma). Non-Hodgkin lymphoma: Includes HIV disease resulting in malignant neoplasms (B21). (Continued on next page)

3 BURDEN OF HPV RELATED CANCERS - 13 - ( Figure 8 continued from previous page) Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014. Figure 9: Ten most frequent cancers in women ages 15-44 yrs in the World compared to developing and developed regions (estimations for 2012) Less developed regions More developed regions World Breast 19.0 Breast 37.7 Breast 21.9 Cervix uteri 11.0 Cervix uteri 11.8 Cervix uteri 11.1 Thyroid 4.7 Thyroid 11.7 Thyroid 5.8 Ovary 2.8 Melanoma of skin 8.2 Ovary 3.1 Colorectum 2.1 Ovary 4.8 Colorectum 2.5 Leukaemia 2.1 Colorectum 4.4 Corpus uteri 2.2 Corpus uteri 2.0 Corpus uteri 3.4 Leukaemia 2.1 Brain, nervous system 1.6 Hodgkin lymphoma 2.9 Brain, nervous system 1.7 Stomach 1.5 Brain, nervous system 2.7 Non Hodgkin lymphoma 1.6 Non Hodgkin lymphoma 1.4 Non Hodgkin lymphoma 2.7 Lung 1.5 0 10 20 30 40 0 10 20 30 40 0 10 20 30 40 Age standardized incidence rate per 100,000 women per year Kaposi sarcoma estimates available for Sub-Saharan Africa countries only. Includes HIV disease resulting in Kaposi sarcoma Cancer of the colorectum: Includes anal cancer (C21). Kaposi Sarcoma: Includes B21.0 (HIV disease resulting in Kaposi sarcoma). Non-Hodgkin lymphoma: Includes HIV disease resulting in malignant neoplasms (B21). Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 14 - Figure 10: Ten most frequent cancers in women ages 15-44 yrs in the World compared to the continents (estimations for 2012) Africa Europe Breast 20.3 Breast 36.1 Cervix uteri 12.5 Cervix uteri 13.2 Kaposi sarcoma 3.9 Melanoma of skin 8.0 Ovary 2.4 Thyroid 7.3 Non Hodgkin lymphoma 2.3 Ovary 5.1 Colorectum 1.9 Colorectum 3.8 Liver 1.6 Hodgkin lymphoma 3.2 Thyroid 1.5 Brain, nervous system 2.8 Leukaemia 1.4 Corpus uteri 2.5 Stomach 0.7 Non Hodgkin lymphoma 2.5 0 10 20 30 40 0 10 20 30 40 Americas Oceania Breast 27.2 Breast 37.2 Cervix uteri 15.3 Melanoma of skin 15.8 Thyroid 12.2 Cervix uteri 12.7 Melanoma of skin 3.9 Thyroid 11.6 Colorectum 3.6 Colorectum 4.2 Ovary 3.2 Ovary 4.0 Leukaemia 2.5 Corpus uteri 2.7 Brain, nervous system 2.4 Non Hodgkin lymphoma 2.6 Corpus uteri 2.3 Hodgkin lymphoma 2.4 Non Hodgkin lymphoma 2.3 Lip, oral cavity 2.4 0 10 20 30 40 0 10 20 30 40 Asia World Breast 18.8 Breast 21.9 Cervix uteri 9.5 Cervix uteri 11.1 Thyroid 5.1 Thyroid 5.8 Ovary 3.0 Ovary 3.1 Corpus uteri 2.5 Colorectum 2.5 Colorectum 2.2 Corpus uteri 2.2 Leukaemia 2.2 Leukaemia 2.1 Brain, nervous system 1.7 Brain, nervous system 1.7 Stomach 1.7 Non Hodgkin lymphoma 1.6 Lung 1.5 Lung 1.5 0 10 20 30 40 0 10 20 30 40 Age standardized incidence rate per 100,000 women per year Kaposi sarcoma estimates available for Sub-Saharan Africa countries only. Includes HIV disease resulting in Kaposi sarcoma Cancer of the colorectum: Includes anal cancer (C21). Kaposi Sarcoma: Includes B21.0 (HIV disease resulting in Kaposi sarcoma). Non-Hodgkin lymphoma: Includes HIV disease resulting in malignant neoplasms (B21). (Continued on next page)

3 BURDEN OF HPV RELATED CANCERS - 15 - ( Figure 10 continued from previous page) Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014. Figure 11: Age-specific incidence of cervical cancer in World and its regions (estimations for 2012) World Africa Americas Asia Europe Oceania Age specific rates of cervical cancer per 100,000 100 75 50 25 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 Rates per 100,000 women per year. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 16 - Figure 12: Annual number of new cases of cervical cancer by age group in developed and developing regions and five continents (estimations for 2012) DEVELOPED AND DEVELOPING REGIONS Less developed regions More developed regions Annual number of new cases of cervical cancer 300000 250000 200000 150000 100000 50000 0 44739 278880 19757 91746 73762 15 39 40 64 65+ 18575 Asia Africa FIVE CONTINENTS Americas Europe Oceania Annual number of new cases of cervical cancer 300000 250000 200000 150000 100000 50000 0 13249 701 188892 22725 55178 19650 32345 58316 1151 42915 17537 40668 15 39 40 64 65+ 343 12775 21014 Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 17 - Figure 13: Annual number of cases and age-specific incidence rates of cervical cancer in World and its regions (estimations for 2012) World Africa Age specific rates of cervical cancer per 100,000 90 60 30 0 90 60 30 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75+ 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75+ 323619* 300000 Annual number of cases of cervical cancer 250000 200000 150000 100000 111503* 92337 150000 100000 50000 58316* 50000 19650* 21014 0 0 15 39 40 64 65+ 15 39 40 64 65+ * World 15-19 yrs: 754 cases. 20-24 yrs: 6445 cases. 25-29 yrs: 19167 cases. 30-34 yrs: 34149 cases. 35-39 yrs: 50988 cases. 40-44 yrs: 66308 cases. 45-49 yrs: 73307 cases. 50-54 yrs: 71492 cases. 55-59 yrs: 63571 cases. 60-64 yrs: 48941 cases. Africa 15-19 yrs: 352 cases. 20-24 yrs: 1091 cases. 25-29 yrs: 3310 cases. 30-34 yrs: 6198 cases. 35-39 yrs: 8686 cases. 40-44 yrs: 10474 cases. 45-49 yrs: 11987 cases. 50-54 yrs: 12753 cases. 55-59 yrs: 12342 cases. 60-64 yrs: 10760 cases. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 18 - Figure 14: Annual number of cases and age-specific incidence rates of cervical cancer in World and its regions (estimations for 2012) (Continued) Americas Europe Age specific rates of cervical cancer per 100,000 90 60 30 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75+ 90 60 30 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75+ Annual number of cases of cervical cancer 150000 100000 50000 0 42915* 22725* 17537 150000 100000 50000 0 32345* 13249* 12775 15 39 40 64 65+ 15 39 40 64 65+ Asia Oceania Age specific rates of cervical cancer per 100,000 90 60 30 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75+ 90 60 30 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75+ 188892* Annual number of cases of cervical cancer 150000 100000 50000 0 55178* 40668 150000 100000 50000 0 701* 1151* 343 15 39 40 64 65+ 15 39 40 64 65+ Age group (years) * Americas 15-19 yrs: 180 cases. 20-24 yrs: 2047 cases. 25-29 yrs: 4668 cases. 30-34 yrs: 6901 cases. 35-39 yrs: 8883 cases. 40-44 yrs: 9817 cases. 45-49 yrs: 9862 cases. 50-54 yrs: 8951 cases. 55-59 yrs: 7771 cases. 60-64 yrs: 6514 cases. Asia 15-19 yrs: 195 cases. 20-24 yrs: 2443 cases. 25-29 yrs: 8394 cases. 30-34 yrs: 16585 cases. 35-39 yrs: 27561 cases. 40-44 yrs: 39251 cases. 45-49 yrs: 44160 cases. 50-54 yrs: 42416 cases. 55-59 yrs: 36759 cases. 60-64 yrs: 26306 cases. Europe 15-19 yrs: 22 cases. 20-24 yrs: 798 cases. 25-29 yrs: 2639 cases. 30-34 yrs: 4235 cases. 35-39 yrs: 5548 cases. 40-44 yrs: 6449 cases. 45-49 yrs: 7020 cases. 50-54 yrs: 7137 cases. 55-59 yrs: 6518 cases. 60-64 yrs: 5221 cases. Oceania 15-19 yrs: 4 cases. 20-24 yrs: 60 cases. 25-29 yrs: 144 cases. 30-34 yrs: 208 cases. 35-39 yrs: 280 cases. 40-44 yrs: 317 cases. 45-49 yrs: 278 cases. 50-54 yrs: 235 cases. 55-59 yrs: 181 cases. 60-64 yrs: 140 cases. (Continued on next page)

3 BURDEN OF HPV RELATED CANCERS - 19 - ( Figure 14 continued from previous page) Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 20 - NOTE. For time trends in cervical cancer incidence please refer to specific countries 3.1.2 Mortality (last update 14 Jul 2014) KEY STATS. About 265,653 new cervical cancer deaths occur annually in World (estimations for 2012). Cervical cancer ranks as the 4 th cause of female cancer deaths in World. Cervical cancer is the 2 nd most common female cancer deaths in women aged 15 to 44 years in World. Figure 15: Age-standardized mortality rates of cervical cancer in World (estimations for 2012) ASR, age-standardized moratlity rates; Rates per 100,000 women per year. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 21 - Table 6: Cervical cancer mortality in regions and sub-regions in the World (estimations for 2012) Cumulative risk (%) Ranking of CC Area N cases Crude rate a ASR a ages 0-74 yrs b All women Women 15-44 yrs World 265653 7.6 6.8 0.8 4 2 Less developed 230158 8.1 8.3 0.9 3 2 regions More developed 35495 5.5 3.3 0.3 9 2 regions Africa 60098 11.2 17.5 2.0 2 2 Eastern Africa 28197 15.9 27.6 3.1 1 1 Middle Africa 7917 11.8 22.2 2.6 1 2 Northern Africa 2717 2.6 3.2 0.4 8 8 Southern Africa 4721 16.0 17.9 1.9 1 1 Western Africa 16546 10.4 18.5 2.1 2 2 Americas 35673 7.4 5.9 0.6 5 2 Caribbean 2254 10.6 8.6 0.9 4 2 Central America 6937 8.5 8.9 1.0 2 1 Northern America 7108 4.0 2.6 0.3 11 2 South America 19374 9.5 8.6 0.9 3 2 Asia 144434 7.0 6.4 0.7 6 2 Central Asia 2286 7.2 7.7 0.8 3 2 Eastern Asia 36320 4.7 3.3 0.3 8 2 South-Eastern 23989 7.9 7.9 0.9 3 2 Asia Southern Asia 79958 9.4 11.0 1.2 2 2 Western Asia 1881 1.6 1.9 0.2 11 9 Europe 24385 6.4 3.8 0.4 7 2 Eastern Europe 15436 9.9 6.2 0.6 7 1 Northern Europe 1944 3.8 2.2 0.2 16 2 Southern Europe 3526 4.4 2.4 0.2 13 3 Western Europe 3479 3.6 1.8 0.2 15 4 Oceania 1063 5.6 4.5 0.5 6 2 Australia & New 357 2.6 1.5 0.2 17 5 Zealand Melanesia 684 15.3 20.7 2.2 1 1 Micronesia 6 2.2 2.7 0.4 6 25 Polynesia 16 4.8 5.1 0.6 4 2 ASR: Age-standardised rate. a Rates per 100,000 women per year. b Cumulative risk (mortality) is the probability or risk of individuals dying from the disease during ages 0-74 years. For cancer, it is expressed as the % of new born children who would be expected to die from a particular cancer before the age of 75 if they had the rates of cancer observed in the period in the absence of competing causes. Western Asia estimates for Globocan 2012 do not include Cyprus. Cyprus accounts for Southern Europe estimates. Standardised rates have ben estimated using the direct method and the World population as the reference. Ranking of cervical cancer mortality to other cancers among all women ages 15-44 years according to highest mortality rates (ranking 1st). Ranking is based on crude mortality rates(actual number of cervical cancer deaths). Ranking using AST may differ. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 22 - Figure 16: World age-standardized mortality rates of cervical cancer compared to regions and subregions (estimations for 2012) World, developed and developing regions Continent's sub regions Less developed regions Eastern Africa 27.6 Middle Africa 22.2 Melanesia 20.7 Western Africa 18.5 World Southern Africa 17.9 Southern Asia 11.0 Central America 8.9 South America 8.6 Caribbean 8.6 More developed regions South Eastern Asia 7.9 0 10 Central Asia 7.7 Africa Five continents 17.5 Eastern Europe Polynesia Eastern Asia 6.2 5.1 3.3 Asia 6.4 Northern Africa Micronesia 3.2 2.7 Northern America 2.6 Americas 5.9 Southern Europe 2.4 Northern Europe 2.2 Oceania 4.5 Western Asia Western Europe 1.9 1.8 Europe 3.8 Australia & New Zealand 1.5 0 10 20 0 10 20 30 Cervical cancer: Age standardized mortality rate per 100,000 women per year World Standard. Female (All ages) Rates per 100,000 women per year. Western Asia estimates for Globocan 2012 do not include Cyprus. Cyprus accounts for Southern Europe estimates. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 23 - Figure 17: Ranking of cervical cancer to others cancers among all women and women ages 15-44 years, according to mortality rates in World (estimations for 2012) Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014. Includes anal cancer (C21).

3 BURDEN OF HPV RELATED CANCERS - 24 - Figure 18: Age-specific mortality of cervical cancer in World and its regions (estimations for 2012) World Europe Africa Americas Oceania Asia Age specific mortality rates of cervical cancer per 100,000 100 80 60 40 20 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 Age group (years) Rates per 100,000 women per year. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 25 - Figure 19: Annual number of deaths of cervical cancer by age group in developed and developing regions and five continents (estimations for 2012) DEVELOPED AND DEVELOPING REGIONS Less developed regions More developed regions Annual number of cervical cancer deaths 150000 100000 50000 0 16940 134922 70041 3071 25130 15 39 40 64 65+ 15484 Asia Africa FIVE CONTINENTS Americas Europe Oceania 150000 11769 545 Annual number of cervical cancer deaths 100000 50000 0 4168 2212 189 8065 13567 33320 18020 88208 13476 42647 15 39 40 64 65+ 329 10404 18669 Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 26 - Figure 20: Annual number of deaths and age-specific mortality rates of cervical cancer in World and its regions (estimations for 2012) World Africa Age specific rates of cervical cancer per 100,000 90 75 60 45 30 15 0 90 75 60 45 30 15 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75+ 15 19 20 24 25 29 30 34 35 39 40 44 45 49 Annual number of deaths of cervical cancer 50 54 55 59 60 64 65 69 70 74 75+ 156000 144000 132000 120000 108000 96000 84000 72000 60000 48000 36000 24000 12000 0 28201* 151862* 85525 90000 80000 70000 60000 50000 40000 30000 20000 10000 0 8065* 33320* 18669 15 39 40 64 65+ 15 39 40 64 65+ * World 15-19 yrs: 314 cases. 20-24 yrs: 1101 cases. 25-29 yrs: 3654 cases. 30-34 yrs: 8158 cases. 35-39 yrs: 14974 cases. 40-44 yrs: 22872 cases. 45-49 yrs: 30105 cases. 50-54 yrs: 33938 cases. 55-59 yrs: 34259 cases. 60-64 yrs: 30688 cases. Africa 15-19 yrs: 265 cases. 20-24 yrs: 553 cases. 25-29 yrs: 1331 cases. 30-34 yrs: 2360 cases. 35-39 yrs: 3551 cases. 40-44 yrs: 4707 cases. 45-49 yrs: 6021 cases. 50-54 yrs: 7190 cases. 55-59 yrs: 7801 cases. 60-64 yrs: 7601 cases. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 27 - Figure 21: Annual number of deaths and age-specific mortality rates of cervical cancer in World and its regions (estimations for 2012) (Continued) Americas Europe Age specific rates of cervical cancer per 100,000 90 75 60 45 30 15 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75+ 90 75 60 45 30 15 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75+ Annual number of deaths of cervical cancer 90000 80000 70000 60000 50000 40000 30000 20000 10000 0 4168* 18020* 13476 90000 80000 70000 60000 50000 40000 30000 20000 10000 0 2212* 11769* 10404 15 39 40 64 65+ 15 39 40 64 65+ Asia Oceania Age specific rates of cervical cancer per 100,000 90 75 60 45 30 15 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75+ 90 75 60 45 30 15 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75+ Annual number of deaths of cervical cancer 90000 80000 70000 60000 50000 40000 30000 20000 10000 0 13567* 88208* 42647 90000 80000 70000 60000 50000 40000 30000 20000 10000 0 189* 545* 329 15 39 40 64 65+ 15 39 40 64 65+ Age group (years) * Americas 15-19 yrs: 12 cases. 20-24 yrs: 137 cases. 25-29 yrs: 620 cases. 30-34 yrs: 1325 cases. 35-39 yrs: 2067 cases. 40-44 yrs: 2852 cases. 45-49 yrs: 3629 cases. 50-54 yrs: 3997 cases. 55-59 yrs: 3944 cases. 60-64 yrs: 3598 cases. Asia 15-19 yrs: 34 cases. 20-24 yrs: 363 cases. 25-29 yrs: 1333 cases. 30-34 yrs: 3699 cases. 35-39 yrs: 8138 cases. 40-44 yrs: 13641 cases. 45-49 yrs: 18256 cases. 50-54 yrs: 19983 cases. 55-59 yrs: 19563 cases. 60-64 yrs: 16765 cases. Europe 15-19 yrs: 2 cases. 20-24 yrs: 32 cases. 25-29 yrs: 332 cases. 30-34 yrs: 715 cases. 35-39 yrs: 1131 cases. 40-44 yrs: 1565 cases. 45-49 yrs: 2088 cases. 50-54 yrs: 2646 cases. 55-59 yrs: 2846 cases. 60-64 yrs: 2624 cases. Oceania 15-19 yrs: 1 cases. 20-24 yrs: 16 cases. 25-29 yrs: 36 cases. 30-34 yrs: 56 cases. 35-39 yrs: 80 cases. 40-44 yrs: 107 cases. 45-49 yrs: 111 cases. 50-54 yrs: 122 cases. 55-59 yrs: 105 cases. 60-64 yrs: 100 cases. (Continued on next page)

3 BURDEN OF HPV RELATED CANCERS - 28 - ( Figure 21 continued from previous page) Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 29-3.1.3 Comparison of incidence and mortality (last update 14 Jul 2014) Figure 22: Age-specific incidence and mortality rates of cervical cancer in World and its regions (estimations for 2012) 110 100 90 80 70 60 50 40 30 20 10 0 World 110 100 90 80 70 60 50 40 30 20 10 0 Americas Age specific rates of cervical cancer per 100,000 110 100 90 80 70 60 50 40 30 20 10 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 Europe 55 59 60 64 65 69 70 74 >=75 110 100 90 80 70 60 50 40 30 20 10 0 15 19 15 19 20 24 20 24 25 29 30 34 35 39 40 44 45 49 25 29 30 34 50 54 55 59 60 64 65 69 70 74 >=75 35 39 40 44 45 49 50 54 55 59 Oceania 15 19 20 24 25 29 30 34 60 64 65 69 70 74 >=75 35 39 40 44 45 49 50 54 55 59 60 64 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 65 69 70 74 >=75 110 100 90 80 70 60 50 40 30 20 10 0 Africa 110 100 90 80 70 60 50 40 30 20 10 0 Asia Incidence 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 Mortality Age group (years) Rates per 100,000 women per year. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 30-3.2 Anogenital cancers other than the cervix Data on HPV role in anogenital cancers other than the cervix are limited, but there is an increasing body of evidence strongly linking HPV DNA with cancers of the anus, vulva, vagina, and penis. Although these cancers are much less frequent compared to cervical cancer, their association with HPV make them potentially preventable and subject to similar preventative strategies as those for cervical cancer. (Vaccine 2006, Vol. 24, Suppl 3; Vaccine 2008, Vol. 26, Suppl 10; Vaccine 2012, Vol. 30, Suppl 5; IARC Monographs 2007, Vol. 90) 3.2.1 Anal cancer (last update 22 Jul 2014) Anal cancer is rare in general population with an average worldwide incidence of 1 per 100,000, but is reported to be increasing in more developed regions. Globally, there are an estimated 27,000 new cases every year (de Martel C et al. Lancet Oncol 2012;13(6):607-15). Women have higher incidences of anal cancer than men. Incidence is particularly high among populations of men who have sex with men (MSM), women with history of cervical or vulvar cancer, and immunosuppressed populations, including those who are HIV-infected and patients with a history of organ transplantation. These cancers are predominantly squamous cell carcinoma, adenocarcinomas, or basaloid and cloacogenic carcinomas. Table 7: Incidence of anal cancer by cancer registry and sex Male Female Country / Registry Period N cases a Crude rate b ASR b N cases a Crude rate c ASR c Algeria Algeria Setif 2003-2007 8 0.2 0.3 1 0.0 0.1 Egypt Gharbiah 2003-2007 36 0.4 0.5 40 0.4 0.5 Gambia National 1997-1998 1 0.1 0.2 2 0.2 0.3 Libya Benghazi 2003-2005 5 0.2 0.3 3 0.1 0.2 Malawi Blantyre 2003-2007 3 0.1 0.2 4 0.2 0.5 Mali Bamako 1994-1996 4 0.3 0.6 6 0.5 1.1 South Africa PROMEC 2003-2007 9 0.4 0.7 3 0.1 0.1 Tunisia North 2003-2005 23 0.3 0.3 11 0.2 0.2 Uganda Kyadondo county 2003-2007 5 0.1 0.3 7 0.1 0.5 Zimbabwe Harare 2003-2006 3 0.1 0.4 2 0.1 0.2 Argentina Argentina Bahia Blanca 2003-2007 3 0.4 0.4 10 1.3 0.8 Cordoba 2004-2007 20 0.8 0.7 16 0.6 0.4 Mendoza 2003-2007 21 0.5 0.4 33 0.8 0.6 Tierra del Fuego 2003-2007 1 0.3 0.2 0 0.0 0.0 Brazil Aracaju 2003-2006 9 1.0 1.4 11 1.0 1.2 Canada Belo Horizonte 2003-2005 25 0.8 0.9 53 1.4 1.4 Cuiaba 2003-2006 10 0.7 0.8 13 0.8 1.2 Fortaleza 2003-2006 13 0.3 0.4 49 1.0 1.2 Goiania 2003-2007 12 0.4 0.6 33 1.1 1.2 Sao Paulo 2003-2007 235 0.9 1.0 387 1.4 1.3 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 31 - Table 7 Continued Male Female Country / Registry Period N cases a Crude rate b ASR b N cases a Crude rate c ASR c Alberta 2003-2007 60 0.7 0.5 135 1.6 1.2 British Columbia 2003-2007 150 1.4 1.0 215 2.0 1.2 Manitoba 2003-2007 28 1.0 0.7 51 1.7 1.1 National 2003-2007 1114 1.4 0.9 1492 1.8 1.1 New Brunswick 2003-2007 23 1.3 0.8 30 1.6 0.9 Newfoundland and 2003-2007 8 0.6 0.4 17 1.3 0.8 Labrador Northwest Territories 2003-2007 0 0.0 0.0 2 1.9 1.7 Nova Scotia 2003-2007 34 1.5 0.9 47 2.0 1.1 Ontario 2003-2007 585 1.9 1.3 693 2.2 1.4 Prince Edward Island 2003-2007 2 0.6 0.4 8 2.3 1.5 Quebec 2003-2007 196 1.0 0.7 257 1.3 0.8 Saskatchewan 2003-2007 27 1.1 0.7 37 1.5 0.8 Yukon 2003-2007 1 1.2 0.8 0 0.0 0.0 Chile Biobio Province 2003-2007 3 0.3 0.3 2 0.2 0.1 Region of Antofagasta 2003-2007 4 0.3 0.4 14 1.1 1.0 Valdivia 2003-2007 5 0.5 0.5 7 0.8 0.7 Colombia Bucaramanga 2003-2007 6 0.2 0.3 35 1.3 1.4 Cali 2003-2007 29 0.6 0.7 101 1.9 1.9 Manizales 2003-2007 12 1.3 1.3 10 1.0 0.8 Pasto 2003-2007 2 0.2 0.3 8 0.8 0.8 Costa Rica National 2003-2007 44 0.4 0.5 56 0.5 0.6 Cuba Villa Clara 2004-2007 13 0.8 0.6 20 1.2 0.8 Ecuador Cuenca 2003-2007 2 0.2 0.2 2 0.2 0.2 Quito 2003-2007 5 0.1 0.2 25 0.6 0.7 Jamaica Kingston and St Andrew 2003-2007 6 0.4 0.4 16 0.9 1.0 Peru Trujillo 1998-2002 4 0.3 0.5 13 0.8 1.2 United States of America NPCR 2003-2007 8243 1.3 0.9 13207 2.0 1.3 Uruguay National 2005-2007 62 1.3 0.9 73 1.4 0.8 Bahrain Bahrain National 2003-2007 6 0.5 0.8 2 0.2 0.3 China Beijing City 2003-2007 35 0.2 0.1 25 0.1 0.1 Cixian County 2003-2007 4 0.3 0.3 2 0.1 0.2 Haining County 2003-2007 6 0.4 0.3 2 0.1 0.1 Hong Kong 2003-2007 108 0.7 0.4 88 0.5 0.3 Jiashan County 2003-2007 3 0.3 0.2 1 0.1 0.0 Jiaxing City 2005-2007 1 0.1 0.1 2 0.3 0.1 Macao 2003-2007 5 0.4 0.3 7 0.6 0.4 Nangang District, 2003-2007 7 0.3 0.2 2 0.1 0.1 Harbin City Qidong County 2003-2007 5 0.2 0.1 7 0.2 0.1 Shanghai City 2003-2007 70 0.4 0.2 67 0.4 0.2 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 32 - Table 7 Continued Male Female Country / Registry Period N cases a Crude rate b ASR b N cases a Crude rate c ASR c Wuhan City 2003-2007 40 0.3 0.3 39 0.3 0.3 Yangcheng County 2003-2007 2 0.2 0.2 0 0.0 0.0 Yanting County 2003-2007 0 0.0 0.0 0 0.0 0.0 Zhongshan City 2004-2007 4 0.1 0.2 4 0.1 0.1 India Bangalore 2005-2007 33 0.3 0.5 23 0.2 0.3 Barshi, Paranda and 2003-2007 3 0.2 0.2 3 0.2 0.3 Bhum Bhopal 2004-2007 10 0.3 0.4 11 0.3 0.5 Chennai 2003-2007 69 0.6 0.7 49 0.4 0.5 Dindigul, Ambillikai 2003-2007 14 0.3 0.3 9 0.2 0.2 Karunagappally 2003-2007 3 0.3 0.3 4 0.4 0.3 Mizoram 2003-2007 1 0.0 0.1 3 0.1 0.2 Mumbai 2003-2007 102 0.3 0.4 70 0.2 0.3 New Delhi 2003-2007 170 0.4 0.7 87 0.2 0.4 Poona 2003-2007 31 0.3 0.4 27 0.3 0.4 Sikkim State 2003-2007 3 0.2 0.4 3 0.2 0.4 Trivandrum 2005-2007 2 0.1 0.1 6 0.3 0.3 Iran Golestan Province 2005-2007 10 0.4 0.6 5 0.2 0.4 Israel National 2003-2007 57 0.3 0.3 101 0.6 0.4 National 2003-2007 56 0.4 0.3 99 0.7 0.5 National 2003-2007 1 0.0 0.0 2 0.1 0.1 Japan Aichi Prefecture 2003-2007 18 0.5 0.3 13 0.4 0.2 Fukui Prefecture 2003-2007 12 0.6 0.2 12 0.6 0.2 Hiroshima 2003-2007 15 0.5 0.3 21 0.7 0.3 Miyagi Prefecture 2003-2007 39 0.7 0.3 38 0.6 0.2 Nagasaki Prefecture 2003-2007 18 0.5 0.2 23 0.6 0.2 Niigata Prefecture 2003-2007 41 0.7 0.3 45 0.7 0.2 Osaka Prefecture 2003-2007 186 0.9 0.4 141 0.6 0.2 Saga Prefecture 2003-2007 11 0.5 0.2 9 0.4 0.1 Korea, Republic of Busan 2003-2007 29 0.3 0.3 31 0.3 0.2 Daegu 2003-2007 24 0.4 0.4 21 0.3 0.3 Daejeon 2003-2007 13 0.4 0.4 25 0.7 0.6 Gwangju 2003-2007 10 0.3 0.3 18 0.5 0.4 Incheon 2003-2007 15 0.2 0.3 23 0.4 0.3 Jejudo 2004-2007 5 0.5 0.5 4 0.4 0.3 National 2003-2007 450 0.4 0.4 482 0.4 0.3 Seoul 2003-2007 106 0.4 0.4 91 0.4 0.3 Ulsan 2003-2007 9 0.3 0.4 5 0.2 0.2 Kuwait National 2003-2007 11 0.1 0.1 9 0.2 0.3 National 2003-2007 4 0.2 0.3 6 0.2 0.4 National 2003-2007 7 0.1 0.1 3 0.1 0.1 Malaysia Penang 2004-2007 6 0.2 0.3 6 0.2 0.2 Penang 2004-2007 2 0.2 0.2 2 0.2 0.1 Penang 2004-2007 0 0.0 0.0 1 0.3 0.3 Penang 2004-2007 4 0.3 0.6 3 0.2 0.4 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 33 - Table 7 Continued Male Female Country / Registry Period N cases a Crude rate b ASR b N cases a Crude rate c ASR c Oman Omani 1998-2001 11 0.3 0.7 1 0.0 0.1 Pakistan South Karachi 1998-2002 19 0.4 0.7 8 0.2 0.4 Philippines Manila 2003-2007 28 0.2 0.3 28 0.2 0.3 Rizal 2003-2007 17 0.1 0.2 19 0.1 0.2 Qatar National 2003-2007 1 0.2 0.5 0 0.0 0.0 Saudi Arabia Riyadh 2003-2007 9 0.1 0.2 14 0.1 0.3 Singapore National 2003-2007 59 0.7 0.6 43 0.5 0.3 National 2003-2007 51 0.8 0.6 38 0.6 0.4 National 2003-2007 1 0.1 0.1 2 0.3 0.2 National 2003-2007 7 0.6 0.7 2 0.2 0.2 Thailand Bangkok 2003-2007 28 0.2 0.2 40 0.2 0.2 Chiang Mai 2003-2007 6 0.2 0.1 16 0.4 0.3 Chonburi 2003-2007 2 0.1 0.1 3 0.1 0.1 Khon Kaen 2003-2007 7 0.2 0.2 6 0.1 0.1 Lampang 2003-2007 1 0.1 0.0 6 0.3 0.2 Songkhla 2004-2007 7 0.3 0.3 2 0.1 0.1 Turkey Antalya 2003-2007 8 0.2 0.2 15 0.4 0.4 Edirne 2004-2007 3 0.4 0.4 1 0.1 0.1 Izmir 2003-2007 33 0.4 0.3 22 0.2 0.2 Trabzon 2005-2007 0 0.0 0.0 0 0.0 0.0 Viet Nam Hanoi 1993-1997 7 0.1 0.2 5 0.1 0.1 Ho Chi Minh City 1995-1998 32 0.4 0.6 36 0.4 0.4 Austria Austria National 2003-2007 196 1.0 0.6 378 1.8 0.9 Tyrol 2003-2007 16 0.9 0.6 38 2.1 1.3 Vorarlberg 2003-2007 4 0.4 0.3 13 1.4 0.8 Belarus National 2003-2007 55 0.2 0.2 109 0.4 0.2 Belgium National 2004-2007 204 1.0 0.6 310 1.4 0.7 Bulgaria National 2003-2007 167 0.9 0.5 127 0.6 0.4 Croatia National 2003-2007 41 0.4 0.3 73 0.6 0.3 Cyprus National 2003-2007 8 0.4 0.3 14 0.7 0.5 Czech Republic National 2003-2007 192 0.8 0.5 348 1.3 0.7 Denmark National 2003-2007 157 1.2 0.7 332 2.4 1.4 Estonia National 2003-2007 17 0.5 0.4 48 1.3 0.6 Finland National 2003-2007 65 0.5 0.3 115 0.9 0.4 France (Continued)

3 BURDEN OF HPV RELATED CANCERS - 34 - Table 7 Continued Male Female Country / Registry Period N cases a Crude rate b ASR b N cases a Crude rate c ASR c Bas-Rhin 2003-2007 12 0.5 0.3 35 1.3 0.7 Calvados 2003-2007 19 1.2 0.8 40 2.3 1.2 Doubs 2003-2007 14 1.1 0.8 21 1.6 1.0 Haut-Rhin 2003-2007 16 0.9 0.6 36 1.9 0.9 Herault 2003-2007 27 1.1 0.8 90 3.5 1.9 Isere 2003-2007 20 0.7 0.5 68 2.3 1.3 Loire Atlantique 2003-2007 32 1.1 0.7 78 2.5 1.5 Manche 2003-2007 11 0.9 0.5 25 2.0 0.7 Martinique 2003-2007 3 0.3 0.2 8 0.8 0.3 Somme 2003-2007 16 1.2 0.6 29 2.0 1.2 Tarn 2003-2007 9 1.0 0.4 19 2.0 0.8 Vendee 2003-2007 11 0.8 0.4 36 2.4 1.3 Germany Brandenburg 2003-2007 66 1.0 0.6 144 2.2 1.0 Bremen 2003-2007 29 1.8 1.1 35 2.0 1.0 Free State Of Saxony 2003-2007 103 1.0 0.5 214 1.9 0.8 Hamburg 2003-2007 109 2.6 1.5 153 3.4 1.8 Mecklenburg-Western 2003-2007 41 1.0 0.6 77 1.8 0.8 Pomerania Munich 2003-2007 107 1.1 0.7 259 2.6 1.3 North Rhine-Westphalia 2003-2007 69 1.1 0.6 126 1.9 1.0 Saarland 2003-2007 33 1.3 0.7 50 1.8 0.9 Schleswig-Holstein 2003-2007 123 1.8 1.0 215 3.0 1.5 Iceland National 2003-2007 6 0.8 0.6 10 1.4 0.8 Ireland National 2003-2007 64 0.6 0.5 94 0.9 0.6 Italy Alto Adige 2003-2006 11 1.2 0.7 31 3.2 1.5 Biella Province 2003-2007 9 2.0 0.8 15 3.1 1.1 Brescia Province 2003-2006 16 0.8 0.4 43 2.0 0.9 Catania and Messina 2003-2005 20 0.8 0.5 24 0.9 0.5 Catanzaro 2003-2007 7 1.2 0.5 9 1.5 0.7 Ferrara Province 2003-2007 21 2.5 0.9 23 2.5 0.7 Florence and Prato 2003-2005 42 2.4 0.9 46 2.5 1.0 Provinces Friuli-Venezia Giulia 2003-2007 41 1.4 0.6 78 2.5 0.8 Genova Province 2003-2006 44 2.7 1.3 72 3.9 1.4 Latina 2003-2007 20 1.6 0.7 37 2.8 1.3 Lombardy, Como 2003-2007 19 1.4 0.8 29 2.0 0.9 Province Lombardy, Lecco 2003-2007 6 0.8 0.4 9 1.1 0.4 Province Lombardy, Mantova 2003-2005 7 1.2 0.5 5 0.8 0.3 Province Lombardy, Milan 2003-2006 22 0.9 0.5 58 2.1 1.0 Lombardy, Varese 2003-2007 31 1.5 0.8 41 1.9 0.8 Province Modena Province 2003-2007 18 1.1 0.4 30 1.8 0.8 Naples 2003-2007 6 0.4 0.3 9 0.6 0.4 Nuoro 2003-2007 4 0.7 0.4 7 1.1 0.4 Palerme 2003-2006 27 1.1 0.7 24 0.9 0.5 Parma Province 2003-2007 12 1.2 0.6 17 1.6 0.6 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 35 - Table 7 Continued Male Female Country / Registry Period N cases a Crude rate b ASR b N cases a Crude rate c ASR c Ragusa Province 2003-2007 9 1.2 0.6 18 2.3 1.2 Reggio Emilia Province 2003-2007 9 0.7 0.4 22 1.8 0.7 Romagna Region 2003-2007 59 2.1 1.1 78 2.6 1.2 Salerno Province 2003-2007 33 1.2 0.7 24 0.9 0.5 Sassari Province 2003-2007 6 0.5 0.3 13 1.1 0.5 Sondrio 2003-2007 8 1.8 1.0 17 3.7 1.8 South Lombardy 2003-2005 5 0.5 0.3 19 1.7 0.7 Syracuse Province 2003-2007 10 1.0 0.6 4 0.4 0.1 Torino 2003-2007 45 2.1 1.0 65 2.8 1.3 Trapani 2003-2006 13 1.6 0.9 11 1.2 0.6 Trento 2003-2006 8 0.8 0.4 14 1.4 0.5 Umbria Region 2003-2007 26 1.2 0.7 40 1.8 0.8 Veneto Region 2003-2006 58 1.3 0.6 72 1.5 0.7 Latvia National 2004-2007 23 0.5 0.4 38 0.8 0.4 Lithuania National 2003-2007 35 0.4 0.3 51 0.6 0.3 Malta National 2003-2007 3 0.3 0.1 8 0.8 0.5 Netherlands Eindhoven 2003-2007 13 0.5 0.3 23 0.9 0.5 National 2003-2007 293 0.7 0.5 374 0.9 0.5 Norway National 2003-2007 97 0.8 0.5 229 2.0 1.0 Poland Cracow 2003-2006 4 0.3 0.2 24 1.5 0.8 Kielce 2003-2007 9 0.3 0.2 15 0.5 0.2 Lower Silesia 2003-2007 55 0.8 0.5 101 1.3 0.7 Rzeszow 2003-2007 22 0.4 0.3 35 0.7 0.3 Portugal Azores 2003-2007 4 0.7 0.6 6 1.0 0.6 Russian Federation St Petersburg 2003-2007 22 0.2 0.1 117 0.9 0.5 Serbia Central 2003-2007 90 0.7 0.4 86 0.6 0.3 Slovakia National 2003-2007 63 0.5 0.4 104 0.8 0.4 Slovenia National 2003-2007 45 0.9 0.6 56 1.1 0.5 Spain Albacete 2003-2007 5 0.5 0.4 1 0.1 0.0 Asturias 2003-2007 29 1.1 0.7 19 0.7 0.3 Basque Country 2003-2007 43 0.8 0.5 40 0.7 0.3 Canary Islands 2003-2006 28 0.9 0.6 27 0.8 0.5 Ciudad Real 2004-2007 7 0.7 0.4 3 0.3 0.1 Cuenca 2003-2007 5 1.0 0.5 5 1.0 0.6 Girona 2003-2007 15 0.9 0.7 14 0.9 0.4 Granada 2003-2007 10 0.5 0.3 13 0.6 0.3 La Rioja 2003-2007 2 0.3 0.1 6 0.8 0.4 Mallorca 2003-2007 29 1.5 1.0 18 0.9 0.5 Murcia 2003-2007 29 0.8 0.6 15 0.5 0.2 Navarra 2003-2007 9 0.6 0.4 9 0.6 0.2 Tarragona 2003-2007 18 1.0 0.5 9 0.5 0.2 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 36 - Table 7 Continued Male Female Country / Registry Period N cases a Crude rate b ASR b N cases a Crude rate c ASR c Sweden National 2003-2007 198 0.9 0.5 459 2.0 1.0 Switzerland Basel 2003-2007 11 1.0 0.6 21 1.9 0.9 Geneva 2003-2007 19 1.9 1.2 63 5.6 3.0 Graubunden and Glarus 2003-2007 4 0.7 0.5 10 1.7 1.0 Neuchatel 2003-2007 12 2.9 1.6 22 5.1 2.2 St Gall-Appenzell 2003-2007 11 0.8 0.6 22 1.6 0.9 Ticino 2003-2007 8 1.0 0.6 36 4.3 2.1 Valais 2003-2007 8 1.1 0.7 19 2.6 1.6 Vaud 2003-2007 24 1.5 0.9 76 4.5 2.3 Zurich 2003-2007 40 1.3 0.8 103 3.2 1.7 Ukraine National 2003-2007 438 0.4 0.3 640 0.5 0.3 United Kingdom England 2003-2007 1491 1.2 0.7 2274 1.8 1.0 England, East of 2003-2007 134 1.0 0.6 270 1.9 1.0 England Region England, North Western 2003-2007 188 1.2 0.7 288 1.7 0.9 England, Northern and 2003-2007 229 1.4 0.8 335 2.0 1.1 Yorkshire England, Oxford Region 2003-2007 67 1.0 0.6 134 1.9 1.1 England, South and 2003-2007 197 1.2 0.7 336 1.9 0.9 Western Regions England, Thames 2003-2007 384 1.3 0.9 513 1.7 1.0 England, Trent 2005-2007 71 1.0 0.6 115 1.5 0.7 England, West Midlands 2003-2007 162 1.2 0.7 211 1.6 0.9 Northern Ireland 2003-2007 50 1.2 0.8 51 1.2 0.8 Scotland 2003-2007 136 1.1 0.7 254 1.9 1.0 Wales 2003-2007 98 1.4 0.7 151 2.0 1.1 Australia Australia Australian Capital 2003-2007 6 0.7 0.6 7 0.8 0.6 Territory National 2003-2007 41 1.1 0.7 46 1.2 0.7 National 2003-2007 45 0.9 0.6 72 1.4 1.0 New South Wales 2003-2007 229 1.4 0.9 248 1.5 0.9 Northern Territory 2003-2007 7 1.3 1.1 10 2.0 2.2 Northern Territory 2003-2007 3 2.0 3.6 5 3.2 4.5 Northern Territory 2003-2007 4 1.0 0.7 5 1.5 1.7 Queensland 2003-2007 137 1.4 0.9 193 1.9 1.3 Tasmania 2003-2007 19 1.6 1.0 27 2.2 1.2 Victoria 2003-2007 155 1.2 0.9 205 1.6 1.0 New Zealand National 2003-2007 8 0.5 0.9 15 0.9 1.1 National 2003-2007 77 0.8 0.5 180 1.7 1.1 National 2003-2007 69 0.9 0.5 164 2.0 1.2 National 2003-2007 0 0.0 0.0 1 0.2 0.1 a Accumulated number of cases during the period in the population covered by the corresponding registry. b Rates per 100,000 men per year. c Rates per 100,000 women per year. Data sources: 1 Forman D, Bray F, Brewster DH, Gombe Mbalawa C, Kohler B, Piñeros M, Steliarova-Foucher E, Swaminathan R and Ferlay J eds (2013). Cancer Incidence in Five Continents, Vol. X (electronic version) Lyon, IARC. http://ci5.iarc.fr last accessed on 2013-12-13 2 Curado. M. P., Edwards, B., Shin. H.R., Storm. H., Ferlay. J., Heanue. M. and Boyle. P., eds (2007). Cancer Incidence in Five Continents, Vol. IX. IARC Scientific Publications No. 160, Lyon, IARC. 3 Parkin, D.M., Whelan, S.L., Ferlay, J., Teppo, L., and Thomas, D.B., eds (2002). Cancer Incidence in Five Continents, Vol. VIII. IARC Scientific Publications No. 155, Lyon, IARC.

3 BURDEN OF HPV RELATED CANCERS - 37 - NOTE. For time trends in anal cancer incidence please refer to specific countries 3.2.2 Vulvar cancer (last update 22 Jul 2014) Cancer of the vulva is rare among women worldwide, with an estimated 27,000 new cases in 2008, representing 4% of all gynaecologic cancers (de Martel C et al. Lancet Oncol 2012;13(6):607-15). Worldwide, about 60% of all vulvar cancer cases occur in more developed countries. Vulvar cancer has two distinct histological patterns with two different risk factor profiles: (1) basaloid/warty types (2) keratinizing types. Basaloid/warty lesions are more common in young women, are very often associated with HPV DNA detection (75-100%), and have a similar risk factor profile as cervical cancer. Keratinizing vulvar carcinomas represent the majority of the vulvar lesions (>60%), they occur more often in older women and are more rarely associated with HPV (IARC Monograph Vol 100B) Table 8: Incidence of vulvar cancer by cancer registry Female Country Cancer registry Period N cases a Crude rate b ASR b Africa Algeria 1 Setif 2003-2007 5 0.1 0.2 Egypt 1 Gharbiah 2003-2007 49 0.5 0.8 Gambia 2 National 1997-1998 1 0.1 0.2 Libya 1 Benghazi 2003-2005 5 0.2 0.4 Malawi 1 Blantyre 2003-2007 16 0.7 1.0 Mali 2 Bamako 1994-1996 1 0.1 0.2 South Africa 1 PROMEC 2003-2007 8 0.3 0.3 Tunisia 1 North 2003-2005 41 0.6 0.6 Uganda 1 Kyadondo county 2003-2007 12 0.2 0.6 Zimbabwe 1 Harare (African) 2003-2006 14 0.5 1.1 Americas Argentina 1 Bahia Blanca 2003-2007 6 0.8 0.3 Cordoba 2004-2007 49 1.8 1.1 Mendoza 2003-2007 69 1.6 1.2 Tierra del Fuego 2003-2007 5 1.8 3.0 Brazil 1 Aracaju 2003-2006 10 1.0 1.0 Belo Horizonte 2003-2005 33 0.9 0.8 Cuiaba 2003-2006 12 0.8 1.0 Fortaleza 2003-2006 17 0.3 0.4 Goiania 2003-2007 34 1.1 1.3 Sao Paulo 2003-2007 510 1.8 1.6 Canada 1 Alberta 2003-2007 189 2.3 1.5 British Columbia 2003-2007 207 2.0 1.0 Manitoba 2003-2007 84 2.8 1.8 National 2003-2007 2044 2.5 1.4 New Brunswick 2003-2007 55 2.9 1.7 Newfoundland and Labrador 2003-2007 36 2.8 1.3 Northwest Territories 2003-2007 1 1.0 1.2 Nova Scotia 2003-2007 83 3.5 1.8 Ontario 2003-2007 827 2.6 1.4 Prince Edward Island 2003-2007 7 2.0 0.8 Quebec 2003-2007 472 2.5 1.2 Saskatchewan 2003-2007 83 3.3 1.6 Yukon 2003-2007 0 0.0 0.0 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 38 - Table 8 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Chile 1 Biobio Province 2003-2007 4 0.4 0.3 Region of Antofagasta 2003-2007 17 1.3 1.3 Valdivia 2003-2007 9 1.0 0.6 Colombia 1 Bucaramanga 2003-2007 20 0.7 0.7 Cali 2003-2007 55 1.0 0.9 Manizales 2003-2007 5 0.5 0.3 Pasto 2003-2007 5 0.5 0.6 Costa Rica 1 National 2003-2007 92 0.9 0.9 Cuba 1 Villa Clara 2004-2007 29 1.8 1.0 Ecuador 1 Cuenca 2003-2007 9 0.7 0.6 Quito 2003-2007 28 0.7 0.8 Jamaica 1 Kingston and St Andrew 2003-2007 8 0.5 0.4 Peru 3 Trujillo 1998-2002 21 1.3 2.0 United States of NPCR 2003-2007 17514 2.6 1.5 America 1 Uruguay 1 National 2005-2007 110 2.1 1.0 Asia Bahrain 1 National (Bahraini) 2003-2007 0 0.0 0.0 China 1 Beijing City 2003-2007 121 0.7 0.4 Cixian County 2003-2007 5 0.3 0.4 Haining County 2003-2007 6 0.4 0.3 Hong Kong 2003-2007 147 0.8 0.5 Jiashan County 2003-2007 4 0.4 0.2 Jiaxing City 2005-2007 6 0.8 0.5 Macao 2003-2007 3 0.2 0.2 Nangang District, Harbin City 2003-2007 10 0.4 0.3 Qidong County 2003-2007 3 0.1 0.0 Shanghai City 2003-2007 98 0.6 0.3 Wuhan City 2003-2007 27 0.2 0.2 Yangcheng County 2003-2007 1 0.1 0.1 Yanting County 2003-2007 5 0.3 0.3 Zhongshan City 2004-2007 13 0.5 0.4 India 1 Bangalore 2005-2007 43 0.4 0.7 Barshi, Paranda and Bhum 2003-2007 2 0.2 0.1 Bhopal 2004-2007 5 0.2 0.3 Chennai 2003-2007 51 0.5 0.5 Dindigul, Ambillikai 2003-2007 20 0.4 0.5 Karunagappally 2003-2007 3 0.3 0.2 Mizoram 2003-2007 13 0.5 0.8 Mumbai 2003-2007 65 0.2 0.3 New Delhi 2003-2007 104 0.3 0.5 Poona 2003-2007 25 0.3 0.3 Sikkim State 2003-2007 2 0.2 0.3 Trivandrum 2005-2007 4 0.2 0.2 Iran 1 Golestan Province 2005-2007 1 0.0 0.1 Israel 1 National 2003-2007 229 1.4 0.9 National (Jews) 2003-2007 213 1.6 0.9 National (Non-Jews) 2003-2007 16 0.5 0.8 Japan 1 Aichi Prefecture 2003-2007 18 0.5 0.2 Fukui Prefecture 2003-2007 22 1.0 0.4 Hiroshima 2003-2007 26 0.9 0.3 Miyagi Prefecture 2003-2007 41 0.7 0.2 Nagasaki Prefecture 2003-2007 46 1.2 0.3 Niigata Prefecture 2003-2007 50 0.8 0.3 Osaka Prefecture 2003-2007 164 0.7 0.3 Saga Prefecture 2003-2007 20 0.9 0.3 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 39 - Table 8 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Korea, Republic of 1 Busan 2003-2007 24 0.3 0.2 Daegu 2003-2007 17 0.3 0.2 Daejeon 2003-2007 4 0.1 0.1 Gwangju 2003-2007 14 0.4 0.3 Incheon 2003-2007 18 0.3 0.2 Jejudo 2004-2007 2 0.2 0.1 National 2003-2007 426 0.4 0.3 Seoul 2003-2007 101 0.4 0.3 Ulsan 2003-2007 8 0.3 0.3 Kuwait 1 National 2003-2007 10 0.2 0.3 National (Kuwaitis) 2003-2007 6 0.2 0.4 National (Non-Kuwaitis) 2003-2007 4 0.1 0.3 Malaysia 1 Penang 2004-2007 10 0.4 0.4 Penang (Chinese) 2004-2007 5 0.4 0.3 Penang (Indian) 2004-2007 2 0.7 0.9 Penang (Malay) 2004-2007 3 0.2 0.3 Oman 3 Omani 1998-2001 3 0.1 0.2 Pakistan 3 South Karachi 1998-2002 3 0.1 0.1 Philippines 1 Manila 2003-2007 42 0.3 0.5 Rizal 2003-2007 41 0.2 0.4 Qatar 1 National (Qatari) 2003-2007 0 0.0 0.0 Saudi Arabia 1 Riyadh (Saudi) 2003-2007 5 0.1 0.1 Singapore 1 National 2003-2007 69 0.8 0.6 National (Chinese) 2003-2007 62 0.9 0.6 National (Indian) 2003-2007 2 0.3 0.3 National (Malay) 2003-2007 4 0.3 0.3 Thailand 1 Bangkok 2003-2007 34 0.2 0.2 Chiang Mai 2003-2007 39 1.0 0.8 Chonburi 2003-2007 15 0.5 0.4 Khon Kaen 2003-2007 17 0.4 0.3 Lampang 2003-2007 21 1.1 0.8 Songkhla 2004-2007 9 0.3 0.3 Turkey 1 Antalya 2003-2007 15 0.4 0.4 Edirne 2004-2007 4 0.5 0.2 Izmir 2003-2007 66 0.7 0.6 Trabzon 2005-2007 4 0.4 0.2 Viet Nam 2 Hanoi 1993-1997 53 0.9 1.0 Ho Chi Minh City 1995-1998 35 0.4 0.4 Europe Austria 1 National 2003-2007 660 3.1 1.5 Tyrol 2003-2007 44 2.5 1.5 Vorarlberg 2003-2007 27 3.0 1.5 Belarus 1 National 2003-2007 755 2.9 1.3 Belgium 1 National 2004-2007 710 3.3 1.5 Bulgaria 1 National 2003-2007 619 3.1 1.3 Croatia 1 National 2003-2007 346 3.0 1.2 Cyprus 1 National 2003-2007 39 2.0 1.1 Czech Republic 1 National 2003-2007 1000 3.8 1.8 Denmark 1 National 2003-2007 471 3.4 1.7 Estonia 1 National 2003-2007 132 3.6 1.4 Finland 1 National 2003-2007 376 2.8 1.2 France 1 Bas-Rhin 2003-2007 84 3.1 1.3 Calvados 2003-2007 26 1.5 0.7 Doubs 2003-2007 46 3.5 1.5 Haut-Rhin 2003-2007 51 2.7 1.3 Herault 2003-2007 42 1.6 0.5 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 40 - Table 8 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Isere 2003-2007 44 1.5 0.7 Loire Atlantique 2003-2007 51 1.6 0.7 Manche 2003-2007 21 1.7 0.8 Martinique 2003-2007 3 0.3 0.2 Somme 2003-2007 29 2.0 0.9 Tarn 2003-2007 20 2.1 0.8 Vendee 2003-2007 22 1.5 0.9 Germany 1 Brandenburg 2003-2007 301 4.7 1.9 Bremen 2003-2007 90 5.3 2.0 Free State Of Saxony 2003-2007 603 5.5 1.8 Hamburg 2003-2007 257 5.8 2.5 Mecklenburg-Western Pomerania 2003-2007 199 4.6 1.7 Munich 2003-2007 420 4.2 1.7 North Rhine-Westphalia 2003-2007 326 4.9 2.1 Saarland 2003-2007 255 9.4 4.1 Schleswig-Holstein 2003-2007 585 8.1 3.6 Iceland 1 National 2003-2007 11 1.5 0.9 Ireland 1 National 2003-2007 217 2.1 1.3 Italy 1 Alto Adige 2003-2006 35 3.6 1.6 Biella Province 2003-2007 27 5.5 1.7 Brescia Province 2003-2006 50 2.3 0.9 Catania and Messina 2003-2005 72 2.7 1.1 Catanzaro 2003-2007 22 3.6 1.6 Ferrara Province 2003-2007 42 4.6 1.5 Florence and Prato Provinces 2003-2005 72 3.9 1.1 Friuli-Venezia Giulia 2003-2007 131 4.2 1.1 Genova Province 2003-2006 101 5.4 1.7 Latina 2003-2007 44 3.3 1.4 Lombardy, Como Province 2003-2007 56 3.9 1.2 Lombardy, Lecco Province 2003-2007 21 2.6 0.9 Lombardy, Mantova Province 2003-2005 27 4.5 1.3 Lombardy, Milan 2003-2006 73 2.7 0.7 Lombardy, Varese Province 2003-2007 67 3.1 1.0 Modena Province 2003-2007 77 4.5 1.3 Naples 2003-2007 41 2.9 1.8 Nuoro 2003-2007 8 1.3 0.6 Palerme 2003-2006 78 3.0 1.4 Parma Province 2003-2007 30 2.8 0.8 Ragusa Province 2003-2007 21 2.7 1.2 Reggio Emilia Province 2003-2007 49 3.9 1.3 Romagna Region 2003-2007 117 4.0 1.1 Salerno Province 2003-2007 77 2.8 1.2 Sassari Province 2003-2007 19 1.6 0.8 Sondrio 2003-2007 19 4.2 1.3 South Lombardy 2003-2005 42 3.8 1.3 Syracuse Province 2003-2007 22 2.2 1.0 Torino 2003-2007 84 3.6 1.0 Trapani 2003-2006 38 4.3 1.5 Trento 2003-2006 41 4.0 1.5 Umbria Region 2003-2007 105 4.7 1.4 Veneto Region 2003-2006 174 3.7 1.3 Latvia 1 National 2004-2007 162 3.3 1.4 Lithuania 1 National 2003-2007 274 3.0 1.3 Malta 1 National 2003-2007 36 3.5 1.6 Netherlands 1 Eindhoven 2003-2007 84 3.3 1.7 National 2003-2007 1416 3.4 1.7 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 41 - Table 8 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Norway 1 National 2003-2007 451 3.9 1.9 Poland 1 Cracow 2003-2006 33 2.0 0.9 Kielce 2003-2007 70 2.1 0.8 Lower Silesia 2003-2007 196 2.6 1.3 Rzeszow 2003-2007 106 2.0 1.0 Portugal 1 Azores 2003-2007 8 1.3 0.7 Russian Federation 1 St Petersburg 2003-2007 354 2.8 1.1 Serbia 1 Central 2003-2007 459 3.3 1.6 Slovakia 1 National 2003-2007 350 2.5 1.3 Slovenia 1 National 2003-2007 247 4.8 2.1 Spain 1 Albacete 2003-2007 29 3.0 1.0 Asturias 2003-2007 101 3.6 1.2 Basque Country 2003-2007 160 3.0 1.2 Canary Islands 2003-2006 62 1.9 1.0 Ciudad Real 2004-2007 24 2.4 1.0 Cuenca 2003-2007 17 3.3 1.2 Girona 2003-2007 43 2.7 1.1 Granada 2003-2007 50 2.3 1.0 La Rioja 2003-2007 22 3.0 0.8 Mallorca 2003-2007 68 3.5 1.5 Murcia 2003-2007 66 2.0 1.0 Navarra 2003-2007 47 3.2 1.0 Tarragona 2003-2007 56 3.3 1.2 Sweden 1 National 2003-2007 803 3.5 1.4 Switzerland 1 Basel 2003-2007 40 3.5 1.2 Geneva 2003-2007 31 2.8 1.3 Graubunden and Glarus 2003-2007 20 3.5 1.6 Neuchatel 2003-2007 12 2.8 1.6 St Gall-Appenzell 2003-2007 34 2.5 1.1 Ticino 2003-2007 24 2.9 0.8 Valais 2003-2007 16 2.2 0.7 Vaud 2003-2007 56 3.3 1.4 Zurich 2003-2007 102 3.2 1.4 Ukraine 1 National 2003-2007 3345 2.6 1.1 United Kingdom 1 England 2003-2007 4408 3.4 1.6 England, East of England Region 2003-2007 440 3.1 1.4 England, North Western 2003-2007 580 3.5 1.7 England, Northern and Yorkshire 2003-2007 649 3.8 1.8 England, Oxford Region 2003-2007 210 3.0 1.6 England, South and Western Regions 2003-2007 731 4.2 1.7 England, Thames 2003-2007 759 2.5 1.3 England, Trent 2005-2007 322 4.3 1.9 England, West Midlands 2003-2007 523 3.8 1.8 Northern Ireland 2003-2007 122 2.8 1.5 Scotland 2003-2007 493 3.7 1.9 Wales 2003-2007 342 4.5 2.0 Oceania Australia 1 Australian Capital Territory 2003-2007 16 1.9 1.3 National 2003-2007 107 2.7 1.2 National 2003-2007 120 2.4 1.4 New South Wales 2003-2007 445 2.6 1.4 Northern Territory 2003-2007 15 3.0 3.0 Northern Territory (Indigenous) 2003-2007 7 4.4 4.6 Northern Territory (Non-Indigenous) 2003-2007 8 2.4 2.5 Queensland 2003-2007 208 2.1 1.2 Tasmania 2003-2007 36 2.9 1.4 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 42 - Table 8 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Victoria 2003-2007 333 2.6 1.4 New Zealand 1 National 2003-2007 245 2.3 1.4 National (Maori) 2003-2007 23 1.4 1.7 National (Other) 2003-2007 219 2.6 1.3 National (Pacific Islander) 2003-2007 3 0.5 0.6 a Accumulated number of cases during the period in the population covered by the corresponding registry. b Rates per 100,000 women per year. Data sources: 1 Forman D, Bray F, Brewster DH, Gombe Mbalawa C, Kohler B, Piñeros M, Steliarova-Foucher E, Swaminathan R and Ferlay J eds (2013). Cancer Incidence in Five Continents, Vol. X (electronic version) Lyon, IARC. http://ci5.iarc.fr last accessed on 2013-12-13 2 Curado. M. P., Edwards, B., Shin. H.R., Storm. H., Ferlay. J., Heanue. M. and Boyle. P., eds (2007). Cancer Incidence in Five Continents, Vol. IX. IARC Scientific Publications No. 160, Lyon, IARC. 3 Parkin, D.M., Whelan, S.L., Ferlay, J., Teppo, L., and Thomas, D.B., eds (2002). Cancer Incidence in Five Continents, Vol. VIII. IARC Scientific Publications No. 155, Lyon, IARC.

3 BURDEN OF HPV RELATED CANCERS - 43 - NOTE. For time trends in vulvar cancer incidence please refer to specific countries 3.2.3 Vaginal cancer (last update 22 Jul 2014) Cancer of the vagina is a rare cancer, with an estimated 13,000 new cases in 2008, representing 2% of all gynaecologic cancers (de Martel C et al. Lancet Oncol 2012;13(6):607-15). Similar to cervical cancer, the majority of vaginal cancer cases (68%) occur in less developed countries. Most vaginal cancers are squamous cell carcinoma (90%) generally attributable to HPV, followed by clear cell adenocarcinomas and melanoma. Vaginal cancers are primarily reported in developed countries. Metastatic cervical cancer can be misclassified as cancer of the vagina. Invasive vaginal cancer is diagnosed primarily in old women (>=65 years) and the diagnosis is rare in women under 45 years whereas the peak incidence of carcinoma in situ is observed between ages 55 and 70 (Vaccine 2008, Vol. 26, Suppl 10) Table 9: Incidence of vaginal cancer by cancer registry Female Country Cancer registry Period N cases a Crude rate b ASR b Africa Algeria 1 Setif 2003-2007 3 0.1 0.1 Egypt 1 Gharbiah 2003-2007 15 0.2 0.2 Gambia 2 National 1997-1998 2 0.2 0.2 Libya 1 Benghazi 2003-2005 3 0.1 0.2 Malawi 1 Blantyre 2003-2007 16 0.7 1.4 Mali 2 Bamako 1994-1996 1 0.1 0.1 South Africa 1 PROMEC 2003-2007 8 0.3 0.3 Tunisia 1 North 2003-2005 20 0.3 0.3 Uganda 1 Kyadondo county 2003-2007 9 0.2 0.6 Zimbabwe 1 Harare (African) 2003-2006 4 0.1 0.2 Americas Argentina 1 Bahia Blanca 2003-2007 11 1.5 1.0 Cordoba 2004-2007 14 0.5 0.4 Mendoza 2003-2007 24 0.6 0.5 Tierra del Fuego 2003-2007 1 0.4 0.4 Brazil 1 Aracaju 2003-2006 6 0.6 0.9 Belo Horizonte 2003-2005 24 0.6 0.6 Cuiaba 2003-2006 7 0.4 0.6 Fortaleza 2003-2006 22 0.4 0.5 Goiania 2003-2007 22 0.7 0.8 Sao Paulo 2003-2007 348 1.2 1.1 Canada 1 Alberta 2003-2007 53 0.6 0.4 British Columbia 2003-2007 84 0.8 0.4 Manitoba 2003-2007 20 0.7 0.4 National 2003-2007 621 0.8 0.4 New Brunswick 2003-2007 21 1.1 0.5 Newfoundland and Labrador 2003-2007 7 0.5 0.3 Northwest Territories 2003-2007 1 1.0 1.7 Nova Scotia 2003-2007 33 1.4 0.7 Ontario 2003-2007 251 0.8 0.5 Prince Edward Island 2003-2007 3 0.9 0.5 Quebec 2003-2007 135 0.7 0.3 Saskatchewan 2003-2007 13 0.5 0.3 Yukon 2003-2007 0 0.0 0.0 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 44 - Table 9 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Chile 1 Biobio Province 2003-2007 9 1.0 0.8 Region of Antofagasta 2003-2007 7 0.5 0.6 Valdivia 2003-2007 2 0.2 0.2 Colombia 1 Bucaramanga 2003-2007 20 0.7 0.8 Cali 2003-2007 31 0.6 0.6 Manizales 2003-2007 5 0.5 0.5 Pasto 2003-2007 0 0.0 0.0 Costa Rica 1 National 2003-2007 25 0.2 0.2 Cuba 1 Villa Clara 2004-2007 4 0.2 0.1 Ecuador 1 Cuenca 2003-2007 5 0.4 0.4 Quito 2003-2007 15 0.4 0.5 Jamaica 1 Kingston and St Andrew 2003-2007 3 0.2 0.1 Peru 3 Trujillo 1998-2002 2 0.1 0.2 United States of NPCR 2003-2007 5057 0.8 0.4 America 1 Uruguay 1 National 2005-2007 39 0.8 0.4 Asia Bahrain 1 National (Bahraini) 2003-2007 0 0.0 0.0 China 1 Beijing City 2003-2007 41 0.2 0.2 Cixian County 2003-2007 2 0.1 0.1 Haining County 2003-2007 2 0.1 0.1 Hong Kong 2003-2007 97 0.5 0.3 Jiashan County 2003-2007 0 0.0 0.0 Jiaxing City 2005-2007 1 0.1 0.1 Macao 2003-2007 6 0.5 0.4 Nangang District, Harbin City 2003-2007 10 0.4 0.3 Qidong County 2003-2007 2 0.1 0.1 Shanghai City 2003-2007 39 0.3 0.1 Wuhan City 2003-2007 29 0.3 0.2 Yangcheng County 2003-2007 3 0.3 0.3 Yanting County 2003-2007 1 0.1 0.1 Zhongshan City 2004-2007 9 0.3 0.3 India 1 Bangalore 2005-2007 54 0.6 0.8 Barshi, Paranda and Bhum 2003-2007 6 0.5 0.5 Bhopal 2004-2007 7 0.2 0.4 Chennai 2003-2007 79 0.7 0.8 Dindigul, Ambillikai 2003-2007 39 0.8 0.8 Karunagappally 2003-2007 2 0.2 0.2 Mizoram 2003-2007 4 0.2 0.3 Mumbai 2003-2007 160 0.6 0.7 New Delhi 2003-2007 97 0.3 0.4 Poona 2003-2007 44 0.4 0.6 Sikkim State 2003-2007 4 0.3 0.6 Trivandrum 2005-2007 8 0.5 0.4 Iran 1 Golestan Province 2005-2007 3 0.1 0.2 Israel 1 National 2003-2007 71 0.4 0.3 National (Jews) 2003-2007 70 0.5 0.3 National (Non-Jews) 2003-2007 1 0.0 0.0 Japan 1 Aichi Prefecture 2003-2007 15 0.4 0.3 Fukui Prefecture 2003-2007 8 0.4 0.2 Hiroshima 2003-2007 11 0.4 0.2 Miyagi Prefecture 2003-2007 23 0.4 0.1 Nagasaki Prefecture 2003-2007 12 0.3 0.1 Niigata Prefecture 2003-2007 21 0.3 0.2 Osaka Prefecture 2003-2007 75 0.3 0.1 Saga Prefecture 2003-2007 15 0.7 0.2 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 45 - Table 9 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Korea, Republic of 1 Busan 2003-2007 15 0.2 0.1 Daegu 2003-2007 24 0.4 0.3 Daejeon 2003-2007 5 0.1 0.1 Gwangju 2003-2007 8 0.2 0.2 Incheon 2003-2007 12 0.2 0.2 Jejudo 2004-2007 3 0.3 0.2 National 2003-2007 295 0.2 0.2 Seoul 2003-2007 67 0.3 0.2 Ulsan 2003-2007 10 0.4 0.4 Kuwait 1 National 2003-2007 1 0.0 0.1 National (Kuwaitis) 2003-2007 1 0.0 0.1 National (Non-Kuwaitis) 2003-2007 0 0.0 0.0 Malaysia 1 Penang 2004-2007 9 0.3 0.3 Penang (Chinese) 2004-2007 4 0.3 0.2 Penang (Indian) 2004-2007 2 0.7 0.8 Penang (Malay) 2004-2007 3 0.2 0.3 Oman 3 Omani 1998-2001 6 0.2 0.3 Pakistan 3 South Karachi 1998-2002 6 0.2 0.3 Philippines 1 Manila 2003-2007 33 0.2 0.3 Rizal 2003-2007 31 0.2 0.3 Qatar 1 National (Qatari) 2003-2007 0 0.0 0.0 Saudi Arabia 1 Riyadh (Saudi) 2003-2007 6 0.1 0.1 Singapore 1 National 2003-2007 38 0.4 0.3 National (Chinese) 2003-2007 31 0.5 0.4 National (Indian) 2003-2007 2 0.3 0.3 National (Malay) 2003-2007 4 0.3 0.3 Thailand 1 Bangkok 2003-2007 47 0.3 0.3 Chiang Mai 2003-2007 13 0.3 0.3 Chonburi 2003-2007 5 0.2 0.2 Khon Kaen 2003-2007 7 0.2 0.1 Lampang 2003-2007 3 0.2 0.1 Songkhla 2004-2007 3 0.1 0.1 Turkey 1 Antalya 2003-2007 6 0.2 0.2 Edirne 2004-2007 1 0.1 0.1 Izmir 2003-2007 16 0.2 0.1 Trabzon 2005-2007 2 0.2 0.1 Viet Nam 2 Hanoi 1993-1997 8 0.1 0.2 Ho Chi Minh City 1995-1998 16 0.2 0.2 Europe Austria 1 National 2003-2007 239 1.1 0.5 Tyrol 2003-2007 19 1.1 0.4 Vorarlberg 2003-2007 13 1.4 0.8 Belarus 1 National 2003-2007 168 0.6 0.4 Belgium 1 National 2004-2007 197 0.9 0.4 Bulgaria 1 National 2003-2007 139 0.7 0.3 Croatia 1 National 2003-2007 76 0.7 0.3 Cyprus 1 National 2003-2007 3 0.2 0.1 Czech Republic 1 National 2003-2007 247 0.9 0.5 Denmark 1 National 2003-2007 122 0.9 0.4 Estonia 1 National 2003-2007 29 0.8 0.4 Finland 1 National 2003-2007 97 0.7 0.3 France 1 Bas-Rhin 2003-2007 15 0.5 0.3 Calvados 2003-2007 12 0.7 0.4 Doubs 2003-2007 5 0.4 0.2 Haut-Rhin 2003-2007 14 0.7 0.3 Herault 2003-2007 15 0.6 0.3 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 46 - Table 9 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Isere 2003-2007 14 0.5 0.2 Loire Atlantique 2003-2007 22 0.7 0.3 Manche 2003-2007 3 0.2 0.1 Martinique 2003-2007 10 0.9 0.5 Somme 2003-2007 12 0.8 0.3 Tarn 2003-2007 5 0.5 0.2 Vendee 2003-2007 12 0.8 0.3 Germany 1 Brandenburg 2003-2007 62 1.0 0.4 Bremen 2003-2007 18 1.1 0.3 Free State Of Saxony 2003-2007 131 1.2 0.4 Hamburg 2003-2007 63 1.4 0.6 Mecklenburg-Western Pomerania 2003-2007 45 1.0 0.4 Munich 2003-2007 97 1.0 0.4 North Rhine-Westphalia 2003-2007 61 0.9 0.4 Saarland 2003-2007 32 1.2 0.5 Schleswig-Holstein 2003-2007 71 1.0 0.4 Iceland 1 National 2003-2007 2 0.3 0.1 Ireland 1 National 2003-2007 59 0.6 0.4 Italy 1 Alto Adige 2003-2006 6 0.6 0.3 Biella Province 2003-2007 3 0.6 0.1 Brescia Province 2003-2006 8 0.4 0.1 Catania and Messina 2003-2005 16 0.6 0.3 Catanzaro 2003-2007 8 1.3 0.5 Ferrara Province 2003-2007 11 1.2 0.2 Florence and Prato Provinces 2003-2005 12 0.6 0.1 Friuli-Venezia Giulia 2003-2007 26 0.8 0.3 Genova Province 2003-2006 18 1.0 0.2 Latina 2003-2007 4 0.3 0.1 Lombardy, Como Province 2003-2007 14 1.0 0.5 Lombardy, Lecco Province 2003-2007 6 0.7 0.2 Lombardy, Mantova Province 2003-2005 6 1.0 0.4 Lombardy, Milan 2003-2006 23 0.8 0.3 Lombardy, Varese Province 2003-2007 15 0.7 0.3 Modena Province 2003-2007 9 0.5 0.3 Naples 2003-2007 6 0.4 0.3 Nuoro 2003-2007 2 0.3 0.1 Palerme 2003-2006 17 0.7 0.3 Parma Province 2003-2007 7 0.7 0.3 Ragusa Province 2003-2007 6 0.8 0.4 Reggio Emilia Province 2003-2007 10 0.8 0.3 Romagna Region 2003-2007 25 0.8 0.3 Salerno Province 2003-2007 17 0.6 0.3 Sassari Province 2003-2007 7 0.6 0.3 Sondrio 2003-2007 1 0.2 0.2 South Lombardy 2003-2005 13 1.2 0.4 Syracuse Province 2003-2007 7 0.7 0.4 Torino 2003-2007 20 0.9 0.3 Trapani 2003-2006 4 0.4 0.3 Trento 2003-2006 11 1.1 0.5 Umbria Region 2003-2007 25 1.1 0.4 Veneto Region 2003-2006 34 0.7 0.2 Latvia 1 National 2004-2007 31 0.6 0.3 Lithuania 1 National 2003-2007 53 0.6 0.3 Malta 1 National 2003-2007 5 0.5 0.2 Netherlands 1 Eindhoven 2003-2007 14 0.5 0.3 National 2003-2007 247 0.6 0.3 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 47 - Table 9 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Norway 1 National 2003-2007 77 0.7 0.3 Poland 1 Cracow 2003-2006 7 0.4 0.2 Kielce 2003-2007 6 0.2 0.1 Lower Silesia 2003-2007 54 0.7 0.4 Rzeszow 2003-2007 29 0.5 0.3 Portugal 1 Azores 2003-2007 5 0.8 0.4 Russian Federation 1 St Petersburg 2003-2007 80 0.6 0.3 Serbia 1 Central 2003-2007 112 0.8 0.4 Slovakia 1 National 2003-2007 94 0.7 0.4 Slovenia 1 National 2003-2007 46 0.9 0.4 Spain 1 Albacete 2003-2007 3 0.3 0.2 Asturias 2003-2007 32 1.1 0.5 Basque Country 2003-2007 34 0.6 0.3 Canary Islands 2003-2006 11 0.3 0.2 Ciudad Real 2004-2007 2 0.2 0.1 Cuenca 2003-2007 0 0.0 0.0 Girona 2003-2007 4 0.2 0.1 Granada 2003-2007 11 0.5 0.2 La Rioja 2003-2007 2 0.3 0.1 Mallorca 2003-2007 8 0.4 0.3 Murcia 2003-2007 14 0.4 0.2 Navarra 2003-2007 3 0.2 0.0 Tarragona 2003-2007 5 0.3 0.2 Sweden 1 National 2003-2007 205 0.9 0.3 Switzerland 1 Basel 2003-2007 11 1.0 0.4 Geneva 2003-2007 5 0.4 0.2 Graubunden and Glarus 2003-2007 5 0.9 0.4 Neuchatel 2003-2007 4 0.9 0.2 St Gall-Appenzell 2003-2007 13 1.0 0.5 Ticino 2003-2007 5 0.6 0.2 Valais 2003-2007 1 0.1 0.1 Vaud 2003-2007 13 0.8 0.3 Zurich 2003-2007 25 0.8 0.4 Ukraine 1 National 2003-2007 765 0.6 0.3 United Kingdom 1 England 2003-2007 1001 0.8 0.4 England, East of England Region 2003-2007 79 0.6 0.3 England, North Western 2003-2007 138 0.8 0.5 England, Northern and Yorkshire 2003-2007 151 0.9 0.4 England, Oxford Region 2003-2007 53 0.8 0.4 England, South and Western Regions 2003-2007 163 0.9 0.4 England, Thames 2003-2007 195 0.7 0.4 England, Trent 2005-2007 79 1.0 0.5 England, West Midlands 2003-2007 102 0.8 0.4 Northern Ireland 2003-2007 21 0.5 0.3 Scotland 2003-2007 104 0.8 0.4 Wales 2003-2007 70 0.9 0.4 Oceania Australia 1 Australian Capital Territory 2003-2007 6 0.7 0.5 National 2003-2007 32 0.8 0.4 National 2003-2007 53 1.1 0.7 New South Wales 2003-2007 130 0.8 0.4 Northern Territory 2003-2007 3 0.6 0.6 Northern Territory (Indigenous) 2003-2007 1 0.6 1.0 Northern Territory (Non-Indigenous) 2003-2007 2 0.6 0.6 Queensland 2003-2007 62 0.6 0.4 Tasmania 2003-2007 6 0.5 0.2 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 48 - Table 9 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Victoria 2003-2007 62 0.5 0.3 New Zealand 1 National 2003-2007 60 0.6 0.4 National (Maori) 2003-2007 8 0.5 0.7 National (Other) 2003-2007 50 0.6 0.3 National (Pacific Islander) 2003-2007 2 0.3 0.4 a Accumulated number of cases during the period in the population covered by the corresponding registry. b Rates per 100,000 women per year. Data sources: 1 Forman D, Bray F, Brewster DH, Gombe Mbalawa C, Kohler B, Piñeros M, Steliarova-Foucher E, Swaminathan R and Ferlay J eds (2013). Cancer Incidence in Five Continents, Vol. X (electronic version) Lyon, IARC. http://ci5.iarc.fr last accessed on 2013-12-13 2 Curado. M. P., Edwards, B., Shin. H.R., Storm. H., Ferlay. J., Heanue. M. and Boyle. P., eds (2007). Cancer Incidence in Five Continents, Vol. IX. IARC Scientific Publications No. 160, Lyon, IARC. 3 Parkin, D.M., Whelan, S.L., Ferlay, J., Teppo, L., and Thomas, D.B., eds (2002). Cancer Incidence in Five Continents, Vol. VIII. IARC Scientific Publications No. 155, Lyon, IARC.

3 BURDEN OF HPV RELATED CANCERS - 49 - NOTE. For time trends in vaginal cancer incidence please refer to specific countries 3.2.4 Penile cancer (last update 22 Jul 2014) The annual burden of penile cancer has been estimated to be 22,000 cases worldwide with incidence rates strongly correlating with those of cervical cancer (de Martel C et al. Lancet Oncol 2012;13(6):607-15). Penile cancer is rare and most commonly affects men aged 50-70 years. Incidence rates are higher in less developed countries than in more developed countries, accounting for up to 10% of male cancers in some parts of Africa, South America and Asia. Precursor cancerous penile lesions (PeIN) are rare. Cancers of the penis are primarily of squamous cell carcinomas (SCC) (95%) and the most common penile SCC histologic sub-types are keratinizing (49%), mixed warty-basaloid (17%), verrucous (8%) warty (6%), and basaloid (4%). HPV is most commonly detected in basaloid and warty tumours but is less common in keratinizing and verrucous tumours. Approximately 60-100% of PeIN lesions are HPV DNA positive. Table 10: Incidence of penile cancer by cancer registry Male Country Cancer registry Period N cases a Crude rate b ASR b Africa Algeria 1 Setif 2003-2007 0 0.0 0.0 Egypt 1 Gharbiah 2003-2007 3 0.0 0.1 Gambia 3 National 1997-1998 5 0.5 0.9 Libya 1 Benghazi 2003-2005 0 0.0 0.0 Malawi 1 Blantyre 2003-2007 33 1.4 2.6 Mali 3 Bamako 1994-1996 0 0.0 0.0 Mozambique 4 Lourenco Marques 1956-1960 5 1.9 2.7 Nigeria 5 Ibadan 1960-1969 2 0.1 0.2 Senegal 6 Dakar 1969-1974 5 0.2 0.4 South Africa 1 PROMEC 2003-2007 11 0.5 0.8 Tunisia 1 North 2003-2005 8 0.1 0.1 Uganda 1 Kyadondo county 2003-2007 30 0.7 2.2 Zimbabwe 1 Harare (African) 2003-2006 14 0.5 1.1 Americas Argentina 1 Bahia Blanca 2003-2007 11 1.6 1.2 Cordoba 2004-2007 33 1.3 1.2 Mendoza 2003-2007 58 1.5 1.4 Tierra del Fuego 2003-2007 2 0.7 1.2 Brazil 1 Aracaju 2003-2006 17 1.8 2.5 Belo Horizonte 2003-2005 24 0.7 0.9 Cuiaba 2003-2006 20 1.3 2.1 Fortaleza 2003-2006 51 1.2 1.7 Goiania 2003-2007 65 2.3 3.3 Sao Paulo 2003-2007 403 1.6 1.7 Canada 1 Alberta 2003-2007 77 0.9 0.7 British Columbia 2003-2007 57 0.5 0.3 Manitoba 2003-2007 31 1.1 0.6 National 2003-2007 662 0.8 0.5 New Brunswick 2003-2007 32 1.7 1.0 Newfoundland and Labrador 2003-2007 18 1.4 0.9 Northwest Territories 2003-2007 0 0.0 0.0 Nova Scotia 2003-2007 30 1.3 0.8 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 50 - Table 10 Continued Male Country Cancer registry Period N cases a Crude rate b ASR b Ontario 2003-2007 233 0.8 0.5 Prince Edward Island 2003-2007 3 0.9 0.5 Quebec 2003-2007 147 0.8 0.5 Saskatchewan 2003-2007 34 1.4 0.9 Yukon 2003-2007 0 0.0 0.0 Chile 1 Biobio Province 2003-2007 8 0.8 0.8 Region of Antofagasta 2003-2007 19 1.3 1.6 Valdivia 2003-2007 10 1.1 0.9 Colombia 1 Bucaramanga 2003-2007 31 1.3 1.4 Cali 2003-2007 54 1.1 1.2 Manizales 2003-2007 20 2.2 2.2 Pasto 2003-2007 11 1.2 1.4 Costa Rica 1 National 2003-2007 110 1.0 1.2 Cuba 1 Villa Clara 2004-2007 41 2.5 1.6 Ecuador 1 Cuenca 2003-2007 1 0.1 0.1 Quito 2003-2007 18 0.5 0.6 Jamaica 1 Kingston and St Andrew 2003-2007 18 1.2 1.1 Paraguay 2 Asuncion Region 1988-1989 46 2.6 4.2 Peru 7 Trujillo 1998-2002 15 1.1 1.8 United States of NPCR 2003-2007 4858 0.7 0.5 America 1 Uruguay 1 National 2005-2007 96 2.0 1.5 Asia Bahrain 1 National (Bahraini) 2003-2007 0 0.0 0.0 China 1 Beijing City 2003-2007 95 0.5 0.3 Cixian County 2003-2007 10 0.6 0.8 Haining County 2003-2007 5 0.3 0.2 Hong Kong 2003-2007 72 0.4 0.3 Jiashan County 2003-2007 5 0.5 0.3 Jiaxing City 2005-2007 5 0.7 0.4 Macao 2003-2007 4 0.3 0.3 Nangang District, Harbin City 2003-2007 17 0.7 0.6 Qidong County 2003-2007 11 0.4 0.3 Shanghai City 2003-2007 107 0.7 0.3 Wuhan City 2003-2007 40 0.3 0.3 Yangcheng County 2003-2007 8 0.8 1.0 Yanting County 2003-2007 6 0.4 0.4 Zhongshan City 2004-2007 27 1.0 1.0 India 1 Bangalore 2005-2007 101 0.9 1.3 Barshi, Paranda and Bhum 2003-2007 25 1.8 2.2 Bhopal 2004-2007 12 0.3 0.6 Chennai 2003-2007 179 1.6 1.8 Dindigul, Ambillikai 2003-2007 72 1.4 1.5 Karunagappally 2003-2007 13 1.3 1.2 Mizoram 2003-2007 26 1.0 1.7 Mumbai 2003-2007 239 0.7 0.9 New Delhi 2003-2007 246 0.6 0.9 Poona 2003-2007 71 0.7 1.0 Sikkim State 2003-2007 10 0.7 1.0 Trivandrum 2005-2007 12 0.7 0.7 Iran 1 Golestan Province 2005-2007 0 0.0 0.0 Israel 1 National 2003-2007 17 0.1 0.1 National (Jews) 2003-2007 14 0.1 0.1 National (Non-Jews) 2003-2007 3 0.1 0.2 Japan 1 Aichi Prefecture 2003-2007 8 0.2 0.1 Fukui Prefecture 2003-2007 9 0.5 0.2 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 51 - Table 10 Continued Male Country Cancer registry Period N cases a Crude rate b ASR b Hiroshima 2003-2007 21 0.8 0.3 Miyagi Prefecture 2003-2007 31 0.5 0.2 Nagasaki Prefecture 2003-2007 28 0.8 0.4 Niigata Prefecture 2003-2007 30 0.5 0.2 Osaka Prefecture 2003-2007 83 0.4 0.2 Saga Prefecture 2003-2007 21 1.0 0.4 Korea, Republic of 1 Busan 2003-2007 24 0.3 0.3 Daegu 2003-2007 11 0.2 0.2 Daejeon 2003-2007 5 0.1 0.1 Gwangju 2003-2007 6 0.2 0.2 Incheon 2003-2007 9 0.1 0.2 Jejudo 2004-2007 3 0.3 0.3 National 2003-2007 282 0.2 0.2 Seoul 2003-2007 44 0.2 0.2 Ulsan 2003-2007 8 0.3 0.4 Kuwait 1 National 2003-2007 1 0.0 0.1 National (Kuwaitis) 2003-2007 0 0.0 0.0 National (Non-Kuwaitis) 2003-2007 1 0.0 0.1 Kyrgyzstan 2 National 1986-1987 7 0.2 0.3 Malaysia 1 Penang 2004-2007 9 0.3 0.5 Penang (Chinese) 2004-2007 6 0.5 0.5 Penang (Indian) 2004-2007 2 0.7 1.3 Penang (Malay) 2004-2007 1 0.1 0.2 Oman 7 Omani 1998-2001 0 0.0 0.0 Pakistan 7 South Karachi 1998-2002 1 0.0 0.0 Philippines 1 Manila 2003-2007 37 0.3 0.5 Rizal 2003-2007 32 0.2 0.4 Qatar 1 National (Qatari) 2003-2007 0 0.0 0.0 Saudi Arabia 1 Riyadh (Saudi) 2003-2007 2 0.0 0.1 Singapore 1 National 2003-2007 52 0.6 0.5 National (Chinese) 2003-2007 43 0.7 0.5 National (Indian) 2003-2007 3 0.4 0.3 National (Malay) 2003-2007 2 0.2 0.2 Thailand 1 Bangkok 2003-2007 64 0.4 0.5 Chiang Mai 2003-2007 70 1.9 1.5 Chonburi 2003-2007 32 1.1 1.3 Khon Kaen 2003-2007 72 1.6 1.6 Lampang 2003-2007 26 1.3 1.1 Songkhla 2004-2007 48 1.8 1.8 Turkey 1 Antalya 2003-2007 1 0.0 0.0 Edirne 2004-2007 0 0.0 0.0 Izmir 2003-2007 8 0.1 0.1 Trabzon 2005-2007 0 0.0 0.0 Viet Nam 3 Hanoi 1993-1997 95 1.7 2.3 Ho Chi Minh City 1995-1998 85 0.9 1.4 Europe Austria 1 National 2003-2007 249 1.2 0.8 Tyrol 2003-2007 14 0.8 0.6 Vorarlberg 2003-2007 5 0.6 0.4 Belarus 1 National 2003-2007 250 1.1 0.8 Belgium 1 National 2004-2007 286 1.4 0.8 Bulgaria 1 National 2003-2007 228 1.2 0.7 Croatia 1 National 2003-2007 114 1.1 0.7 Cyprus 1 National 2003-2007 28 1.5 1.1 Czech Republic 1 National 2003-2007 403 1.6 1.0 Denmark 1 National 2003-2007 234 1.7 1.0 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 52 - Table 10 Continued Male Country Cancer registry Period N cases a Crude rate b ASR b Estonia 1 National 2003-2007 44 1.4 1.0 Finland 1 National 2003-2007 119 0.9 0.6 France 1 Bas-Rhin 2003-2007 42 1.6 1.0 Calvados 2003-2007 22 1.4 0.7 Doubs 2003-2007 18 1.4 0.9 Haut-Rhin 2003-2007 22 1.2 0.7 Herault 2003-2007 37 1.6 0.8 Isere 2003-2007 22 0.8 0.4 Loire Atlantique 2003-2007 19 0.6 0.4 Manche 2003-2007 19 1.6 0.9 Martinique 2003-2007 14 1.5 0.9 Somme 2003-2007 19 1.4 1.0 Tarn 2003-2007 17 1.9 0.7 Vendee 2003-2007 10 0.7 0.4 Germany 1 Brandenburg 2003-2007 126 2.0 1.1 Bremen 2003-2007 23 1.4 0.7 Free State Of Saxony 2003-2007 177 1.7 0.8 Hamburg 2003-2007 61 1.4 0.8 Mecklenburg-Western Pomerania 2003-2007 93 2.2 1.2 Munich 2003-2007 116 1.2 0.7 North Rhine-Westphalia 2003-2007 94 1.5 0.8 Saarland 2003-2007 46 1.8 0.9 Schleswig-Holstein 2003-2007 134 1.9 1.0 Hungary 2 County Szabolcs-Szatmar 1983-1987 12 0.8 0.7 County Vas 1983-1987 4 0.6 0.4 Iceland 1 National 2003-2007 11 1.5 0.9 Ireland 1 National 2003-2007 111 1.1 0.8 Italy 1 Alto Adige 2003-2006 10 1.1 0.6 Biella Province 2003-2007 11 2.5 1.0 Brescia Province 2003-2006 18 0.9 0.5 Catania and Messina 2003-2005 56 2.2 1.2 Catanzaro 2003-2007 9 1.6 0.9 Ferrara Province 2003-2007 20 2.4 1.0 Florence and Prato Provinces 2003-2005 28 1.6 0.7 Friuli-Venezia Giulia 2003-2007 51 1.7 0.8 Genova Province 2003-2006 23 1.4 0.5 Latina 2003-2007 30 2.3 1.3 Lombardy, Como Province 2003-2007 9 0.7 0.3 Lombardy, Lecco Province 2003-2007 8 1.0 0.6 Lombardy, Mantova Province 2003-2005 12 2.1 1.1 Lombardy, Milan 2003-2006 21 0.9 0.4 Lombardy, Varese Province 2003-2007 18 0.9 0.4 Modena Province 2003-2007 20 1.2 0.6 Naples 2003-2007 18 1.3 1.0 Nuoro 2003-2007 9 1.5 1.0 Palerme 2003-2006 38 1.6 1.0 Parma Province 2003-2007 11 1.1 0.6 Ragusa Province 2003-2007 10 1.3 0.8 Reggio Emilia Province 2003-2007 9 0.7 0.4 Romagna Region 2003-2007 44 1.6 0.7 Salerno Province 2003-2007 53 2.0 1.0 Sassari Province 2003-2007 9 0.8 0.5 Sondrio 2003-2007 5 1.1 0.6 South Lombardy 2003-2005 13 1.2 0.5 Syracuse Province 2003-2007 12 1.2 0.8 Torino 2003-2007 25 1.2 0.5 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 53 - Table 10 Continued Male Country Cancer registry Period N cases a Crude rate b ASR b Trapani 2003-2006 17 2.0 1.1 Trento 2003-2006 15 1.5 0.8 Umbria Region 2003-2007 52 2.5 1.1 Veneto Region 2003-2006 54 1.2 0.6 Latvia 1 National 2004-2007 64 1.5 1.0 Lithuania 1 National 2003-2007 108 1.4 1.0 Malta 1 National 2003-2007 15 1.5 0.9 Montenegro 3 Vojvodina 1993-1997 46 0.9 1.3 Netherlands 1 Eindhoven 2003-2007 23 0.9 0.6 National 2003-2007 560 1.4 0.8 Norway 1 National 2003-2007 197 1.7 1.0 Poland 1 Cracow 2003-2006 21 1.5 0.9 Kielce 2003-2007 39 1.2 0.8 Lower Silesia 2003-2007 61 0.9 0.7 Rzeszow 2003-2007 48 0.9 0.7 Portugal 1 Azores 2003-2007 7 1.2 0.9 Romania 2 County Cluj 1983-1987 17 0.9 0.8 Russian Federation 1 St Petersburg 2003-2007 73 0.7 0.5 Serbia 1 Central 2003-2007 175 1.3 0.8 Slovakia 1 National 2003-2007 147 1.1 0.9 Slovenia 1 National 2003-2007 52 1.1 0.7 Spain 1 Albacete 2003-2007 20 2.1 1.1 Asturias 2003-2007 53 2.1 1.0 Basque Country 2003-2007 101 2.0 0.9 Canary Islands 2003-2006 51 1.6 1.1 Ciudad Real 2004-2007 21 2.1 1.2 Cuenca 2003-2007 20 3.9 1.9 Girona 2003-2007 24 1.5 0.8 Granada 2003-2007 42 2.0 1.2 La Rioja 2003-2007 11 1.5 0.6 Mallorca 2003-2007 35 1.8 1.1 Murcia 2003-2007 68 2.0 1.3 Navarra 2003-2007 23 1.6 0.8 Tarragona 2003-2007 44 2.5 1.4 Sweden 1 National 2003-2007 412 1.8 1.0 Switzerland 1 Basel 2003-2007 12 1.1 0.5 Geneva 2003-2007 19 1.9 1.1 Graubunden and Glarus 2003-2007 10 1.8 0.9 Neuchatel 2003-2007 9 2.2 1.4 St Gall-Appenzell 2003-2007 18 1.4 0.8 Ticino 2003-2007 13 1.7 0.8 Valais 2003-2007 6 0.8 0.6 Vaud 2003-2007 24 1.5 0.9 Zurich 2003-2007 36 1.2 0.6 Ukraine 1 National 2003-2007 980 0.9 0.6 United Kingdom 1 England 2003-2007 1870 1.5 0.9 England, East of England Region 2003-2007 193 1.4 0.8 England, North Western 2003-2007 276 1.7 1.1 England, Northern and Yorkshire 2003-2007 261 1.6 1.0 England, Oxford Region 2003-2007 91 1.3 0.9 England, South and Western Regions 2003-2007 291 1.7 1.0 England, Thames 2003-2007 320 1.1 0.7 England, Trent 2005-2007 128 1.7 1.0 England, West Midlands 2003-2007 229 1.7 1.0 Northern Ireland 2003-2007 78 1.8 1.3 Scotland 2003-2007 212 1.7 1.0 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 54 - Table 10 Continued Male Country Cancer registry Period N cases a Crude rate b ASR b Wales 2003-2007 135 1.9 1.1 Oceania Australia 1 Australian Capital Territory 2003-2007 1 0.1 0.1 National 2003-2007 30 0.8 0.4 National 2003-2007 39 0.8 0.6 New South Wales 2003-2007 139 0.8 0.5 Northern Territory 2003-2007 1 0.2 0.1 Northern Territory (Indigenous) 2003-2007 0 0.0 0.0 Northern Territory (Non-Indigenous) 2003-2007 1 0.3 0.2 Queensland 2003-2007 68 0.7 0.5 Tasmania 2003-2007 7 0.6 0.3 Victoria 2003-2007 87 0.7 0.4 New Zealand 1 National 2003-2007 59 0.6 0.4 National (Maori) 2003-2007 0 0.0 0.0 National (Other) 2003-2007 57 0.7 0.4 National (Pacific Islander) 2003-2007 2 0.3 0.5 a Accumulated number of cases during the period in the population covered by the corresponding registry. b Rates per 100,000 men per year. Data sources: 1 Forman D, Bray F, Brewster DH, Gombe Mbalawa C, Kohler B, Piñeros M, Steliarova-Foucher E, Swaminathan R and Ferlay J eds (2013). Cancer Incidence in Five Continents, Vol. X (electronic version) Lyon, IARC. http://ci5.iarc.fr last accessed on 2013-12-13 2 Curado. M. P., Edwards, B., Shin. H.R., Storm. H., Ferlay. J., Heanue. M. and Boyle. P., eds (2007). Cancer Incidence in Five Continents, Vol. IX. IARC Scientific Publications No. 160, Lyon, IARC. 3 Parkin, D.M., Whelan, S.L., Ferlay, J., Teppo, L., and Thomas, D.B., eds (2002). Cancer Incidence in Five Continents, Vol. VIII. IARC Scientific Publications No. 155, Lyon, IARC. 4 Parkin, D.M.,Muir, C.S.,Whelan, S.L.,Gao, Y.-T.,Ferlay, J.,Powell, J., eds (1992). Cancer Incidence in Five Continents, Vol. VI. IARC Scientific Publications No. 120, Lyon, IARC. 5 Waterhouse, J.,Muir, C.S.,Shanmugaratnam, K.,Powell, J., eds (1982). Cancer Incidence in Five Continents, Vol. IV. IARC Scientific Publications No. 42, Lyon, IARC. 6 Waterhouse, J.,Muir, C.S.,Correa, P.,Powell, J., eds (1976). Cancer Incidence in Five Continents, Vol. III. IARC Scientific Publications No. 15, Lyon, IARC. 7 Doll, R.,Payne, P.,Waterhouse, J.A.H., eds (1966). Cancer Incidence in Five Continents, Vol. I. Union Internationale Contre le Cancer, Geneva. NOTE. For time trends in penile cancer incidence please refer to specific countries

3 BURDEN OF HPV RELATED CANCERS - 55-3.3 Head and neck cancers The majority of head and neck cancers are associated with high tobacco and alcohol consumption. However, increasing trends in the incidence at specific sites suggest that other etiological factors are involved, and infection by certain high-risk types of human papillomavirus (i.e. HPV16) have been reported to be associated with head and neck cancers, in particular with oropharyngeal cancer. Current evidence suggests that HPV16 is associated with tonsil cancer (including Waldeyer ring cancer), base of tongue cancer and other oropharyngeal cancer sites. Associations with other head and neck cancer sites such as oral cancer are neither strong nor consistent when compared to molecular-epidemiological data on HPV and oropharyngeal cancer. Association with laryngeal cancer is still unclear (IARC Monograph Vol 100B). 3.3.1 Pharyngeal cancer (excluding nasopharynx) (last update 15 Jan 2014) Table 11: Incidence of cancer of pharyngeal cancer (excluding nasopharynx) by sex, world by regions and sub-regions. Includes ICD-10 codes:c09-10,c12-14 (estimations for 2012) MALE FEMALE Area N cases Crude a ASR a Cum risk b N cases Crude a ASR a Cum risk b rate (%) ages rate (%) ages 0-74 0-74 World 115131 3.2 3.2 0.4 27256 0.8 0.7 0.1 Less developed regions 70731 2.4 2.8 0.3 18059 0.6 0.7 0.1 More developed regions 44400 7.3 4.7 0.6 9197 1.4 0.8 0.1 Africa 3369 0.6 1.1 0.1 1928 0.4 0.6 0.1 Eastern Africa 906 0.5 1.0 0.1 567 0.3 0.6 0.1 Middle Africa 585 0.9 1.7 0.2 208 0.3 0.6 0.1 Northern Africa 621 0.6 0.8 0.1 611 0.6 0.7 0.1 Southern Africa 784 2.7 3.9 0.5 392 1.3 1.5 0.2 Western Africa 473 0.3 0.6 0.1 150 0.1 0.1 0.0 Americas 17637 3.7 3.3 0.4 4471 0.9 0.7 0.1 Caribbean 815 3.9 3.6 0.4 227 1.1 0.9 0.1 Central America 694 0.9 1.0 0.1 218 0.3 0.3 0.0 Northern America 10493 6.1 4.2 0.5 2756 1.6 1.0 0.1 South America 5635 2.8 3.0 0.3 1270 0.6 0.5 0.1 Asia 65016 3.0 3.1 0.4 14997 0.7 0.7 0.1 Central Asia 717 2.3 3.2 0.4 321 1.0 1.1 0.1 Eastern Asia 13441 1.6 1.3 0.1 1884 0.2 0.2 0.0 South-Eastern Asia 6933 2.3 2.6 0.3 1965 0.6 0.7 0.1 Southern Asia 43190 4.8 6.3 0.8 10454 1.2 1.5 0.2 Western Asia 735 0.6 0.8 0.1 373 0.3 0.4 0.0 Europe 28394 7.9 5.2 0.6 5700 1.5 0.9 0.1 Eastern Europe 10187 7.4 5.3 0.6 1401 0.9 0.5 0.1 Northern Europe 2594 5.3 3.4 0.4 844 1.7 1.0 0.1 Southern Europe 4137 5.3 3.4 0.4 731 0.9 0.5 0.1 Western Europe 11476 12.3 7.5 0.9 2724 2.8 1.6 0.2 Oceania 715 3.8 3.0 0.4 160 0.8 0.6 0.1 Australia & New Zealand 633 4.6 3.2 0.4 146 1.1 0.7 0.1 Melanesia 71 1.5 3.4 0.6 14 0.3 0.4 0.0 Micronesia 0 0.0 0.0 0.0 0 0.0 0.0 0.0 Polynesia 11 3.2 3.8 0.5 0 0.0 0.0 0.0 a Male: Rates per 100,000 men per year. Female: Rates per 100,000 women per year. b Cumulative risk (incidence) is the probability or risk of individuals getting from the disease during ages 0-74 years. For cancer, it is expressed as the % of new born children who would be expected to develop from a particular cancer before the age of 75 if they had the rates of cancer observed in the period in the absence of competing causes. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014. Table 12: Mortality of cancer of pharyngeal cancer (excluding nasopharynx) by sex, world regions and sub-regions. Includes ICD-10 codes:c09-10,c12-14 (estimations for 2012) MALE FEMALE Area N cases Crude a ASR a Cum risk b N cases Crude a ASR a Cum risk b rate (%) ages rate (%) ages 0-74 0-74 World 77585 2.2 2.2 0.3 18505 0.5 0.5 0.1 (Continued)

3 BURDEN OF HPV RELATED CANCERS - 56 - MALE FEMALE Area N cases Crude a ASR a Cum risk b N cases Crude a ASR a Cum risk b rate (%) ages rate (%) ages 0-74 0-74 Less developed regions 56165 1.9 2.2 0.3 14440 0.5 0.5 0.1 More developed regions 21420 3.5 2.2 0.3 4065 0.6 0.3 0.0 Africa 2631 0.5 0.9 0.1 1459 0.3 0.4 0.1 Eastern Africa 786 0.4 0.9 0.1 496 0.3 0.5 0.1 Middle Africa 518 0.8 1.6 0.2 191 0.3 0.6 0.1 Northern Africa 483 0.5 0.6 0.1 494 0.5 0.6 0.1 Southern Africa 426 1.5 2.2 0.3 145 0.5 0.6 0.1 Western Africa 418 0.3 0.5 0.1 133 0.1 0.1 0.0 Americas 8381 1.8 1.5 0.2 2173 0.5 0.3 0.0 Caribbean 568 2.7 2.4 0.3 159 0.7 0.6 0.1 Central America 482 0.6 0.7 0.1 153 0.2 0.2 0.0 Northern America 3145 1.8 1.2 0.1 970 0.5 0.3 0.0 South America 4186 2.1 2.2 0.3 891 0.4 0.4 0.0 Asia 51005 2.3 2.4 0.3 12126 0.6 0.5 0.1 Central Asia 516 1.7 2.4 0.3 231 0.7 0.8 0.1 Eastern Asia 7867 1.0 0.7 0.1 1352 0.2 0.1 0.0 South-Eastern Asia 5414 1.8 2.1 0.2 1545 0.5 0.5 0.1 Southern Asia 36667 4.1 5.4 0.6 8710 1.0 1.2 0.1 Western Asia 541 0.4 0.6 0.1 288 0.2 0.3 0.0 Europe 15245 4.3 2.7 0.3 2662 0.7 0.4 0.0 Eastern Europe 7277 5.3 3.8 0.5 885 0.6 0.3 0.0 Northern Europe 1118 2.3 1.4 0.2 352 0.7 0.3 0.0 Southern Europe 2342 3.0 1.8 0.2 430 0.5 0.3 0.0 Western Europe 4508 4.9 2.7 0.3 995 1.0 0.5 0.1 Oceania 323 1.7 1.3 0.2 85 0.5 0.3 0.0 Australia & New Zealand 261 1.9 1.2 0.1 70 0.5 0.3 0.0 Melanesia 56 1.2 2.8 0.5 14 0.3 0.4 0.0 Micronesia 0 0.0 0.0 0.0 0 0.0 0.0 0.0 Polynesia 6 1.7 2.0 0.2 1 0.3 0.3 0.0 a Male: Rates per 100,000 men per year. Female: Rates per 100,000 women per year. b Cumulative risk (mortality) is the probability or risk of individuals dying from the disease during ages 0-74 years. For cancer, it is expressed as the % of new born children who would be expected to die from a particular cancer before the age of 75 if they had the rates of cancer observed in the period in the absence of competing causes. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 57 - Figure 23: Comparison of incidence and mortality rates of cancer of pharyngeal cancer (excluding nasopharynx) by sex and age group in the World. Includes ICD-10 codes:c09-10,c12-14 (estimations for 2012) MALE 25 World 25 Less developed regions 25 More developed regions 20 20 20 Age specific rates of pharyngeal cancer (excluding nasopharynx) per 100,000 15 10 5 0 20 15 10 5 0 14 15 39 40 44 45 49 50 54 55 59 25 World 60 64 65 69 70 74 >=75 15 10 5 0 20 15 10 5 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 FEMALE 25 Less developed regions >=75 15 10 5 0 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 25 More developed regions 20 15 10 5 >=75 0 0 0 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 Incidence 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 0 14 15 39 40 44 45 49 50 54 Mortality 55 59 60 64 65 69 70 74 >=75 Rates per 100,000 per year. Data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 58 - Figure 24: Comparison of incidence and mortality rates of cancer of pharyngeal cancer (excluding nasopharynx) in male by age group in the World. Includes ICD-10 codes:c09-10,c12-14 (estimations for 2012) 30 World 25 20 15 30 Asia 25 20 15 Age specific rates of pharyngeal cancer (excluding nasopharynx) per 100,000 10 5 0 30 Africa 25 20 15 10 5 0 30 Americas 25 20 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 10 5 0 30 Europe 25 20 15 10 5 0 30 Oceania 25 20 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 15 15 10 5 0 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 Incidence 10 5 0 Mortality 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 Age group (years) Rates per 100,000 men per year. Data sources: (Continued on next page)

3 BURDEN OF HPV RELATED CANCERS - 59 - ( Figure 25 continued from previous page) Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

3 BURDEN OF HPV RELATED CANCERS - 60 - Figure 25: Comparison of incidence and mortality rates of cancer of pharyngeal cancer (excluding nasopharynx) in female by age group in the World. Includes ICD-10 codes:c09-10,c12-14 (estimations for 2012) 5 World 5 Asia 4 4 3 3 Age specific rates of pharyngeal cancer (excluding nasopharynx) per 100,000 2 1 0 5 Africa 4 3 2 1 0 5 Americas 4 3 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 2 1 0 5 Europe 4 3 2 1 0 5 Oceania 4 3 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 2 1 0 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 Incidence 2 1 0 Mortality 0 14 15 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 Age group (years) Rates per 100,000 women per year. Data sources: (Continued on next page)

3 BURDEN OF HPV RELATED CANCERS - 61 - ( Figure 25 continued from previous page) Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/01/2014.

- 62-4 HPV related statistics HPV infection is commonly found in the anogenital tract of men and women with and without clinical lesions. The aetiological role of HPV infection among women with cervical cancer is well-established, and there is growing evidence of its central role in other anogenital sites. HPV is also responsible for other diseases such as recurrent juvenile respiratory papillomatosis and genital warts, both mainly caused by HPV types 6 and 11(Lacey CJ, Vaccine 2006; 24(S3):35). For this section, the methodologies used to compile the information on HPV burden are derived from systematic reviews and meta-analyses of the literature. Due to the limitations of HPV DNA detection methods and study designs used, these data should be interpreted cautiously and used only as a guidance to assess the burden of HPV infection in the population. (Vaccine 2006, Vol. 24, Suppl 3; Vaccine 2008, Vol. 26, Suppl 10; Vaccine 2012, Vol. 30, Suppl 5; IARC Monographs 2007, Vol. 90). 4.1 HPV burden in women with normal cytology, precancerous cervical lesions or invasive cervical cancer The statistics shown in this section focus on HPV infection in the cervix uteri. HPV cervical infection results in cervical morphological lesions ranging from normalcy (cytologically normal women) to different stages of precancerous lesions (CIN-1, CIN-2, CIN-3/CIS) and invasive cervical cancer. HPV infection is measured by means of HPV DNA detection in cervical cells (fresh tissue, paraffin embedded or exfoliated cells). The prevalence of HPV increases with severity of the lesion. HPV causes virtually 100% of cases of cervical cancer, and an underestimation of HPV prevalence in cervical cancer is most likely due to the limitations of study methodologies. Worldwide, HPV-16 and 18, the two vaccine-preventable types. contribute to over 70% of all cervical cancer cases, between 41%-67% of high-grade cervical lesions and 16-32% of low-grade cervical lesions. After HPV-16/18, the six most common HPV types are the same in all world regions, namely 31, 33, 35, 45, 52 and 58; these account for an additional 20% of cervical cancers worldwide (Clifford G et al. Vaccine 2006;24(S3):26-34). Methods: Prevalence and type distribution of human papillomavirus in cervical carcinoma, low-grade cervical lesions, high-grade cervical lesions and normal cytology: systematic review and meta-analysis Systematic review of the literature was conducted on the worldwide HPV-prevalence and type distribution for cervical carcinoma, low-grade cervical lesions, high-grade cervical lesions and normal cytology from 1990 to data as of indicated in each section. Search terms were HPV AND cerv* using Pubmed. There were no limits in publication language. References cited in selected articles were also investigated. Inclusion criteria were: HPV DNA detection by means of PCR or HC2, a minimum of 20 cases for cervical carcinoma, 20 cases for low-grade cervical lesions, 20 cases for high-grade cervical lesions and 100 normal cytology and a detailed description of HPV DNA detection and genotyping techniques used. The number of cases tested and HPV positive extracted for each study were pooled to estimate the prevalence of HPV DNA and the HPV type distribution globally and by geographical region. Binomial 95% confidence intervals were calculated for each HPV prevalence. For more details refer to the methods document.

- 63-4.1.1 HPV prevalence in women with normal cytology Figure 26: Prevalence of HPV among women with normal cytology in the World Data updated at 15 Dec 2014 (data as of 31 Oct 2014). The samples for HPV testing come from cervical specimens (fresh / fixed biopsies or exfoliated cells Data sources: See references in Section 9.

- 64 - Figure 27: Crude age-specific HPV prevalence (%) and 95% confidence interval (grey shadow) in women with normal cytology in the World HPV prevalence (%) 50 40 30 20 10 0 Europe 50 40 30 20 10 0 Oceania <25 25 34 35 44 45 54 55 64 65+ <25 25 34 35 44 45 54 55 64 65+ HPV prevalence (%) 50 40 30 20 10 0 Africa 50 40 30 20 10 0 Asia <25 25 34 35 44 45 54 55 64 65+ <25 25 34 35 44 45 54 55 64 65+ HPV prevalence (%) 50 40 30 20 10 0 Americas 50 40 30 20 10 0 World <25 25 34 35 44 45 54 55 64 65+ <25 25 34 35 44 45 54 55 64 65+ Age group (years) Data updated at 15 Dec 2014 (data as of 31 Oct 2014). Data sources: See references in Section 9.

- 65 - Figure 28: Prevalence of HPV among women with normal cytology in Africa by country and study Country Algeria Benin Cameroon Congo Côte d'ivoire Egypt Ethiopia Gabon Gambia Guinea Kenya Mali Morocco Mozambique Nigeria Hammouda 2005 Algiers Hammouda 2011 Zeralda (Algiers) Piras 2011(A) Untiet 2014(a) Yaoundé Hovland 2010 Bukavu Sangwa Lugoma 2011 Mbuku, Kinshasa La Ruche 1998 Abidjan La Ruche 1998 Abidjan Adjorlolo Johnson 2010 Abidjan Abdel Aziz 2006 Cairo Ruland 2006(a) Gurage Leyh Bannurah 2014(a) Gurage Si Mohamed 2005(a) Libreville Wall 2005 Farafenni Keita 2009 Conakry Temmerman 1999(a) Nairobi De Vuyst 2003 Nairobi Yamada 2008(a) Nairobi De Vuyst 2010 Mombasa Maranga 2013 Nairobi Tracy 2011(a) Bamako Schluterman 2013(a) Naréna Chaouki 1998 Rabat Amrani 2003 Rabat Alhamany 2010 Rabat Bennani 2012 Fez Castellsagué 2001 Manhiça Naucler 2011(a) Maputo Gage 2012 Irun Akarolo Anthony 2013(a) Abuja Age range (mean age) 31 80 (52.7) yrs 15 65 yrs 15 70 yrs 20 89 (44.0) yrs >=30 yrs 20 50 (27.9) yrs 20 50 (30.0) yrs 23 69 (43.5) yrs 20 60 (37.3) yrs 18 65 (34.0) yrs 15 64 yrs 18 44 (26.4) yrs 15 54 (33.0) yrs 15 64 (35.0) yrs 19 54 (29.7) yrs 25 55 (35.7) yrs 16 61 (29.9) yrs >=15 yrs 21 50 (35.3) yrs 15 65 (34.2) yrs 15 65 (33.8) yrs 18 70 (40.7) yrs 25 54 (38.0) yrs 17 80 (42.5) yrs 17 81 (40.0) yrs 14 61 (36.0) yrs >=25 (33.0) yrs >=15 yrs (37.6) yrs 0 10 20 30 40 50 HPV prevalence (%) N 133 10.5 (6.4 16.9) 732 258 26.7 (21.7 32.5) 694 16.7 (14.1 19.7) 287 13.9 (10.4 18.4) 1138 120 27.5 (20.3 36.1) 194 16.5 (11.9 22.4) 110 29.1 (21.4 38.2) 156 10.3 (6.4 16.0) 189 15.9 (11.4 21.8) 537 17.5 (14.5 20.9) 195 41.5 (34.9 48.6) 576 11.5 (9.1 14.3) 752 47.9 (44.3 51.4) 513 17.0 (14.0 20.4) 369 38.8 (33.9 43.8) 333 16.8 (13.2 21.2) 454 40.3 (35.9 44.9) 101 41.6 (32.5 51.3) 202 11.9 (8.1 17.1) 212 23.1 (17.9 29.2) 172 21.5 (16.0 28.2) 306 % (95% CI) 5.3 (3.9 7.2) 8.7 (7.2 10.5) 4.2 (2.5 7.1) 785 15.8 (13.4 18.5) 751 42.5 (39.0 46.0) 196 32.1 (26.0 39.0) 203 41.4 (34.8 48.3) 1075 10.5 (8.8 12.5) 108 10.2 (5.8 17.3) (Continued on next page) A Abomey, Atakora, Cotonou, Djougou, Lagune, Lokossa, Parakou, Porto-Novo and Tanguetà; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. Data sources: See references in Section 9.

- 66 - Figure 29: Prevalence of HPV among women with normal cytology in Africa by country and study (continued) Country Nigeria Rwanda Senegal South Africa Tanzania Tunisia Uganda Zimbabwe Thomas 2004 Idikan (Ibadan) Gage 2012 Irun Pimentel 2013(B) Singh 2009(a) Veldhuijzen 2012(a) Kigali Astori 1999 Dakar Hawes 2003(a) Dakar Xi 2003 Dakar Hanisch 2013(a) Dakar Mbaye 2014(a) Saint Louis Mbaye 2014 Louga Mbaye 2014 Dakar Mbaye 2014 Thiès Wright 2000 Cape Town Denny 2005(a) Khayelitsha Jones 2007 Cape Town Allan 2008 Cape Town Mbulawa 2010(C) McDonald 2012 Khayelitsha Richter 2013(D)(a) Vidal 2011 Kilimanjaro Watson Jones 2013 Mwanza Dartell 2014(E) Hassen 2003 Sousse Safaeian 2007(a) Rakai Asiimwe 2008(a) Bushenyi District Banura 2008(a) Kampala Taube 2010 Kampala Odida 2011 Kampala Jeronimo 2014 Kampala Baay 2004(a) Mupfure Age range (mean age) 15 98 (43.7) yrs >=15 yrs 19 85 (36.2) yrs >=25 (42.0) yrs 20 75 (34.0) yrs >=15 (31.9) yrs 35 80 (42.7) yrs 15 84 (43.0) yrs 18 80 (41.8) yrs 18 80 (41.8) yrs 18 80 (42.1) yrs 18 80 (41.8) yrs 35 65 (39.0) yrs 35 65 (43.3) yrs >=18 yrs 21 59 (44.0) yrs 17 65 yrs 16 83 (39.0) yrs >=18 (40.3) yrs 10 25 (18.0) yrs 15 82 (38.0) yrs 20 45 (35.0) yrs 15 49 (30.0) yrs 25 37 (30.0) yrs 12 24 (20.0) yrs 18 30 yrs 18 74 (41.0) yrs 25 60 (36.8) yrs 15 49 yrs 0 10 20 30 40 50 60 70 80 HPV prevalence (%) N % (95% CI) 844 24.8 (22.0 27.8) 1075 10.5 (8.8 12.5) 374 12.3 (9.3 16.0) 188 14.4 (10.1 20.1) 144 16.7 (11.5 23.6) 158 13.9 (9.4 20.2) 3633 25.3 (23.9 26.7) 1639 12.5 (11.0 14.2) 2139 27.1 (25.2 29.0) 145 20.0 (14.3 27.2) 108 23.1 (16.2 31.9) 498 20.9 (17.5 24.7) 185 30.3 (24.1 37.2) 1269 15.5 (13.6 17.6) 6555 21.4 (20.4 22.4) 368 41.0 (36.1 46.1) 848 20.4 (17.8 23.2) 155 45.8 (38.2 53.7) 7569 16.9 (16.1 17.8) 1445 74.6 (72.3 76.8) 148 13.5 (8.9 20.0) 117 73.5 (64.9 80.7) 2737 12.8 (11.6 14.1) 96 14.6 (8.9 23.0) 505 15.6 (12.7 19.1) 305 15.7 (12.1 20.2) 868 73.2 (70.1 76.0) 157 56.7 (48.9 64.2) 251 26.3 (21.2 32.1) 2676 15.2 (13.9 16.7) 174 27.0 (21.0 34.1) (Continued on next page) B Okene, Abuja and Katari; C Gugulethu (Cape Town); D Tshwane District, Gauteng province; E Dar es Salaam, Pwani, Mwanza; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. Data sources: See references in Section 9.

- 67 - Figure 30: Prevalence of HPV among women with normal cytology in Africa by country and study (continued) Country Argentina Belize Bolivia Brazil Abba 2003 La Plata Matos 2003 Entre Ríos Badano 2011 Posadas City Chouhy 2013(A) Chouhy 2013 Buenos Aires Cathro 2009 Belize City Cervantes 2003(a) Amazonian lowland Franco 1995(a) Paraiba Muñoz 1996 Sao Paulo Lorenzato 2000 Recife Noronha 2005 Para Carestiato 2006 Rio de Janeiro Oliveira 2007(a) Pacoti, Ceara Fernandes 2009 Natal Silva 2009 Itaboraí Silva 2009 Maricá Girianelli 2010(B) Lippman 2010 Sao Paulo Oliveira 2010(C) Pinto 2011(a) Pará Pinto 2011 Tucuruí Roteli Martins 2011(a) Miranda 2012(D) Coser 2013 Cruz Alta Figueiredo Alves 2013(a) Goiana Lorenzi 2013 Barretos (Sao Paulo) Rocha 2013(E) Augusto 2014 Niterói City Cassel 2014 Porto Alegre Entiauspe 2014 Pelotas Age range (mean age) 15 70 (32.4) yrs 13 78 (40.5) yrs 18 62 (31.0) yrs 14 77 (31.6) yrs 15 69 (31.2) yrs (39.6) yrs 16 71 (36.0) yrs 15 65 (33.0) yrs 26 77 (52.2) yrs 13 84 (36.5) yrs 30 45 (36.6) yrs 11 70 (27.2) yrs 13 49 (31.0) yrs 15 65 yrs 14 79 (33.0) yrs 14 79 (33.0) yrs 25 59 yrs 18 40 yrs 14 24 (19.6) yrs >=13 (36.9) yrs >=13 (34.1) yrs 15 25 (20.0) yrs 18 65 yrs 15 19 (17.2) yrs 18 76 yrs 18 78 (36.4) yrs 14 79 (38.4) yrs (42.7) yrs 18 45 (33.3) yrs 0 10 20 30 40 50 HPV prevalence (%) N 152 46.1 (38.3 54.0) 843 15.4 (13.1 18.0) 139 33.1 (25.8 41.3) 403 37.5 (32.9 42.3) 371 49.9 (44.8 54.9) 426 10.1 (7.6 13.3) 135 525 18.3 (15.2 21.8) 194 17.0 (12.4 22.9) 215 19.5 (14.8 25.3) 433 672 12.6 (10.3 15.4) 579 11.7 (9.4 14.6) 110 24.5 (17.5 33.4) 128 21.9 (15.6 29.8) 130 1800 12.3 (10.9 13.9) 209 34.9 (28.8 41.6) 225 28.0 (22.5 34.2) 233 15.0 (11.0 20.2) 211 14.2 (10.1 19.6) 1509 29.7 (27.4 32.0) 399 11.0 (8.3 14.5) 327 32.7 (27.9 38.0) 432 28.0 (24.0 32.4) 1921 10.5 (9.2 11.9) 314 29.9 (25.1 35.2) 338 % (95% CI) 5.9 (3.0 11.3) 6.9 (4.9 9.7) 2.3 (0.8 6.6) 8.0 (5.5 11.4) 158 12.7 (8.3 18.7) 136 27.9 (21.1 36.0) F Chitungwiza and Harare; G Chitungwiza, Epworth (Harare); H Chitungwiza and Harare; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. Data sources: See references in Section 9.

- 68 - Figure 31: Prevalence of HPV among women with normal cytology in Americas by country and study Country Argentina Belize Bolivia Brazil Abba 2003 La Plata Matos 2003 Entre Ríos Badano 2011 Posadas City Chouhy 2013(A) Chouhy 2013 Buenos Aires Cathro 2009 Belize City Cervantes 2003(a) Amazonian lowland Franco 1995(a) Paraiba Muñoz 1996 Sao Paulo Lorenzato 2000 Recife Noronha 2005 Para Carestiato 2006 Rio de Janeiro Oliveira 2007(a) Pacoti, Ceara Fernandes 2009 Natal Silva 2009 Itaboraí Silva 2009 Maricá Girianelli 2010(B) Lippman 2010 Sao Paulo Oliveira 2010(C) Pinto 2011(a) Pará Pinto 2011 Tucuruí Roteli Martins 2011(a) Miranda 2012(D) Coser 2013 Cruz Alta Figueiredo Alves 2013(a) Goiana Lorenzi 2013 Barretos (Sao Paulo) Rocha 2013(E) Augusto 2014 Niterói City Cassel 2014 Porto Alegre Entiauspe 2014 Pelotas Age range (mean age) 15 70 (32.4) yrs 13 78 (40.5) yrs 18 62 (31.0) yrs 14 77 (31.6) yrs 15 69 (31.2) yrs (39.6) yrs 16 71 (36.0) yrs 15 65 (33.0) yrs 26 77 (52.2) yrs 13 84 (36.5) yrs 30 45 (36.6) yrs 11 70 (27.2) yrs 13 49 (31.0) yrs 15 65 yrs 14 79 (33.0) yrs 14 79 (33.0) yrs 25 59 yrs 18 40 yrs 14 24 (19.6) yrs >=13 (36.9) yrs >=13 (34.1) yrs 15 25 (20.0) yrs 18 65 yrs 15 19 (17.2) yrs 18 76 yrs 18 78 (36.4) yrs 14 79 (38.4) yrs (42.7) yrs 18 45 (33.3) yrs 0 10 20 30 40 50 HPV prevalence (%) N 152 46.1 (38.3 54.0) 843 15.4 (13.1 18.0) 139 33.1 (25.8 41.3) 403 37.5 (32.9 42.3) 371 49.9 (44.8 54.9) 426 10.1 (7.6 13.3) 135 525 18.3 (15.2 21.8) 194 17.0 (12.4 22.9) 215 19.5 (14.8 25.3) 433 672 12.6 (10.3 15.4) 579 11.7 (9.4 14.6) 110 24.5 (17.5 33.4) 128 21.9 (15.6 29.8) 130 1800 12.3 (10.9 13.9) 209 34.9 (28.8 41.6) 225 28.0 (22.5 34.2) 233 15.0 (11.0 20.2) 211 14.2 (10.1 19.6) 1509 29.7 (27.4 32.0) 399 11.0 (8.3 14.5) 327 32.7 (27.9 38.0) 432 28.0 (24.0 32.4) 1921 10.5 (9.2 11.9) 314 29.9 (25.1 35.2) 338 % (95% CI) 5.9 (3.0 11.3) 6.9 (4.9 9.7) 2.3 (0.8 6.6) 8.0 (5.5 11.4) 158 12.7 (8.3 18.7) 136 27.9 (21.1 36.0) (Continued on next page) A Granadero Baigorria City (Santa Fe Province); B Duque de Caxias and Nova Iguaçu (State of Rio de Janeiro); C Niterói City (Rio de Janeiro); D Ouro Preto city (Minas Gerais); E Coari (Amazonas State); Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. Data sources: See references in Section 9.

- 69 - Figure 32: Prevalence of HPV among women with normal cytology in Americas by country and study (continued) Country Brazil Trottier 2006 Sao Paulo Silva 2009 Maricá da Silva 2012 Paiçandú (Paraná) de Abreu 2012(F) Age range (mean age) 18 59 (32.9) yrs 14 79 (33.0) yrs 15 83 (42.8) yrs 15 83 (41.0) yrs N % (95% CI) 1988 15.1 (13.6 16.7) 130 2.3 (0.8 6.6) 418 6.7 (4.7 9.5) 370 7.6 (5.3 10.7) Canada de Oliveira 2013(a) Rio Grande Tamegão Lopes 2014 Juruti (Pará) Young 1997 Winnipeg Sellors 2000 Ontario Richardson 2003 Montreal Mayrand 2006(G) >=14 (32.7) yrs (34.0) yrs 15 49 yrs 17 42 (23.0) yrs 30 69 (43.0) yrs 162 13.6 (9.1 19.7) 120 35.0 (27.1 43.9) 1132 30.6 (28.0 33.3) 878 10.3 (8.4 12.4) 568 27.1 (23.6 30.9) 9245 5.2 (4.7 5.6) Kapala 2007 Ontario Moore 2009 British Columbia Roteli Martins 2011 >=15 (40.0) yrs 15 25 (21.1) yrs 222 15.8 (11.6 21.1) 4003 12.3 (11.3 13.3) 185 23.2 (17.7 29.8) Demers 2012 Manitoba Jiang 2013(H) >=18 (43.0) yrs 14 69 (38.0) yrs 517 17.2 (14.2 20.7) 13379 21.6 (20.9 22.3) Chile Ogilvie 2013(a) British Columbia Louvanto 2014(a) Montreal Ferreccio 2004 Santiago Ferreccio 2008(a) 30 65 yrs 15 86 (43.4) yrs 16 97 (41.9) yrs 4330 12.2 (11.3 13.3) 23739 6.9 (6.6 7.3) 913 11.2 (9.3 13.4) 1100 28.0 (25.4 30.7) Colombia Montalvo 2011 Arica Ferreccio 2013 Santiago Muñoz 1996 Cali Molano 2002 Bogota Leon 2009 Girardot Soto De Leon 2011(I) 18 25 (21.6) yrs 16 78 (42.2) yrs 19 74 (42.8) yrs 13 85 (33.0) yrs 14 80 (41.6) yrs 14 77 (39.0) yrs 195 2.6 (1.1 5.9) 8127 9.8 (9.1 10.4) 307 13.4 (10.0 17.6) 1831 14.6 (13.1 16.3) 744 19.9 (17.2 22.9) 1564 49.7 (47.2 52.2) Costa Rica Cuba Ecuador Guatemala Guyana Herrero 2005 Guanacaste Safaeian 2007 Guanacaste Soto 2014 La Havana Brown 2009 Guayas Vallès 2009 Escuintla Kightlinger 2010 18 94 (41.0) yrs 18 25 (21.0) yrs 30 69 (40.0) yrs 18 78 (37.7) yrs 18 49 (29.7) yrs 13 80 (36.9) yrs 7459 22.4 (21.4 23.3) 4857 42.2 (40.9 43.6) 111 41.4 (32.7 50.7) 285 20.7 (16.4 25.8) 274 33.2 (27.9 39.0) 1168 11.5 (9.8 13.4) 0 10 20 30 40 50 HPV prevalence (%) (Continued on next page) F Maringá, Paiçandú and Uniao da Vitoria (Paraná State); G Montreal and Newfoundland; H Northwest Territories, Nunavut, Labrador, Yukon.; I Bogotá, Leticia, Chaparral, Giradot and Tumaco; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. Data sources: See references in Section 9.

- 70 - Figure 33: Prevalence of HPV among women with normal cytology in Americas by country and study (continued) Country Guyana Honduras Jamaica Mexico Nicaragua Paraguay Peru Kightlinger 2010 Ferrera 1999 Tegucigalpa Tábora 2005 Tegucigalpa Tábora 2009 Tegucigalpa Watt 2009(a) Western Jamaica Lewis Bell 2013 Hernández Avila 1997(a) Mexico City Giuliano 2001 Sonora Lazcano Ponce 2001 Morelos Salmerón 2003 Morelos Giuliano 2005 Sonora Hernández Girón 2005(a) Cuernavaca Piña Sánchez 2006 Mexico City Sánchez Anguiano 2006 Durango City Rojo Contreras 2008 Guadalajara Illades Aguiar 2009 Acapulco Illades Aguiar 2010(J) Lazcano Ponce 2010(K) Monroy 2010 Mexico City Velázquez Márquez 2010(b) Tlaxcala López Rivera 2012 Mexico City Carrillo García 2014 Jeronimo 2014 Masaya Province Rolón 2000 Asunción Torres 2009 Asunción Mendoza 2011 Asunción Santos 2001 Lima García 2004 Almonte 2007 San Martin Martorell 2012 Iquitos and Loretos Silva Caso 2014 Cajamarca Age range (mean age) 13 80 (36.9) yrs 15 65 (40.4) yrs 18 35 (24.0) yrs 18 65 yrs (35.0) yrs 16 49 (32.0) yrs 25 75 (44.3) yrs 15 79 (34.3) yrs 18 82 (41.6) yrs 15 85 (42.5) yrs 40 82 (51.2) yrs 17 39 yrs 19 64 (36.5) yrs 20 69 (39.0) yrs 18 55 (36.0) yrs (50.2) yrs 15 97 (36.2) yrs 20 70 yrs 17 51 (33.3) yrs 18 74 (37.7) yrs 18 76 yrs 30 49 (37.9) yrs 25 73 (45.1) yrs 17 65 (34.0) yrs 16 77 (35.0) yrs 21 82 (49.2) yrs 18 65 (35.4) yrs 25 49 (35.0) yrs 18 65 yrs 995 7545 258 487 49053 4340 4218 0 10 30 50 70 90 HPV prevalence (%) N 1168 11.5 (9.8 13.4) 438 38.8 (34.4 43.5) 100 28.0 (20.1 37.5) 562 51.4 (47.3 55.5) 99 83.8 (75.3 89.8) 765 50.8 (47.3 54.4) 204 13.2 (9.3 18.6) 1340 12.5 (10.9 14.4) 1060 14.2 (12.3 16.5) 159 11.9 (7.8 17.9) 189 33.9 (27.5 40.9) 256 35.5 (29.9 41.6) 3117 40.9 (39.2 42.6) 272 12.9 (9.4 17.4) 100 22.0 (15.0 31.1) 916 518 37.8 (33.8 42.1) 91 19.8 (12.9 29.1) 159 25.2 (19.1 32.4) 207 20.8 (15.8 26.8) 175 17.7 (12.8 24.0) 501 % (95% CI) 8.8 (7.2 10.8) 7.8 (7.2 8.4) 7.0 (4.5 10.8) 4.1 (2.7 6.3) 8.0 (7.8 8.3) 7.9 (6.3 9.8) 9.8 (8.9 10.7) 3.8 (2.4 5.8) 7.5 (6.8 8.4) 203 36.0 (29.7 42.8) 241 17.8 (13.5 23.2) (Continued on next page) J Acapulco, Chilpancingo and Iguala (State of Guerrero); K Northern and Southern Mexico City, State of Mexico,Guerrero, Michoacán, Morelos, Jalisco, Nuevo León,Oaxaca, Querétaro, Veracruz and Yucatán; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. b Few HPV types tested: 6, 11, 16, 18, 31 only. Data sources: See references in Section 9.

- 71 - Figure 34: Prevalence of HPV among women with normal cytology in Americas by country and study (continued) Country Bahrain Bangladesh Bhutan China Hajjaj 2006 Nahar 2014(a) Dhaka and Mirzapur Tshomo 2014 Thimphu Belinson 2001(A) Age range (mean age) 20 60 (37.0) yrs 13 64 (32.0) yrs 18 69 yrs 35 45 (39.1) yrs N % (95% CI) 91 12.1 (6.9 20.4) 1902 7.6 (6.5 8.9) 2272 23.0 (21.3 24.7) 1784 14.2 (12.6 15.9) Chan 2002 Hong Kong Belinson 2003(B) 19 83 (43.8) yrs 27 56 (40.9) yrs 1962 5.6 (4.6 6.7) 6643 14.4 (13.6 15.3) Dai 2006 Shanxi Li 2006 Shenyang He 2008 Hangzhou Lin 2008(a) Guandong Chan 2009(a) Hong Kong Jin 2010(C) 19 59 (40.4) yrs 17 59 (41.2) yrs (40.0) yrs 20 68 (39.0) yrs 19 83 (43.3) yrs 19 65 (38.1) yrs 601 10.6 (8.4 13.4) 663 13.7 (11.3 16.6) 480 15.2 (12.3 18.7) 1705 9.0 (7.8 10.5) 2604 6.7 (5.8 7.7) 2847 7.4 (6.5 8.4) Li 2010 Beijing Moy 2010(D) 25 54 (39.6) yrs 30 54 (39.0) yrs 5530 7367 6.6 (6.0 7.3) 9.5 (8.9 10.2) Sun 2010 Liaoning Province Belinson 2011 Guangdong Province Hu 2011 Jaingsu Province Chen 2012(a) Chaozhou Chui 2012(a) Macau DU 2012(a) Shenzhen Sun 2012(E)(a) 25 59 (38.9) yrs 18 25 (23.2) yrs 35 60 yrs 20 66 (38.0) yrs 20 59 yrs 18 65 (38.0) yrs 165 21.8 (16.2 28.7) 7525 7.9 (7.3 8.5) 257 10.5 (7.3 14.9) 48559 7.9 (7.7 8.1) 402 29.9 (25.6 34.5) 10017 16.3 (15.6 17.0) 5936 8.3 (7.6 9.1) Wang 2012(F)(a) 18 60 yrs 24041 45.6 (45.0 46.2) Bian 2013 Beijing Chen 2013(a) Urumqi Li 2013 Hunan Province Sui 2013(G)(a) 20 55 (39.0) yrs 18 69 (39.6) yrs 17 74 (41.5) yrs 16 59 (36.3) yrs 379 20.8 (17.1 25.2) 2269 20.3 (18.7 22.0) 3115 14.5 (13.3 15.8) 883 8.8 (7.1 10.9) Wang 2013(a) Huzhou Wang 2013 Shenzhen Ding 2014 Beijing Mai 2014(H) 20 35 (29.0) yrs >=15 yrs 18 68 (36.5) yrs >=18 (36.4) yrs 292 19.2 (15.1 24.1) 4413 13.8 (12.8 14.8) 165 9.7 (6.1 15.2) 22114 19.0 (18.5 19.5) 0 10 20 30 40 50 HPV prevalence (%) L Boston, Baltimore, New Orleans, Denver, Seattle, Los Angeles; M San Francisco Bay, Sacramento, Central Valley, Northwest Oregon and Southwest Washington Areas; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. Data sources: See references in Section 9.

- 72 - Figure 35: Prevalence of HPV among women with normal cytology in Asia by country and study Country Bahrain Bangladesh Bhutan China Hajjaj 2006 Nahar 2014(a) Dhaka and Mirzapur Tshomo 2014 Thimphu Belinson 2001(A) Age range (mean age) 20 60 (37.0) yrs 13 64 (32.0) yrs 18 69 yrs 35 45 (39.1) yrs N % (95% CI) 91 12.1 (6.9 20.4) 1902 7.6 (6.5 8.9) 2272 23.0 (21.3 24.7) 1784 14.2 (12.6 15.9) Chan 2002 Hong Kong Belinson 2003(B) 19 83 (43.8) yrs 27 56 (40.9) yrs 1962 5.6 (4.6 6.7) 6643 14.4 (13.6 15.3) Dai 2006 Shanxi Li 2006 Shenyang He 2008 Hangzhou Lin 2008(a) Guandong Chan 2009(a) Hong Kong Jin 2010(C) 19 59 (40.4) yrs 17 59 (41.2) yrs (40.0) yrs 20 68 (39.0) yrs 19 83 (43.3) yrs 19 65 (38.1) yrs 601 10.6 (8.4 13.4) 663 13.7 (11.3 16.6) 480 15.2 (12.3 18.7) 1705 9.0 (7.8 10.5) 2604 6.7 (5.8 7.7) 2847 7.4 (6.5 8.4) Li 2010 Beijing Moy 2010(D) 25 54 (39.6) yrs 30 54 (39.0) yrs 5530 7367 6.6 (6.0 7.3) 9.5 (8.9 10.2) Sun 2010 Liaoning Province Belinson 2011 Guangdong Province Hu 2011 Jaingsu Province Chen 2012(a) Chaozhou Chui 2012(a) Macau DU 2012(a) Shenzhen Sun 2012(E)(a) 25 59 (38.9) yrs 18 25 (23.2) yrs 35 60 yrs 20 66 (38.0) yrs 20 59 yrs 18 65 (38.0) yrs 165 21.8 (16.2 28.7) 7525 7.9 (7.3 8.5) 257 10.5 (7.3 14.9) 48559 7.9 (7.7 8.1) 402 29.9 (25.6 34.5) 10017 16.3 (15.6 17.0) 5936 8.3 (7.6 9.1) Wang 2012(F)(a) 18 60 yrs 24041 45.6 (45.0 46.2) Bian 2013 Beijing Chen 2013(a) Urumqi Li 2013 Hunan Province Sui 2013(G)(a) 20 55 (39.0) yrs 18 69 (39.6) yrs 17 74 (41.5) yrs 16 59 (36.3) yrs 379 20.8 (17.1 25.2) 2269 20.3 (18.7 22.0) 3115 14.5 (13.3 15.8) 883 8.8 (7.1 10.9) Wang 2013(a) Huzhou Wang 2013 Shenzhen Ding 2014 Beijing Mai 2014(H) 20 35 (29.0) yrs >=15 yrs 18 68 (36.5) yrs >=18 (36.4) yrs 292 19.2 (15.1 24.1) 4413 13.8 (12.8 14.8) 165 9.7 (6.1 15.2) 22114 19.0 (18.5 19.5) 0 10 20 30 40 50 HPV prevalence (%) (Continued on next page) A Yangcheng and Xiangyuan (Shanxi); B Yangcheng and Xiangyuan (Shanxi); C Tibetan Autonomous Region; D Shanxi, Jiangxi and Gansu Provinces; E Qujing (Yunnan Province); F Shenyang (Liaoning Province); G Uyghur (Yutian County, Xingjian Province); H Shantou City (Guandong Province); Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. Data sources: See references in Section 9.

- 73 - Figure 36: Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Country China Georgia India Yeoh 2006 Hong Kong Wu 2007 Shenzhen Zhang 2008(a) Shangai Wu 2010(a) Fujian Province Wu 2010(I) Ye 2010(J)(a) Ye 2010 Zhejiang Province Yip 2010(a) Macao Yuan 2011 Shandong Province Zhang 2012(K)(a) Wang 2013 Shenzhen Wu 2013(L) Yu 2013(M)(a) Zhang 2013(a) Shangai Zhao 2013(N) Wei 2014(O)(a) Wei 2014(P) Zhao 2014 Jiangsi Province Alibegashvili 2011 Tbilisi Arora 2005 New Delhi Franceschi 2005 Tamil Nadu Aggarwal 2006 Chandigarh Bhatla 2008 New Delhi Gupta 2009 New Delhi Datta 2010(Q)(a) Gravitt 2010(R)(a) Dutta 2012 Eastern India Basu 2013(a) West Bengal Kashyap 2013(b) Jeronimo 2014 Hyderabad Jeronimo 2014 Rural Uttar Pradesh Age range (mean age) (37.0) yrs 15 59 (35.0) yrs 18 78 (34.3) yrs 20 70 (40.5) yrs 25 59 (35.9) yrs 25 65 yrs 20 79 (39.7) yrs 20 60 yrs 20 61 yrs 20 64 yrs >=15 yrs 17 54 (37.4) yrs 20 60 yrs 17 89 (41.0) yrs 25 65 yrs 18 81 yrs 18 81 yrs 18 25 (23.0) yrs 15 59 yrs 20 60 (35.8) yrs 17 59 (32.4) yrs 19 75 (37.5) yrs 30 65 (37.6) yrs 18 45 (28.7) yrs 16 24 yrs >=25 (37.4) yrs 25 65 (36.8) yrs 30 65 yrs 46 58 yrs 30 49 (36.3) yrs 30 59 (37.9) yrs 0 10 20 30 40 HPV prevalence (%) N 1090 25.7 (23.2 28.4) 942 11.9 (10.0 14.1) 6405 29.1 (28.0 30.2) 314 19.4 (15.4 24.2) 2000 16.5 (14.9 18.2) 734 20.2 (17.4 23.2) 4987 13.3 (12.4 14.3) 1600 3112 1032 11.1 (9.4 13.2) 4413 13.8 (12.8 14.8) 3737 373 12.6 (9.6 16.4) 10000 12.6 (11.9 13.2) 7089 10.9 (10.2 11.7) 67172 118096 18.3 (18.1 18.5) 5416 13.3 (12.5 14.3) 1247 11.5 (9.8 13.4) 160 10.0 (6.2 15.6) 1799 14.0 (12.5 15.7) 472 36.9 (32.6 41.3) 458 769 16.6 (14.2 19.4) 1300 11.2 (9.6 13.0) 2331 10.3 (9.1 11.6) 2313 28039 207 4385 4547 % (95% CI) 8.8 (7.5 10.2) 9.6 (8.6 10.7) 8.9 (8.0 9.9) 1.7 (1.6 1.8) 7.6 (5.5 10.4) 9.2 (8.1 10.4) 5.8 (5.5 6.1) 5.8 (3.3 9.9) 4.4 (3.9 5.1) 2.3 (1.9 2.8) (Continued on next page) I Shenzhen (Guangdong Province); J Lishui County (Zhejiang Province); K Wufeng County (Hubei Province); L Beijing, Shanghai, Shanxi, Henan, Xinjiang; M Shiquan County (Shaanxi Province); N Yangcheng, Xinmi and Tonggu; O Shenyang (Liaoning Province); P Shenyang (Liaoning Province); Q Govindpuri (New Delhi); R Medchal Mandal (Andhra Pradesh); Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. b Few HPV types tested: 16 only. Data sources: See references in Section 9.

- 74 - Figure 37: Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Country India Indonesia Iran Japan Age range (mean age) Sankaranarayanan 2004 Kolkata (1) 25 65 (35.0) yrs Sankaranarayanan 2004 Mumbai 25 65 (40.0) yrs Sankaranarayanan 2004 Trivandrum 25 65 (42.0) yrs Sankaranarayanan 2004 Kolkata (2) 25 65 (35.0) yrs Sankaranarayanan 2005(a) 30 59 (39.3) yrs Osnamabad Laikangbam 2007 West Bengal 14 80 (30.7) yrs Laikangbam 2007 Sikkim 19 75 (36.6) yrs Laikangbam 2007 Manipur 20 80 (41.0) yrs Singh 2009 North India Kerkar 2011 Mumbai (25.3) yrs Sarkar 2011(b) West Bengal >=15 (30.0) yrs Pandey 2012(a) Lucknow 20 70 (35.5) yrs Srivastava 2012(a) Varanasi 17 80 yrs Vinodhini 2012 Tamil Nadu (47.2) yrs Kashyap 2013(c) 46 58 yrs Mittal 2014(a) Kolkata de Boer 2006 Jakarta Vet 2008(a) Tasikmalaya Vet 2008 Bali Vet 2008 Jakarta Rachmadi 2012(S) Zavarei 2008 Tehran Safaei 2010 Shiraz Zandi 2010(a) Bushehr Moradi 2011 Gorgan Shahramian 2011(a) Zabol Eghbali 2012(a) Bushehr Port Khodakarami 2012 Tehran Asato 2004 Okinawa Inoue 2006 Ishikawa Chen 2013(a) Nagasaki 30 60 yrs 21 75 (44.2) yrs 12 70 (40.0) yrs 12 70 (39.0) yrs 12 70 (40.0) yrs 18 60 (39.9) yrs 15 55 yrs 20 72 (35.2) yrs 15 75 (37.5) yrs 17 50 (36.0) yrs 18 59 yrs 18 85 (52.4) yrs 14 94 (36.0) yrs 3390 3365 4332 6278 672 470 1106 2480 207 9630 600 400 200 799 7564 0 10 20 30 40 HPV prevalence (%) N 27301 10.3 (9.9 10.7) 1007 11.6 (9.8 13.7) 359 11.1 (8.3 14.8) 109 10.1 (5.7 17.2) 890 11.7 (9.7 14.0) 257 30.4 (25.1 36.2) 200 31.0 (25.0 37.7) 919 887 11.5 (9.6 13.8) 880 13.9 (11.7 16.3) 101 16.8 (10.8 25.3) 226 18.1 (13.7 23.7) 265 32.5 (27.1 38.3) 791 % (95% CI) 7.8 (6.9 8.7) 6.3 (5.5 7.1) 4.8 (4.2 5.5) 5.2 (4.6 5.7) 6.7 (5.0 8.8) 8.1 (5.9 10.9) 9.1 (7.6 11.0) 9.7 (8.6 10.9) 5.8 (3.3 9.9) 4.6 (4.2 5.0) 8.8 (7.1 10.8) 5.7 (4.1 7.8) 5.5 (3.7 8.2) 5.5 (3.1 9.6) 0.6 (0.3 1.5) 6.6 (5.0 8.5) 3249 10.2 (9.3 11.3) 6.6 (6.0 7.2) 1111 18.2 (16.0 20.6) (Continued on next page) S Jakarta, Tasikmalaya and Bali; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. b Few HPV types tested: 16, 18 only. c Few HPV types tested: 16 only. Data sources: See references in Section 9.

- 75 - Figure 38: Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Country Japan Kazakhstan Korea, Rep. Saito 1995 Osaka Sasagawa 1997 Ishikawa and Toyama Yoshikawa 1999 Sasagawa 2001(T) Ishi 2004 Chiba Masumoto 2004 Tokyo Maehama 2005 Okinawa Sasagawa 2005 Hokuriku Inoue 2006 Ishikawa Nishiwaki 2008 Onuki 2009 Ibaraki Konno 2011(U) Takehara 2011(a) Satoh 2013 Tsukuba, Tokyo Buleshov 2011(b) South An 2003 Kyonggi do Cho 2003 Kyonggi do Hwang 2004 Bae 2009(b) Gyeonggi, Seoul Bae 2009 Kim 2010(b) Cho 2011(b) Hwang 2012(b) Kim 2012(c) Seoul Kim 2012 Kim 2012 Kim 2013 Gwangju Kim 2013 Seoul Kim 2013 Seoul Bae 2014 Seoul Kim 2014(b) Busan Age range (mean age) 18 72 (40.9) yrs 16 82 (40.0) yrs <=55 (40.7) yrs 16 72 yrs 17 73 (35.0) yrs 20 89 (46.0) yrs 20 89 (53.0) yrs 15 59 (29.0) yrs 14 94 (36.0) yrs 19 70 (38.7) yrs 15 78 (35.0) yrs 20 25 (22.5) yrs 15 98 (44.4) yrs 19 88 (41.9) yrs 35 60 yrs (42.0) yrs 22 70 (42.9) yrs 18 62 yrs 30 84 (30.0) yrs 15 75 yrs 20 59 yrs 21 77 (42.0) yrs (48.0) yrs 20 59 yrs 21 76 (40.1) yrs (48.2) yrs 18 85 (46.7) yrs 22 83 (12.5) yrs 0 10 20 30 40 50 60 70 HPV prevalence (%) N 800 778 130 14.6 (9.6 21.7) 1562 420 12.1 (9.4 15.6) 414 16.9 (13.6 20.8) 4078 10.6 (9.7 11.6) 637 16.8 (14.1 19.9) 7564 292 14.7 (11.1 19.2) 1517 22.5 (20.5 24.7) 908 26.1 (23.3 29.1) 2068 109 23.9 (16.8 32.7) 17000 11.0 (10.5 11.5) 1143 35.1 (32.4 37.9) 414 31.9 (27.6 36.5) 1609 37.4 (35.0 39.7) 4111 1750 27.0 (25.0 29.2) 902 12.6 (10.6 15.0) 624 47.3 (43.4 51.2) 177 54.8 (47.4 62.0) 11800 902 1214 14.6 (12.7 16.7) 206 % (95% CI) 6.6 (5.1 8.6) 4.5 (3.3 6.2) 9.7 (8.3 11.2) 6.6 (6.0 7.2) 9.4 (8.2 10.7) 6.5 (5.8 7.3) 6.2 (5.8 6.6) 4.9 (3.7 6.5) 8.3 (5.2 12.8) 2146 18.1 (16.6 19.8) 6681 17.3 (16.4 18.2) 471 21.0 (17.6 24.9) 315 70.2 (64.9 74.9) (Continued on next page) T Hokuriku(Fukui, Ishikawa and Toyama); U Aomori, Tokyo, Fukui, Osaka, Hiroshima, Miyazaki and Kagoshima; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Few HPV types tested: 16, 18, 52, 58 only. b Women from the general population, including some with cytological cervical abnormalities. c Few HPV types tested: 6, 11, 42, 43, 44 only. Data sources: See references in Section 9.

- 76 - Figure 39: Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Country Korea, Rep. Oh 2001 Seoul Lee 2003 Seoul Shin 2003 Busan Shin 2004(a) Busan Oh 2009 Busan and Suwon Shim 2010 Seoul Lee 2011 Age range (mean age) 23 72 (45.0) yrs (49.0) yrs 20 74 (45.4) yrs 16 29 (19.0) yrs 20 69 yrs 21 48 (37.9) yrs N % (95% CI) 1144 0.7 (0.4 1.4) 746 7.2 (5.6 9.3) 821 8.5 (6.8 10.6) 672 15.2 (12.7 18.1) 4467 7.0 (6.3 7.8) 235 22.6 (17.7 28.3) 101 20.8 (14.0 29.7) Um 2011 122 23.0 (16.4 31.2) Lee 2012(a) 18 79 (44.0) yrs 60775 34.2 (33.8 34.6) Lee 2012 Suwon Kim 2014(a) Busan Kim 2014 Cheonan Kim 2014 Gangnam (Seoul) Lee 2014(V)(a) 22 83 (12.5) yrs 19 78 (39.9) yrs 25 81 (49.6) yrs 25 79 yrs 26980 20.3 (19.9 20.8) 315 70.2 (64.9 74.9) 5494 14.4 (13.5 15.3) 799 12.1 (10.1 14.6) 912 7.9 (6.3 9.8) Park 2014(a) 43 57 (50.0) yrs 1938 14.1 (12.7 15.8) Kuwait Al Awadhi 2011 18 81 (41.0) yrs 3011 2.4 (1.9 3.0) Lebanon Mroueh 2002 18 70 (41.0) yrs 1026 4.9 (3.7 6.4) Malaysia Mongolia Karam 2005 Tay 2009 Johor and Singapore Chong 2010(a) Southern Selangor Othman 2014(W) Chimeddorj 2008(b) 20 67 (39.6) yrs 18 77 (42.0) yrs 19 69 (39.0) yrs (43.0) yrs 246 10.2 (7.0 14.6) 745 22.0 (19.2 25.1) 180 46.7 (39.5 53.9) 588 3.1 (1.9 4.8) 100 1.0 (0.2 5.4) Nepal Dondog 2008 Ulaanbaatar Sherpa 2010(X) 15 59 (36.4) yrs 15 59 yrs 842 30.5 (27.5 33.7) 898 8.1 (6.5 10.1) Johnson 2014(Y) 16 60 (33.8) yrs 211 2.8 (1.3 6.1) Pakistan Philippines Saudi Arabia Taiwan Raza 2010 Karachi Ngelangel 1998 Manila Al Ahdal 2014 Riyadh Jeng 2005 Taipei Huang 2008 15 59 yrs 21 72 (46.8) yrs 20 74 (37.0) yrs 21 65 (40.0) yrs 23 80 (43.0) yrs 877 2.2 (1.4 3.4) 377 9.3 (6.8 12.6) 455 28.6 (24.6 32.9) 1279 17.9 (15.9 20.1) 1310 8.2 (6.9 9.9) Chen 2011(Z) 30 65 (46.3) yrs 10190 13.8 (13.2 14.5) 0 10 20 30 40 50 60 70 HPV prevalence (%) (Continued on next page) V Seoul, Busan, Cheonan; W North-Eastern region os West Malaysia; X Bharatpur (Chitawan Province); Y Sanphebagar Village (Achham District); Z Sanchi, Chutung, Potzu,Kaoshu, Makung, Paihsa and Huhsi; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. b Few HPV types tested: 16 only. Data sources: See references in Section 9.

- 77 - Figure 40: Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Country Taiwan Thailand Turkey Liaw 1995 Jeng 2005 Taipei Lin 2005 Kaohsiung Tsai 2005 Kaohsiung County Lin 2006(a) South Taiwan Wang 2010(AA)(a) Lai 2012 Taoyuan Siritantikorn 1997 Bangkok Chichareon 1998 Songkla Thomas 2001(a) Bangkok Sukvirach 2003 Songkla Sukvirach 2003 Lampang Settheetham Ishida 2005 Khon Kaen Chandeying 2006(BB)(a) Sriamporn 2006 Khon Kaen Chaiwongkot 2007 Khon Kaen Wongworapat 2008(a) Chiang Mai Chopjitt 2009 Khon Kaen Suwannarurk 2009(b) Pathumthani Chansaenroj 2010 Bangkok Ekalaksananan 2010 Khon Kaen Swangvaree 2010 Bangkok Marks 2011(CC)(a) Natphopsuk 2013 Khon Kaen Laowahutanont 2014 Bangkok Paengchit 2014 Lampang Province Siriaunkgul 2014 Chiang Mai Altun 2011 Adana Bayram 2011 Gaziantep Demir 2012(DD) Akcali 2013(a) Manisa Age range (mean age) 30 64 (43.0) yrs 21 65 (40.0) yrs >=20 (46.2) yrs 16 78 (40.0) yrs 14 87 (41.0) yrs 30 94 (46.7) yrs 16 77 (32.0) yrs 19 78 (49.7) yrs 24 60 (43.9) yrs 15 85 (47.8) yrs 15 76 (46.3) yrs 25 70 yrs 15 47 (28.9) yrs >=35 (54.5) yrs 20 65 (44.0) yrs (43.4) yrs 18 54 (36.0) yrs 20 77 (46.4) yrs 20 37 (29.6) yrs 26 81 yrs >=20 (39.0) yrs 30 70 (47.8) yrs 30 60 (46.6) yrs 20 68 yrs 18 56 (33.6) yrs 15 68 (36.8) yrs (34.9) yrs 260 102 687 972 430 1622 14205 2735 1961 2633 460 0 10 20 30 40 50 HPV prevalence (%) N 1279 17.9 (15.9 20.1) 127 15.0 (9.8 22.2) 175 16.6 (11.8 22.8) 4383 19.4 (18.2 20.6) 10543 15.0 (14.3 15.7) 14724 11.0 (10.6 11.6) 261 15.7 (11.8 20.6) 291 100 13.0 (7.8 21.0) 113 10.6 (6.2 17.6) 140 38.6 (30.9 46.8) 531 11.5 (9.0 14.5) 160 33.8 (26.9 41.4) 225 28.9 (23.4 35.1) 155 40.6 (33.2 48.5) 1070 19.8 (17.5 22.3) 198 14.1 (10.0 19.7) 502 15.1 (12.3 18.5) 530 17.9 (14.9 21.4) 410 % (95% CI) 9.2 (6.3 13.4) 4.9 (2.1 11.0) 6.9 (4.5 10.4) 3.3 (2.2 5.0) 5.9 (4.6 7.5) 4.7 (3.0 7.1) 7.8 (6.6 9.2) 6.2 (5.8 6.6) 6.7 (5.8 7.7) 4.0 (3.2 5.0) 4.3 (3.5 5.1) 5.2 (3.5 7.6) 8.5 (6.2 11.6) (Continued on next page) AA Taipei, Taoyuan, Chungli, Hsinchu, Keelung); BB Hat Yai (South Thailand); CC Chiang Mai, Khon Kaen, Bangkok, Songkla and Hat Yai; DD Istanbul, Ankara, Antalya, Nigde and Elazig; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. b Few HPV types tested: 16, 18, 31, 33 only. Data sources: See references in Section 9.

- 78 - Figure 41: Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Country Belarus Belgium Croatia Czech Rep. Denmark Estonia Europe Finland France Rogovskaya 2013 Minsk Baay 2001 Antwerp Depuydt 2003 Flanders Baay 2005 Antwerp Arbyn 2009 Antwerp Depuydt 2010(a) Flanders Depuydt 2012 Schmitt 2013 Flanders Weyn 2013 Brussels Merckx 2014(A)(a) Grahovac 2007 Zagreb,Rijeka Kaliterna 2007(B)(a) Tachezy 2013 Svare 1998 Nielsen 2008 Copenhagen Nielsen 2008 Copenhagen Nielsen 2012(b) Copenhagen Bonde 2014(C) Kjær 2014(c) Copenhagen Uusküla 2010(a) Tartu Paavonen 2008(D) Auvinen 2005(a) Helsinki Leinonen 2008 Uusimaa Clavel 2001 Reims Dalstein 2003 Besançon Beby Defaux 2004 Poitiers Boulanger 2004 Amiens Casalegno 2011 Lyon Heard 2013(E) Baudu 2014 Franche Comté Age range (mean age) 15 63 (28.2) yrs 17 78 (39.4) yrs 17 85 (40.1) yrs 20 50 (35.8) yrs 15 85 (42.0) yrs 14 97 yrs 30 65 (45.0) yrs 15 86 (39.0) yrs >=20 (41.0) yrs 4 18 (16.9) yrs (29.7) yrs 18 62 (40.0) yrs 14 79 (33.5) yrs 20 39 (30.0) yrs 40 50 (45.0) yrs 20 29 (25.0) yrs 14 95 (37.0) yrs 16 89 (37.3) yrs 14 95 (37.0) yrs 18 35 (26.9) yrs 16 24 (19.7) yrs 19 47 (24.0) yrs 25 65 (47.0) yrs 15 76 (34.0) yrs 16 76 (35.7) yrs 17 77 (44.0) yrs 20 62 (38.9) yrs 15 88 (39.6) yrs (40.1) yrs 15 23 (21.1) yrs 0 10 20 30 40 50 HPV prevalence (%) N 322 23.6 (19.3 28.5) 286 10.8 (7.7 15.0) 287 24.0 (19.5 29.3) 2293 8729 11.9 (11.3 12.6) 57876 14.8 (14.5 15.1) 1139 913 33.3 (30.3 36.4) 906 10.8 (9.0 13.0) 4180 15.7 (14.6 16.8) 205 35.6 (29.4 42.4) 570 35.1 (31.3 39.1) 1302 25.6 (23.3 28.0) 119 21.8 (15.4 30.1) 1443 10220 15.9 (15.2 16.6) 37958 4671 33.4 (32.1 34.8) 37958 17.0 (16.6 17.4) 326 36.8 (31.8 42.2) 9162 15.9 (15.2 16.7) 1469 33.0 (30.7 35.5) 16895 7339 10.5 (9.9 11.3) 652 27.0 (23.7 30.5) 613 % (95% CI) 6.9 (5.9 8.0) 8.2 (6.7 9.9) 4.4 (3.4 5.5) 6.3 (6.1 6.5) 7.5 (7.2 7.9) 5.2 (3.7 7.3) 3617 12.6 (11.6 13.7) 302 48.3 (42.8 54.0) 3023 13.7 (12.5 15.0) 948 24.1 (21.4 26.9) EE Istanbul, Ankara, Antalya, Nigde and Elazig; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. Data sources: See references in Section 9.

- 79 - Figure 42: Prevalence of HPV among women with normal cytology in Europe by country and study Country Belarus Belgium Croatia Czech Rep. Denmark Estonia Europe Finland France Rogovskaya 2013 Minsk Baay 2001 Antwerp Depuydt 2003 Flanders Baay 2005 Antwerp Arbyn 2009 Antwerp Depuydt 2010(a) Flanders Depuydt 2012 Schmitt 2013 Flanders Weyn 2013 Brussels Merckx 2014(A)(a) Grahovac 2007 Zagreb,Rijeka Kaliterna 2007(B)(a) Tachezy 2013 Svare 1998 Nielsen 2008 Copenhagen Nielsen 2008 Copenhagen Nielsen 2012(b) Copenhagen Bonde 2014(C) Kjær 2014(c) Copenhagen Uusküla 2010(a) Tartu Paavonen 2008(D) Auvinen 2005(a) Helsinki Leinonen 2008 Uusimaa Clavel 2001 Reims Dalstein 2003 Besançon Beby Defaux 2004 Poitiers Boulanger 2004 Amiens Casalegno 2011 Lyon Heard 2013(E) Baudu 2014 Franche Comté Age range (mean age) 15 63 (28.2) yrs 17 78 (39.4) yrs 17 85 (40.1) yrs 20 50 (35.8) yrs 15 85 (42.0) yrs 14 97 yrs 30 65 (45.0) yrs 15 86 (39.0) yrs >=20 (41.0) yrs 4 18 (16.9) yrs (29.7) yrs 18 62 (40.0) yrs 14 79 (33.5) yrs 20 39 (30.0) yrs 40 50 (45.0) yrs 20 29 (25.0) yrs 14 95 (37.0) yrs 16 89 (37.3) yrs 14 95 (37.0) yrs 18 35 (26.9) yrs 16 24 (19.7) yrs 19 47 (24.0) yrs 25 65 (47.0) yrs 15 76 (34.0) yrs 16 76 (35.7) yrs 17 77 (44.0) yrs 20 62 (38.9) yrs 15 88 (39.6) yrs (40.1) yrs 15 23 (21.1) yrs 0 10 20 30 40 50 HPV prevalence (%) N 322 23.6 (19.3 28.5) 286 10.8 (7.7 15.0) 287 24.0 (19.5 29.3) 2293 8729 11.9 (11.3 12.6) 57876 14.8 (14.5 15.1) 1139 913 33.3 (30.3 36.4) 906 10.8 (9.0 13.0) 4180 15.7 (14.6 16.8) 205 35.6 (29.4 42.4) 570 35.1 (31.3 39.1) 1302 25.6 (23.3 28.0) 119 21.8 (15.4 30.1) 1443 10220 15.9 (15.2 16.6) 37958 4671 33.4 (32.1 34.8) 37958 17.0 (16.6 17.4) 326 36.8 (31.8 42.2) 9162 15.9 (15.2 16.7) 1469 33.0 (30.7 35.5) 16895 7339 10.5 (9.9 11.3) 652 27.0 (23.7 30.5) 613 % (95% CI) 6.9 (5.9 8.0) 8.2 (6.7 9.9) 4.4 (3.4 5.5) 6.3 (6.1 6.5) 7.5 (7.2 7.9) 5.2 (3.7 7.3) 3617 12.6 (11.6 13.7) 302 48.3 (42.8 54.0) 3023 13.7 (12.5 15.0) 948 24.1 (21.4 26.9) (Continued on next page) A Flanders and Brussels; B Split and Dalmatian County; C Copenhagen and Frederiksberg; D Czech Republic, Denmark, England, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Spain, and Sweden; E Alsace, Auvergne, Centre - Pays de Loire, Ile-de-France and Vaucluse; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. b Few HPV types tested: 6, 11, 42, 43, 44 only. c HPV prevalence for high-risk HPV types. Data sources: See references in Section 9.

- 80 - Figure 43: Prevalence of HPV among women with normal cytology in Europe by country and study (continued) Country France Germany Riethmuller 1999 Besançon, Belfort Monsonego 2005 Paris Pannier Stockman 2008 Amiens Monsonego 2011 Paris Vaucel 2011 Nantes Heard 2013(F) Schneider 2000 East Thuringia Petry 2003(G) Age range (mean age) 16 76 (36.2) yrs 19 79 (39.4) yrs 18 78 (41.6) yrs 20 65 yrs 17 86 (38.5) yrs (40.1) yrs 18 70 (35.0) yrs 30 85 (42.7) yrs N % (95% CI) 426 25.1 (21.2 29.4) 221 28.5 (23.0 34.8) 289 28.7 (23.8 34.2) 4004 12.6 (11.6 13.7) 980 13.1 (11.1 15.3) 3023 13.7 (12.5 15.0) 4604 7.1 (6.4 7.9) 7832 5.9 (5.4 6.4) Luyten 2009 Wolfsburg Iftner 2010 >=30 (47.7) yrs 10 30 (21.5) yrs 16386 4.8 (4.5 5.1) 1692 22.3 (20.4 24.3) de Jonge 2013(H) >=20 (39.6) yrs 1463 29.8 (27.5 32.2) Greece Paraskevaidis 2001 Ioannina Agorastos 2004(I) 17 79 (38.0) yrs 17 69 (43.0) yrs 738 1272 6.4 (4.8 8.4) 2.0 (1.4 3.0) Panotopoulou 2007 Athens Agorastos 2009(a) 18 48 (32.2) yrs 639 26.4 (23.2 30.0) 4139 5.9 (5.2 6.7) Tsiodras 2010 Athens Tsiodras 2011 21 45 (34.2) yrs (41.9) yrs 1029 10.2 (8.5 12.2) 1348 39.5 (36.9 42.1) Hungary Argyri 2013 Athens Nyári 2006 14 70 (34.2) yrs 20 60 (31.1) yrs 2218 15.7 (14.2 17.3) 491 5.5 (3.8 7.9) Ireland Italy Keegan 2007 Dublin Anderson 2013 Northern Ireland Astori 1997 Udine Carozzi 2000 Florence Centurioni 2005 Genova Ammatuna 2008 Sicily Del Prete 2008(a) Apulia Agarossi 2009 16 72 (35.0) yrs 20 64 (39.0) yrs 18 67 (37.7) yrs 25 64 (36.0) yrs 20 81 (51.0) yrs 18 24 (21.6) yrs >=20 (37.0) yrs 15 73 (38.4) yrs 886 11.4 (9.5 13.7) 5068 13.2 (12.3 14.2) 197 20.3 (15.3 26.5) 332 5.1 (3.2 8.0) 500 15.4 (12.5 18.8) 894 22.4 (19.8 25.2) 871 23.2 (20.5 26.1) 9148 11.3 (10.7 12.0) Masia 2009 Sardinia Giorgi Rossi 2011(J) 18 46 yrs 25 64 yrs 309 17.8 (13.9 22.5) 3151 9.7 (8.8 10.8) Giambi 2013(K) 18 26 (23.8) yrs 907 13.6 (11.5 15.9) Panatto 2013(L) 16 26 (19.7) yrs 566 18.2 (15.2 21.6) 0 10 20 30 40 HPV prevalence (%) (Continued on next page) F Alsace, Auvergne, Centre - Pays de Loire, Ile-de-France and Vaucluse; G Hannover and Tuebingen; H Nordrhein-Westfalen, Niedersachsen, Schleswig-Holstein, Bremen and Hamburg; I Thessaloniki, Thermi, Mihaniona, Corfu, Veria and Serres; J Abruzzo, Campania, Lazio, Sardinia and Sicily; K Abruzzo, Campania, Lazio, Tuscany, Emilia- Romagna and Piedmont; L Turin, Milan and Genoa; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. Data sources: See references in Section 9.

- 81 - Figure 44: Prevalence of HPV among women with normal cytology in Europe by country and study (continued) Country Italy Tenti 1997 Pavia Ronco 2005 Turin Ronco 2006(M) Age range (mean age) 16 47 (29.0) yrs 25 70 (46.8) yrs 25 34 (30.0) yrs N % (95% CI) 1064 12.3 (10.5 14.4) 997 7.8 (6.3 9.7) 5334 9.6 (8.8 10.4) Ronco 2006(N) 35 60 (45.0) yrs 15361 5.5 (5.2 5.9) Tornesello 2006 Milan, Naples Tornesello 2008 Naples Verteramo 2009 Rome Zappacosta 2009 Molise Piana 2011 North Sardinia Panatto 2013(O) 18 63 (41.0) yrs (32.5) yrs 17 57 (32.7) yrs 21 64 (38.1) yrs 15 54 (37.0) yrs 16 26 (19.7) yrs 183 19.7 (14.6 26.0) 107 11.2 (6.5 18.6) 737 21.7 (18.9 24.8) 220 6.4 (3.8 10.4) 242 32.2 (26.7 38.4) 566 18.2 (15.2 21.6) Latvia Sammarco 2013 Molise Silins 2004(a) 18 63 yrs 18 89 (50.8) yrs 398 32.4 (28.0 37.2) 237 8.0 (5.2 12.2) Lithuania Gudleviciene 2005 Vilnius Kliucinskas 2006(a) 16 64 (29.8) yrs 18 50 (30.0) yrs 332 24.1 (19.8 29.0) 1001 25.1 (22.5 27.9) Netherlands Simanaviciene 2014 Vilnius Jacobs 2000 Amsterdam Rozendaal 2000 Amsterdam Zielinski 2001 Zeeland Bulkmans 2004 Amsterdam Lenselink 2008(P)(a) 18 81 (40.4) yrs 16 68 (45.3) yrs 34 54 (43.0) yrs 34 54 (43.0) yrs 30 60 (42.8) yrs 18 29 (23.4) yrs 277 24.2 (19.5 29.6) 3299 4.4 (3.8 5.2) 2250 5.4 (4.5 6.4) 114 6.1 (3.0 12.1) 21245 3.6 (3.3 3.9) 2065 19.0 (17.4 20.8) Rijkaart 2012 30 56 (40.0) yrs 19373 4.0 (3.7 4.2) Norway Rijkaart 2012 Utrecht Hesselink 2013 Utrecht region Boers 2014 Gjøoen 1996 Oslo Molden 2005 Oslo Molden 2006 Oslo Skjeldestad 2008(Q)(a) 29 61 (44.0) yrs 31 60 (41.0) yrs 30 60 yrs 20 44 (32.7) yrs 30 69 (48.9) yrs <=30 (26.9) yrs 16 24 (21.2) yrs 25196 4.1 (3.8 4.3) 858 8.2 (6.5 10.2) 900 3.8 (2.7 5.2) 222 15.3 (11.2 20.6) 3970 9.3 (8.4 10.2) 275 30.9 (25.7 36.6) 896 25.9 (23.1 28.9) Poland Portugal Bardin 2008 Warsaw Dutra 2008(a) Açores Pista 2011(R) 18 59 (38.0) yrs 16 81 (41.0) yrs 18 67 (34.3) yrs 799 14.4 (12.1 17.0) 286 10.5 (7.4 14.6) 425 25.4 (21.5 29.8) 0 10 20 30 40 HPV prevalence (%) (Continued on next page) M Turin, Trento, Veneto, Emilia Romagna, Florence and Lazio; N Turin, Trento, Veneto, Emilia Romagna, Florence and Lazio; O Turin, Milan and Genoa; P Arnhem, Nijmegen, and Den Bosch; Q Oslo, Trondheim, and Levanger; R Lisbon area and southern region; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. Data sources: See references in Section 9.

- 82 - Figure 45: Prevalence of HPV among women with normal cytology in Europe by country and study (continued) Country Portugal Romania Russia Slovenia Spain Sweden Switzerland UK Pista 2011(S) Pista 2011 Vieira 2013 Ursu 2011 Northeast Moga 2014 Brasov County Alexandrova 1999 St. Petersburg Kubanov 2005 Moscow Bdaizieva 2010(a) Moscow Komarova 2010 Moscow Goncharevskaya 2011 Moscow Shargorodskaya 2011 Moscow Shipitsyna 2011 St Petersburg Shipulina 2011 Moscow Rogovskaya 2013 Moscow and Novgorod Ucakar 2012 Ucakar 2014 Muñoz 1996(T) de Sanjose 2003 Barcelona González 2006 Alicante Ortiz 2006(a) Madrid and Alicante Bernal 2008 Zaragoza Dillner 2008 Maresme Martorell 2010(a) Valencia Castellsagué 2012 Kjellberg 1998 Västerbotten County Ylitalo 2000 Uppsala Naucler 2007(U) Stenvall 2007(a) Uppsala Elfström 2014(V)(a) Bigras 2005(W) Cuschieri 2004 Edinburgh Age range (mean age) 18 67 (34.3) yrs 18 64 (32.4) yrs 18 76 (39.0) yrs 17 57 (32.7) yrs 15 45 (30.2) yrs 15 69 yrs 16 76 (32.1) yrs 15 77 (45.0) yrs 18 30 (22.0) yrs 30 65 (39.5) yrs 13 19 yrs 16 76 (35.6) yrs 20 64 yrs 20 64 (36.5) yrs 18 75 (42.7) yrs 14 75 (43.0) yrs (32.7) yrs 14 67 (34.0) yrs (36.0) yrs 14 82 (37.9) yrs 18 64 yrs 18 65 yrs 20 63 (40.0) yrs 15 49 (26.0) yrs 29 46 (35.1) yrs 35 50 (41.0) yrs 32 38 yrs 17 93 (44.4) yrs 16 78 (36.6) yrs 0 10 20 30 40 50 HPV prevalence (%) N 425 25.4 (21.5 29.8) 2172 16.5 (15.0 18.1) 464 17.0 (13.9 20.7) 164 25.6 (19.5 32.8) 801 34.3 (31.1 37.7) 309 29.1 (24.3 34.4) 8533 15.0 (14.3 15.8) 33112 25.7 (25.2 26.1) 352 48.3 (43.1 53.5) 5182 13.4 (12.5 14.4) 266 28.2 (23.1 33.9) 741 177 40.1 (33.2 47.5) 833 25.9 (23.1 29.0) 4199 10.7 (9.8 11.7) 944 329 847 703 818 10.8 (8.8 13.1) 1200 17.5 (15.5 19.8) 939 1956 13.0 (11.6 14.5) 3059 13.0 (11.9 14.2) 295 617 5877 117 25.6 (18.6 34.2) 5772 13349 % (95% CI) 9.9 (7.9 12.2) 8.8 (7.1 10.8) 5.2 (3.3 8.1) 1.3 (0.7 2.3) 7.8 (6.1 10.0) 7.3 (5.8 9.2) 4.1 (2.3 7.0) 5.8 (4.2 8.0) 5.5 (4.9 6.1) 9.7 (9.0 10.5) 6.3 (5.9 6.7) 3089 12.7 (11.6 13.9) (Continued on next page) S Lisbon area and southern region; T Alava, Girona, Guipuzcoa, Murcia, Navarra, Salamanca, Sevilla, Vizcaya, Zaragoza; U Gothenburg, Malmö, Uppsala, Umeå, and Stockholm; V Gothenburg, Malmö, Uppsala, Umeå, and Stockholm; W Geneve, Vaud, Neuchatel, Fribourg, Valais and Tessin; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. Data sources: See references in Section 9.

- 83 - Figure 46: Prevalence of HPV among women with normal cytology in Europe by country and study (continued) Country Australia Bowden 2005(A)(a) Age range (mean age) 16 19 (16.8) yrs N % (95% CI) 161 11.2 (7.2 17.0) Tabrizi 2012(B)(b) 18 24 (21.1) yrs 338 46.4 (41.2 51.8) Tabrizi 2014 15 66 (32.0) yrs 2271 33.0 (31.1 34.9) Fiji Foliaki 2014(a) 16 63 (36.9) yrs 1244 24.0 (21.7 26.4) Suva Vanuatu McAdam 2010(C) 30 50 (39.3) yrs 379 5.3 (3.4 8.0) Aruhuri 2012(D) 18 64 yrs 726 22.7 (19.8 25.9) 0 10 20 30 40 50 HPV prevalence (%) X Birmingham, Edinburg, London, Manchester and Mansfield; Y Gateshead, Birmingham, London, Gloucestershire and Norfolk; Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 84 - Figure 47: Prevalence of HPV among women with normal cytology in Oceania by country and study Country Australia Bowden 2005(A)(a) Age range (mean age) 16 19 (16.8) yrs N % (95% CI) 161 11.2 (7.2 17.0) Tabrizi 2012(B)(b) 18 24 (21.1) yrs 338 46.4 (41.2 51.8) Tabrizi 2014 15 66 (32.0) yrs 2271 33.0 (31.1 34.9) Fiji Foliaki 2014(a) 16 63 (36.9) yrs 1244 24.0 (21.7 26.4) Suva Vanuatu McAdam 2010(C) 30 50 (39.3) yrs 379 5.3 (3.4 8.0) Aruhuri 2012(D) 18 64 yrs 726 22.7 (19.8 25.9) 0 10 20 30 40 50 HPV prevalence (%) A Australian Capital Territory; B Sydney, Melbourne and Perth; C Port Vila (Efate Island); D Santo Urban (Espiritu Santo Island) and Porto Vila (Efate Island); Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Women from the general population, including some with cytological cervical abnormalities. b HPV prevalence in HPV vaccinated women. Data sources: See references in Section 9.

- 85-4.1.2 HPV type distribution among women with normal cytology, precancerous cervical lesions and cervical cancer Table 13: Prevalence of HPV 16/18 in women with normal cytology, precancerous cervical lesions and invasive cervical cancer by regions and sub-regions in the World Normal cytology Low-grade lesions High-grade lesions Cervical cancer Country /Region No. HPV Prev No. HPV Prev No. HPV Prev No. HPV Prev tested (95% CI) tested (95% CI) tested (95% CI) tested (95% CI) World 453,184 3.9 (3.8-4.0) 43,189 25.5 (25.1-25.9) 44,566 51.5 (51.0-52.0) 53,309 70.0 (69.6-70.4) Less developed regions 168,376 3.8 (3.7-3.9) 10,043 24.5 (23.7-25.3) 11,504 46.1 (45.2-47.0) 21,568 71.9 (71.3-72.5) More developed regions 282,155 3.8 (3.7-3.9) 33,146 25.9 (25.4-26.4) 29,959 53.6 (53.0-54.2) 23,201 71.5 (70.9-72.1) Africa 19,726 3.8 (3.5-4.1) 926 21.0 (18.5-23.7) 714 35.7 (32.3-39.3) 3,232 68.5 (66.9-70.1) Eastern Africa 4,115 4.7 (4.1-5.4) 196 26.5 (20.8-33.1) 164 43.9 (36.5-51.6) 1,274 68.3 (65.7-70.8) Middle Africa - - - 24 12.5 (4.3-31.0) 38 34.2 (21.2-50.1) - - - Northern Africa 2,224 3.0 (2.4-3.8) 27 18.5 (8.2-36.7) 10 40.0 (16.8-68.7) 532 81.2 (77.7-84.3) Southern Africa 8,661 3.2 (2.8-3.6) 318 17.9 (14.1-22.5) 290 30.3 (25.3-35.9) 605 61.8 (57.9-65.6) Western Africa 4,726 4.3 (3.8-4.9) 361 21.1 (17.2-25.6) 212 36.8 (30.6-43.5) 718 56.7 (53.0-60.3) Americas 105,042 4.5 (4.4-4.6) 13,574 26.3 (25.6-27.0) 11,855 56.9 (56.0-57.8) 8,640 69.0 (68.0-70.0) Caribbean 323 15.8 (12.2-20.2) 420 11.4 (8.7-14.8) 393 34.6 (30.1-39.4) 144 57.6 (49.5-65.4) Central America 16,786 4.1 (3.8-4.4) 1,424 15.0 (13.3-17.0) 559 40.8 (36.8-44.9) 1,486 59.8 (57.3-62.3) Northern America 77,952 4.4 (4.3-4.5) 9,562 26.8 (25.9-27.7) 8,863 58.4 (57.4-59.4) 3,560 71.9 (70.4-73.4) South America 10,180 5.8 (5.4-6.3) 2,168 34.3 (32.3-36.3) 2,040 59.1 (57.0-61.2) 6,404 63.3 (62.1-64.5) Asia 142,676 3.4 (3.3-3.5) 7,764 21.2 (20.3-22.1) 11,190 41.1 (40.2-42.0) 18,959 70.9 (70.2-71.5) Central Asia - - - - - - - - - - - - Eastern Asia 111,548 3.4 (3.3-3.5) 6,882 20.6 (19.7-21.6) 9,532 41.5 (40.5-42.5) 13,974 67.3 (66.5-68.1) South-Eastern Asia 8,755 3.0 (2.7-3.4) 374 25.1 (21.0-29.8) 967 31.3 (28.5-34.3) 3,020 72.3 (70.7-73.9) Southern Asia 14,520 4.4 (4.1-4.7) 229 30.1 (24.6-36.4) 311 64.6 (59.2-69.7) 2,463 81.2 (79.6-82.7) Western Asia 7,853 2.5 (2.2-2.9) 279 24.0 (19.4-29.4) 380 35.8 (31.1-40.7) 787 72.0 (68.8-75.1) Europe 180,090 3.8 (3.7-3.9) 20,452 26.9 (26.3-27.5) 19,390 54.1 (53.4-54.8) 16,690 73.4 (72.7-74.1) Eastern Europe 7,818 9.7 (9.1-10.4) 842 31.6 (28.5-34.8) 696 59.3 (55.6-62.9) 1,601 84.8 (83.0-86.5) Northern Europe 86,821 4.2 (4.1-4.3) 4,949 30.6 (29.3-31.9) 6,383 55.4 (54.2-56.6) 4,276 76.6 (75.3-77.8) Southern Europe 31,831 3.8 (3.6-4.0) 10,607 25.5 (24.7-26.3) 5,249 51.1 (49.7-52.4) 3,970 67.8 (66.3-69.2) Western Europe 56,074 2.6 (2.5-2.7) 4,054 25.1 (23.8-26.5) 3,959 58.3 (56.8-59.8) 3,100 78.3 (76.8-79.7) Oceania 2,997 8.3 (7.4-9.4) 473 27.1 (23.3-31.2) 1,417 58.4 (55.8-61.0) 855 76.6 (73.7-79.3) Australia & New Zealand 2,271 8.5 (7.4-9.7) 473 27.1 (23.3-31.2) 1,305 57.5 (54.8-60.1) 785 76.1 (72.9-78.9) Melanesia 726 7.7 (6.0-9.9) - - - 112 68.8 (59.7-76.6) 70 82.9 (72.4-89.9) Micronesia - - - - - - - - - - - - Polynesia - - - - - - - - - - - - Data updated at 15 Dec 2014 (data as of 30 Jun 2014 / 31 Oct 2014). Low-grade lesions: LSIL or CIN-1; 95% CI: 95% Confidence Interval; High-grade lesions: CIN-2, CIN-3, CIS or HSIL; 95% CI:95% Confidence Interval. a Kahng 2014 includes lesions CIN2 or worse. Data sources: See references in Section 9.

- 86 - Figure 48: Prevalence of HPV 16 among women with normal cytology in Africa by country and study Country Algeria Benin Guinea Kenya Morocco Mozambique Nigeria Senegal South Africa Tanzania Tunisia Uganda Hammouda 2005 Hammouda 2011 Piras 2011 Keita 2009 De Vuyst 2003 De Vuyst 2010 Chaouki 1998 Amrani 2003 Alhamany 2010 Castellsagué 2001 Thomas 2004 Gage 2012 Astori 1999 Xi 2003 Jones 2007 Allan 2008 McDonald 2012 Watson Jones 2013 Dartell 2014 Hassen 2003 Odida 2011 N 133 732 258 752 369 454 172 306 785 187 844 1075 158 1639 368 848 7445 117 2737 96 251 6.8 (3.6 12.4) 0.5 (0.2 1.4) 4.3 (2.4 7.5) 6.6 (5.1 8.7) 3.5 (2.1 5.9) 7.5 (5.4 10.3) 4.1 (2.0 8.2) 1.3 (0.5 3.3) 2.2 (1.4 3.4) 4.8 (2.6 8.9) 3.0 (2.0 4.3) 1.5 (0.9 2.4) 5.7 (3.0 10.5) 1.0 (0.6 1.7) 1.6 (0.7 3.5) 2.0 (1.3 3.2) 2.0 (1.7 2.3) 12.8 1.8 % (95% CI) (7.9 20.1) (1.3 2.3) 5.2 (2.2 11.6) 2.8 (1.4 5.6) 0 10 20 30 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 87 - Figure 49: Prevalence of HPV 16 among women with normal cytology in Americas by country and study Country Argentina Belize Brazil Canada Chile Colombia Costa Rica Cuba Greenland Guatemala Honduras Mexico Paraguay Peru Trinidad & Tob. USA Abba 2003 Matos 2003 Badano 2011 Chouhy 2013 Cathro 2009 Muñoz 1996 Lorenzato 2000 Noronha 2005 Miranda 2012 da Silva 2012 de Abreu 2012 Fernandes 2013 Rocha 2013 Cassel 2014 Tamegão Lopes 2014 Moore 2009 Demers 2012 Jiang 2013 Ferreccio 2004 Muñoz 1996 Molano 2002 Herrero 2005 Soto 2014 Svare 1998 Vallès 2009 Ferrera 1999 Tábora 2005 Giuliano 2001 Lazcano Ponce 2001 Giuliano 2005 Piña Sánchez 2006 Sánchez Anguiano 2006 Rojo Contreras 2008 Illades Aguiar 2009 Illades Aguiar 2010 Monroy 2010 Velázquez Márquez 2010 López Rivera 2012 Rolón 2000 Mendoza 2011 Santos 2001 García 2004 Martorell 2012 Ragin 2007 Giuliano 2001 Hernandez 2004 Chaturvedi 2005 Evans 2006 Cibas 2007 Goodman 2008 N 152 843 139 774 426 194 215 433 399 418 370 110 314 158 120 4003 517 13379 913 307 1831 7459 111 118 274 438 100 995 1340 258 159 487 189 256 3117 272 100 916 202 91 175 501 203 212 881 183 173 300 1000 2356 % (95% CI) 15.1 (10.3 21.7) 3.2 (2.2 4.6) 6.5 (3.4 11.8) 8.3 (6.5 10.4) 1.2 (0.5 2.7) 5.2 (2.8 9.2) 7.0 (4.3 11.2) 0.5 (0.1 1.7) 5.0 (3.3 7.6) 1.2 (0.5 2.8) 1.4 (0.6 3.1) 14.5 (9.2 22.3) 9.6 (6.8 13.3) 8.9 (5.4 14.3) 9.2 (5.2 15.7) 8.7 (7.9 9.6) 1.9 (1.1 3.5) 3.6 (3.3 4.0) 2.1 (1.3 3.2) 5.5 (3.5 8.7) 3.3 (2.6 4.3) 2.2 (1.9 2.6) 35.1 (26.9 44.4) 21.2 (14.8 29.4) 3.3 (1.7 6.1) 11.0 (8.4 14.2) 6.0 (2.8 12.5) 1.2 (0.7 2.1) 1.7 (1.1 2.6) 0.8 (0.2 2.8) 3.8 (1.7 8.0) 2.9 (1.7 4.8) 9.0 (5.7 13.9) 11.3 (8.0 15.8) 2.3 (1.9 2.9) 1.1 (0.4 3.2) 9.0 (4.8 16.2) 1.0 (0.5 1.9) 5.5 (2.4 12.2) 4.5 (2.4 8.2) 4.0 (2.0 8.0) 2.4 (1.4 4.1) 12.3 (8.5 17.5) 2.4 (1.0 5.4) 2.6 (1.7 3.9) 1.6 (0.6 4.7) 1.2 (0.3 4.1) 9.7 (6.8 13.5) 0.5 (0.2 1.2) 4.7 (3.9 5.6) 0 10 20 30 40 50 HPV prevalence (%) (Continued on next page) Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 88 - Figure 50: Prevalence of HPV 16 among women with normal cytology in Americas by country and study (continued) Country Uruguay Ramas 2013 N 236 % (95% CI) 2.1 (0.9 4.9) Berois 2014 883 3.4 (2.4 4.8) USA Wideroff 1998 958 2.7 (1.9 3.9) Swan 1999 270 3.0 (1.5 5.7) Moscicki 2001 547 26.7 (23.2 30.6) Hernandez 2004 183 1.6 (0.6 4.7) Insinga 2007 1203 6.8 (5.5 8.4) Schiffman 2011 18450 2.2 (2.0 2.4) Wheeler 2013 33614 2.6 (2.4 2.8) 0 10 20 30 40 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 89 - Figure 51: Prevalence of HPV 16 among women with normal cytology in Asia by country and study Country Bahrain Bhutan China Georgia India Indonesia Iran Japan Korea, Rep. Kuwait Lebanon Hajjaj 2006 Tshomo 2014 Dai 2006 Li 2006 Wu 2007 Zhao 2009 Jin 2010 Sun 2010 Wu 2010 Yuan 2011 Bian 2013 Li 2013 Wu 2013 Mai 2014 Zhao 2014 Alibegashvili 2011 Arora 2005 Franceschi 2005 Aggarwal 2006 Laikangbam 2007 Bhatla 2008 Gupta 2009 Singh 2009 Kerkar 2011 Dutta 2012 Vinodhini 2012 de Boer 2006 Safaei 2010 Moradi 2011 Khodakarami 2012 Sasagawa 1997 Yoshikawa 1999 Sasagawa 2001 Asato 2004 Maehama 2005 Inoue 2006 Nishiwaki 2008 Onuki 2009 Konno 2011 Takehara 2011 Oh 2001 An 2003 Cho 2003 Lee 2003 Shin 2003 Hwang 2004 Kim 2012 Kim 2013 Al Awadhi 2011 Mroueh 2002 0 10 20 30 HPV prevalence (%) N 91 2272 601 663 942 5284 2847 165 314 3112 379 3115 3737 22114 5416 1247 160 1799 472 2038 458 769 109 470 2313 257 200 400 226 791 778 130 1562 3249 4078 7260 292 1517 908 2068 1144 1143 414 746 821 1609 1214 6681 3011 1026 1.1 (0.2 6.0) 3.4 (2.8 4.3) 3.5 2.1 1.9 1.7 1.0 10.9 3.5 2.3 4.7 2.9 1.0 3.6 2.1 0.5 (0.2 1.0) 9.4 (5.8 14.9) 2.8 (2.2 3.7) 3.6 (2.3 5.7) 4.7 (3.9 5.7) 2.2 (1.2 4.0) 10.1 (8.2 12.5) 8.3 (4.4 15.0) 1.5 (0.7 3.0) 0.5 (0.3 0.9) 8.9 (6.0 13.1) 2.0 (0.8 5.0) 2.0 (1.0 3.9) 4.0 (2.1 7.4) 1.8 (1.1 2.9) 1.0 (0.5 2.0) 0.8 (0.1 4.2) 1.3 (0.8 2.0) 0.5 (0.3 0.8) 0.3 (0.2 0.5) 1.2 (1.0 1.5) 4.5 (2.6 7.5) 2.6 (1.9 3.6) 4.1 (3.0 5.6) 1.5 (1.0 2.1) 0.6 22.4 22.9 4.3 0.7 6.3 9.9 1.6 % (95% CI) (2.3 5.3) (1.3 3.5) (1.2 3.0) (1.4 2.0) (0.7 1.4) (7.0 16.6) (2.0 6.2) (1.8 2.9) (3.0 7.4) (2.3 3.5) (0.7 1.4) (3.4 3.9) (1.7 2.5) (0.3 1.3) (20.1 24.9) (19.2 27.2) (3.1 6.0) (0.3 1.6) (5.2 7.6) (8.3 11.7) (1.3 1.9) 0.2 (0.1 0.5) 3.0 (2.1 4.3) (Continued on next page) Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 90 - Figure 52: Prevalence of HPV 16 among women with normal cytology in Asia by country and study (continued) Country Lebanon Malaysia Mongolia Nepal Pakistan Philippines Taiwan Thailand Siritantikorn 1997 Chichareon 1998 Sukvirach 2003 Settheetham Ishida 2005 Sriamporn 2006 Chaiwongkot 2007 Chopjitt 2009 Suwannarurk 2009 Natphopsuk 2013 Laowahutanont 2014 Turkey Viet Nam Mroueh 2002 Othman 2014 Dondog 2008 Sherpa 2010 Johnson 2014 Raza 2010 Ngelangel 1998 Lin 2005 Tsai 2005 Huang 2008 Chen 2011 Lai 2012 Dursun 2009 Altun 2011 Bayram 2011 Demir 2012 Ozalp 2012 Tezcan 2014 Pham 2003 N 1026 588 842 898 211 877 377 127 175 1310 10067 14724 102 261 1659 100 113 140 160 225 198 2735 310 460 234 530 564 380 1897 3.0 (2.1 4.3) 0.9 (0.4 2.0) 4.8 (3.5 6.4) 1.4 (0.8 2.5) 0.9 (0.3 3.4) 0.5 (0.2 1.2) 1.3 (0.6 3.1) 3.1 (1.2 7.8) 2.9 (1.2 6.5) 1.1 (0.6 1.8) 1.4 (1.2 1.6) 0.2 (0.2 0.3) 1.0 4.6 0.7 8.0 7.1 12.9 5.6 4.0 5.6 1.2 % (95% CI) (0.2 5.3) (2.6 7.9) (0.4 1.3) (4.1 15.0) (3.6 13.4) (8.3 19.4) (3.0 10.3) (2.1 7.4) (3.1 9.7) (0.9 1.7) 7.1 (4.7 10.5) 1.7 (0.9 3.4) 2.6 (1.2 5.5) 3.6 (2.3 5.5) 1.4 (0.7 2.8) 4.2 (2.6 6.7) 1.5 (1.0 2.1) 0 10 20 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 91 - Figure 53: Prevalence of HPV 16 among women with normal cytology in Europe by country and study Country Belarus Belgium Croatia Czech Rep. Denmark France Germany Greece Ireland Italy Lithuania Netherlands Norway Poland Portugal Romania Russia Rogovskaya 2013 Baay 2001 Depuydt 2003 Baay 2005 Arbyn 2009 Schmitt 2013 Weyn 2013 Grahovac 2007 Tachezy 2013 Svare 1998 Kjaer 2008 Nielsen 2008 Bonde 2014 Beby Defaux 2004 Pannier Stockman 2008 Casalegno 2011 Vaucel 2011 Heard 2013 Klug 2007 Iftner 2010 de Jonge 2013 Agorastos 2004 Panotopoulou 2007 Tsiodras 2010 Tsiodras 2011 Argyri 2013 Keegan 2007 Anderson 2013 Astori 1997 Centurioni 2005 Ronco 2005 Tornesello 2006 Tornesello 2008 Agarossi 2009 Giorgi Rossi 2011 Panatto 2013 Sammarco 2013 Gudleviciene 2005 Simanaviciene 2014 Jacobs 2000 Rozendaal 2000 Zielinski 2001 Bulkmans 2007 Gjøoen 1996 Molden 2005 Bardin 2008 Pista 2011 Moga 2014 Alexandrova 1999 Komarova 2010 N 322 286 287 2293 8729 913 906 205 1302 119 10918 11663 4435 170 289 302 980 3023 7833 1692 1463 1272 639 1029 1348 2218 579 5068 197 500 997 183 107 9148 3151 566 244 332 277 3299 2250 114 21245 222 3970 799 425 801 309 257 7.1 (4.8 10.5) 2.8 (1.4 5.4) 4.2 (2.4 7.2) 2.1 (1.6 2.8) 2.3 (2.1 2.7) 5.6 (4.3 7.3) 2.1 (1.3 3.3) 15.6 (11.3 21.2) 4.8 (3.8 6.1) 8.4 (4.6 14.8) 4.8 (4.4 5.2) 4.0 (3.6 4.3) 5.3 (4.7 6.0) 1.8 9.3 10.6 3.6 3.0 % (95% CI) (0.6 5.1) (6.5 13.3) (7.6 14.6) (2.6 4.9) (2.5 3.7) 1.1 (0.9 1.4) 6.6 (5.5 7.8) 4.9 (3.9 6.2) 0.4 (0.2 0.9) 0.5 (0.2 1.4) 0.0 (0.0 0.4) 4.0 (3.1 5.2) 2.6 (2.0 3.4) 1.7 (0.9 3.1) 3.2 (2.7 3.7) 5.1 (2.8 9.1) 8.8 (6.6 11.6) 2.7 (1.9 3.9) 8.7 (5.5 13.7) 2.8 (1.0 7.9) 3.0 (2.7 3.4) 2.1 (1.7 2.7) 2.8 (1.7 4.5) 6.6 (4.1 10.4) 6.9 (4.7 10.2) 4.3 (2.5 7.4) 0.9 (0.7 1.3) 2.7 (2.1 3.4) 1.8 (0.5 6.2) 1.0 (0.9 1.1) 6.3 (3.8 10.3) 1.3 (1.0 1.7) 2.8 (1.8 4.1) 5.2 (3.4 7.7) 7.5 (5.9 9.5) 7.4 (5.0 10.9) 24.1 (19.3 29.7) 0 10 20 30 HPV prevalence (%) (Continued on next page) Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 92 - Figure 54: Prevalence of HPV 16 among women with normal cytology in Europe by country and study (continued) Country Russia Komarova 2010 Shipitsyna 2011 Rogovskaya 2013 N 257 741 833 % (95% CI) 24.1 (19.3 29.7) 2.7 (1.8 4.1) 7.1 (5.5 9.0) Slovenia Ucakar 2012 4199 3.7 (3.2 4.3) Spain Muñoz 1996 de Sanjose 2003 González 2006 Dillner 2008 Castellsagué 2012 329 847 447 721 3059 1.8 (0.8 3.9) 0.4 (0.1 1.0) 1.3 (0.6 2.9) 3.1 (2.0 4.6) 2.5 (2.0 3.1) Sweden Kjellberg 1998 Ylitalo 2000 Naucler 2007 295 617 5877 1.0 (0.3 2.9) 5.8 (4.2 8.0) 1.7 (1.4 2.0) UK Cuzick 1995 Cuzick 1999 Cuschieri 2004 Grainge 2005 Hibbitts 2006 Sargent 2008 Hibbitts 2014 1818 2855 3089 656 1777 21364 10890 1.3 (0.9 2.0) 0.1 (0.0 0.3) 4.4 (3.7 5.2) 1.4 (0.7 2.6) 1.4 (0.9 2.0) 1.5 (1.3 1.7) 4.3 (3.9 4.7) 0 10 20 30 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 93 - Figure 55: Prevalence of HPV 16 among women with normal cytology in Oceania by country and study Country Australia Tabrizi 2014 N 2271 % (95% CI) 5.8 (4.9 6.8) Vanuatu Aruhuri 2012 726 6.5 (4.9 8.5) 0 10 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 31 Oct 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 94 - Figure 56: Prevalence of HPV 16 among women with low-grade cervical lesions in Africa by country and study Country Algeria Congo, DR Côte d'ivoire Ethiopia Guinea Kenya Morocco Nigeria Rwanda Senegal South Africa Tanzania Zimbabwe Hammouda 2011 Hovland 2010 La Ruche 1998 Abate 2013 Keita 2009 De Vuyst 2003 De Vuyst 2010 De Vuyst 2012 Alhamany 2010 Thomas 2004 Gage 2012 Singh 2009 Chabaud 1996 Xi 2003 Allan 2008 McDonald 2014 Dartell 2014 Sawaya 2008 0 20 40 60 80 100 HPV prevalence (%) N 3 10 151 11 100.0 (74.1 100.0) 16 30 12 1 24 34 32 5 42 86 261 57 40 97 0.0 (0.0 56.1) 0.0 (0.0 27.8) 10.6 (6.6 16.5) 18.8 (6.6 43.0) 13.3 (5.3 29.7) 8.3 (1.5 35.4) 0.0 (0.0 79.3) 16.7 (6.7 35.9) 5.9 (1.6 19.1) 6.3 (1.7 20.1) 0.0 (0.0 43.4) 40.5 8.1 12.3 8.8 % (95% CI) (27.0 55.5) (4.0 15.9) (6.1 23.2) (5.9 12.9) 12.5 (5.5 26.1) 19.6 (12.9 28.6) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; Low-grade lesions: LSIL or CIN-1; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 95 - Figure 57: Prevalence of HPV 16 among women with low-grade cervical lesions in Americas by country and study Country Argentina Belize Brazil Canada Chile Colombia Cuba Ecuador Haiti Honduras Jamaica Mexico Nicaragua Paraguay Peru USA Tonon 1999 Abba 2003 Deluca 2004 Chouhy 2006 Eiguchi 2008 Venezuela 2012 Cathro 2009 Franco 1999 Lorenzato 2000 Carestiato 2006 Freitas 2007 Krambeck 2008 Fernandes 2009 Pitta 2010 Tomita 2010 Ribeiro 2011 Resende 2014 Sellors 2000 Sellors 2000 Richardson 2003 Tran Thanh 2003 Koushik 2005 Antonishyn 2008 Moore 2009 Coutlée 2011 Jiang 2011 López M 2010 Ili 2011 Molano 2002 García 2011 Soto 2007 Tornesello 2008 Walmer 2013 Ferreira 2008 Rattray 1996 Strickler 1999 Torroella Kouri 1998 Giuliano 2001 Carrillo 2004 González Losa 2004 Piña Sánchez 2006 Velázquez Márquez 2009 Illades Aguiar 2010 Hindryckx 2006 Tonon 1999 Mendoza 2011 Martorell 2012 Adam 2000 Brown 2002 Bell 2007 N 279 55 36 22 37 120 10 27 62 55 15 82 9 22 143 66 82 24 44 22 80 53 344 505 508 108 116 90 70 56 15 29 157 44 186 62 33 21 104 21 233 95 784 79 164 55 22 161 25 12 74.5 26.5 8.3 18.2 18.9 14.2 10.0 (1.8 40.4) 25.9 19.4 29.1 20.0 0.0 18.3 0.0 28.7 27.3 23.2 37.5 50.0 18.2 15.0 26.4 14.2 35.2 27.6 19.4 22.4 55.6 10.0 80.4 6.7 (1.2 29.8) 34.5 (19.9 52.7) 11.5 (7.4 17.4) 11.4 (5.0 24.0) 6.5 (2.5 15.4) 4.3 (2.2 8.3) 4.8 15.2 19.0 5.8 25.3 12.9 10.6 7.6 (3.5 15.6) 74.5 (61.7 84.2) 19.5 (14.2 26.2) 22.7 (10.1 43.4) 45.3 40.0 8.3 % (95% CI) (61.7 84.2) (21.7 32.0) (2.9 21.8) (7.3 38.5) (9.5 34.2) (9.0 21.5) (13.2 44.7) (11.4 30.9) (18.8 42.1) (7.0 45.2) (0.0 29.9) (11.4 28.0) (0.0 14.9) (21.9 36.6) (18.0 39.0) (15.4 33.4) (21.2 57.3) (30.7 69.3) (9.5 32.0) (8.8 24.4) (16.4 39.6) (10.9 18.3) (31.2 39.5) (23.9 31.6) (13.1 27.9) (15.8 30.8) (45.3 65.4) (4.9 19.2) (68.2 88.7) (0.8 22.7) (6.7 30.9) (7.7 40.0) (2.7 12.0) (17.6 34.8) (9.2 17.8) (8.6 12.9) (37.8 53.1) (23.4 59.3) (1.5 35.4) 0 20 40 60 80 100 HPV prevalence (%) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; Low-grade lesions: LSIL or CIN-1; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 96 - Figure 58: Prevalence of HPV 16 among women with low-grade cervical lesions in Americas by country and study (continued) Country USA Brown 2002 Castle 2011 Tortolero Luna 1998 Liaw 1999 Swan 1999 Schiff 2000 Giuliano 2001 Evans 2002 Kulasingam 2002 Jarboe 2004 Hu 2005 Evans 2006 Wheeler 2006 Einstein 2007 Guo 2007 Kong 2007 Park 2007 Zuna 2007 Moscicki 2008 Lee 2009 Voss 2009 Wentzensen 2009 Wheeler 2009 Stoler 2011 Wheeler 2013 Vidal 2014 Brown 2002 Castle 2011 Tortolero Luna 1998 Liaw 1999 Swan 1999 Schiff 2000 Giuliano 2001 Evans 2002 Kulasingam 2002 Jarboe 2004 Hu 2005 Evans 2006 Wheeler 2006 Einstein 2007 Guo 2007 Kong 2007 Park 2007 Zuna 2007 Moscicki 2008 Lee 2009 Voss 2009 Wentzensen 2009 Wheeler 2009 Stoler 2011 Wheeler 2013 Vidal 2014 0 20 40 60 80 100 HPV prevalence (%) N 106 25 175 173 149 190 166 287 200 45 95 1273 207 27 157 67 30 11 431 59 76 158 67 3540 239 106 25 175 173 149 190 166 287 200 45 95 1273 207 27 157 67 30 11 431 59 76 158 67 3540 239 40.0 8.5 12.6 7.5 10.1 5.8 14.3 7.1 15.7 7.4 8.9 15.5 21.3 6.3 0.0 27.3 16.7 14.9 19.7 3.9 18.6 22.5 26.9 10.8 19.3 10.0 40.0 8.5 12.6 7.5 10.1 5.8 14.3 7.1 15.7 7.4 8.9 15.5 21.3 6.3 0.0 27.3 16.7 14.9 19.7 3.9 18.6 22.5 26.9 10.8 19.3 10.0 % (95% CI) (23.4 59.3) (4.5 15.4) (8.5 18.3) (4.4 12.4) (6.2 15.9) (3.3 10.1) (2.6 51.3) (2.0 22.6) (10.9 22.0) (3.6 14.4) (3.5 20.7) (11.1 21.2) (19.1 23.6) (3.7 10.4) (0.0 12.5) (9.7 56.6) (7.3 33.6) (8.3 25.3) (14.3 26.7) (1.4 11.0) (10.7 30.4) (18.8 26.7) (17.7 38.5) (6.8 16.6) (18.0 20.6) (6.8 14.5) (23.4 59.3) (4.5 15.4) (8.5 18.3) (4.4 12.4) (6.2 15.9) (3.3 10.1) (2.6 51.3) (2.0 22.6) (10.9 22.0) (3.6 14.4) (3.5 20.7) (11.1 21.2) (19.1 23.6) (3.7 10.4) (0.0 12.5) (9.7 56.6) (7.3 33.6) (8.3 25.3) (14.3 26.7) (1.4 11.0) (10.7 30.4) (18.8 26.7) (17.7 38.5) (6.8 16.6) (18.0 20.6) (6.8 14.5) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; Low-grade lesions: LSIL or CIN-1; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 97 - Figure 59: Prevalence of HPV 16 among women with low-grade cervical lesions in Asia by country and study Country Bangladesh China India Iran Japan Korea, Rep. Kuwait Malaysia Myanmar Pakistan Banik 2013 Chan 1999 Chan 2006 Tao 2006 Hong 2008 Liu 2008 Zhao 2008 Guo 2010 Jin 2010 Liu 2010 Wu 2010 Yuan 2011 Chan 2012 Li 2012 Li 2013 Wu 2013 Zhang 2013 Sun 2014 Zhao 2014 Nair 1999 Nagpal 2002 Franceschi 2005 Berlin Grace 2009 Singh 2009 Ghaffari 2006 Esmaeili 2008 Khodakarami 2012 Saito 2001 Sasagawa 2001 Tsuda 2003 Yoshida 2004 Inoue 2006 Nishiwaki 2008 Futai 2009 Onuki 2009 Konno 2011 Matsumoto 2011 Takehara 2011 Yamasaki 2011 Oh 2001 An 2003 Cho 2003 Hwang 2003 Lee 2007 Kang 2009 Al Awadhi 2011 Al Awadhi 2013 Sharifah 2009 Mu Mu Shwe 2014 Raza 2010 0 20 40 60 80 100 HPV prevalence (%) N 13 769 51 101 105 90 56 201 44 180 129 302 769 143 165 94 77 207 81 37 26 14 20 80 23 12 3 151 145 128 129 120 44 318 479 75 447 125 200 28 150 24 167 90 71 71 23 15 15.4 (4.3 42.2) 21.6 14.0 21.8 13.3 5.6 12.5 20.4 9.1 34.4 11.6 15.9 13.9 16.1 12.7 18.2 17.0 21.0 20.8 18.9 35.7 30.8 0.0 23.8 41.7 (19.3 68.0) 39.1 (22.2 59.2) 0.0 (0.0 56.1) 2.6 9.0 11.1 8.3 17.2 13.3 25.0 8.5 20.0 9.2 11.4 19.2 17.9 36.5 26.7 16.7 19.2 17.8 % (95% CI) (12.5 34.6) (11.8 16.7) (14.8 30.8) (8.1 21.1) (2.4 12.4) (6.2 23.6) (15.4 26.5) (3.6 21.2) (27.9 41.6) (7.2 18.3) (12.2 20.4) (11.6 16.5) (11.0 23.0) (8.5 18.7) (11.2 28.2) (10.8 25.9) (13.5 31.1) (15.8 26.8) (9.5 34.2) (16.3 61.2) (16.5 50.0) (0.0 16.1) (15.8 34.1) (1.0 6.6) (5.3 14.7) (2.0 43.5) (1.5 35.4) (11.6 24.7) (8.4 20.6) (14.6 39.4) (5.9 12.1) (12.5 30.4) (6.9 12.1) (8.8 14.7) (13.3 27.0) (7.9 35.6) (30.1 43.4) (20.2 34.3) (6.7 35.9) (13.9 25.8) (11.2 26.9) 18.3 (11.0 28.8) 18.3 (11.0 28.8) 26.1 (12.5 46.5) 60.0 (35.7 80.2) 1 100.0 (20.7 100.0) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; Low-grade lesions: LSIL or CIN-1; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 98 - Figure 60: Prevalence of HPV 16 among women with low-grade cervical lesions in Asia by country and study (continued) Country Pakistan Raza 2010 N % (95% CI) 1 100.0 (20.7 100.0) Taiwan Chao 2008 Ding 2008 Huang 2008 51 542 13 3.9 (1.1 13.2) 6.1 (4.4 8.4) 0.0 (0.0 22.8) Thailand Turkey Ekalaksananan 2001 Bhattarakosol 2002 Chaiwongkot 2007 Suwannarurk 2009 Chansaenroj 2010 Chansaenroj 2014 Ergünay 2008 Ozgul 2008 Sahiner 2012 Yuce 2012 Tezcan 2014 0 20 40 60 80 100 HPV prevalence (%) 45 27 140 12 12 100 14 13 45 51 14 4.4 0.0 14.3 25.0 0.0 27.0 28.6 15.4 22.2 19.6 7.1 (1.2 14.8) (0.0 12.5) (9.4 21.0) (8.9 53.2) (0.0 24.2) (19.3 36.4) (11.7 54.6) (4.3 42.2) (12.5 36.3) (11.0 32.5) (1.3 31.5) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; Low-grade lesions: LSIL or CIN-1; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 99 - Figure 61: Prevalence of HPV 16 among women with low-grade cervical lesions in Europe by country and study Country Belarus Belgium Croatia Czech Rep. Denmark France Germany Greece Ireland Italy Kulmala 2007 Baay 2001 Depuydt 2003 Beerens 2005 Arbyn 2009 Weyn 2013 Grce 1997 Grce 2001 Grce 2004 Tachezy 2011 Hording 1995 Kjaer 2008 Kjær 2014 Bergeron 1992 Humbey 2002 Monsonego 2008 Prétet 2008 Vaucel 2011 Heard 2013 Merkelbach Bruse 1999 Nindl 1999 Meyer 2001 Klug 2007 de Jonge 2013 Labropoulou 1997 Kroupis 2007 Panotopoulou 2007 Mammas 2008 Adamopoulou 2009 Tsiodras 2011 Argyri 2013 Butler 2000 Murphy 2003 Keegan 2014 Astori 1997 Laconi 2000 Voglino 2000 Venturoli 2002 Tornesello 2006 Gargiulo 2007 Capra 2008 Venturoli 2008 Agarossi 2009 Agodi 2009 Menegazzi 2009 Sandri 2009 Spinillo 2009 Chironna 2010 Giorgi Rossi 2010 Spinillo 2014 N 94 369 58 324 243 211 183 1028 60 338 287 86 41 48 397 37 40 117 1179 130 49 16 441 52 235 51 516 46 314 7 821 26 29 49 111 1499 20 40 101 83 149 383 10 96 343 47 21 385 1240 76 35.1 (26.2 45.2) 24.1 20.3 18.5 23.5 10.0 6.0 (3.4 10.4) 11.6 (9.8 13.7) 8.3 (3.6 18.1) 28.4 (23.9 33.4) 31.7 12.8 17.1 20.8 30.0 5.4 21.4 14.5 20.9 68.8 12.2 13.1 11.5 17.5 11.8 23.4 6.8 21.7 14.3 17.8 14.5 0.0 72.4 40.8 24.3 30.0 24.7 7.5 36.6 15.7 11.4 20.0 19.8 32.3 23.8 21.3 36.7 13.0 21.1 25.6 % (95% CI) (15.0 36.5) (16.5 24.7) (14.7 23.1) (18.6 29.2) (6.6 14.7) (19.6 47.0) (7.3 21.5) (13.2 21.9) (11.7 34.3) (18.1 45.4) (1.5 17.7) (17.7 25.7) (9.3 22.0) (18.6 23.3) (44.4 85.8) (5.7 24.2) (8.3 19.9) (5.4 23.0) (14.2 21.3) (5.5 23.4) (18.4 29.2) (4.9 9.3) (12.3 35.6) (2.6 51.3) (14.0 22.4) (12.3 17.1) (0.0 12.9) (54.3 85.3) (28.2 54.8) (17.3 33.1) (14.5 51.9) (22.6 27.0) (2.6 19.9) (27.9 46.4) (9.4 25.0) (7.2 17.5) (5.7 51.0) (16.2 24.1) (23.8 42.2) (10.6 45.1) (12.0 34.9) (31.8 42.0) (10.0 16.7) (13.4 31.5) (23.2 28.1) 0 20 40 60 80 100 HPV prevalence (%) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; Low-grade lesions: LSIL or CIN-1; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 100 - Figure 62: Prevalence of HPV 16 among women with low-grade cervical lesions in Europe by country and study (continued) Italy Latvia Lithuania Netherlands Norway Poland Portugal Romania Russia Slovenia Spain Sweden Switzerland UK Country Voglino 2000 Zerbini 2001 Kulmala 2007 Gudleviciene 2005 Bollen 1997 Reesink Peters 2001 Prinsen 2007 Molden 2005 Roberts 2006 Ciszek 2012 Medeiros 2005 Nobre 2010 Anton 2011 Ursu 2011 Moga 2014 Kulmala 2007 Ucakar 2012 Conesa Zamora 2009 García Sierra 2009 de Méndez 2009 Doménech Peris 2010 de Oña 2010 Martín 2011 Herraez Hernandez 2013 Zehbe 1996 Kalantari 1997 Andersson 2005 Brismar Wendel 2009 Söderlund Strand 2011 Dobec 2011 Arends 1993 Cuzick 1994 Cuzick 1999 Giannoudis 1999 Southern 2001 Cuschieri 2004 Hibbitts 2008 Sargent 2008 Jamison 2009 Howell Jones 2010 Woo 2010 Anderson 2013 N 1499 43 94 15 134 35 38 20 40 33 416 28 107 87 56 94 69 108 75 1356 213 387 236 141 45 223 50 1035 136 20 118 50 13 49 243 126 878 697 97 60 417 24.7 14.0 35.1 (26.2 45.2) 6.7 (1.2 29.8) 12.7 28.6 7.9 25.0 5.0 45.5 (29.8 62.0) 44.2 10.7 11.5 (6.4 19.9) 5.6 (2.6 11.7) 23.2 (14.1 35.8) 35.1 (26.2 45.2) 26.1 (17.2 37.5) 29.3 17.6 66.7 23.8 12.2 24.8 39.8 40.0 17.7 20.0 20.6 24.2 25.0 (18.5 32.9) 15.0 23.1 12.0 12.7 10.2 28.0 27.8 17.3 27.8 20.5 41.7 24.0 % (95% CI) (22.6 27.0) (6.6 27.3) (8.1 19.4) (16.3 45.1) (2.7 20.8) (11.2 46.9) (1.4 16.5) (39.5 49.0) (3.7 27.2) (20.2 40.4) (11.6 25.8) (20.8 93.9) (10.6 45.1) (10.6 14.1) (20.8 29.3) (33.8 46.2) (27.0 54.5) (12.3 24.9) (11.2 33.0) (15.8 26.4) (21.6 26.9) (5.2 36.0) (8.2 50.3) (5.6 23.8) (7.9 19.9) (4.4 21.8) (22.7 33.9) (20.7 36.2) (15.0 20.0) (19.9 37.5) (17.7 23.7) (30.1 54.3) (20.1 28.3) 0 20 40 60 80 100 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; Low-grade lesions: LSIL or CIN-1; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 101 - Figure 63: Prevalence of HPV 16 among women with low-grade cervical lesions in Oceania by country and study Country N % (95% CI) Australia Brestovac 2005 38 28.9 (17.0 44.8) Stevens 2009 196 13.3 (9.2 18.7) Garland 2011 239 24.3 (19.3 30.1) 0 20 40 60 80 100 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; Low-grade lesions: LSIL or CIN-1; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 102 - Figure 64: Prevalence of HPV 16 among women with High-grade cervical lesions in Africa by country and study Country Algeria Cameroon Congo, DR Côte d'ivoire Eq. Guinea Ethiopia Guinea Kenya Morocco Nigeria Rwanda Senegal South Africa Tanzania Zimbabwe Hammouda 2011 Untiet 2014 Hovland 2010 La Ruche 1998 García Espinosa 2009 Abate 2013 Keita 2009 De Vuyst 2003 De Vuyst 2010 De Vuyst 2012 Alhamany 2010 Gage 2012 Gage 2012 Singh 2009 Chabaud 1996 Xi 2003 Allan 2008 Said 2009 De Vuyst 2012 McDonald 2014 Dartell 2014 Sawaya 2008 0 20 40 60 80 100 HPV prevalence (%) N 3 6 16 49 16 13 15 29 7 2 7 27 32 6 23 66 53 220 98 96 11 % (95% CI) 33.3 (6.1 79.2) 16.7 (3.0 56.4) 31.3 (14.2 55.6) 30.6 (19.5 44.5) 18.8 (6.6 43.0) 61.5 (35.5 82.3) 20.0 (7.0 45.2) 34.5 (19.9 52.7) 28.6 (8.2 64.1) 50.0 (9.5 90.5) 14.3 (2.6 51.3) 22.2 (10.6 40.8) 21.9 (11.0 38.8) 0.0 (0.0 39.0) 43.5 (25.6 63.2) 19.7 (11.9 30.8) 18.9 (10.6 31.4) 12.5 (2.2 47.1) 55.6 (26.7 81.1) 22.7 (17.7 28.7) 30.2 (21.9 40.0) 9.1 (1.6 37.7) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; High-grade lesions: CIN-2, CIN-3, CIS or HSIL; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 103 - Figure 65: Prevalence of HPV 16 among women with High-grade cervical lesions in Americas by country and study Argentina Belize Brazil Canada Chile Colombia Costa Rica Cuba Haiti Honduras Jamaica Mexico Nicaragua Paraguay Peru USA Country Abba 2003 Alonio 2003 Deluca 2004 Chouhy 2006 Cathro 2009 Lorenzato 2000 Camara 2003 Carestiato 2006 Freitas 2007 Terra 2007 Krambeck 2008 Fernandes 2009 Fernandes 2010 Pitta 2010 Tomita 2010 Ribeiro 2011 Resende 2014 Antonishyn 2008 Moore 2009 Coutlée 2011 Ili 2011 Muñoz 1992 Bosch 1993 García 2011 Herrero 2005 Soto 2007 Walmer 2013 Ferreira 2008 Rattray 1996 Strickler 1999 Torroella Kouri 1998 Giuliano 2001 Piña Sánchez 2006 Velázquez Márquez 2009 Illades Aguiar 2010 Hindryckx 2006 Mendoza 2011 Martorell 2012 Adam 1998 Giuliano 2001 Evans 2003 Hu 2005 Evans 2006 Bell 2007 Einstein 2007 Guo 2007 Castle 2010 Castle 2011 Hariri 2012 Hariri 2012 N 82 50 12 5 15 60 95 10 3 33 102 56 16 367 85 223 83 305 365 63 110 135 125 49 108 45 99 81 183 66 24 22 59 91 51 108 74 32 257 22 8 97 199 10 97 608 61 367 3058 180 % (95% CI) 48.8 (38.3 59.4) 54.0 (40.4 67.0) 60.0 (23.1 88.2) 58.3 (32.0 80.7) 46.7 (24.8 69.9) 56.7 (44.1 68.4) 30.5 (22.2 40.4) 66.7 (20.8 93.9) 40.0 (16.8 68.7) 69.7 (52.7 82.6) 25.0 (10.2 49.5) 53.6 (40.7 66.0) 61.8 (52.1 70.6) 51.8 (41.3 62.1) 59.9 (54.9 64.8) 48.2 (37.8 58.8) 48.9 (42.4 55.4) 46.9 (41.4 52.5) 52.4 (40.3 64.2) 65.5 (60.5 70.2) 55.5 (46.1 64.4) 34.8 (27.3 43.2) 32.8 (25.2 41.4) 91.8 (80.8 96.8) 45.4 (36.3 54.8) 31.1 (19.5 45.7) 26.3 (18.6 35.7) 35.8 (26.2 46.7) 24.2 (15.5 35.8) 23.5 (17.9 30.1) 58.3 (38.8 75.5) 27.3 (13.2 48.2) 42.4 (30.6 55.1) 13.7 (6.8 25.7) 27.5 (19.4 37.4) 26.9 (19.4 35.9) 41.9 (31.3 53.3) 50.0 (33.6 66.4) 51.0 (44.9 57.0) 12.5 (2.2 47.1) 68.2 (47.3 83.6) 40.2 (31.0 50.2) 49.2 (42.4 56.1) 40.0 (16.8 68.7) 41.2 (32.0 51.2) 36.1 (25.2 48.6) 59.9 (55.9 63.7) 44.4 (39.4 49.5) 47.2 (45.4 49.0) 48.9 (41.7 56.1) 0 20 40 60 80 100 HPV prevalence (%) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; High-grade lesions: CIN-2, CIN-3, CIS or HSIL; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 104 - Figure 66: Prevalence of HPV 16 among women with High-grade cervical lesions in Americas by country and study (continued) USA Country Hu 2005 Wheeler 2006 Kong 2007 Zuna 2007 Moscicki 2008 Lee 2009 Voss 2009 Wentzensen 2009 Wheeler 2009 Stoler 2011 Wheeler 2013 Vidal 2014 N 97 331 14 122 122 10 26 626 1230 80 517 88 % (95% CI) 40.2 (31.0 50.2) 47.7 (42.4 53.1) 50.0 (26.8 73.2) 43.4 (35.0 52.3) 47.5 (38.9 56.3) 60.0 (31.3 83.2) 61.5 (42.5 77.6) 58.8 (54.9 62.6) 56.3 (53.5 59.0) 51.2 (40.5 61.9) 46.8 (42.5 51.1) 29.5 (21.0 39.8) Venezuela Sánchez Lander 2012 233 53.6 (47.2 59.9) 0 20 40 60 80 100 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; High-grade lesions: CIN-2, CIN-3, CIS or HSIL; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 105 - Figure 67: Prevalence of HPV 16 among women with High-grade cervical lesions in Asia by country and study Country Bangladesh China India Iran Israel Japan Korea, Rep. Kuwait Malaysia Banik 2013 Wu 1994 Chan 1996 Chan 1999 Chan 2006 Tao 2006 Liu 2008 Zhao 2008 Guo 2010 Jin 2010 Li 2011 Yuan 2011 Chan 2012 Li 2012 Li 2013 Wu 2013 Zhang 2013 Sun 2014 Zhao 2014 Nagpal 2002 Franceschi 2005 Singh 2009 Deodhar 2012 Ghaffari 2006 Esmaeili 2008 Khodakarami 2012 Laskov 2013 Nagai 2000 Sasagawa 2001 Ichimura 2003 Niwa 2003 Tsuda 2003 Yoshida 2004 Inoue 2006 Nishiwaki 2008 Futai 2009 Onuki 2009 Konno 2011 Matsumoto 2011 Takehara 2011 Yamasaki 2011 Azuma 2014 Oh 2001 Cho 2003 Hwang 2003 Kang 2009 Quek 2013 Kahng 2014 Al Awadhi 2011 Quek 2013 34 45 89 1577 153 99 140 156 33 63 518 1577 457 147 72 68 50 46 0 20 40 60 80 100 HPV prevalence (%) N 9 25 20 62 146 38 7 2 32 137 58 22 31 26 33 83 168 73 307 449 917 128 498 42 72 317 73 100 100 12 73 % (95% CI) 66.7 (35.4 87.9) 35.3 (21.5 52.1) 24.4 (14.2 38.7) 25.8 (17.9 35.8) 35.7 (33.4 38.1) 39.9 (32.5 47.8) 36.4 (27.6 46.2) 32.1 (25.0 40.3) 35.3 (28.2 43.0) 15.2 (6.7 30.9) 34.9 (24.3 47.2) 47.5 (43.2 51.8) 35.8 (33.5 38.2) 44.6 (40.1 49.2) 42.9 (35.1 50.9) 59.7 (48.2 70.3) 64.7 (52.8 75.0) 44.0 (31.2 57.7) 63.0 (48.6 75.5) 48.0 (30.0 66.5) 35.0 (18.1 56.7) 45.2 (33.4 57.5) 65.1 (57.0 72.3) 71.4 (35.9 91.8) 63.2 (47.3 76.6) 50.0 (9.5 90.5) 71.9 (54.6 84.4) 37.9 (26.6 50.8) 35.8 (28.2 44.1) 41.9 (26.4 59.2) 36.4 (19.7 57.0) 11.5 (4.0 29.0) 33.3 (19.8 50.4) 33.7 (24.5 44.4) 28.8 (19.7 40.0) 36.9 (30.0 44.4) 22.8 (18.5 27.8) 57.1 (25.0 84.2) 15.4 (9.4 24.2) 28.1 (24.1 32.4) 43.8 (35.5 52.4) 39.8 (35.6 44.1) 40.5 (27.0 55.5) 51.4 (40.1 62.6) 24.7 (16.2 35.6) 39.7 (34.5 45.2) 36.0 (27.3 45.8) 45.0 (35.6 54.8) 33.3 (13.8 60.9) 41.1 (30.5 52.6) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; High-grade lesions: CIN-2, CIN-3, CIS or HSIL; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 106 - Figure 68: Prevalence of HPV 16 among women with High-grade cervical lesions in Asia by country and study (continued) Country Malaysia Myanmar Pakistan Philippines Singapore Taiwan Thailand Turkey Viet Nam Quek 2013 Mu Mu Shwe 2014 Raza 2010 Quek 2013 Quek 2013 Lai 2003 Yang 2004 Ho 2005 Lin 2005 Chao 2008 Chao 2010 Limpaiboon 2000 Suwannarurk 2009 Chansaenroj 2010 Sukasem 2011 Swangvaree 2013 Chansaenroj 2014 Sahiner 2012 Yuce 2012 Baser 2014 Tezcan 2014 Quek 2013 131 97 2 20 57 1086 0 20 40 60 80 100 HPV prevalence (%) N 73 6 2 6 106 21 166 83 355 100 20 292 16 8 123 % (95% CI) 41.1 (30.5 52.6) 50.0 (18.8 81.2) 50.0 (9.5 90.5) 0.0 (0.0 39.0) 39.6 (30.8 49.1) 27.5 (20.6 35.7) 50.0 (9.5 90.5) 18.6 (12.1 27.4) 35.0 (18.1 56.7) 17.5 (9.8 29.4) 24.1 (21.7 26.8) 33.3 (17.2 54.6) 33.3 (6.1 79.2) 25.0 (7.1 59.1) 33.7 (27.0 41.2) 12.4 (9.4 16.2) 27.0 (19.3 36.4) 60.0 (38.7 78.1) 25.0 (10.2 49.5) 25.3 (20.7 30.6) 25.0 (7.1 59.1) 34.1 (26.4 42.9) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; High-grade lesions: CIN-2, CIN-3, CIS or HSIL; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 107 - Figure 69: Prevalence of HPV 16 among women with High-grade cervical lesions in Europe by country and study Austria Belarus Belgium Croatia Czech Rep. Denmark Europe France Germany Greece Hungary Iceland Ireland Italy Latvia Country Rössler 2013 Kulmala 2007 Baay 2001 Depuydt 2003 Beerens 2005 Arbyn 2009 Grce 2001 Grce 2004 Tachezy 2011 Sebbelov 1994 Hording 1995 Kjaer 2008 Kirschner 2013 Kjær 2014 Tjalma 2013 Monsonego 2008 Prétet 2008 Vaucel 2011 Heard 2013 Nindl 1997 Merkelbach Bruse 1999 Nindl 1999 Meyer 2001 Klug 2007 de Jonge 2013 Labropoulou 1997 Paraskevaidis 2001 Agorastos 2005 Daponte 2006 Kroupis 2007 Panotopoulou 2007 Tsiodras 2011 Szoke 2003 Sigurdsson 2007 O'Leary 1998 Butler 2000 Murphy 2003 Keegan 2014 Laconi 2000 Zerbini 2001 Tornesello 2006 Gargiulo 2007 Capra 2008 Venturoli 2008 Agarossi 2009 Sandri 2009 Carozzi 2010 Giorgi Rossi 2010 Spinillo 2014 Kulmala 2007 N 204 91 97 134 123 109 783 158 311 34 30 177 225 670 3103 54 493 141 897 85 288 65 88 46 247 50 28 43 29 54 60 26 75 441 20 27 64 111 36 89 65 67 56 14 73 529 76 812 8 91 % (95% CI) 55.9 (49.0 62.5) 56.0 (45.8 65.8) 56.7 (46.8 66.1) 50.0 (41.7 58.3) 43.1 (34.7 51.9) 34.9 (26.6 44.2) 17.1 (14.6 19.9) 20.3 (14.7 27.2) 58.2 (52.7 63.5) 85.3 (69.9 93.6) 50.0 (33.2 66.8) 48.0 (40.8 55.3) 46.2 (39.8 52.7) 49.0 (45.2 52.7) 47.2 (45.5 49.0) 33.3 (22.2 46.6) 62.3 (57.9 66.4) 42.6 (34.7 50.8) 49.2 (45.9 52.4) 36.5 (27.0 47.1) 61.4 (50.9 70.9) 56.9 (44.8 68.2) 46.2 (40.5 52.0) 54.3 (40.2 67.8) 34.4 (28.8 40.5) 36.0 (24.1 49.9) 35.7 (20.7 54.2) 58.1 (43.3 71.6) 51.7 (34.4 68.6) 50.0 (32.1 67.9) 36.7 (25.6 49.3) 50.0 (37.1 62.9) 57.3 (46.1 67.9) 51.2 (46.6 55.9) 95.0 (76.4 99.1) 70.4 (51.5 84.1) 78.1 (66.6 86.5) 75.7 (66.9 82.7) 50.0 (34.5 65.5) 50.6 (40.4 60.7) 47.7 (36.0 59.6) 38.8 (28.0 50.8) 42.9 (21.4 67.4) 60.7 (47.6 72.4) 53.4 (42.1 64.4) 73.7 (62.8 82.3) 62.9 (58.8 67.0) 37.5 (13.7 69.4) 45.9 (42.5 49.4) 56.0 (45.8 65.8) 0 20 40 60 80 100 HPV prevalence (%) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; High-grade lesions: CIN-2, CIN-3, CIS or HSIL; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 108 - Figure 70: Prevalence of HPV 16 among women with High-grade cervical lesions in Europe by country and study (continued) Latvia Lithuania Netherlands Norway Portugal Romania Russia Slovenia Spain Sweden Switzerland UK Country Kulmala 2007 Gudleviciene 2005 Cornelissen 1992 Reesink Peters 2001 van Duin 2003 Bulkmans 2005 Prinsen 2007 Tang 2009 Kraus 2004 Molden 2005 Roberts 2006 Sjoeborg 2010 Medeiros 2005 Nobre 2010 Pista 2011 Pista 2013 Beca 2014 Anton 2011 Ursu 2011 Moga 2014 Kulmala 2007 Kovanda 2009 Ucakar 2012 Muñoz 1992 Bosch 1993 Conesa Zamora 2009 García Sierra 2009 de Méndez 2009 de Oña 2010 Martín 2011 Herraez Hernandez 2013 Zehbe 1996 Kalantari 1997 Andersson 2005 Dobec 2011 Arends 1993 Cuzick 1994 Herrington 1995 Southern 1998 Cuschieri 2004 Hibbitts 2008 Sargent 2008 Jamison 2009 Howell Jones 2010 Anderson 2013 N 91 29 216 89 236 20 253 41 885 25 67 630 132 34 191 518 176 52 35 41 91 261 43 157 157 25 39 306 4 82 68 103 164 116 33 40 38 73 26 562 93 94 1425 51 72 % (95% CI) 56.0 (45.8 65.8) 48.3 (31.4 65.6) 52.8 (42.5 62.8) 56.9 (50.3 63.4) 65.0 (43.3 81.9) 60.6 (54.2 66.6) 51.2 (36.5 65.7) 70.8 (64.9 76.0) 49.3 (37.7 60.9) 28.0 (14.3 47.6) 44.1 (40.8 47.4) 20.6 (17.7 24.0) 74.2 (66.2 80.9) 32.4 (19.1 49.2) 27.7 (21.9 34.5) 55.6 (51.3 59.8) 48.9 (41.6 56.2) 48.1 (35.1 61.3) 31.7 (19.6 47.0) 31.4 (18.6 48.0) 56.0 (45.8 65.8) 62.5 (56.4 68.1) 41.9 (28.4 56.7) 51.0 (43.2 58.7) 49.0 (41.3 56.8) 33.3 (20.6 49.0) 36.0 (20.2 55.5) 75.0 (30.1 95.4) 28.8 (24.0 34.1) 48.8 (38.3 59.4) 69.1 (57.4 78.8) 50.5 (41.0 59.9) 35.4 (28.5 42.9) 37.1 (28.8 46.1) 57.6 (40.8 72.8) 50.0 (35.2 64.8) 63.0 (51.5 73.2) 57.9 (42.2 72.1) 61.5 (42.5 77.6) 48.9 (39.1 58.9) 40.9 (31.4 51.0) 46.8 (42.7 50.9) 49.0 (35.9 62.3) 54.1 (51.5 56.7) 56.9 (45.4 67.7) 0 20 40 60 80 100 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; High-grade lesions: CIN-2, CIN-3, CIS or HSIL; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 109 - Figure 71: Prevalence of HPV 16 among women with High-grade cervical lesions in Oceania by country and study Country Australia Brestovac 2005 Stevens 2006 Stevens 2009 Garland 2011 N 48 302 533 47 33.3 37.1 51.4 51.1 % (95% CI) (21.7 47.5) (31.8 42.7) (47.2 55.6) (37.2 64.7) Fiji Tabrizi 2011 112 64.3 (55.1 72.6) New Zealand Simonella 2013 375 51.2 (46.2 56.2) 0 20 40 60 80 100 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; High-grade lesions: CIN-2, CIN-3, CIS or HSIL; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 110 - Figure 72: Prevalence of HPV 16 among women with invasive cervical cancer in Africa by country and study Country Africa Algeria Benin Botswana Ethiopia Ghana Guinea Kenya Mali Morocco Mozambique Nigeria Senegal South Africa Sudan Tanzania Uganda Zimbabwe de Sanjose 2010 Bosch 1995 Hammouda 2005 Bosch 1995 Ermel 2014 Fanta 2005 Abate 2013 Denny 2014 Bosch 1995 Keita 2009 De Vuyst 2008 Bosch 1995 Bayo 2002 Chaouki 1998 El khair 2010 Naucler 2004 Denny 2014 Lin 2001 Xi 2003 Williamson 1994 Pegoraro 2002 Kay 2003 Denny 2014 Abate 2013 ter Meulen 1992 Bosch 1995 Bosch 1995 Odida 2008 Stanczuk 2003 0 20 40 60 80 100 HPV prevalence (%) N 667 171 12 6 117 163 136 121 66 18 153 58 65 152 113 72 145 20 51 67 190 50 181 84 53 49 112 42 98 % (95% CI) 38.4 (34.8 42.1) 33.3 (13.8 60.9) 61.4 (53.9 68.4) 50.0 (18.8 81.2) 32.5 (24.7 41.4) 71.8 (64.4 78.1) 86.0 (79.2 90.9) 55.4 (46.5 63.9) 38.9 (20.3 61.4) 42.4 (31.2 54.4) 43.8 (36.2 51.7) 34.5 (23.6 47.3) 47.7 (36.0 59.6) 58.6 (50.6 66.1) 56.6 (47.4 65.4) 55.6 (44.1 66.5) 52.4 (44.3 60.4) 37.3 (25.3 51.0) 35.0 (18.1 56.7) 44.8 (33.5 56.6) 46.8 (39.9 53.9) 82.0 (69.2 90.2) 47.5 (40.4 54.8) 77.4 (67.4 85.0) 37.7 (25.9 51.2) 44.9 (31.9 58.7) 52.4 (37.7 66.6) 48.2 (39.2 57.4) 61.2 (51.3 70.3) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Includes cases from Algeria, Mozambique, Nigeria, and Uganda Data sources: See references in Section 9.

- 111 - Figure 73: Prevalence of HPV 16 among women with invasive cervical cancer in Americas by country and study (continued) Country Argentina Bolivia Brazil Canada Chile Colombia Costa Rica Cuba Greenland Honduras Jamaica Mexico Nicaragua Panama Paraguay Peru Suriname Trinidad & Tob. USA Bosch 1995 Turazza 1997 Alonio 2003 Golijow 2005 Bosch 1995 Eluf Neto 1994 Bosch 1995 Lorenzato 2000 Rabelo Santos 2003 Cambruzzi 2005 Rabelo Santos 2009 Tomita 2010 de Oliveira 2013 Serrano 2014 Bosch 1995 Duggan 1995 Tran Thanh 2003 Bosch 1995 Roa 2009 Valdivia 2010 Muñoz 1992 Bosch 1995 Moreno Acosta 2008 Murillo 2009 Herrero 2005 Bosch 1995 Sebbelov 2000 Ferreira 2008 Strickler 1999 Meyer 1998 Torroella Kouri 1998 González Losa 2004 Piña Sánchez 2006 Alarcón Romero 2009 Illades Aguiar 2009 Serrano 2014 Hindryckx 2006 Bosch 1995 Rolón 2000 Kasamatsu 2012 Santos 2001 Martorell 2012 De Boer 2005 Hosein 2013 Burnett 1992 Bosch 1995 Burger 1996 Ferguson 1998 Bryan 2006 Guo 2007 N 139 57 39 35 47 186 46 229 53 59 109 13 172 526 45 50 76 293 80 90 111 217 59 38 35 45 32 104 14 60 66 108 15 133 15 545 19 71 113 417 196 53 116 85 20 393 11 24 27 29 % (95% CI) 59.6 (46.7 71.4) 61.9 (53.6 69.5) 56.4 (41.0 70.7) 68.6 (52.0 81.4) 34.0 (22.2 48.3) 58.6 (51.4 65.4) 52.2 (38.1 65.9) 59.3 (46.6 70.9) 56.6 (43.3 69.0) 27.1 (21.7 33.2) 53.8 (29.1 76.8) 58.7 (49.3 67.5) 76.7 (69.9 82.4) 51.7 (47.4 56.0) 60.0 (45.5 73.0) 35.5 (25.7 46.7) 54.0 (40.4 67.0) 45.0 (34.6 55.9) 76.8 (71.6 81.3) 61.1 (50.8 70.5) 54.1 (44.8 63.0) 52.6 (37.3 67.5) 57.6 (44.9 69.4) 51.2 (44.5 57.7) 45.7 (30.5 61.8) 57.8 (43.3 71.0) 81.3 (64.7 91.1) 43.3 (34.2 52.9) 21.4 (7.6 47.6) 43.3 (31.6 55.9) 43.9 (32.6 55.9) 26.7 (10.9 52.0) 72.2 (63.1 79.8) 66.7 (41.7 84.8) 66.9 (58.5 74.3) 47.9 (43.7 52.1) 52.6 (31.7 72.7) 46.5 (35.4 58.0) 59.3 (50.1 67.9) 48.0 (43.2 52.8) 56.1 (49.1 62.9) 50.9 (37.9 63.9) 35.3 (27.2 44.4) 43.5 (33.5 54.1) 70.0 (48.1 85.5) 54.5 (28.0 78.7) 51.4 (46.5 56.3) 25.9 (13.2 44.7) 58.3 (38.8 75.5) 69.0 (50.8 82.7) 0 20 40 60 80 100 HPV prevalence (%) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). (Continued on next page)

- 112 - ( Figure 81 continued from previous page) 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 113 - Figure 74: Prevalence of HPV 16 among women with invasive cervical cancer in Americas by country and study (continued) Country N % (95% CI) Uruguay Berois 2013 176 67.6 (60.4 74.1) USA Resnick 1990 33 75.8 (59.0 87.2) Paquette 1993 45 48.9 (35.0 63.0) Wistuba 1997 20 60.0 (38.7 78.1) Pirog 2000 82 36.6 (27.0 47.4) Sebbelov 2000 53 77.4 (64.5 86.5) Schwartz 2001 452 59.1 (54.5 63.5) Guo 2007 29 69.0 (50.8 82.7) Zuna 2007 93 55.9 (45.8 65.6) Patel 2009 77 59.7 (48.6 70.0) Quint 2009 40 60.0 (44.6 73.7) Wentzensen 2009 107 55.1 (45.7 64.2) Wheeler 2009 808 53.2 (49.8 56.6) de Sanjose 2010 173 65.3 (58.0 72.0) Hariri 2012 93 53.8 (43.7 63.5) Hopenhayn 2014 777 50.8 (47.3 54.3) Venezuela Sánchez Lander 2012 96 67.7 (57.8 76.2) 0 20 40 60 80 100 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 114 - Figure 75: Prevalence of HPV 16 among women with invasive cervical cancer in Asia by country and study (continued) Country Asia China Georgia India Indonesia Iran de Sanjose 2010 Peng 1991 Huang 1997 Lin 1998 Stephen 2000 Lo 2001 Lo 2002 Gao 2003 Yu 2003 Liu 2004 Liu 2005 Tao 2006 Qiu 2007 Cai 2008 Hong 2008 Liu 2008 Wu 2008 Wu 2008 Zhao 2008 Cai 2009 Chan 2009 Chen 2009 Shah 2009 Wu 2009 Liu 2010 Yuan 2011 Chan 2012 Li 2013 Alibegashvili 2011 Munirajan 1998 Nair 1999 Nagpal 2002 Franceschi 2003 Sowjanya 2005 Bhatla 2006 Peedicayil 2006 Neyaz 2008 Basu 2009 Gheit 2009 Munagala 2009 Nambaru 2009 Peedicayil 2009 Deodhar 2012 Bosch 1995 Schellekens 2004 De Boer 2005 Tobing 2014 Ghaffari 2006 Esmaeili 2008 Haghshenas 2013 0 20 40 60 80 100 HPV prevalence (%) N 940 101 40 77 121 31 809 106 50 65 50 27 145 110 181 96 190 300 100 112 435 630 108 134 77 198 444 78 91 43 110 191 71 106 41 119 273 60 180 121 43 113 28 47 40 74 74 70 7 67 % (95% CI) 58.0 (54.8 61.1) 31.7 (23.4 41.3) 27.5 (16.1 42.8) 48.1 (37.3 59.0) 58.1 (40.8 73.6) 48.8 (40.0 57.6) 66.9 (63.6 70.0) 40.0 (29.0 52.1) 70.0 (56.2 80.9) 50.0 (40.6 59.4) 66.0 (52.2 77.6) 55.6 (37.3 72.4) 78.6 (71.3 84.5) 81.8 (73.6 87.9) 65.2 (58.0 71.8) 45.8 (36.2 55.8) 73.7 (67.0 79.4) 68.7 (63.2 73.7) 52.0 (42.3 61.5) 81.3 (73.0 87.4) 56.1 (51.4 60.7) 76.7 (73.2 79.8) 66.7 (57.3 74.8) 83.1 (73.2 89.9) 73.1 (65.1 79.9) 65.2 (58.3 71.4) 59.0 (54.4 63.5) 53.8 (42.9 64.5) 58.2 (48.0 67.8) 53.5 (38.9 67.5) 69.1 (59.9 77.0) 60.6 (48.9 71.1) 62.8 (55.8 69.4) 58.5 (43.4 72.2) 73.6 (64.5 81.0) 60.5 (51.5 68.8) 86.7 (75.8 93.1) 65.9 (60.1 71.3) 81.7 (75.4 86.6) 65.1 (50.2 77.6) 72.7 (64.2 79.9) 78.6 (60.5 89.8) 76.1 (67.5 83.0) 31.9 (20.4 46.2) 41.9 (31.3 53.3) 33.8 (24.0 45.1) 90.0 (76.9 96.0) 85.7 (48.7 97.4) 54.3 (42.7 65.4) 28.4 (19.0 40.1) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Includes cases from Bangladesh, India, Israel, Kuwait, Lebanon and Turkey Data sources: See references in Section 9.

- 115 - Figure 76: Prevalence of HPV 16 among women with invasive cervical cancer in Asia by country and study (continued) Country Iran Israel Japan Jordan Korea, Rep. Malaysia Yadav 1995 Cheah 2008 Sharifah 2009 Quek 2013 Hamzi Abdul Raub 2014 Mongolia Nepal Pakistan Hamkar 2002 Mortazavi 2002 Khodakarami 2012 Haghshenas 2013 Laskov 2013 Fujinaga 1991 Maki 1991 Kashiwabara 1992 Yamakawa 1994 Nawa 1995 Nakagawa 1996 Saito 2000 Ishikawa 2001 Sasagawa 2001 Harima 2002 Nakagawa 2002 Tsuda 2003 Asato 2004 Kanao 2004 Yoshida 2004 Maehama 2005 Inoue 2006 Futai 2009 Onuki 2009 Yoshida 2009 Takehara 2011 Watari 2011 Yamasaki 2011 Imajoh 2012 Azuma 2014 Sughayer 2010 Kim 1995 Hwang 1999 An 2003 Cho 2003 Hwang 2003 An 2005 Lee 2007 Song 2007 Tong 2007 Kim 2009 Park 2013 Quek 2013 Chimeddorj 2008 Sherpa 2010 Khan 2007 N 42 69 45 67 38 39 29 64 91 23 146 84 52 66 84 356 53 28 25 383 15 86 12 140 105 20 60 64 71 147 41 30 40 50 135 72 49 160 169 97 29 196 97 23 101 13 11 280 147 61 60 % (95% CI) 28.6 (17.2 43.6) 73.9 (62.5 82.8) 60.0 (45.5 73.0) 28.4 (19.0 40.1) 60.5 (44.7 74.4) 48.7 (33.9 63.8) 44.8 (28.4 62.5) 42.9 (33.2 53.1) 32.8 (22.6 45.0) 73.9 (53.5 87.5) 37.7 (30.2 45.8) 34.8 (24.5 46.9) 53.8 (40.5 66.7) 42.9 (32.8 53.5) 26.2 (18.0 36.5) 39.3 (23.6 57.6) 28.3 (18.0 41.6) 37.1 (32.2 42.2) 32.0 (17.2 51.6) 33.3 (15.2 58.3) 29.0 (24.7 33.7) 33.3 (13.8 60.9) 48.8 (38.6 59.2) 37.9 (30.2 46.1) 35.0 (18.1 56.7) 41.9 (32.9 51.5) 83.3 (72.0 90.7) 42.3 (31.5 53.8) 12.5 (6.5 22.8) 48.3 (40.4 56.3) 68.3 (53.0 80.4) 53.3 (36.1 69.8) 37.5 (24.2 53.0) 64.0 (50.1 75.9) 61.2 (47.2 73.6) 52.8 (41.4 63.9) 44.4 (36.3 52.9) 51.9 (44.2 59.5) 65.5 (47.3 80.1) 51.5 (41.7 61.2) 65.7 (58.2 72.4) 39.8 (33.2 46.8) 58.8 (48.8 68.0) 73.9 (53.5 87.5) 72.7 (43.4 90.3) 15.4 (4.3 42.2) 36.6 (27.9 46.4) 57.5 (51.6 63.2) 48.3 (40.4 56.3) 60.7 (48.1 71.9) 95.0 (86.3 98.3) 0 20 40 60 80 100 HPV prevalence (%) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Includes cases from Bangladesh, India, Israel, Kuwait, Lebanon and Turkey Data sources: See references in Section 9.

- 116 - Figure 77: Prevalence of HPV 16 among women with invasive cervical cancer in Asia by country and study (continued) Country Pakistan Philippines Saudi Arabia Singapore Sri LankaSamarawickrema 2011 Karunaratne 2014 Syria Taiwan Thailand Bosch 1995 Bhattarakosol 1996 Siritantikorn 1997 Chichareon 1998 Settheetham Ishida 2005 Siriaunkgul 2008 Chopjitt 2009 Chinchai 2012 Natphopsuk 2013 Siriaunkgul 2013 Chansaenroj 2014 Turkey Viet Nam Khan 2007 Raza 2010 Bosch 1995 Ngelangel 1998 Quek 2013 Al Badawi 2011 Alsbeih 2011 Alsbeih 2013 Quek 2013 Darnel 2010 Chen 1993 Chen 1994 Yang 1997 Lai 1999 Huang 2004 Huang 2004 Yang 2004 Ho 2005 Lin 2005 Lai 2007 Su 2007 Ding 2008 Chao 2009 Ozgul 2008 Usubütün 2009 Quek 2013 N 60 91 24 356 103 100 90 100 65 108 98 44 430 43 134 93 149 152 25 2106 28 81 137 263 25 100 27 377 23 90 155 40 99 198 150 416 260 23 134 % (95% CI) 95.0 (86.3 98.3) 75.8 (66.1 83.5) 45.8 (27.9 64.9) 38.8 (33.8 43.9) 31.1 (22.9 40.5) 63.3 (53.0 72.6) 67.0 (57.3 75.4) 64.0 (54.2 72.7) 36.9 (26.2 49.1) 77.8 (69.1 84.6) 68.4 (58.6 76.7) 47.7 (33.8 62.1) 46.5 (32.5 61.1) 46.0 (41.4 50.8) 64.2 (55.8 71.8) 51.6 (41.6 61.5) 98.7 (95.2 99.6) 65.8 (57.9 72.9) 36.0 (20.2 55.5) 30.9 (21.9 41.6) 53.6 (35.8 70.5) 50.3 (48.2 52.4) 58.4 (50.0 66.3) 43.7 (37.9 49.8) 72.0 (52.4 85.7) 59.3 (40.7 75.5) 35.0 (26.4 44.7) 56.5 (36.8 74.4) 54.6 (49.6 59.6) 61.1 (50.8 70.5) 77.8 (68.6 84.8) 75.0 (59.8 85.8) 51.0 (43.2 58.7) 48.0 (41.1 54.9) 29.3 (22.6 37.1) 51.0 (46.2 55.7) 52.2 (33.0 70.8) 55.4 (49.3 61.3) 48.5 (40.2 56.9) 0 20 40 60 80 100 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Includes cases from Bangladesh, India, Israel, Kuwait, Lebanon and Turkey Data sources: See references in Section 9.

- 117 - Figure 78: Prevalence of HPV 16 among women with invasive cervical cancer in Europe by country and study (continued) Country Austria Belarus Belgium Bulgaria Croatia Czech Rep. Denmark Europe Finland France Germany Greece Hungary Iceland Ireland Italy Bachtiary 2002 Widschwendter 2003 Kulmala 2007 Baay 2001 Beerens 2005 Todorova 2010 Hadzisejdic 2006 Dabic 2008 Tachezy 1999 Slama 2009 Tachezy 2011 Hording 1997 Sebbelov 2000 Kjaer 2008 Kirschner 2013 Kjær 2014 de Sanjose 2010 Tjalma 2013 Iwasawa 1996 Riou 1990 Lombard 1998 Prétet 2008 de Cremoux 2009 Heard 2013 Bosch 1995 Milde Langosch 1995 Klug 2007 Koffa 1994 Labropoulou 1997 Dokianakis 1999 Daponte 2006 Panotopoulou 2007 Adamopoulou 2009 Kónya 1995 Sigurdsson 2007 O'Leary 1998 Skyldberg 1999 Butler 2000 Fay 2009 Garzetti 1998 Ciotti 2006 Del Mistro 2006 Tornesello 2006 Gargiulo 2007 Lillo 2008 Rolla 2009 Sideri 2009 Carozzi 2010 Tornesello 2011 Spinillo 2014 N 106 94 26 111 9 127 66 51 49 49 86 50 34 245 6 27 2302 2881 460 106 297 516 515 50 51 17 1 39 35 77 165 9 17 44 140 20 38 29 10 102 32 45 65 13 31 268 18 193 171 88 65.1 (55.6 73.5) 75.5 (66.0 83.1) 65.4 (46.2 80.6) 68.5 (59.3 76.4) 33.3 (12.1 64.6) 70.9 (62.4 78.1) 30.3 (20.6 42.2) 62.7 (49.0 74.7) 59.2 (45.2 71.8) 61.2 (47.2 73.6) 73.3 (63.1 81.5) 18.0 (9.8 30.8) 70.6 (53.8 83.2) 33.3 (9.7 70.0) 60.8 (54.6 66.7) 40.7 (24.5 59.3) 57.4 (55.4 59.4) 55.9 (54.1 57.7) 63.5 (59.0 67.7) 54.7 (45.2 63.9) 50.5 (44.8 56.1) 72.9 (68.9 76.5) 55.5 (51.2 59.8) 54.0 (40.4 67.0) 76.5 51.0 100.0 35.9 54.3 2.6 100.0 24.2 47.1 % (95% CI) (52.7 90.4) (37.7 64.1) (20.7 100.0) (22.7 51.6) (38.2 69.5) (0.7 9.0) (70.1 100.0) (18.3 31.3) (26.2 69.0) 56.8 (42.2 70.3) 57.1 (48.9 65.0) 80.0 (58.4 91.9) 23.7 (13.0 39.2) 93.1 (78.0 98.1) 80.0 (49.0 94.3) 50.0 (33.6 66.4) 57.8 (48.1 67.0) 71.1 (56.6 82.3) 60.0 (47.9 71.0) 61.3 (43.8 76.3) 61.5 (35.5 82.3) 66.7 (43.7 83.7) 63.4 (57.5 69.0) 67.9 (61.0 74.1) 58.5 (51.0 65.6) 54.5 (44.2 64.5) 0 20 40 60 80 100 HPV prevalence (%) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. (Continued on next page)

- 118 - ( Figure 81 continued from previous page) a Includes cases from Bosnia-Herzegovina, Croatia, Czech Republic, France, Greece, Italy, Netherlands, Poland, Portugal, and Spain Data sources: See references in Section 9.

- 119 - Figure 79: Prevalence of HPV 16 among women with invasive cervical cancer in Europe by country and study (continued) Country Italy Latvia Lithuania Luxembourg Netherlands Norway Poland Portugal Russia Slovenia Spain Sweden UK Voglino 2000 Venturoli 2008 Tornesello 2011 Silins 2004 Kulmala 2007 Gudleviciene 2005 Ressler 2007 Resnick 1990 Van Den Brule 1991 Baay 1996 Krul 1999 Zielinski 2003 Bulkmans 2005 De Boer 2005 Bulk 2006 Tang 2009 Baalbergen 2013 Karlsen 1996 Bertelsen 2006 Bosch 1995 Pirog 2000 Dybikowska 2002 Bardin 2008 Baay 2009 Kwasniewska 2009 Biesaga 2012 Medeiros 2005 Nobre 2010 Pista 2013 Kleter 1999 Kulmala 2007 Jancar 2009 Muñoz 1992 Bosch 1995 Rodriguez 1998 González Bosquet 2008 Darwich 2011 Martró 2012 Mazarico 2012 Hagmar 1992 Zehbe 1997 Skyldberg 1999 Wallin 1999 Andersson 2001 Andersson 2003 Graflund 2004 Andersson 2005 Du 2011 Crook 1992 Arends 1993 Cuschieri 2010 N 145 171 6 221 26 191 58 162 50 33 128 77 105 8 153 340 113 361 89 23 82 113 88 53 570 85 44 60 64 180 26 264 159 54 46 72 21 37 73 45 71 38 104 131 82 110 45 154 363 47 28 % (95% CI) 71.0 (63.2 77.8) 50.0 (18.8 81.2) 58.5 (51.0 65.6) 60.6 (54.1 66.8) 65.4 (46.2 80.6) 56.5 (49.5 63.4) 79.3 (67.2 87.7) 75.8 (59.0 87.2) 84.0 (71.5 91.7) 61.7 (54.1 68.9) 58.6 (49.9 66.8) 32.5 (23.1 43.5) 62.5 (30.6 86.3) 43.8 (34.7 53.4) 54.2 (46.3 61.9) 63.5 (58.3 68.5) 32.7 (24.8 41.8) 68.4 (63.5 73.0) 52.8 (42.5 62.8) 78.3 (58.1 90.3) 36.6 (27.0 47.4) 47.2 (34.4 60.3) 73.9 (63.8 81.9) 85.8 (78.2 91.1) 58.4 (54.3 62.4) 80.0 (70.3 87.1) 80.0 (68.2 88.2) 61.4 (46.6 74.3) 70.3 (58.2 80.1) 64.4 (57.2 71.1) 65.4 (46.2 80.6) 65.2 (59.2 70.6) 54.1 (46.3 61.6) 54.3 (40.2 67.8) 61.1 (47.8 73.0) 52.4 (32.4 71.7) 79.2 (68.4 86.9) 47.9 (36.9 59.2) 43.2 (28.7 59.1) 38.0 (27.6 49.7) 53.3 (39.1 67.1) 23.7 (13.0 39.2) 47.1 (37.8 56.6) 23.7 (17.2 31.6) 34.1 (24.8 44.9) 79.1 (70.6 85.6) 66.7 (52.1 78.6) 58.4 (50.5 65.9) 71.4 (52.9 84.7) 53.2 (39.2 66.7) 56.5 (51.3 61.5) 0 20 40 60 80 100 HPV prevalence (%) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Includes cases from Bosnia-Herzegovina, Croatia, Czech Republic, France, Greece, Italy, Netherlands, Poland, Portugal, and Spain Data sources: See references in Section 9.

- 120 - Figure 80: Prevalence of HPV 16 among women with invasive cervical cancer in Europe by country and study (continued) Country UK Giannoudis 1999 N 43 % (95% CI) 81.4 (67.4 90.3) Cuzick 2000 116 65.5 (56.5 73.5) Tawfik El Mansi 2006 119 46.2 (37.5 55.2) Sargent 2008 9 33.3 (12.1 64.6) Powell 2009 269 67.7 (61.9 73.0) Cuschieri 2010 363 56.5 (51.3 61.5) Howell Jones 2010 555 62.5 (58.4 66.5) 0 20 40 60 80 100 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. a Includes cases from Bosnia-Herzegovina, Croatia, Czech Republic, France, Greece, Italy, Netherlands, Poland, Portugal, and Spain Data sources: See references in Section 9.

- 121 - Figure 81: Prevalence of HPV 16 among women with invasive cervical cancer in Oceania by country and study Country Australia Thompson 1994 N 103 % (95% CI) 65.0 (55.5 73.6) Chen 1999 170 55.9 (48.4 63.1) Plunkett 2003 50 28.0 (17.5 41.7) Liu 2004 79 64.6 (53.6 74.2) Brestovac 2005 32 68.8 (51.4 82.0) Stevens 2006 191 52.9 (45.8 59.8) de Sanjose 2010 160 60.0 (52.3 67.3) Papua N. Guinea Tabone 2012 70 57.1 (45.5 68.1) 0 20 40 60 80 100 HPV prevalence (%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; N: number of women tested; The samples for HPV testing come from cervical specimens (fresh/fixed biopsies or exfoliated cells). The small triangle points HPV prevalence, the line represents the 95% confidence interval and the shadowed square is proportional to the sample size. Data sources: See references in Section 9.

- 122 - Figure 82: Ten most frequent HPV oncogenic types among women with and without cervical lesions in World compared to developing and developed regions World Less developed regions More developed regions Normal cytology HPV type 16 52 53 31 51 18 58 66 39 70 2.8 1.5 1.2 1.2 1.1 1.1 1.0 0.9 0.9 0.8 16 52 58 18 53 33 31 70 68 51 2.6 1.8 1.4 1.2 1.0 0.9 0.8 0.7 0.7 0.7 16 53 52 51 31 66 39 18 70 58 2.8 1.4 1.3 1.3 1.3 1.0 1.0 1.0 0.8 0.8 Low grade lesions HPV type 16 51 52 31 53 56 66 58 18 39 19.1 10.2 8.7 7.8 7.7 7.6 6.7 6.4 6.4 6.1 16 52 58 18 33 51 66 53 56 31 18.3 9.8 8.6 6.2 5.3 4.9 4.5 4.4 4.0 3.8 16 51 53 31 56 52 66 39 18 58 19.4 11.8 9.1 9.0 8.7 8.3 7.4 7.0 6.5 5.7 High grade lesions HPV type 16 52 31 58 33 18 51 35 53 39 10.8 9.9 8.4 7.4 6.9 5.8 3.5 3.4 3.1 44.6 16 52 58 18 33 31 51 53 35 45 13.5 12.6 7.3 6.5 6.3 4.2 2.8 2.6 2.6 38.8 16 31 52 33 58 18 51 35 39 53 11.7 10.6 7.6 7.3 7.1 7.0 4.0 3.9 3.7 46.5 Cervical Cancer HPV type 16 18 45 33 58 31 52 35 39 59 14.6 4.8 4.2 3.8 3.5 3.4 1.6 1.4 1.1 55.4 16 18 45 58 33 52 31 35 39 59 14.9 5.4 4.6 3.9 3.8 3.4 1.9 1.4 1.4 57.0 16 18 33 58 45 31 52 35 39 56 16.2 4.8 4.0 3.9 3.7 3.3 1.5 1.4 0.9 55.3 0 20 40 60 Prevalence (%) 0 20 40 60 Prevalence (%) 0 20 40 60 Prevalence (%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). Low-grade lesions: LSIL or CIN-1; High-grade lesions: CIN-2, CIN-3, CIS or HSIL; The samples for HPV testing come from cervical specimens (fresh / fixed biopsies or exfoliated cells). Data sources: See references in Section 9.

- 123 - Figure 83: Ten most frequent HPV types among women with invasive cervical cancer by histology in the World compared to developing and developed regions World Less developed regions More developed regions Any Histology HPV type 16 18 45 33 58 31 52 35 39 59 14.6 4.8 4.2 3.8 3.5 3.4 1.6 1.4 1.1 55.4 16 18 45 58 33 52 31 35 39 59 14.9 5.4 4.6 3.9 3.8 3.4 1.9 1.4 1.4 57.0 16 18 33 58 45 31 52 35 39 56 16.2 4.8 4.0 3.9 3.7 3.3 1.5 1.4 0.9 55.3 Squamous cell carcinoma HPV type 16 18 45 33 58 31 52 35 39 59 11.2 4.6 4.5 3.9 3.7 3.6 1.6 1.5 1.1 57.5 16 18 45 58 33 52 31 35 39 59 12.3 5.3 4.4 3.9 3.9 3.4 1.9 1.4 1.2 58.3 16 18 33 58 52 31 45 39 35 56 11.7 5.3 4.7 3.8 3.8 3.6 1.6 1.4 1.1 58.7 Adenocarcinoma HPV type 18 16 45 31 33 58 52 39 51 59 5.7 1.9 1.8 1.2 1.2 0.9 0.7 0.6 36.2 35.9 18 16 45 33 31 52 58 59 56 39 5.4 2.1 1.7 1.7 1.4 1.2 1.0 0.8 38.9 35.9 18 16 45 31 33 58 52 39 51 35 5.3 2.3 1.9 1.4 1.3 1.1 0.9 0.6 37.9 36.9 Unespecified HPV type 16 18 45 33 58 31 52 35 59 39 13.6 5.1 4.9 4.8 4.0 3.5 2.4 1.8 1.5 59.0 16 18 58 45 33 52 31 35 59 39 12.9 6.3 5.7 4.4 4.1 3.8 2.5 2.1 1.3 60.6 16 18 33 45 31 58 52 35 73 39 14.4 5.4 4.3 4.2 3.0 2.8 2.2 1.9 1.8 57.1 0 20 40 60 Prevalence (%) 0 20 40 60 Prevalence (%) 0 20 40 60 Prevalence (%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). The samples for HPV testing come from cervical specimens (fresh / fixed biopsies or exfoliated cells). Data sources: See references in Section 9.

- 124 - Table 14: Type-specific HPV prevalence in women with normal cytology, precancerous cervical lesions and invasive cervical cancer in the World Normal cytology Low-grade lesions High-grade lesions Cervical cancer HPV Type No. HPV Prev No. HPV Prev No. HPV Prev No. HPV Prev tested % (95% CI) tested % (95% CI) tested % (95% CI) tested % (95% CI) ONCOGENIC HPV TYPES 16 453,184 2.8 (2.8-2.9) 43,142 19.1 (18.8-19.5) 44,566 44.6 (44.1-45.0) 53,309 55.4 (55.0-55.8) 18 440,810 1.1 (1.1-1.1) 42,660 6.4 (6.2-6.7) 43,933 6.9 (6.6-7.1) 52,798 14.6 (14.3-14.9) 31 415,367 1.2 (1.2-1.2) 40,889 7.8 (7.6-8.1) 42,815 9.9 (9.7-10.2) 46,340 3.5 (3.4-3.7) 33 413,075 0.7 (0.7-0.7) 40,390 4.3 (4.1-4.5) 42,709 7.4 (7.1-7.6) 47,673 4.2 (4.1-4.4) 35 396,307 0.5 (0.5-0.5) 35,871 3.3 (3.1-3.5) 39,291 3.5 (3.3-3.7) 43,022 1.6 (1.5-1.8) 39 389,537 0.9 (0.8-0.9) 33,623 6.1 (5.9-6.4) 38,041 3.1 (3.0-3.3) 40,312 1.4 (1.3-1.5) 45 394,993 0.7 (0.7-0.7) 35,926 3.3 (3.1-3.5) 39,420 3.0 (2.8-3.2) 42,447 4.8 (4.6-5.0) 51 387,242 1.1 (1.1-1.1) 31,984 10.2 (9.8-10.5) 38,090 5.8 (5.6-6.0) 39,841 0.9 (0.8-1.0) 52 394,732 1.5 (1.4-1.5) 33,824 8.7 (8.4-9.0) 39,212 10.8 (10.5-11.1) 44,083 3.4 (3.2-3.6) 56 393,968 0.8 (0.7-0.8) 33,252 7.6 (7.3-7.9) 37,396 2.5 (2.3-2.6) 39,491 0.8 (0.8-0.9) 58 403,023 1.0 (1.0-1.0) 36,164 6.4 (6.2-6.7) 39,229 8.4 (8.1-8.6) 44,887 3.8 (3.7-4.0) 59 380,168 0.7 (0.7-0.7) 33,183 4.4 (4.2-4.6) 36,591 2.1 (2.0-2.3) 40,299 1.1 (1.0-1.2) 68 377,775 0.6 (0.6-0.6) 31,625 3.0 (2.8-3.2) 32,985 1.8 (1.7-2.0) 36,480 0.7 (0.6-0.8) 26 172,084 0.1 (0.1-0.1) 17,682 0.6 (0.5-0.7) 20,413 0.7 (0.6-0.8) 28,023 0.3 (0.2-0.3) 53 252,159 1.2 (1.2-1.2) 24,700 7.7 (7.4-8.1) 29,101 3.4 (3.2-3.7) 31,808 0.5 (0.4-0.6) 66 311,898 0.9 (0.9-0.9) 31,434 6.7 (6.4-7.0) 35,252 2.5 (2.3-2.6) 37,976 0.4 (0.3-0.4) 67 147,847 0.4 (0.3-0.4) 14,332 2.6 (2.3-2.8) 16,182 0.9 (0.8-1.1) 21,457 0.3 (0.2-0.4) 70 219,134 0.8 (0.7-0.8) 23,439 2.1 (1.9-2.3) 23,185 1.5 (1.3-1.6) 30,938 0.2 (0.2-0.3) 73 167,487 0.4 (0.4-0.4) 22,452 2.7 (2.5-2.9) 21,629 1.6 (1.5-1.8) 26,974 0.5 (0.4-0.6) 82 190,793 0.2 (0.2-0.3) 22,197 2.0 (1.8-2.2) 23,924 2.0 (1.8-2.1) 28,299 0.2 (0.1-0.2) NON-ONCOGENIC HPV TYPES 6 418,946 0.9 (0.8-0.9) 31,853 6.3 (6.0-6.5) 31,392 2.3 (2.1-2.5) 35,535 0.4 (0.3-0.5) 11 406,162 0.5 (0.4-0.5) 31,122 2.5 (2.4-2.7) 30,232 1.3 (1.2-1.5) 35,228 0.4 (0.3-0.5) 30 56,013 0.2 (0.2-0.3) 3,545 0.6 (0.4-0.9) 1,873 0.4 (0.2-0.8) 14,094 0.3 (0.2-0.4) 34 127,467 0.1 (0.1-0.1) 6,978 0.3 (0.2-0.5) 8,158 0.1 (0.0-0.2) 20,360 0.1 (0.1-0.2) 40 186,634 0.3 (0.3-0.3) 10,497 1.6 (1.4-1.9) 9,310 0.5 (0.3-0.6) 21,700 0.0 (0.0-0.0) 42 326,078 0.6 (0.5-0.6) 9,810 6.6 (6.2-7.1) 6,748 1.5 (1.2-1.8) 23,208 0.1 (0.1-0.2) 43 259,930 0.2 (0.2-0.2) 5,337 1.0 (0.8-1.3) 3,931 0.4 (0.2-0.6) 19,427 0.0 (0.0-0.0) 44 326,418 0.5 (0.5-0.5) 5,968 1.7 (1.4-2.1) 9,073 1.3 (1.1-1.5) 20,620 0.1 (0.1-0.2) 54 205,468 0.9 (0.8-0.9) 8,225 4.3 (3.9-4.8) 8,982 1.5 (1.3-1.8) 23,124 0.2 (0.1-0.2) 61 143,959 0.8 (0.8-0.9) 6,499 4.7 (4.2-5.3) 7,021 1.6 (1.3-1.9) 20,905 0.1 (0.1-0.1) 62 111,832 1.4 (1.4-1.5) 5,977 7.2 (6.6-7.9) 6,413 2.1 (1.8-2.5) 5,833 0.3 (0.2-0.5) 69 146,851 0.1 (0.1-0.1) 15,542 0.3 (0.2-0.4) 16,585 0.4 (0.3-0.5) 17,860 0.1 (0.1-0.2) 71 133,034 0.3 (0.3-0.3) 6,767 0.5 (0.4-0.7) 6,969 0.3 (0.2-0.5) 7,431 0.1 (0.1-0.2) 72 137,305 0.4 (0.4-0.4) 5,612 1.1 (0.8-1.4) 6,210 0.3 (0.2-0.5) 8,567 0.1 (0.1-0.2) 74 108,745 0.6 (0.6-0.7) 2,135 0.6 (0.4-1.0) 1,725 1.1 (0.7-1.7) 15,227 0.1 (0.0-0.1) 81 232,278 0.7 (0.7-0.8) 6,071 3.7 (3.3-4.2) 6,952 1.2 (1.0-1.5) 7,808 0.2 (0.1-0.3) 83 150,356 0.5 (0.5-0.6) 5,359 2.7 (2.3-3.2) 6,871 0.5 (0.3-0.7) 8,253 0.1 (0.1-0.2) 84 149,356 0.9 (0.8-0.9) 6,272 6.3 (5.7-6.9) 6,979 1.0 (0.8-1.3) 6,618 0.3 (0.2-0.4) 89 107,016 1.0 (0.9-1.0) 4,864 7.8 (7.1-8.6) 5,738 1.3 (1.1-1.7) 6,949 0.1 (0.0-0.2) Data updated at 15 Dec 2014 (data as of 30 Jun 2014 / 31 Oct 2014). 95% CI: 95% Confidence Interval; Low-grade lesions: LSIL or CIN-1; High-grade lesions: CIN-2, CIN-3, CIS or HSIL; a Kahng 2014 includes lesions CIN2 or worse. Data sources: See references in Section 9.

- 125 - Table 15: Type-specific HPV prevalence among invasive cervical cancer cases by histology in the World Any Histology Squamous cell carcinoma Adenocarcinoma Unespecified HPV Type No. HPV Prev No. HPV Prev No. HPV Prev No. HPV Prev tested % (95% CI) tested % (95% CI) tested % (95% CI) tested % (95% CI) ONCOGENIC HPV TYPES 16 53,309 55.4 (55.0-55.8) 36,463 57.5 (57.0-58.0) 6,166 35.9 (34.7-37.1) 11,925 59.0 (58.1-59.8) 18 52,798 14.6 (14.3-14.9) 36,114 11.2 (10.9-11.5) 6,141 36.2 (35.0-37.4) 11,788 13.6 (13.0-14.2) 31 46,340 3.5 (3.4-3.7) 32,684 3.7 (3.5-3.9) 5,062 1.9 (1.5-2.3) 9,839 4.0 (3.7-4.4) 33 47,673 4.2 (4.1-4.4) 33,583 4.5 (4.3-4.7) 5,164 1.8 (1.4-2.2) 10,171 4.9 (4.5-5.3) 35 43,022 1.6 (1.5-1.8) 30,838 1.6 (1.5-1.8) 4,658 0.5 (0.3-0.8) 8,771 2.4 (2.1-2.7) 39 40,312 1.4 (1.3-1.5) 29,779 1.5 (1.3-1.6) 4,426 0.9 (0.6-1.2) 7,144 1.5 (1.2-1.8) 45 42,447 4.8 (4.6-5.0) 30,464 4.6 (4.3-4.8) 4,889 5.7 (5.1-6.4) 8,339 5.1 (4.7-5.6) 51 39,841 0.9 (0.8-1.0) 29,032 1.0 (0.9-1.1) 4,412 0.7 (0.5-0.9) 7,434 1.0 (0.8-1.2) 52 44,083 3.4 (3.2-3.6) 31,902 3.6 (3.4-3.8) 4,858 1.2 (1.0-1.6) 8,568 3.5 (3.2-3.9) 56 39,491 0.8 (0.8-0.9) 28,959 0.9 (0.8-1.0) 4,402 0.5 (0.3-0.7) 7,375 0.8 (0.7-1.1) 58 44,887 3.8 (3.7-4.0) 32,288 3.9 (3.7-4.1) 4,686 1.2 (0.9-1.5) 9,158 4.8 (4.4-5.3) 59 40,299 1.1 (1.0-1.2) 29,736 1.1 (1.0-1.2) 4,548 0.6 (0.4-0.9) 7,260 1.8 (1.5-2.2) 68 36,480 0.7 (0.6-0.8) 26,858 0.7 (0.6-0.8) 4,059 0.4 (0.2-0.6) 5,800 0.8 (0.6-1.1) 53 31,808 0.5 (0.4-0.6) 23,897 0.5 (0.4-0.5) 3,308 0.4 (0.2-0.7) 5,500 0.8 (0.6-1.1) 66 37,976 0.4 (0.3-0.4) 28,502 0.3 (0.3-0.4) 4,073 0.1 (0.1-0.3) 6,298 0.7 (0.5-0.9) 67 21,457 0.3 (0.2-0.4) 16,747 0.3 (0.2-0.4) 1,743 0.1 (0.0-0.3) 3,082 0.2 (0.1-0.4) 70 30,938 0.2 (0.2-0.3) 23,220 0.2 (0.2-0.3) 2,904 0.1 (0.0-0.3) 5,137 0.3 (0.2-0.5) 73 26,974 0.5 (0.4-0.6) 20,791 0.5 (0.4-0.6) 2,205 0.0 (0.0-0.3) 4,093 1.0 (0.7-1.3) 82 28,299 0.2 (0.1-0.2) 21,345 0.1 (0.1-0.2) 2,239 0.0 (0.0-0.3) 4,830 0.4 (0.2-0.6) NON-ONCOGENIC HPV TYPES 6 35,535 0.4 (0.3-0.5) 12,496 0.4 (0.3-0.5) 1,443 0.5 (0.2-1.0) 851 0.5 (0.2-1.2) 11 35,228 0.4 (0.3-0.5) 27,142 0.3 (0.2-0.4) 3,366 0.2 (0.1-0.4) 5,710 1.1 (0.8-1.4) 30 14,094 0.3 (0.2-0.4) 11,938 0.3 (0.2-0.4) 1,096 0.1 (0.0-0.5) 1,060 0.1 (0.0-0.5) 34 20,360 0.1 (0.1-0.2) 15,823 0.1 (0.1-0.2) 2,101 0.0 (0.0-0.3) 2,436 0.1 (0.0-0.4) 42 23,208 0.1 (0.1-0.2) 18,415 0.1 (0.1-0.2) 2,007 0.0 (0.0-0.3) 3,568 0.2 (0.1-0.4) 44 20,620 0.1 (0.1-0.2) 17,099 0.1 (0.1-0.2) 2,013 0.0 (0.0-0.3) 2,498 0.4 (0.2-0.7) 54 23,124 0.2 (0.1-0.2) 18,733 0.1 (0.1-0.2) 2,096 0.1 (0.0-0.3) 3,285 0.3 (0.2-0.6) 62 5,833 0.3 (0.2-0.5) 2,950 0.5 (0.3-0.8) 313 0.3 (0.1-1.8) 2,570 0.2 (0.1-0.4) 69 17,860 0.1 (0.1-0.2) 14,029 0.1 (0.1-0.2) 1,395 0.1 (0.0-0.5) 2,436 0.0 (0.0-0.2) 71 7,431 0.1 (0.1-0.2) 4,665 0.2 (0.1-0.3) 526 0.2 (0.0-1.1) 2,448 0.0 (0.0-0.2) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; Data sources: See references in Section 9.

- 126-4.1.3 Terminology Cytologically normal women No abnormal cells are observed on the surface of their cervix upon cytology. Cervical Intraepithelial Neoplasia (CIN) / Squamous Intraepithelial Lesions (SIL) SIL and CIN are two commonly used terms to describe precancerous lesions or the abnormal growth of squamous cells observed in the cervix. SIL is an abnormal result derived from cervical cytological screening or Pap smear testing. CIN is a histological diagnosis made upon analysis of cervical tissue obtained by biopsy or surgical excision. The condition is graded as CIN 1, 2 or 3, according to the thickness of the abnormal epithelium (1/3, 2/3 or the entire thickness). Low-grade cervical lesions (LSIL/CIN-1) Low-grade cervical lesions are defined by early changes in size, shape, and number of abnormal cells formed on the surface of the cervix and may be referred to as mild dysplasia, LSIL, or CIN-1. High-grade cervical lesions (HSIL/ CIN-2 / CIN-3 / CIS) High-grade cervical lesions are defined by a large number of precancerous cells on the surface of the cervix that are distinctly different from normal cells. They have the potential to become cancerous cells and invade deeper tissues of the cervix. These lesions may be referred to as moderate or severe dysplasia, HSIL, CIN-2, CIN-3 or cervical carcinoma in situ (CIS). Carcinoma in situ (CIS) Preinvasive malignancy limited to the epithelium without invasion of the basement membrane. CIN 3 encompasses the squamous carcinoma in situ. Invasive cervical cancer (ICC) / Cervical cancer If the high-grade precancerous cells invade the basement membrane is called ICC. ICC stages range from stage I (cancer is in the cervix or uterus only) to stage IV (the cancer has spread to distant organs, such as the liver). Invasive squamous cell carcinoma Invasive carcinoma composed of cells resembling those of squamous epithelium. Adenocarcinoma Invasive tumour with glandular and squamous elements intermingled.

- 127-4.2 HPV burden in anogenital cancers other than the cervix Methods: Prevalence and type distribution of human papillomavirus in carcinoma of the vulva, vagina, anus and penis: systematic review and meta-analysis Systematic review of the literature was conducted on the worldwide HPV-prevalence and type distribution for anogenital carcinomas other than cervix from January 1986 to data as of indicated in each section. Search terms were HPV AND (anus OR anal) OR (penile) OR vagin* OR vulv* using Pubmed. There were no limits in publication language. References cited in selected articles were also investigated. Inclusion criteria were: HPV DNA detection by means of PCR, a minimum of 10 cases by lesion and a detailed description of HPV DNA detection and genotyping techniques used. The number of cases tested and HPV positive extracted for each study were pooled to estimate the prevalence of HPV DNA and the HPV type distribution globally and by geographical region. Binomial 95% confidence intervals were calculated for each HPV prevalence. 4.2.1 Anal cancer and precancerous anal lesions Anal cancer is similar to cervical cancer with respect to overall HPV DNA positivity, with approximately 88% of cases associated with HPV infection worldwide (de Martel C et al. Lancet Oncol 2012;13(6):607-15). HPV16 is the most common detected type, representing 73% of all HPV-positive tumours. HPV18 is the second most common type detected and is found in approximately 5% of cases. HPV DNA is also detected in the majority of precancerous anal lesions (AIN) (91.5% in AIN1 and 93.9% in AIN2/3) (De Vuyst H et al. Int J Cancer 2009; 124: 1626-36). In this section, the burden of HPV among cases of anal cancers in the World is presented. Alemany (Asia) Table 16: Studies on HPV prevalence among cases of anal cancer in the World HPV detection Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) 2015 a Hillman 2014 (Australia) Ouhoummane 2013 (Canada) Lai 1998 (China) Tachezy 2011 (Czech Rep.) Serup-Hansen 2014 (Denmark) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) PCR L1-Consensus primer, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 69, 70, 71, 73, 74, 82) PCR-GP5+/6+, PCR L1-Consensus primer, LBA (HPV 6, 11, 16, 18, 26, 31, 33, 34, 35, 39, 40, 42, 45, 51, 52, 53, 54, 56, 58, 59, 61, 62, 66, 67, 68, 69, 70, 71, 72, 73, 81, 82, 83, 84, 89) PCR MY09/11 and DBH (HPV6, 11, 16, 18 and 33) PCR-GP5+/6+, EIA, RLBM, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81(CP8304), 82/MM4, 82/IS39, 83(MM7), 84(MM8), CP6108) PCR-E6, PCR-E7, PCR- MULTIPLEX (HPV 16, 18, 31, 33, 45, 52, 58) 52 80.8 (68.1-89.2) HPV 16 (67.3%) HPV 18 (3.8%) HPV 35 (3.8%) HPV 56 (1.9%) HPV 58 (1.9%) 105 97.1 (91.9-99.0) HPV 16 (77.1%) HPV 52 (13.3%) HPV 6 (10.5%) HPV 54 (9.5%) HPV 11 (5.7%) 96 91.7 (84.4-95.7) HPV 16 (82.3%) HPV 6 (3.1%) HPV 33 (3.1%) HPV 18 (2.1%) HPV 58 (2.1%) 72 1.4 (0.2-7.5) - 22 81.8 (61.5-92.7) HPV 16 (81.8%) 137 87.6 (81.0-92.1) HPV 16 (81.0%) HPV 33 (5.1%) HPV 18 (2.2%) HPV 58 (0.7%) (Continued on next page)

- 128 - HPV detection ( Table 16 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Alemany 2015 b PCR-SPF10, EIA, LiPA (HPV 6, 169 87.6 (81.8-91.7) HPV 16 (73.4%) (Europe) 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) HPV 6 (3.6%) HPV 18 (3.6%) HPV 11 (3.0%) HPV 33 (2.4%) Abramowitz 2011 (France) Valmary-Degano 2013 (France) Vincent-Salomon 1996 (France) Kreuter 2010 (Germany) Rödel 2015 (Germany) Varnai 2006 (Germany) Indinnimeo 1999 (Italy) Yhim 2011 (Korea, Rep.) Alemany 2015 c (Latin America & Caribbean) Frisch 1997 d (Northern Europe) Laytragoon-Lewin 2007 (Sweden) Poletti 1998 (Switzerland) PCR-SPF10, LIPA, (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 43-45, 51-54, 56, 58, 59, 66, 68, 69, 70, 71, 73, 74, 82) PCR, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 69, 70, 71, 73, 74, 82) SBH (6/11/42, 16/18/33, 31/35/39), PCR-TS (HPV 6, 11, 16, 18, 33) PCR-A5/A10, A6/A8, EIA,RHA, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81-84, 89) PCR-GP5+/6+, PCR-SPF10, PCR- MULTIPLEX, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 69, 70, 71, 73, 74, 81, 82) PCR-GP5+/6+, MY09/MY11, sequencing PCR-TS (HPV 6, 11, 16, 18, 31, 33) PCR, TS (HPV 6, 11, 16, 18, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 56, 58, 59, 66, 68, 69) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) PCR-GP5+/6+, TS (HPV 6, 11, 16, 18, 31, 33) PCR-GP5+/6+, MY09/MY11, sequencing PCR-PU-1M-31B (Fujinaga 91)- (HPV 6, 11, 16, 18, 31, 33, 52, 58) 366 96.7 (94.4-98.1) HPV 16 (75.4%) HPV 11 (7.4%) HPV 6 (6.0%) HPV 18 (6.0%) HPV 52 (5.2%) 73 98.6 (92.6-99.8) HPV 16 (89.0%) HPV 39 (4.1%) HPV 33 (2.7%) HPV 6 (1.4%) HPV 11 (1.4%) 27 74.1 (55.3-86.8) HPV 16 (63.0%) HPV 18 (7.4%) 11 100.0 (74.1-100.0) HPV 16 (90.9%) HPV 31 (54.5%) HPV 44 (36.4%) HPV 52 (36.4%) HPV 58 (36.4%) 91 100.0 (95.9-100.0) HPV 16 (94.5%) HPV 11 (2.2%) HPV 31 (2.2%) HPV 35 (2.2%) HPV 18 (1.1%) 47 80.9 (67.5-89.6) HPV 16 (74.5%) HPV 33 (6.4%) HPV 18 (2.1%) HPV 31 (2.1%) HPV 45 (2.1%) 14 64.3 (38.8-83.7) HPV 16 (42.9%) 47 74.5 (60.5-84.7) HPV 16 (66.0%) HPV 58 (6.4%) HPV 35 (2.1%) 157 90.4 (84.8-94.1) HPV 16 (70.1%) HPV 33 (5.7%) HPV 58 (3.2%) HPV 18 (2.5%) HPV 31 (1.9%) 388 87.6 (84.0-90.5) - 72 90.3 (81.3-95.2) HPV 16 (69.4%) HPV 18 (34.7%) HPV 33 (2.8%) 33 39.4 (24.7-56.3) - Crook 1991 (UK) SBH, PCR-TS (HPV 16,18) 50 84.0 (71.5-91.7) HPV 16 (76.0%) HPV 18 (8.0%) Ogunbiyi 1993 PCR- E6/E7, TS (HPV 16) 46 73.9 (59.7-84.4) HPV 16 (73.9%) (UK) (Continued on next page)

- 129 - HPV detection ( Table 16 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Alemany 2015 (USA) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) 96 95.8 (89.8-98.4) HPV 16 (81.3%) HPV 18 (7.3%) HPV 31 (4.2%) HPV 39 (3.1%) HPV 52 (3.1%) Daling 2004 MY09/11 for 6/11, 16, 18/45, 31 248 87.9 (83.3-91.4) - (USA) Meyer 2013 (USA) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 70, 73, 74) 42 100.0 (91.6-100.0) HPV 16 (73.8%) HPV 18 (26.2%) HPV 31 (14.3%) HPV 52 (14.3%) HPV 39 (7.1%) Noffsinger 1995 PCR primers for HPV 6, 16, 18 56 46.4 (34.0-59.3) - (USA) Palefsky 1991 PCR primers for 6/11, 16, 18, 31, 13 84.6 (57.8-95.7) - (USA) 33 and 35 Shroyer 1995 PCR MY09/11 and SBH (HPV6, 27 81.5 (63.3-91.8) - (USA) 11, 16, 18, 31 and 33) Zaki 1992 (USA) PCR primers for 6, 11, 16, 18 and 33 11 72.7 (43.4-90.3) - Alemany 2015 e (Western Africa) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) 21 61.9 (40.9-79.2) HPV 16 (28.6%) HPV 6 (9.5%) HPV 18 (9.5%) HPV 31 (4.8%) HPV 35 (4.8%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; DBH: Dot Blot Hybridization; EIA: Enzyme ImmunoAssay; LBA: Line-Blot Assay; LiPA: Line Probe Assay; PCR: Polymerase Chain Reaction; RHA: Reverse Hybridization Assay; RLBM: Reverse Line Blotting Method; SBH: Southern Blot Hybridization; SPF: Short Primer Fragment; TS: Type Specific; a Includes cases from Bangladesh, India and South Korea b Includes cases from Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom c Includes cases from Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico and Paraguay d Includes cases from Denmark and Sweden. Includes both in situ and invasive SCC cases. e Includes cases from Mali, Nigeria and Senegal Data sources: See references in Section 9. Table 17: Studies on HPV prevalence among cases of AIN 2/3 in the World HPV detection Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Hillman 2012 (Australia) Gimenez 2011 (Brazil) Gohy 2008 a (Canada) Salit (Canada) 2009 a HC2, LBA (HPV 16, 18, 31, 33) 21 95.2 (77.3-99.2) HPV 16 (33.3%) HPV 31 (19.0%) HPV 18 (4.8%) PCR 18 88.9 (67.2-96.9) - PCR-MY09/11, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 81, 82, 83, 84, 89) PCR-PGMY09/11, PCR L1-Consensus primer, LBA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 57, 58, 59, 66, 68) 62 93.5 (84.6-97.5) HPV 16 (35.5%) HPV 18 (16.1%) HPV 58 (16.1%) HPV 42 (9.7%) HPV 45 (9.7%) 74 100.0 (95.1-100.0) HPV 16 (52.7%) HPV 18 (32.4%) HPV 31 (31.1%) HPV 6 (28.4%) HPV 52 (27.0%) (Continued on next page)

- 130 - HPV detection ( Table 17 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Alemany 2015 b PCR-SPF10, EIA, LiPA (HPV 6, 23 95.7 (79.0-99.2) HPV 16 (65.2%) (Europe) 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) HPV 6 (8.7%) HPV 18 (8.7%) HPV 51 (8.7%) HPV 74 (8.7%) Hampl 2007 (Germany) Kreuter 2010 (Germany) Silling 2012 a (Germany) Varnai 2006 (Germany) Wieland 2006 a (Germany) PCR-MY09/11, GP5/GP6, TS (HPV 6, 11, 16, 18, 31, 33, 35, 40, 42, 44, 45, 51, 52, 53, 55, 56, 58, 61, 66-68, 73, 74, 91, IS887/MM4, HPVIA18) PCR-A5/A10, A6/A8, EIA, RHA, TS (HPV 6, 11, 16, 18, 26, 31, 33, 34, 35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81-84, 89) PCR- MULTIPLEX (HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) PCR-GP5+/6+, MY09/MY11, sequencing PCR, EIA (HPV 6, 11, 16, 18, 26, 31, 33, 34, 35, 42, 44, 45, 52, 53, 54, 56, 58, 59, 61, 66, 68, 70, 72, 73, 81, 82, 83, 84, 89) 24 100.0 (86.2-100.0) HPV 16 (79.2%) HPV 6 (8.3%) HPV 33 (8.3%) HPV 31 (4.2%) HPV 40 (4.2%) 156 98.1 (94.5-99.3) HPV 16 (67.9%) 42 100.0 (91.6-100.0) HPV 16 (69.0%) HPV 18 (23.8%) HPV 68 (11.9%) HPV 73 (11.9%) HPV 26 (9.5%) 24 95.8 (79.8-99.3) HPV 16 (70.8%) HPV 11 (12.5%) HPV 6 (8.3%) HPV 58 (4.2%) 20 100.0 (83.9-100.0) HPV 16 (85.0%) HPV 18 (45.0%) HPV 83 (45.0%) HPV 52 (35.0%) HPV 58 (30.0%) Tanzi 2009 (Italy) PCR-L1, MY09/MY11, RFLP 62 91.9 (82.5-96.5) HPV 6 (38.7%) HPV 16 (37.1%) HPV 11 (27.4%) HPV 58 (8.1%) HPV 18 (4.8%) Alemany 2015 c (Latin America & Caribbean) Richel 2014 a (Netherlands) Cañadas (Spain) 2010 a García-Espinosa 2013 a (Spain) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) PCR L1-Consensus primer, PCR-SPF10, EIA, LiPA (HPV 11, 16, 18, 26, 31, 35, 39, 52, 53, 58, 59, 67, 69, 74) PCR-E6/E7, TS (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) PCR-GP5/6, PCR L1-Consensus primer, DBH (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 57, 58, 59, 61, 66, 68, 70, 71, 72, 73, 81, 82, 84) 12 100.0 (75.8-100.0) - 17 100.0 (81.6-100.0) HPV 16 (58.8%) HPV 31 (17.6%) HPV 18 (11.8%) HPV 53 (11.8%) HPV 58 (11.8%) 30 100.0 (88.6-100.0) HPV 16 (43.3%) HPV 33 (36.7%) HPV 51 (36.7%) HPV 58 (36.7%) HPV 6 (33.3%) 20 100.0 (83.9-100.0) HPV 16 (50.0%) HPV 58 (35.0%) HPV 6 (30.0%) HPV 31 (30.0%) HPV 43 (30.0%) (Continued on next page)

- 131 - HPV detection ( Table 17 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Hidalgo-Tenorio 2014 a (Spain) Sirera (Spain) Torres (Spain) 2013 a 2013 a Phanuphak 2013 (Thailand) Fox 2005 (UK) Ogunbiyi 1993 (UK) Ogunbiyi 1994 (UK) Berry 2009 a (USA) Sahasrabuddhe 2013 a (USA) PCR (HPV 6, 11, 16, 18, 51, 61, 68, 84) PCR- MULTIPLEX (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) LBA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 81, 82, 83, 84) PCR L1-Consensus primer, PCR-E6, PCR-E7, LBA (HPV 16/18) PCR-MY09/11, GP5+/6+, RHA,TS (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82) 28 100.0 (87.9-100.0) HPV 16 (39.3%) HPV 6 (25.0%) HPV 11 (21.4%) HPV 18 (21.4%) HPV 51 (21.4%) 69 84.1 (73.7-90.9) HPV 16 (55.1%) HPV 58 (34.8%) HPV 33 (29.0%) HPV 51 (23.2%) HPV 18 (21.7%) 44 97.7 (88.2-99.6) HPV 16 (59.1%) HPV 6 (34.1%) HPV 66 (31.8%) HPV 52 (29.5%) HPV 53 (29.5%) 34 50.0 (34.1-65.9) HPV 16/18 (23.5%) 74 97.3 (90.7-99.3) HPV 16 (64.9%) HPV 18 (25.7%) HPV 33 (24.3%) HPV 58 (21.6%) HPV 31 (18.9%) PCR- E6/E7,TS (HPV 16) 27 66.7 (47.8-81.4) HPV 16 (66.7%) PCR- E6/E7,TS (HPV 16) 11 90.9 (62.3-98.4) HPV 16 (90.9%) PCR-MY09/11, PCR L1-Consensus primer, TS (HPV 16) PCR-PGMY09/11, LBA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 81, 82, 83, 84) 35 80.0 (64.1-90.0) HPV 16 (37.1%) 104 99.0 (94.8-99.8) HPV 16 (54.8%) HPV 6 (26.0%) HPV 31 (22.1%) HPV 42 (22.1%) HPV 66 (21.2%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; AIN 2/3: Anal intraepithelial neoplasia of grade 2/3; DBH: Dot Blot Hybridization; EIA: Enzyme ImmunoAssay; HC2: Hybrid Capture 2; LBA: Line-Blot Assay; LiPA: Line Probe Assay; PCR: Polymerase Chain Reaction; RFLP: Restriction Fragment Length Polymorphism; RHA: Reverse Hybridization Assay; SPF: Short Primer Fragment; TS: Type Specific; a HIV positive cases b Includes cases from Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom c Includes cases from Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico and Paraguay Data sources: See references in Section 9.

- 132 - Figure 84: Ten most frequent HPV types among cases of anal cancer in Africa compared to the World Africa (a) World (b) 16 28.6 16 71.4 18 9.5 18 4.2 6 9.5 33 3.0 31 4.8 6 2.4 35 4.8 31 2.0 45 4.8 35 1.6 51 4.8 58 1.6 8th* 11 1.4 9th* 39 1.2 10th* 0 10 20 30 40 50 60 70 80 52 1.2 0 10 20 30 40 50 60 70 80 Type specific HPV prevalence (%) of anal cancer cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). AIN 2/3: Anal intraepithelial neoplasia of grade 2/3; a Includes cases from Mali, Nigeria and Senegal. b Includes cases from Europe (Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom); America (Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay and United States); Africa (Mali, Nigeria and Senegal); Asia (Bangladesh,India and South Korea) Data sources: See references in Section 9. Figure 85: Ten most frequent HPV types among cases of anal cancer in Americas compared to the World Americas (a) World (b) 16 74.3 16 71.4 18 4.3 18 4.2 33 4.3 33 3.0 31 2.8 6 2.4 58 2.8 31 2.0 39 2.4 35 1.6 52 2.0 58 1.6 6 1.6 11 1.4 45 1.2 39 1.2 11 0.8 0 10 20 30 40 50 60 70 80 52 1.2 0 10 20 30 40 50 60 70 80 Type specific HPV prevalence (%) of anal cancer cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). AIN 2/3: Anal intraepithelial neoplasia of grade 2/3; a Includes cases from Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay and United States b Includes cases from Europe (Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom); America (Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay and United States); Africa (Mali, Nigeria and Senegal); Asia (Bangladesh,India and South Korea) Data sources: See references in Section 9.

- 133 - Figure 86: Ten most frequent HPV types among cases of anal cancer in Asia compared to the World Asia (a) World (b) 16 67.3 16 71.4 18 3.8 18 4.2 35 3.8 33 3.0 56 1.9 6 2.4 58 1.9 31 2.0 6 35 1.6 11 58 1.6 26 11 1.4 30 39 1.2 31 0 10 20 30 40 50 60 70 80 52 1.2 0 10 20 30 40 50 60 70 80 Type specific HPV prevalence (%) of anal cancer cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). AIN 2/3: Anal intraepithelial neoplasia of grade 2/3; a Includes cases from Bangladesh,India and South Korea b Includes cases from Europe (Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom); America (Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay and United States); Africa (Mali, Nigeria and Senegal); Asia (Bangladesh,India and South Korea) Data sources: See references in Section 9. Figure 87: Ten most frequent HPV types among cases of anal cancer in Europe compared to the World Europe (a) World (b) 16 73.4 16 71.4 6 3.6 18 4.2 18 3.6 33 3.0 11 3.0 6 2.4 33 2.4 31 2.0 35 1.8 35 1.6 74 1.8 58 1.6 31 1.2 11 1.4 30 0.6 39 1.2 52 0.6 0 10 20 30 40 50 60 70 80 52 1.2 0 10 20 30 40 50 60 70 80 Type specific HPV prevalence (%) of anal cancer cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). AIN 2/3: Anal intraepithelial neoplasia of grade 2/3; a Includes cases from Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom. b Includes cases from Europe (Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom); America (Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay and United States); Africa (Mali, Nigeria and Senegal); Asia (Bangladesh,India and South Korea) Data sources: See references in Section 9.

- 134 - Figure 88: Ten most frequent HPV types among cases of anal cancer in Oceania compared to the World Oceania World (a) 1st* 16 71.4 2nd* 18 4.2 3rd* 33 3.0 4th* 6 2.4 5th* 6th* No data available 31 35 2.0 1.6 7th* 58 1.6 8th* 11 1.4 9th* 39 1.2 10th* 52 1.2 0 10 20 30 40 50 60 70 80 Type specific HPV prevalence (%) of anal cancer cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). AIN 2/3: Anal intraepithelial neoplasia of grade 2/3; a Includes cases from Europe (Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom); America (Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay and United States); Africa (Mali, Nigeria and Senegal); Asia (Bangladesh,India and South Korea) Data sources: See references in Section 9. Figure 89: Ten most frequent HPV types among cases of AIN 2/3 in Africa compared to the World Africa World (a) 1st* 16 72.1 2nd* 6 9.3 3rd* 11 7.0 4th* 18 4.7 5th* 6th* No data available 31 51 4.7 4.7 7th* 74 4.7 8th* 35 2.3 9th* 44 2.3 10th* 45 2.3 0 10 20 30 40 50 60 70 80 Type specific HPV prevalence (%) of AIN 2/3 cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). AIN 2/3: Anal intraepithelial neoplasia of grade 2/3; a Includes cases from Europe (Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom); America (Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico and Paraguay) Data sources: See references in Section 9.

- 135 - Figure 90: Ten most frequent HPV types among cases of AIN 2/3 in Americas compared to the World Americas (a) World (b) 16 91.7 16 72.1 11 8.3 6 9.3 6 8.3 11 7.0 4th* 18 4.7 5th* 31 4.7 6th* 51 4.7 7th* 74 4.7 8th* 35 2.3 9th* 44 2.3 10th* 0 10 30 50 70 90 45 2.3 0 10 30 50 70 90 Type specific HPV prevalence (%) of AIN 2/3 cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). AIN 2/3: Anal intraepithelial neoplasia of grade 2/3; a Includes cases from Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico and Paraguay b Includes cases from Europe (Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom); America (Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico and Paraguay) Data sources: See references in Section 9. Figure 91: Ten most frequent HPV types among cases of AIN 2/3 in Asia compared to the World Asia World (a) 1st* 16 72.1 2nd* 6 9.3 3rd* 11 7.0 4th* 18 4.7 5th* 6th* No data available 31 51 4.7 4.7 7th* 74 4.7 8th* 35 2.3 9th* 44 2.3 10th* 45 2.3 0 10 20 30 40 50 60 70 80 Type specific HPV prevalence (%) of AIN 2/3 cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). AIN 2/3: Anal intraepithelial neoplasia of grade 2/3; a Includes cases from Europe (Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom); America (Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico and Paraguay) Data sources: See references in Section 9.

- 136 - Figure 92: Ten most frequent HPV types among cases of AIN 2/3 in Europe compared to the World Europe (a) World (b) 16 65.2 16 72.1 18 8.7 6 9.3 51 8.7 11 7.0 6 8.7 18 4.7 74 8.7 31 4.7 11 4.3 51 4.7 31 4.3 74 4.7 35 4.3 35 2.3 44 4.3 44 2.3 45 4.3 0 10 20 30 40 50 60 70 80 45 2.3 0 10 20 30 40 50 60 70 80 Type specific HPV prevalence (%) of AIN 2/3 cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). AIN 2/3: Anal intraepithelial neoplasia of grade 2/3; a Includes cases from Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom. b Includes cases from Europe (Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom); America (Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico and Paraguay) Data sources: See references in Section 9. Figure 93: Ten most frequent HPV types among cases of AIN 2/3 in Oceania compared to the World Oceania World (a) 1st* 16 72.1 2nd* 6 9.3 3rd* 11 7.0 4th* 18 4.7 5th* 6th* No data available 31 51 4.7 4.7 7th* 74 4.7 8th* 35 2.3 9th* 44 2.3 10th* 45 2.3 0 10 20 30 40 50 60 70 80 Type specific HPV prevalence (%) of AIN 2/3 cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). AIN 2/3: Anal intraepithelial neoplasia of grade 2/3; a Includes cases from Europe (Bosnia-Herzegovina, Czech Republic, France, Germany, Poland, Portugal, Slovenia, Spain and United Kingdom); America (Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico and Paraguay) Data sources: See references in Section 9.

- 137-4.2.2 Vulvar cancer and precancerous vulvar lesions HPV attribution for vulvar cancer is 43% worldwide (de Martel C et al. Lancet Oncol 2012;13(6):607-15). Vulvar cancer has two distinct histological patterns with two different risk factor profiles: (1) basaloid/warty types (2) keratinizing types. Basaloid/warty lesions are more common in young women, are frequently found adjacent to VIN, are very often associated with HPV DNA detection (86%), and have a similar risk factor profile as cervical cancer. Keratinizing vulvar carcinomas represent the majority of the vulvar lesions (>60%). These lesions develop from non-hpv-related chronic vulvar dermatoses, especially lichen sclerosus and/or squamous hyperplasia, their immediate cancer precursor lesion is differentiated VIN, they occur more often in older women, and are rarely associated with HPV (6%) or with any of the other risk factors typical of cervical cancer. HPV prevalence is frequently detected among cases of high-grade VIN (VIN2/3) (85.3%). HPV 16 is the most common detected type followed by HPV 33 (De Vuyst H et al. Int J Cancer 2009; 124:1626-36). In this section, the HPV burden among cases of vulvar cancers in Europe is presented. Table 18: Studies on HPV prevalence among cases of vulvar cancer in the World HPV detection Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) de Sanjosé 2013 a (Africa) de Sanjosé 2013 b (Asia) Allen 2002 (Australia) Tan 2013 (Australia) de Melo Maia 2012 (Brazil) Pinto 1999 (Brazil) Al-Ghamdi 2002 (Canada) Gao 1997 (China) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) MY09/11 and Type-specific for 6, 11, 16, 18, 31, 33, 35, 39, 45, 51 and 52 PCR L1-Consensus primer, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 69, 70, 71, 73, 74, 82) LBA, qpcr (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 81, 82, 83, 84) GP5+/GP6+, and HPV Type specific for 6/11, 16, 18, 45 independently, 31/33/34/35/39 and 40/42/43/44/45, and 51/52/54/56/58 combined MY09/11, GP5/GP6 and type-specific for HPV16 and 18 L1-PCR for HPV6/11 and HPV16/18 24 70.8 (50.8-85.1) HPV 16 (58.3%) HPV 18 (4.2%) HPV 45 (4.2%) HPV 52 (4.2%) 188 28.7 (22.7-35.6) HPV 16 (18.1%) HPV 18 (1.6%) HPV 44 (1.6%) HPV 45 (1.1%) HPV 52 (1.1%) 18 55.6 (33.7-75.4) - 20 90.0 (69.9-97.2) HPV 16 (80.0%) HPV 33 (5.0%) HPV 35 (5.0%) HPV 52 (5.0%) HPV 54 (5.0%) 139 58.3 (50.0-66.1) HPV 16 (25.9%) HPV 33 (16.5%) 158 24.1 (18.1-31.3) - 20 85.0 (64.0-94.8) - 13 23.1 (8.2-50.3) - Guo 1996 (China) PCR HPV6/11, 16, 18 37 27.0 (15.4-43.0) - Ngan 1999 (China) L1-PCR for HPV16 and 18 48 47.9 (34.5-61.7) - (Continued on next page)

- 138 - HPV detection ( Table 18 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Skapa 2007 (Czech Rep.) Tachezy 2011 (Czech Rep.) Bryndorf 2004 (Denmark) Hørding 1991 (Denmark) Hørding 1993 (Denmark) Hørding 1994 (Denmark) Madsen 2008 (Denmark) de Sanjosé 2013 c (Europe) Iwasawa 1997 (Finland) Choschzick 2011 (Germany) Hampl 2006 (Germany) Hampl 2008 (Germany) Milde-Langosch 1995 (Germany) Reuschenbach 2013 (Germany) PCR-GP5+/GP6+, TS (HPV 3, 7, 6, 10, 11, 13, 16, 18, 26-35, 39, 40, 42-45, 51, 53-59, 61, 62, 66-74, 77, 81-87, 89-91) PCR-GP5+/6+, RLBM, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81-84 and CP6108) PCR-SPF10, LIPA, (HPV 6, 11, 16, 18, 31, 33-35, 39, 40, 42-45, 51-54, 56, 58, 59, 66, 68, 70, 74) 46 41.3 (28.3-55.7) HPV 16 (23.9%) HPV 33 (8.7%) HPV 6 (2.2%) HPV 42 (2.2%) HPV 45 (2.2%) 49 34.7 (22.9-48.7) HPV 16 (24.5%) HPV 33 (6.1%) HPV 42 (2.0%) HPV 45 (2.0%) 10 60.0 (31.3-83.2) HPV 16 (40.0%) HPV 33 (20.0%) HPV 56 (10.0%) PCR-E6/E7, TS (HPV 16) 24 58.3 (38.8-75.5) HPV 16 (58.3%) PCR-E6/E7,TS (HPV 6, 11, 16, 18, 33) PCR-E6/E7,TS (HPV 6, 11, 16, 18, 33) PCR-GP5+/6+,EIA, RLBM, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81(CP8304), 82/MM4, 82/IS39, 83(MM7), 84(MM8), CP6108) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) PCR-MY09/11,TS (HPV 6, 11, 16, 18, 33) PCR-(MY09/11, GP5+/GP6+), TS (HPV 6, 11, 16, 18, 31, 33, 35, 40, 42, 44, 45, 51, 52, 53, 55, 56, 58, 61, 66-68, 73, 74, 91, IS887/MM4, HPVIA18) PCR-(MY09/11, GP5+/GP6+), TS (HPV 6, 11, 16, 18, 31, 33, 35, 40, 42, 44, 45, 51, 52, 53, 55, 56, 58, 61, 66-68, 73, 74, 91, IS887/MM4, HPVIA18), sequencing PCR-(MY09/11, GP5+/6+), TS, Sequencing PCR-MY09/11,TS (HPV6, 11, 16, 18, 31, 33, 35) PCR- MULTIPLEX (HPV 6, 11, 16, 18, 31, 33, 39) 62 30.6 (20.6-43.0) HPV 16 (21.0%) HPV 18 (4.8%) HPV 33 (4.8%) 78 30.8 (21.6-41.7) HPV 16 (28.2%) HPV 33 (3.8%) 60 51.7 (39.3-63.8) HPV 16 (36.7%) HPV 33 (11.7%) HPV 73 (3.3%) HPV 6 (1.7%) HPV 51 (1.7%) 903 19.3 (16.8-22.0) HPV 16 (13.8%) HPV 33 (1.2%) HPV 18 (0.6%) HPV 31 (0.6%) HPV 44 (0.4%) 74 36.5 (26.4-47.9) HPV 16 (25.7%) HPV 18 (12.2%) HPV 33 (1.4%) 39 46.2 (31.6-61.4) HPV 16 (43.6%) HPV 33 (2.6%) 48 60.4 (46.3-73.0) HPV 16 (39.6%) HPV 33 (8.3%) HPV 31 (4.2%) HPV 18 (2.1%) 36 50.0 (34.5-65.5) HPV 16 (30.6%) HPV 33 (5.6%) HPV 6 (2.8%) HPV 11 (2.8%) HPV 18 (2.8%) 40 27.5 (16.1-42.8) HPV 16 (25.0%) 186 43.0 (36.1-50.2) HPV 16 (35.5%) HPV 18 (2.7%) HPV 33 (1.1%) HPV 6 (0.5%) HPV 11 (0.5%) (Continued on next page)

- 139 - HPV detection ( Table 18 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Bonvicini 2005 (Italy) Della Torre 1992 (Italy) ISH, PCR-MY09/11, TS (HPV 16, 18, 31, 33, 35, 45, 52, 58) 16 0.0 (0.0-19.4) - PCR-,TS (HPV 6, 11, 16, 18) 11 54.5 (28.0-78.7) HPV 16 (36.4%) HPV 11 (9.1%) HPV 18 (9.1%) Pilotti 1995 (Italy) PCR-,TS (HPV 6, 11, 16, 18) 23 47.8 (29.2-67.0) HPV 16 (43.5%) HPV 18 (4.3%) Koyamatsu 2003 E7 (115-158 bp) for HPV16, HPV 31 12.9 (5.1-28.9) - (Japan) 18, L1 (250bp) for HPV 6,11,16,18,31,33, 42,52,58 Nagano 1996 (Japan) Osakabe 2007 (Japan) de Sanjosé 2013 d (Latin America & Caribbean) Ansink 1994 (Netherlands) Kagie 1997 (Netherlands) Trietsch 2013 (Netherlands) van de Nieuwenhof 2009 (Netherlands) van der Avoort 2006 (Netherlands) de Sanjosé 2013 e (Oceania) Bujko 2012 (Poland) Kowalewska 2010 (Poland) L1-PCR (L1C1 and L1C2) for HPV6, 11, 16, 18, 30, 31, 33, 34, 35, 39, 42, 45, 51, 52, 53, 56 and 58 PCR-RFLP (HPV6, 11, 16, 18, 31, 33, 42, 52, 58) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) PCR-GP5/GP6, TS (HPV 6, 11, 13, 16, 18, 30-33, 45, 51) 11 72.7 (43.4-90.3) - 21 23.8 (10.6-45.1) - 324 40.1 (34.9-45.5) HPV 16 (25.3%) HPV 18 (2.8%) HPV 45 (2.5%) HPV 33 (2.2%) HPV 6 (1.2%) 60 31.7 (21.3-44.2) - PCR-CPI/IIG, sequencing 66 18.2 (10.7-29.1) HPV 16 (15.2%) HPV 33 (1.5%) HPV 45 (1.5%) PCR, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 69, 70, 71, 73, 74, 82) PCR-SPF10, LIPA, (HPV 6, 11, 16, 18, 31, 33-35, 39, 40, 42, 43, 45, 51-54, 56, 58, 59, 66, 68, 70, 73, 74) PCR-SPF10,LIPA, (HPV 6, 11, 16, 18, 31, 33-35, 39, 40, 42-45, 51-54, 56, 58, 59, 66, 68, 70, 74) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) PCR, LBA (HPV 6, 11, 16, 18, 52, 53, 55, 58, 61, 73) PCR-(PGMY,L1), RLBM,(HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81-84 and CP6108) Liss 1998 (Poland) PCR-MY09/11, TS(HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 52, 58) 108 16.7 (10.8-24.8) HPV 16 (10.2%) HPV 33 (5.6%) HPV 18 (1.9%) 130 34.6 (27.0-43.1) HPV 16 (15.4%) HPV 33 (5.4%) HPV 18 (2.3%) HPV 52 (1.5%) HPV 54 (1.5%) 16 0.0 (0.0-19.4) - 220 40.0 (33.8-46.6) HPV 16 (27.3%) HPV 33 (3.6%) HPV 18 (2.7%) HPV 6 (1.4%) HPV 39 (1.4%) 44 34.1 (21.9-48.9) HPV 16 (20.5%) HPV 11 (11.4%) HPV 52 (4.5%) HPV 55 (4.5%) HPV 58 (4.5%) 44 15.9 (7.9-29.4) HPV 16 (11.4%) HPV 6 (2.3%) HPV 58 (2.3%) 18 16.7 (5.8-39.2) HPV 16 (16.7%) (Continued on next page)

- 140 - HPV detection ( Table 18 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Alonso 2011 (Spain) Guerrero 2011 (Spain) Lerma 1999 (Spain) Santos 2006 (Spain) Larsson 2012 (Sweden) Lindell 2010 (Sweden) Ngamkham 2013 (Thailand) Abdel-Hady 2001 (UK) PCR-SPF10, LIPA, (HPV 6, 11, 16, 18, 31, 33-35, 39, 40, 42, 43, 45, 51-54, 56, 58, 59, 66, 68, 70, 74) PCR-GP5+/6+, PCR L1-Consensus primer, LiPA (HPV 6, 16, 18, 59) 98 19.4 (12.8-28.3) HPV 16 (14.3%) HPV 33 (2.0%) HPV 31 (1.0%) HPV 51 (1.0%) HPV 52 (1.0%) 30 16.7 (7.3-33.6) HPV 59 (10.0%) HPV 6 (3.3%) HPV 16 (3.3%) HPV 18 (3.3%) PCR-L1,TS (HPV 16, 18) 57 12.3 (6.1-23.2) HPV 16 (12.3%) PCR-GP5+/GP6+,SPF10, LIPA, TS (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 43-45, 51-54, 56, 58, 59, 66, 68, 69, 70, 71, 73, 74, 82) PCR-E6, RT-PCR (HPV 6, 11, 16, 18, 31, 33, 39, 45, 51, 52, 56, 58, 59) PCR-(GP5+/6+,CPI/IIG),TS, sequencing PCR-GP5+/6+, EIA (HPV 6, 11, 16, 18, 26, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 57, 58, 59, 66, 68, 70, 71, 72, 73, 81, 82, 83, 84, 89) PCR-(MY09/11, CPI/IIG), sequencing 92 17.4 (11.0-26.4) HPV 16 (13.0%) HPV 33 (3.3%) HPV 6 (2.2%) HPV 51 (1.1%) 130 30.8 (23.5-39.2) HPV 16 (23.8%) HPV 33 (3.8%) HPV 18 (1.5%) HPV 56 (0.8%) HPV 59 (0.8%) 75 30.7 (21.4-41.8) HPV 16 (21.3%) HPV 18 (2.7%) HPV 33 (2.7%) HPV 52 (1.3%) 25 44.0 (26.7-62.9) HPV 16 (36.0%) HPV 33 (8.0%) HPV 35 (8.0%) HPV 18 (4.0%) HPV 58 (4.0%) 11 27.3 (9.7-56.6) HPV 16 (27.3%) HPV 33 (18.2%) HPV 18 (9.1%) Gasco 2002 (UK) PCR- E6/E7,TS (HPV 16) 36 36.1 (22.5-52.4) HPV 16 (36.1%) Ogunbiyi 1994 (UK) PCR-GP5+/6+, TS (HPV 6, 11, 16, 18, 31, 33) 33 75.8 (59.0-87.2) HPV 16 (75.8%) Bloss 1991 (USA) SBH (HPV6, 11, 16, 18 and 31) and E6/E7 primers 21 47.6 (28.3-67.6) - Bodelon 2012 PCR (HPV 16/18) 429 81.6 (77.6-85.0) HPV 16/18 (74.4%) (USA) Carter 2001 (USA) de Sanjosé 2013 (USA) Gargano 2012 (USA) Kim 1996 (USA) MY09/11 and RFLP; type-specific for HPV16, 18 PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) PCR, LBA, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 74, 81, 82, 83, 84) MY09/11 for HPV16 and HPV18, SBH and type-specific for HPV6, 11, 16, 18, 31 38 79.0 (63.7-88.9) - 50 50.0 (36.6-63.4) HPV 16 (34.0%) HPV 33 (8.0%) HPV 6 (2.0%) HPV 18 (2.0%) HPV 44 (2.0%) 176 68.8 (61.6-75.1) HPV 16 (48.3%) HPV 33 (10.2%) HPV 52 (2.8%) HPV 18 (1.7%) HPV 31 (1.1%) 18 38.9 (20.3-61.4) - (Continued on next page)

- 141 - HPV detection ( Table 18 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Lee 1994 (USA) MY09/11, GP5/GP6, SBH and type-specific for HPV6, 11, 16, 18, 31 21 57.1 (36.5-75.5) - Madeleine 1997 MY09/11 (HPV6/11, 16, 18/45, 55 50.9 (38.1-63.6) - (USA) 31/33/52) or RFLP Monk 1995 (USA) MY09/11, GP5/GP6, SBH and 55 60.0 (46.8-71.9) - type-specific for HPV6, 16, 18 Nuovo 1991 (USA) SBH and probes for HPV6, 11, 23 30.4 (15.6-50.9) - 16, 18, 31, 33 and 35 Pinto 1999 (USA) PCR-RFLP MY09/11 16 50.0 (28.0-72.0) - Sagerman 1996 (USA) Sutton 2008 (USA) E6 for HPV6/11 and HPV16/18 and E1/E2 for HPV33. MY09/11. SBH. PCR with Linear Array HPV for HPV types 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 81, 82, 83, 84, IS39, CP6108 19 15.8 (5.5-37.6) - 116 69.8 (60.9-77.4) - Tate 1994 (USA) MY09/11 13 53.9 (29.1-76.8) - Riethdorf (World) 2004 f PCR-GP5+/6+, PCR L1-Consensus primer, TS (HPV 16) 71 87.3 (77.6-93.2) HPV 16 (87.3%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; EIA: Enzyme ImmunoAssay; ISH: In Situ Hybridization; LBA: Line-Blot Assay; LiPA: Line Probe Assay; PCR: Polymerase Chain Reaction; RFLP: Restriction Fragment Length Polymorphism; RLBM: Reverse Line Blotting Method; RT-PCR: Real Time Polymerase Chain Reaction; SBH: Southern Blot Hybridization; SPF: Short Primer Fragment; TS: Type Specific; a Includes cases from Mali, Mozambique, Nigeria, and Senegal b Includes cases from Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey c Includes cases from Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom d Includes cases from Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay, and Venezuela e Includes cases from Australia and New Zealand f Includes cases from Germany and United States of America Data sources: See references in Section 9. Table 19: Studies on HPV prevalence among cases of VIN 2/3 in the World HPV detection Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) de Sanjosé 2013 a (Asia) Tan 2013 (Australia) Goffin 2006 (Canada) Skapa 2007 (Czech Rep.) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) PCR L1-Consensus primer, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 69, 70, 71, 73, 74, 82) 20 100.0 (83.9-100.0) HPV 16 (80.0%) HPV 6 (5.0%) HPV 18 (5.0%) HPV 33 (5.0%) HPV 35 (5.0%) 44 90.9 (78.8-96.4) HPV 16 (68.2%) HPV 26 (4.5%) HPV 33 (4.5%) HPV 52 (4.5%) HPV 82 (4.5%) HC2 22 63.6 (43.0-80.3) - PCR-GP5+/GP6+, TS (HPV 3, 7, 6, 10, 11, 13, 16, 18, 26-35, 39, 40, 42-45, 51, 53-59, 61, 62, 66-74, 77, 81-87, 89-91) 48 89.6 (77.8-95.5) HPV 16 (70.8%) HPV 18 (6.3%) HPV 45 (4.2%) HPV 6 (2.1%) HPV 11 (2.1%) (Continued on next page)

- 142 - HPV detection ( Table 19 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Bryndorf 2004 (Denmark) Hørding 1991 (Denmark) Junge 1995 (Denmark) de Sanjosé 2013 b (Europe) Hampl 2006 (Germany) Hillemanns 2006 (Germany) Tsimplaki 2012 (Greece) Bonvicini 2005 (Italy) de Sanjosé 2013 c (Latin America & Caribbean) van Beurden 1995 (Netherlands) van der Avoort 2006 (Netherlands) van Seters 2008 (Netherlands) de Sanjosé 2013 d (Oceania) Lerma 1999 (Spain) Abdel-Hady 2001 (UK) PCR-SPF10, LIPA, (HPV 6, 11, 16, 18, 31, 33-35, 39, 40, 42-45, 51-54, 56, 58, 59, 66, 68, 70, 74) 10 90.0 (59.6-98.2) HPV 16 (70.0%) HPV 33 (30.0%) PCR-E6/E7, TS (HPV 16) 19 78.9 (56.7-91.5) HPV 16 (78.9%) PCR-E6/E7, ISH (6/11, 16/18, 31/33) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) PCR-MY09/11, GP5/GP6, TS (HPV 6, 11, 16, 18, 31, 33, 35, 40, 42, 44, 45, 51, 52, 53, 55, 56, 58, 61, 66-68, 73, 74, 91, IS887/MM4, HPVIA18) HC2 (HPV 6, 11, 16, 18, 31, 33, 35, 39, 42, 43, 44, 45, 51, 52, 56, 58, 59, 68), TS (HPV16, 18) PCR-E1, hybridization, MABA, (HPV 6, 11, 16, 18, 31, 33, 35, 39, 40, 42-45, 51-53, 55, 56, 58, 59, 66, 68, 70, 73, 82) ISH, PCR-MY09/11, TS (HPV 16, 18, 31, 33, 35, 45, 52, 58) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) 55 89.1 (78.2-94.9) HPV 16 (78.2%) HPV 33 (10.9%) 312 86.9 (82.7-90.2) HPV 16 (69.6%) HPV 33 (11.2%) HPV 18 (2.2%) HPV 6 (1.6%) HPV 52 (1.3%) 168 100.0 (97.8-100.0) HPV 16 (79.8%) HPV 33 (10.7%) HPV 31 (4.2%) HPV 18 (3.0%) 29 86.2 (69.4-94.5) HPV 16 (79.3%) HPV 6 (13.8%) HPV 18 (3.4%) 14 78.6 (52.4-92.4) HPV 16 (64.3%) HPV 18 (7.1%) HPV 51 (7.1%) HPV 52 (7.1%) HPV 53 (7.1%) 25 44.0 (26.7-62.9) HPV 16 (36.0%) HPV 35 (8.0%) HPV 33 (4.0%) HPV 52 (4.0%) 126 77.8 (69.8-84.2) HPV 16 (57.1%) HPV 33 (8.7%) HPV 6 (4.8%) HPV 31 (4.0%) HPV 11 (1.6%) PCR-CPI/IIG, sequencing 46 95.7 (85.5-98.8) HPV 16 (89.1%) HPV 33 (2.2%) HPV 45 (2.2%) PCR-SPF10, LIPA, (HPV 6, 11, 16, 18, 31, 33-35, 39, 40, 42-45, 51-54, 56, 58, 59, 66, 68, 70, 74) PCR-GP5+/6+, RLBM, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81-84, CP6108) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 67, 68, 69, 70, 73, 74, 82, 83, 87, 89, 91) 32 56.3 (39.3-71.8) HPV 16 (40.6%) HPV 6 (6.3%) HPV 31 (6.3%) HPV 33 (3.1%) 52 96.2 (87.0-98.9) HPV 16 (78.8%) HPV 33 (15.4%) HPV 18 (1.9%) 125 94.4 (88.9-97.3) HPV 16 (71.2%) HPV 33 (10.4%) HPV 18 (4.0%) HPV 31 (3.2%) HPV 6 (1.6%) PCR-L1,TS (HPV 16, 18) 12 41.7 (19.3-68.0) HPV 16 (41.7%) PCR-GP5+/6+, TS (HPV 6, 11, 16, 18, 31, 33) 26 84.6 (66.5-93.8) HPV 16 (76.9%) HPV 31 (3.8%) HPV 33 (3.8%) (Continued on next page)

- 143 - HPV detection ( Table 19 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Baldwin 2003 (UK) Bryant 2011 (UK) Daayana 2010 (UK) Ekeowa-Anderson 2012 (UK) Gasco 2002 (UK) Winters 2008 (UK) Gargano 2012 (USA) Rufforny 2005 (USA) Srodon 2006 (USA) Riethdorf (World) 2004 e PCR-GP5+/6+, sequencing 11 100.0 (74.1-100.0) HPV 16 (90.9%) HPV 16 (90.9%) HPV 33 (9.1%) HPV 33 (9.1%) PCR-E1, hybridization, MABA, (HPV 6, 11, 16, 18, 31, 33, 35, 39, 40, 42-45, 51-53, 55, 56, 58, 59, 66, 68, 70, 73, 82 PCR-GP5+/6+,EIA,RLBM, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81(CP8304), 82/MM4, 82/IS39, 83(MM7), 84(MM8), CP6108 49 81.6 (68.6-90.0) HPV 16 (67.3%) HPV 33 (16.3%) HPV 6 (10.2%) HPV 18 (2.0%) HPV 31 (2.0%) 19 78.9 (56.7-91.5) HPV 16 (73.7%) HPV 33 (5.3%) HPV 42 (5.3%) HPV 84 (5.3%) PCR-SPF10, LiPA (HPV 16) 14 78.6 (52.4-92.4) HPV 16 (78.6%) PCR-(MY09/11, CPI/IIG), sequencing PCR-GP5+/6+,EIA,RLBM, HPV (6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70, 71(CP8061), 72, 73, 81(CP8304), 82/MM4, 82/IS39, 83(MM7), 84(MM8), CP6108) PCR, LBA, LiPA (HPV 16, 18, 33, 52, 59) 28 42.9 (26.5-60.9) HPV 16 (42.9%) 18 94.4 (74.2-99.0) HPV 16 (83.3%) HPV 18 (5.6%) HPV 33 (5.6%) 68 97.1 (89.9-99.2) HPV 16 (80.9%) HPV 33 (8.8%) HPV 59 (2.9%) HPV 18 (1.5%) IHS, RT-PCR, TS (HPV 16) 24 79.2 (59.5-90.8) HPV 16 (79.2%) PCR-PGMY09/11, PCR-SPF10, LiPA (HPV 6, 11, 16, 18, 31, 32, 33, 35, 39, 40, 42, 43, 44, 51, 52, 53, 54, 56, 58, 59, 61, 62, 66, 67, 68, 70, 72, 81, 84, 91) PCR-GP5+/6+, PCR L1-Consensus primer, TS (HPV 16) 34 100.0 (89.8-100.0) HPV 16 (91.2%) HPV 18 (5.9%) HPV 35 (5.9%) HPV 11 (2.9%) HPV 33 (2.9%) 60 68.3 (55.8-78.7) HPV 16 (68.3%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; VIN 2/3: Vulvar intraepithelial neoplasia of grade 2/3; EIA: Enzyme ImmunoAssay; HC2: Hybrid Capture 2; ISH: In Situ Hybridization; LBA: Line-Blot Assay; LiPA: Line Probe Assay; MABA: Micro Array-Based Assay; PCR: Polymerase Chain Reaction; RLBM: Reverse Line Blotting Method; RT-PCR: Real Time Polymerase Chain Reaction; SPF: Short Primer Fragment; TS: Type Specific; a Includes cases from Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey b Includes cases from Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom c Includes cases from Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay, and Venezuela d Includes cases from Australia and New Zealand e Includes cases from Germany and United States of America Data sources: See references in Section 9.

- 144 - Figure 94: Ten most frequent HPV types among cases of vulvar cancer in Africa compared to the World Africa (a) World (b) 16 58. 16 19.4 18 4.2 33 1.8 45 4.2 18 1.5 52 4.2 45 0.9 5th* 6 0.6 6th* 31 0.6 7th* 44 0.6 8th* 52 0.5 9th* 51 0.4 10th* 0 10 20 30 40 50 60 56 0.4 0 10 20 30 40 50 60 Type specific HPV prevalence (%) of vulvar cancer cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VIN 2/3: Vulvar intraepithelial neoplasia of grade 2/3; a Includes cases from Mali, Mozambique, Nigeria, and Senegal. b Includes cases from America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay, United States of America and Venezuela); Africa (Mali, Mozambique, Nigeria, and Senegal); Oceania (Australia and New Zealand); Europe (Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom); and in Asia (Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey) Data sources: See references in Section 9. Figure 95: Ten most frequent HPV types among cases of vulvar cancer in Americas compared to the World Americas (a) World (b) 16 26.5 16 19.4 33 2.9 33 1.8 18 2.7 18 1.5 45 2.1 45 0.9 6 1.3 6 0.6 52 0.8 31 0.6 56 0.8 44 0.6 31 0.5 52 0.5 39 0.5 51 0.4 51 0.5 0 10 20 30 56 0.4 0 10 20 30 Type specific HPV prevalence (%) of vulvar cancer cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VIN 2/3: Vulvar intraepithelial neoplasia of grade 2/3; a Includes cases from Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay, United States of America and Venezuela b Includes cases from America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay, United States of America and Venezuela); Africa (Mali, Mozambique, Nigeria, and Senegal); Oceania (Australia and New Zealand); Europe (Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom); and in Asia (Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey) Data sources: See references in Section 9.

- 145 - Figure 96: Ten most frequent HPV types among cases of vulvar cancer in Asia compared to the World Asia (a) World (b) 16 18.1 16 19.4 18 1.6 33 1.8 44 1.6 18 1.5 45 1.1 45 0.9 52 1.1 6 0.6 58 1.1 31 0.6 11 0.5 44 0.6 26 0.5 52 0.5 30 0.5 51 0.4 31 0.5 0 10 20 56 0.4 0 10 20 Type specific HPV prevalence (%) of vulvar cancer cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VIN 2/3: Vulvar intraepithelial neoplasia of grade 2/3; a Includes cases from Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey. b Includes cases from America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay, United States of America and Venezuela); Africa (Mali, Mozambique, Nigeria, and Senegal); Oceania (Australia and New Zealand); Europe (Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom); and in Asia (Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey) Data sources: See references in Section 9. Figure 97: Ten most frequent HPV types among cases of vulvar cancer in Europe compared to the World Europe (a) World (b) 16 13.8 16 19.4 33 1.2 33 1.8 18 0.6 18 1.5 31 0.6 45 0.9 44 0.4 6 0.6 51 0.4 31 0.6 53 0.3 44 0.6 58 0.3 52 0.5 74 0.3 51 0.4 35 0.2 0 10 20 56 0.4 0 10 20 Type specific HPV prevalence (%) of vulvar cancer cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VIN 2/3: Vulvar intraepithelial neoplasia of grade 2/3; a Includes cases from Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom. b Includes cases from America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay, United States of America and Venezuela); Africa (Mali, Mozambique, Nigeria, and Senegal); Oceania (Australia and New Zealand); Europe (Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom); and in Asia (Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey) Data sources: See references in Section 9.

- 146 - Figure 98: Ten most frequent HPV types among cases of vulvar cancer in Oceania compared to the World Oceania (a) World (b) 16 27.3 16 19.4 33 3.6 33 1.8 18 2.7 18 1.5 39 1.4 45 0.9 6 1.4 6 0.6 31 0.9 31 0.6 44 0.9 44 0.6 45 0.9 52 0.5 52 0.9 51 0.4 56 0.9 0 10 20 30 56 0.4 0 10 20 30 Type specific HPV prevalence (%) of vulvar cancer cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VIN 2/3: Vulvar intraepithelial neoplasia of grade 2/3; a Includes cases from Australia and New Zealand b Includes cases from America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay, United States of America and Venezuela); Africa (Mali, Mozambique, Nigeria, and Senegal); Oceania (Australia and New Zealand); Europe (Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom); and in Asia (Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey) Data sources: See references in Section 9. Figure 99: Ten most frequent HPV types among cases of VIN 2/3 in Africa compared to the World Africa World (a) 1st* 16 67.1 2nd* 33 10.2 3rd* 6 2.4 4th* 18 2.4 5th* 6th* No data available 31 52 1.9 1.4 7th* 51 1.2 8th* 56 0.9 9th* 74 0.9 10th* 66 0.7 0 10 20 30 40 50 60 70 Type specific HPV prevalence (%) of VIN 2/3 cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VIN 2/3: Vulvar intraepithelial neoplasia of grade 2/3; a Includes cases from America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay and Venezuela); Oceania (Australia and New Zealand); Europe (Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom); and in Asia (Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey) Data sources: See references in Section 9.

- 147 - Figure 100: Ten most frequent HPV types among cases of VIN 2/3 in Americas compared to the World Americas (a) World (b) 16 56.7 16 67.1 33 8.7 33 10.2 6 4.7 6 2.4 31 3.9 18 2.4 11 1.6 31 1.9 45 1.6 52 1.4 51 1.6 51 1.2 52 1.6 56 0.9 58 1.6 74 0.9 18 0.8 0 10 20 30 40 50 60 70 66 0.7 0 10 20 30 40 50 60 70 Type specific HPV prevalence (%) of VIN 2/3 cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VIN 2/3: Vulvar intraepithelial neoplasia of grade 2/3; a Includes cases from Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay and Venezuela b Includes cases from America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay and Venezuela); Oceania (Australia and New Zealand); Europe (Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom); and in Asia (Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey) Data sources: See references in Section 9. Figure 101: Ten most frequent HPV types among cases of VIN 2/3 in Asia compared to the World Asia (a) World (b) 16 80.0 16 67.1 6 5.0 33 10.2 18 5.0 6 2.4 33 5.0 18 2.4 35 5.0 31 1.9 54 5.0 52 1.4 7th* 51 1.2 8th* 56 0.9 9th* 74 0.9 10th* 0 10 20 30 40 50 60 70 80 90 66 0.7 0 10 20 30 40 50 60 70 80 90 Type specific HPV prevalence (%) of VIN 2/3 cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VIN 2/3: Vulvar intraepithelial neoplasia of grade 2/3; a Includes cases from Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey. b Includes cases from America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay and Venezuela); Oceania (Australia and New Zealand); Europe (Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom); and in Asia (Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey) Data sources: See references in Section 9.

- 148 - Figure 102: Ten most frequent HPV types among cases of VIN 2/3 in Europe compared to the World Europe (a) World (b) 16 69 16 67.1 33 11.2 33 10.2 18 2.2 6 2.4 6 1.6 18 2.4 52 1.3 31 1.9 56 1.3 52 1.4 44 1.0 51 1.2 66 1.0 56 0.9 74 1.0 74 0.9 31 0.6 0 10 20 30 40 50 60 70 66 0.7 0 10 20 30 40 50 60 70 Type specific HPV prevalence (%) of VIN 2/3 cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VIN 2/3: Vulvar intraepithelial neoplasia of grade 2/3; a Includes cases from Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom. b Includes cases from America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay and Venezuela); Oceania (Australia and New Zealand); Europe (Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom); and in Asia (Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey) Data sources: See references in Section 9. Figure 103: Ten most frequent HPV types among cases of VIN 2/3 in Oceania compared to the World Oceania (a) World (b) 16 71.2 16 67.1 33 10.4 33 10.2 18 4.0 6 2.4 31 3.2 18 2.4 6 1.6 31 1.9 51 1.6 52 1.4 11 0.8 51 1.2 34 0.8 56 0.9 40 0.8 74 0.9 42 0.8 0 10 20 30 40 50 60 70 80 66 0.7 0 10 20 30 40 50 60 70 80 Type specific HPV prevalence (%) of VIN 2/3 cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VIN 2/3: Vulvar intraepithelial neoplasia of grade 2/3; a Includes cases from Australia and New Zealand b Includes cases from America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Uruguay and Venezuela); Oceania (Australia and New Zealand); Europe (Austria, Belarus, Bosnia-Herzegovina, Czech Republic, France, Germany, Greece, Italy, Poland, Portugal, Spain and United Kingdom); and in Asia (Bangladesh, India, Israel, South Korea, Kuwait, Lebanon, Philippines, Taiwan and Turkey) Data sources: See references in Section 9.

- 149-4.2.3 Vaginal cancer and precancerous vaginal lesions Vaginal and cervical cancers share similar risk factors and it is generally accepted that both carcinomas share the same aetiology of HPV infection although there is limited evidence available. Women with vaginal cancer are more likely to have a history of other ano-genital cancers, particularly of the cervix, and these two carcinomas are frequently diagnosed simultaneously. HPV DNA is detected among 70% of invasive vaginal carcinomas and 91% of high-grade vaginal neoplasias (VaIN2/3). HPV16 is the most common type in high grade vaginal neoplasias and it is detected in at least 70% of HPV-positive carcinomas (de Martel C et al. Lancet Oncol 2012;13(6):607-15; De Vuyst H et al. Int J Cancer 2009; 124: 1626-36). Alemany (Africa) Table 20: Studies on HPV prevalence among cases of vaginal cancer in the World HPV detection Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) 2014 a Alemany 2014 b (Americas) Alemany 2014 c (Asia-Pacific) Madsen 2008 (Denmark) Alemany (Europe) 2014 d Koyamatsu 2003 (Japan) Alonso 2012 e (Portugal) Ferreira 2008 (Portugal) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 35, 39, 42, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 73, 82) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 35, 39, 42, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 73, 82) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 35, 39, 42, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 73, 82) PCR-GP5+/6+,EIA, RLBM, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81(CP8304), 82/MM4, 82/IS39, 83(MM7), 84(MM8), CP6108) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 35, 39, 42, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 73, 82) E7 (115-158 bp) for HPV16, HPV 18, L1 (250bp) for HPV 6,11,16,18,31,33,42,52,58. PCR L1-Consensus primer, PCR-SPF10, LiPA (HPV 16, 18, 31, 33, 35, 51, 52, 58, 59) PCR-SPF10, LIPA, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-54, 56, 58, 59, 66, 68-71, 73, 74) 19 68.4 (46.0-84.6) HPV 16 (31.6%) HPV 45 (10.5%) HPV 18 (5.3%) HPV 31 (5.3%) HPV 33 (5.3%) 191 78.0 (71.6-83.3) HPV 16 (42.4%) HPV 31 (5.8%) HPV 18 (4.2%) HPV 33 (4.2%) HPV 52 (3.1%) 46 71.7 (57.5-82.7) HPV 16 (41.3%) HPV 33 (4.3%) HPV 68 (4.3%) HPV 18 (2.2%) HPV 26 (2.2%) 27 77.8 (59.2-89.4) HPV 16 (77.8%) HPV 33 (7.4%) HPV 18 (3.7%) HPV 39 (3.7%) HPV 45 (3.7%) 152 71.1 (63.4-77.7) HPV 16 (47.4%) HPV 18 (3.3%) HPV 73 (3.3%) HPV 33 (2.6%) HPV 56 (2.6%) 16 43.8 (23.1-66.8) - 57 70.2 (57.3-80.5) HPV 16 (47.4%) HPV 33 (5.3%) HPV 18 (3.5%) HPV 31 (3.5%) HPV 52 (3.5%) 21 33.3 (17.2-54.6) HPV 16 (33.3%) HPV 31 (28.6%) HPV 40 (14.3%) HPV 6 (9.5%) HPV 18 (9.5%) (Continued on next page)

- 150 - HPV detection ( Table 20 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Fuste 2010 (Spain) Larsson 2013 (Sweden) Carter 2001 (USA) Daling 2002 (USA) Kiyabu 1989 (USA) PCR-SPF10,LIPA, (HPV 6, 11, 16, 18, 31, 33, 34, 35, 39, 40, 42, 43, 45, 51-54, 56, 58, 59, 66, 68, 70, 74) PCR-E6, RT-PCR (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) MY09/11 and RFLP; type-specific for 16, 18. 32 56.3 (39.3-71.8) HPV 16 (56.3%) HPV 52 (6.3%) HPV 35 (3.1%) HPV 51 (3.1%) HPV 58 (3.1%) 69 53.6 (42.0-64.9) HPV 16 (37.7%) HPV 18 (2.9%) HPV 31 (2.9%) HPV 33 (2.9%) HPV 52 (2.9%) 54 90.7 (80.1-96.0) - MY09/11 for 6/11, 16, 18/45, 31. 25 64.0 (44.5-79.8) - E6 for HPV16 and HPV18. 14 64.3 (38.8-83.7) - Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; EIA: Enzyme ImmunoAssay; LiPA: Line Probe Assay; PCR: Polymerase Chain Reaction; RFLP: Restriction Fragment Length Polymorphism; RLBM: Reverse Line Blotting Method; RT-PCR: Real Time Polymerase Chain Reaction; SPF: Short Primer Fragment; a Includes cases from Mozambique, Nigeria b Includes cases from Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United States of America and Venezuela c Includes cases from Australia, Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey d Includes cases from Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom e Includes cases from Portugal and Spain Data sources: See references in Section 9. Table 21: Studies on HPV prevalence among cases of VAIN 2/3 in the World HPV detection Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Alemany 2014 a (Americas) Alemany 2014 b (Asia-Pacific) Chao 2012 (China) Alemany (Europe) 2014 c Hampl 2006 (Germany) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 35, 39, 42, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 73, 82, 89) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 35, 39, 42, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 73, 82, 89) PCR L1-Consensus primer, PCR-E6, DBH, TS, Sequencing (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 26, 30, 31, 33, 35, 39, 42, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 73, 82) PCR-MY09/11, GP5/GP6, TS (HPV 6, 11, 16, 18, 31, 33, 35, 40, 42, 44, 45, 51, 52, 53, 55, 56, 58, 61, 66-68, 73, 74, 91, IS887/MM4, HPVIA18) 80 92.5 (84.6-96.5) HPV 16 (46.3%) HPV 18 (6.3%) HPV 52 (6.3%) HPV 73 (6.3%) HPV 6 (3.8%) 13 100.0 (77.2-100.0) HPV 16 (53.8%) HPV 52 (15.4%) HPV 59 (15.4%) HPV 45 (7.7%) HPV 73 (7.7%) 200 79.5 (73.4-84.5) HPV 16 (39.5%) HPV 58 (10.5%) HPV 33 (7.5%) HPV 39 (7.0%) HPV 52 (6.0%) 96 97.9 (92.7-99.4) HPV 16 (65.6%) HPV 33 (7.3%) HPV 18 (5.2%) HPV 52 (3.1%) HPV 73 (3.1%) 11 90.9 (62.3-98.4) HPV 16 (63.6%) (Continued on next page)

- 151 - HPV detection ( Table 21 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Hampl 2007 (Germany) Tsimplaki 2012 (Greece) PCR-MY09/11, GP5/GP6, TS (HPV 6, 11, 16, 18, 31, 33, 35, 40, 42, 44, 45, 51, 52, 53, 55, 56, 58, 61, 66-68, 73, 74, 91, IS887/MM4, HPVIA18) PCR-E1, hybridization, MABA, (HPV 6, 11, 16, 18, 31, 33, 35, 39, 40, 42-45, 51-53, 55, 56, 58, 59, 66, 68, 70, 73, 82) 17 94.1 (73.0-99.0) HPV 16 (64.7%) HPV 6 (11.8%) HPV 42 (11.8%) HPV 56 (11.8%) HPV 31 (5.9%) 10 40.0 (16.8-68.7) HPV 16 (20.0%) HPV 33 (20.0%) Frega 2007 (Italy) TS (HPV 16, 18) 30 100.0 (88.6-100.0) HPV 16 (86.7%) HPV 18 (13.3%) So 2009 (Korea, HC2 13 92.3 (66.7-98.6) - Rep.) Rhodes 2014 HC2 64 62.5 (50.3-73.3) - (USA) Srodon 2006 (USA) PCR-PGMY09/11, PCR-SPF10, LiPA (HPV 6, 11, 16, 18, 31, 32, 33, 35, 39, 40, 42, 43, 44, 51, 52, 53, 54, 56, 58, 59, 61, 62, 66, 67, 68, 70, 72, 81, 84, 91) 16 93.8 (71.7-98.9) HPV 16 (50.0%) HPV 58 (18.8%) HPV 31 (12.5%) HPV 35 (6.3%) HPV 51 (6.3%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; VAIN 2/3: Vaginal intraepithelial neoplasia of grade 2/3; DBH: Dot Blot Hybridization; EIA: Enzyme ImmunoAssay; HC2: Hybrid Capture 2; LiPA: Line Probe Assay; MABA: Micro Array-Based Assay; PCR: Polymerase Chain Reaction; SPF: Short Primer Fragment; TS: Type Specific; a Includes cases from Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United States of America and Venezuela b Includes cases from Australia, Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey c Includes cases from Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom Data sources: See references in Section 9. Figure 104: Ten most frequent HPV types among cases of vaginal cancer in Africa compared to the World Africa (a) World (b) 16 31.6 16 43.6 45 10.5 31 3.9 18 5.3 18 3.7 31 5.3 33 3.7 33 5.3 45 2.7 39 5.3 58 2.7 7th* 52 2.2 8th* 51 1.7 9th* 73 1.7 10th* 0 10 20 30 40 50 39 1.5 0 10 20 30 40 50 Type specific HPV prevalence (%) of vaginal cancer cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VAIN 2/3: Vaginal intraepithelial neoplasia of grade 2/3; a Includes cases from Mozambique, Nigeria. b Includes cases from Europe (Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom); America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela); Africa (Mozambique, Nigeria); Asia (Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey); and Oceania (Australia) Data sources: See references in Section 9.

- 152 - Figure 105: Ten most frequent HPV types among cases of vaginal cancer in Americas compared to the World Americas (a) World (b) 16 42.4 16 43.6 31 5.8 31 3.9 18 4.2 18 3.7 33 4.2 33 3.7 52 3.1 45 2.7 58 3.1 58 2.7 45 2.6 52 2.2 51 2.6 51 1.7 39 2.1 73 1.7 59 1.6 0 10 20 30 40 50 39 1.5 0 10 20 30 40 50 Type specific HPV prevalence (%) of vaginal cancer cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VAIN 2/3: Vaginal intraepithelial neoplasia of grade 2/3; a Includes cases from Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela b Includes cases from Europe (Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom); America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela); Africa (Mozambique, Nigeria); Asia (Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey); and Oceania (Australia) Data sources: See references in Section 9. Figure 106: Ten most frequent HPV types among cases of vaginal cancer in Asia compared to the World Asia (a) World (b) 16 39.4 16 43.6 33 3.0 31 3.9 68 3.0 18 3.7 18 3.0 33 3.7 26 3.0 45 2.7 45 3.0 58 2.7 51 3.0 52 2.2 52 3.0 51 1.7 56 3.0 73 1.7 59 3.0 0 10 20 30 40 50 39 1.5 0 10 20 30 40 50 Type specific HPV prevalence (%) of vaginal cancer cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VAIN 2/3: Vaginal intraepithelial neoplasia of grade 2/3; a Includes cases from Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey b Includes cases from Europe (Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom); America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela); Africa (Mozambique, Nigeria); Asia (Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey); and Oceania (Australia) Data sources: See references in Section 9.

- 153 - Figure 107: Ten most frequent HPV types among cases of vaginal cancer in Europe compared to the World Europe (a) World (b) 16 47.4 16 43.6 18 3.3 31 3.9 73 3.3 18 3.7 33 2.6 33 3.7 56 2.6 45 2.7 58 2.6 58 2.7 31 2.0 52 2.2 35 1.3 51 1.7 45 1.3 73 1.7 52 1.3 0 10 20 30 40 50 39 1.5 0 10 20 30 40 50 Type specific HPV prevalence (%) of vaginal cancer cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VAIN 2/3: Vaginal intraepithelial neoplasia of grade 2/3; a Includes cases from Austria, Belarus, Czech Republic, France, Germany, Greece,Poland, Spain and United Kingdom b Includes cases from Europe (Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom); America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela); Africa (Mozambique, Nigeria); Asia (Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey); and Oceania (Australia) Data sources: See references in Section 9. Figure 108: Ten most frequent HPV types among cases of vaginal cancer in Oceania compared to the World Oceania (a) World (b) 16 46.2 16 43.6 33 7.7 31 3.9 68 7.7 18 3.7 31 7.7 33 3.7 58 7.7 45 2.7 6th* 58 2.7 7th* 52 2.2 8th* 51 1.7 9th* 73 1.7 10th* 0 10 20 30 40 50 39 1.5 0 10 20 30 40 50 Type specific HPV prevalence (%) of vaginal cancer cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). VAIN 2/3: Vaginal intraepithelial neoplasia of grade 2/3; a Includes cases from Australia b Includes cases from Europe (Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom); America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela); Africa (Mozambique, Nigeria); Asia (Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey); and Oceania (Australia) Data sources: See references in Section 9.

- 154 - Figure 109: Ten most frequent HPV types among cases of VaIN 2/3 in Africa compared to the World Africa World (a) 1st* 16 56.1 2nd* 18 5.3 3rd* 52 5.3 4th* 73 4.8 5th* 6th* No data available 33 59 4.2 3.7 7th* 56 2.6 8th* 51 2.1 9th* 6 1.6 10th* 35 1.6 0 10 20 30 40 50 60 Type specific HPV prevalence (%) of VaIN 2/3 cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). a Includes cases from Europe (Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom); America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela); Asia (Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey); and Oceania (Australia) Data sources: See references in Section 9. Figure 110: Ten most frequent HPV types among cases of VaIN 2/3 in Americas compared to the World Americas (a) World (b) 16 46.3 16 56.1 18 6.3 18 5.3 52 6.3 52 5.3 73 6.3 73 4.8 51 3.8 33 4.2 56 3.8 59 3.7 6 3.8 56 2.6 31 2.5 51 2.1 58 2.5 6 1.6 59 2.5 0 10 20 30 40 50 60 35 1.6 0 10 20 30 40 50 60 Type specific HPV prevalence (%) of VaIN 2/3 cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). a Includes cases from Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela b Includes cases from Europe (Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom); America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela); Asia (Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey); and Oceania (Australia) Data sources: See references in Section 9.

- 155 - Figure 111: Ten most frequent HPV types among cases of VaIN 2/3 in Asia compared to the World Asia (a) World (b) 16 53.8 16 56.1 52 15.4 18 5.3 59 15.4 52 5.3 45 7.7 73 4.8 73 7.7 33 4.2 6th* 59 3.7 7th* 56 2.6 8th* 51 2.1 9th* 6 1.6 10th* 0 10 20 30 40 50 60 35 1.6 0 10 20 30 40 50 60 Type specific HPV prevalence (%) of VaIN 2/3 cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). a Includes cases from Australia, Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey. b Includes cases from Europe (Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom); America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela); Asia (Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey); and Oceania (Australia) Data sources: See references in Section 9. Figure 112: Ten most frequent HPV types among cases of VaIN 2/3 in Europe compared to the World Europe (a) World (b) 16 65.6 16 56.1 33 7.3 18 5.3 18 5.2 52 5.3 52 3.1 73 4.8 73 3.1 33 4.2 35 2.1 59 3.7 53 2.1 56 2.6 56 2.1 51 2.1 59 2.1 6 1.6 30 1.0 0 10 20 30 40 50 60 70 35 1.6 0 10 20 30 40 50 60 70 Type specific HPV prevalence (%) of VaIN 2/3 cases Data updated at 20 Mar 2015 (data as of 30 Jun 2014). a Includes cases from Austria,Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom b Includes cases from Europe (Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom); America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela); Asia (Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey); and Oceania (Australia) Data sources: See references in Section 9.

- 156 - Figure 113: Ten most frequent HPV types among cases of VaIN 2/3 in Oceania compared to the World Oceania (a) World (b) 16 53.8 16 56.1 52 15.4 18 5.3 59 15.4 52 5.3 45 7.7 73 4.8 73 7.7 33 4.2 6th* 59 3.7 7th* 56 2.6 8th* 51 2.1 9th* 6 1.6 10th* 0 10 20 30 40 50 60 35 1.6 0 10 20 30 40 50 60 Type specific HPV prevalence (%) of VaIN 2/3 cases *No data available. No more types than shown were tested or were positive. Data updated at 20 Mar 2015 (data as of 30 Jun 2014). a Includes cases from Australia, Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey. b Includes cases from Europe (Austria, Belarus, Czech Republic, France, Germany, Greece, Poland, Spain and United Kingdom); America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Paraguay, Uruguay, United states of America and Venezuela); Asia (Bangladesh, India, Israel, South Korea, Kuwait, Philippines, Taiwan and Turkey); and Oceania (Australia) Data sources: See references in Section 9.

- 157-4.2.4 Penile cancer and precancerous penile lesions HPV DNA is detectable in approximately 50% of all penile cancers ((de Martel C et al. Lancet Oncol 2012;13(6):607-15). Among HPV-related penile tumours, HPV16 is the most common type detected, followed by HPV18 and HPV types 6/11 (Miralles C et al. J Clin Pathol 2009;62:870-8). Over 95% of invasive penile cancers are SCC and the most common penile SCC histologic sub-types are keratinizing (49%), mixed warty-basaloid (17%), verrucous (8%), warty (6%), and basaloid (4%). HPV is most commonly detected in basaloid and warty tumours but is less common in keratinizing and verrucous tumours. In this section, the HPV burden among cases of penile cancers in the World is presented. Table 22: Studies on HPV prevalence among cases of penile cancer in the World HPV detection Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Cubilla 1998 (Americas) Gregoire 1995 (Americas) Rubin 2001 (Americas) Picconi 2000 (Argentina) Aumayr 2013 (Austria) Mannweiler 2013 (Austria) D Hauwers 2012 (Belgium) Afonso 2012 (Brazil) Bezerra 2001 (Brazil) Calmon 2013 (Brazil) Fonseca 2013 (Brazil) PCR and southern Blot. Type specific for 6,11,16,18,31,33,35,52 11 81.8 (52.3-94.9) - PCR Type specific for: 6,11,16 109 23.9 (16.8-32.7) - and 18 + Primers for wide range including 16,18,31,33,35,52 PCR SPF10 + INO-LIPA 142 42.3 (34.4-50.5) - PCR GP5+/6+ and typing by PCR-SSCP PCR-GP5+/6+, PCR L1-Consensus primer, TS (HPV 16, 18, 31, 33) PCR L1-Consensus primer, PCR-SPF10, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 69, 70, 71, 72, 73, 74, 82) PCR-E6, PCR-E7, qpcr (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68) PCR-MY09/11, PCR L1-Consensus primer, PCR-E6, RFLP (HPV 6, 11, 16, 18, 26, 31, 33, 35, 45, 53, 62, 70, 71, 73) 38 71.1 (55.2-83.0) - 26 69.2 (50.0-83.5) HPV 16 (65.4%) HPV 18 (3.8%) HPV 31 (3.8%) 123 58.5 (49.7-66.9) HPV 16 (45.5%) HPV 33 (4.9%) HPV 18 (4.1%) HPV 45 (3.3%) HPV 6 (0.8%) 36 61.1 (44.9-75.2) HPV 16 (47.2%) HPV 59 (5.6%) HPV 6 (2.8%) HPV 11 (2.8%) HPV 33 (2.8%) 133 56.4 (47.9-64.5) HPV 16 (17.3%) HPV 45 (12.8%) HPV 6 (6.8%) HPV 18 (3.8%) HPV 31 (3.0%) PCR consensus primers and probing forhpv types: 82 30.5 (21.6-41.1) - 6,11,16,18,31,33,34,35,39,40,42,43,44,45,51,52,54,56 and 58 PCR-GP5+/6+, PCR L1-Consensus primer, qpcr, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 69, 70, 71, 73, 74, 82) PCR-GP5+/6+, Sequencing (HPV 6, 11, 16, 18, 33, 45, 51, 52, 53, 58, 68) (Continued on next page) 47 48.9 (35.3-62.8) HPV 16 (40.4%) HPV 11 (10.6%) HPV 35 (2.1%) 82 61.0 (50.2-70.8) HPV 11 (39.0%) HPV 6 (19.5%) HPV 16 (18.3%) HPV 53 (11.0%) HPV 33 (2.4%)

- 158 - HPV detection ( Table 22 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Levi 1998 (Brazil) Scheiner 2008 (Brazil) Maden 1993 (Canada) Chan 1994 (China) Krustrup 2009 (Denmark) Humbey 2003 (France) Perceau 2003 (Germany) Poetsch 2011 (Germany) Gentile 2006 (Italy) Tornesello 2008 (Italy) Iwasawa 1993 (Japan) Suzuki 1994 (Japan) Yanagawa 2008 (Japan) López-Romero 2013 (Mexico) Salazar 2005 (Mexico) Heideman 2007 (Netherlands) Lont 2006 (Netherlands) PCR MY09/11 and probing for 6,11,16,18,31 PCR-GP5+/6+, PCR-MY09/11, RFLP (HPV 6, 16, 18, 31, 33, 45, 71) 50 56.0 (42.3-68.8) - 80 72.5 (61.9-81.1) HPV 16 (15.0%) HPV 6 (5.0%) HPV 18 (1.3%) HPV 31 (1.3%) HPV 33 (1.3%) PCR E6/E7 for HPV6,16 and 18 67 49.3 (37.7-60.9) - PCR Type specific for HPV16/18 41 19.5 (10.2-34.0) - PCR-GP5+/6+, EIA, RLBM, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81(CP8304), 82/MM4, 82/IS39, 83(MM7), 84(MM8), CP6108) PCR-(MY09/MY11, FAP59/FAP64), TS (HPV 5, 6, 8, 11, 16, 18, 31, 33, 35, 45, 51, 52, 58, 68), sequencing PCR-GP5+/6+, TS (HPV 16, 18, 31, 33) 145 61.4 (53.3-68.9) HPV 16 (53.8%) HPV 6 (3.4%) HPV 33 (2.1%) HPV 11 (0.7%) HPV 31 (0.7%) 36 66.7 (50.3-79.8) HPV 16 (25.0%) HPV 5 (5.6%) 17 35.3 (17.3-58.7) HPV 16 (17.6%) PCR-,TS (HPV 6/11, 16, 18) 52 38.5 (26.5-52.0) HPV 16 (32.7%) HPV 18 (1.9%) PCR-(MY09/11, GP5+/6+), sequencing PCR-GP5+/6+, PCR-MY09/11, PCR-L1C1/C2, PCR-E6, PCR-E7, Sequencing (HPV 6, 16, 18, 33, 35) PCR type specific for HPV 16,18 and 33 PCR consensus primers on L1 and E6 (6,11,16,18,31,33,42,52,58 PCR-L1C1/C2, RFLP (HPV 6, 11, 16, 18, 31, 33, 42, 52, 58) PCR-E6, RT-PCR, Sequencing (HPV 11, 16, 18, 31, 33, 58, 59) 11 72.7 (43.4-90.3) HPV 16 (45.5%) HPV 18 (18.2%) HPV 53 (9.1%) 61 47.5 (35.5-59.8) HPV 16 (42.6%) HPV 18 (3.3%) HPV 35 (1.6%) 111 63.1 (53.8-71.5) - 13 53.8 (29.1-76.8) - 26 11.5 (4.0-29.0) HPV 16 (11.5%) 76 75.0 (64.2-83.4) HPV 16 (61.8%) HPV 11 (3.9%) HPV 31 (3.9%) HPV 18 (1.3%) HPV 33 (1.3%) PCR Specific for HPV16 57 59.6 (46.7-71.4) - PCR-GP5+/6+, EIA, RLBM, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81(CP8304), 82/MM4, 82/IS39, 83(MM7), 84(MM8), CP6108) PCR-GP5+/6+, RLBM, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81(CP8304), 82/MM4, 82/IS39, 83(MM7), 84(MM8), CP6108) 83 55.4 (44.7-65.6) HPV 16 (28.9%) HPV 18 (3.6%) HPV 6 (2.4%) HPV 45 (2.4%) HPV 33 (1.2%) 171 29.2 (22.9-36.5) HPV 16 (22.2%) HPV 18 (1.8%) HPV 45 (1.8%) HPV 33 (1.2%) HPV 56 (0.6%) (Continued on next page)

- 159 - HPV detection ( Table 22 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Cubilla 2010 (Paraguay) Lebelo 2014 (South Africa) Ferrándiz-Pulido 2013 (Spain) Guerrero 2008 (Spain) Pascual 2007 (Spain) Kirrander 2011 (Sweden) Senba 2006 (Thailand) Tornesello 2008 (Uganda) PCR-SPF10, LiPA (HPV 6, 11, 16, 18, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 70, 73, 74) PCR L1-Consensus primer, PCR-E6, PCR-E7, qpcr (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68) PCR-SPF10, EIA, LiPA (HPV 6, 11, 16, 18, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 70, 73, 74) PCR-GP5+/6+, RLBM, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-59, 61, 66, 68, 70-73, 81(CP8304), 82/MM4, 82/IS39, 83(MM7), 84(MM8), CP6108) PCR-(MY09/11, GP5+/6+), sequencing PCR-(HPV 6,11, 16,18,31,33,35,39,45,51,52,56,58,59), sequencing 202 31.7 (25.7-38.4) HPV 16 (22.8%) HPV 6 (3.0%) HPV 18 (2.0%) HPV 11 (1.5%) HPV 35 (1.5%) 40 87.5 (73.9-94.5) HPV 16 (55.0%) HPV 11 (30.0%) HPV 18 (10.0%) HPV 45 (5.0%) HPV 6 (2.5%) 78 37.2 (27.3-48.3) HPV 16 (26.9%) HPV 58 (3.8%) HPV 6 (2.6%) HPV 33 (1.3%) HPV 45 (1.3%) 24 45.8 (27.9-64.9) HPV 16 (45.8%) HPV 26 (4.2%) HPV 39 (4.2%) 49 77.6 (64.1-87.0) HPV 16 (65.3%) HPV 18 (8.2%) 151 80.8 (73.8-86.3) HPV 16 (60.3%) HPV 18 (27.2%) HPV 6 (9.3%) HPV 45 (2.0%) HPV 52 (2.0%) PCR SPF10, ISH 65 81.5 (70.4-89.1) - PCR-GP5+/6+, PCR-MY09/11, PCR-L1C1/C2, PCR-E6, PCR-E7, Sequencing (HPV 6, 16, 18, 33, 35) Prowse 2008 (UK) PCR-SPF10, LIPA, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-54, 56, 58, 59, 66, 68-71, 73, 74) Stankiewicz 2011 (UK) Cupp 1995 (USA) Daling 2005 (USA) Sarkar 1992 (USA) Varma 1991 (USA) PCR-SPF10, LIPA, (HPV 6, 11, 16, 18, 26, 31, 33-35, 39, 40, 42-45, 51-54, 56, 58, 59, 66, 68-71, 73, 74) PCR L1-Consensus primer, PCR-E6, TS (HPV 16, 18) 17 64.7 (41.3-82.7) HPV 16 (58.8%) HPV 6 (11.8%) HPV 18 (11.8%) HPV 33 (5.9%) 26 53.8 (35.5-71.2) HPV 16 (42.3%) HPV 56 (11.5%) HPV 52 (7.7%) HPV 6 (3.8%) HPV 18 (3.8%) 102 55.9 (46.2-65.1) HPV 16 (45.1%) HPV 11 (9.8%) HPV 6 (5.9%) HPV 45 (5.9%) HPV 31 (4.9%) 42 54.8 (39.9-68.8) HPV 16 (40.5%) HPV 18 (4.8%) PCR MY09/11 94 79.8 (70.6-86.7) - PCR type specific for 6b/11, 16 and 18 + Southern Blot PCR Type specific for HPV 6/11 and 16 and ISH for 6,11,16,18,31,33 and 35 27 59.3 (40.7-75.5) - 30 66.7 (48.8-80.8) - (Continued on next page)

- 160 - HPV detection ( Table 22 continued from previous page) Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Do 2013 (Viet Nam) PCR-SPF10, PCR-E6, qpcr, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 43, 44, 45, 51, 52, 54, 56, 58, 59, 66, 68, 69, 70, 71, 73, 74, 82) 120 22.5 (15.9-30.8) HPV 16 (20.0%) HPV 11 (0.8%) HPV 18 (0.8%) HPV 33 (0.8%) HPV 58 (0.8%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; EIA: Enzyme ImmunoAssay; ISH: In Situ Hybridization; LiPA: Line Probe Assay; PCR: Polymerase Chain Reaction; RFLP: Restriction Fragment Length Polymorphism; RLBM: Reverse Line Blotting Method; RT-PCR: Real Time Polymerase Chain Reaction; SPF: Short Primer Fragment; TS: Type Specific; Data sources: See references in Section 9. Table 23: Studies on HPV prevalence among cases of PeIN 2/3 in the World HPV detection Prevalence of 5 most method and targeted HPV prevalence frequent HPVs Study HPV types No. Tested % (95% CI) HPV type (%) Mannweiler 2013 (Austria) D Hauwers 2012 (Belgium) López-Romero 2013 (Mexico) Kirrander 2011 (Sweden) Wikström 2012 (Sweden) Cupp 1995 (USA) PCR L1-Consensus primer, PCR-SPF10, LiPA (HPV 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 43, 44, 45, 51, 52, 53, 54, 56, 58, 66, 68, 69, 70, 71, 72, 73, 74, 82) PCR-E6, PCR-E7, qpcr (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68) PCR-E6, RT-PCR, Sequencing (HPV 16) PCR-(HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59), sequencing PCR-GP5+/6+, PCR-MY09/11, PCR L1-Consensus primer (HPV 6, 11, 16, 18, 31, 33, 42, 45, 52, 58, 70, 73) PCR L1-Consensus primer, PCR-E6, TS (HPV 16, 18) 43 76.7 (62.3-86.8) HPV 16 (62.8%) HPV 18 (9.3%) HPV 33 (2.3%) HPV 73 (2.3%) 13 84.6 (57.8-95.7) HPV 16 (61.5%) HPV 18 (23.1%) HPV 11 (15.4%) HPV 53 (15.4%) HPV 56 (15.4%) 10 100.0 (72.2-100.0) HPV 16 (100.0%) 62 88.7 (78.5-94.4) HPV 16 (71.0%) HPV 18 (29.0%) HPV 33 (6.5%) HPV 6 (4.8%) HPV 11 (3.2%) 28 85.7 (68.5-94.3) HPV 16 (39.3%) HPV 6 (21.4%) HPV 31 (7.1%) HPV 33 (7.1%) HPV 45 (7.1%) 25 92.0 (75.0-97.8) HPV 16 (80.0%) HPV 18 (8.0%) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). 95% CI: 95% Confidence Interval; PeIN 2/3: Penile intraepithelial neoplasia of grade 2/3; LiPA: Line Probe Assay; PCR: Polymerase Chain Reaction; RT-PCR: Real Time Polymerase Chain Reaction; SPF: Short Primer Fragment; TS: Type Specific; Data sources: See references in Section 9.

- 161-4.3 HPV burden in men The information to date regarding anogenital HPV infection is primarily derived from cross-sectional studies of selected populations such as general population, university students, military recruits, and studies that examined husbands of control women, as well as from prospective studies. Special subgroups include mainly studies that examined STD (sexually transmitted diseases) clinic attendees, MSM (men who have sex with men), HIV positive men, and partners of women with HPV lesions, CIN (cervical intraepithelial neoplasia), cervical cancer or cervical carcinoma in situ. Globally, prevalence of penile and external genital HPV in men is higher than cervical HPV in women, but persistence is less likely. As with genital HPV prevalence, high numbers of sexual partners increase acquisition of oncogenic HPV infections (Vaccine 2012, Vol. 30, Suppl 5). In this section, the HPV burden among men in World is presented. Brief methods: Prevalence of human papillomavirus in men: based on systematic reviews and meta-analyses The HPV-prevalence for HPV burden in men was based on published systematic reviews and metaanalyses (Dunne EF, J Infect Dis 2006; 194: 1044, Smith JS, J Adolesc Health 2011; 48: 540, and Hebnes JB, J Sex Med 2014; 11: 2630) up to September 15, 2014. Search terms were human papillomavirus, men, polymerase chain reaction (PCR), hybrid capture (HC), and viral DNA. References cited in selected articles were also investigated. Inclusion criteria were: HPV DNA detection by means of PCR or HC, a minimum of 20 cases for men and a detailed description of HPV DNA detection and genotyping techniques used. The number of cases tested and HPV positive extracted for each study were pooled to estimate the prevalence of HPV DNA globally and by geographical region. Binomial 95% confidence intervals were calculated for each HPV prevalence.

- 162 - Table 24: Studies on anogenital HPV prevalence among men in the World Anatomic sites HPV detection Age HPV prev Country Study samples method Population (years) No % (95% CI) Brazil Brazil Brazil Brazil Brazil Chile Nyitray 2011 Rosenblatt 2004 Nyitray 2011 Giuliano 2008b Franceschi 2002 Guzmán 2008 Anal canal PCR-PGMY09/11 HIV- MSW from general population and population from a STD clinic Shaft, dorsal and prebalanic area, prepuce, urethral meatus HC2 HR Partners of women without CIN Anal canal PCR-PGMY09/11 HIV- MSM from general population and population from a STD clinic Corona sulcus, glans, shaft and scrotum Glans, corona, urethra China Liu 2014 Coronal sulcus, shaft, glans, and scrotum Colombia Franceschi 2002 PCR-PGMY09/11 and GP5/6+ PCR-GP5+/6+ 18-70 1305 12.2 (10.5-14.1) - 60 15.0 (7.1-26.6) 18-70 176 47.2 (39.6-54.8) General population 18-70 382 72.3 (67.5-76.7) Husbands of control women 24-81 56 39.3 (26.5-53.2) Corona and shaft PCR-GP5+/6+ University students 20-51 61 83.6 (71.9-91.8) Glans, corona, urethra PCR-SPF1/GP6+ PCR-GP5+/6+ Croatia Grce 1996 Urethra Filter hybridization (slot-blot, TS 6,11,16,18) Denmark Kjaer 2005 Glans and corona sulcus Finland Hippeläinen 1993 Glans, prepuce, corona sulcus, urethral meatus PCR-GP5+/6+ TS oligoprobes PCR-MY09/11 TS 6,11,16,18,31,33 Finland Kero 2011 Urethra PCR-MY09/11 and GP5+/6+ Germany Grussendorf- Conen 1987 Coronal sulcus and glans India Gupta 2006 Coronal sulcus, distal and intrameatal urethra and glans ISH PCR-L1 and TS 16,18 Italy Nasca 2006 Penis PCR-MY09/11 and GP5+/6+ Italy Japan Lorenzon 2014 Takahashi 2003 Coronal sulcus, shaft, prepuce, and urethral Glans, corona, prepuce Kenya Ng ayo 2008 Glans, corona sulcus, shaft of the penis, scrotum and the perianal region Kenya Smith 2010 Shaft, glans, coronal sulcus, and inner and external foreskin tissue Korea, Republic of Shin 2004 Glans, corona, scrotum, prepuce, urethra PCR-Roche Linear Array HPV Genotyping test Population-based esophageal cancer cohort study Husbands of control women Family planning clinic attendees 25-65 1279 41.1 (38.4-43.9) 23-82 128 18.8 (12.4-26.6) - 79 26.6 (17.3-37.7) Military conscripts 18-29 337 33.8 (28.8-39.2) Voluntary conscripts Mean 20 285 16.5 (12.4-21.3) Sexual partners of pregnant women Blood donors or patients from department of dermatology Partners of women with normal cytology Hospital based controls attending clinic for nongenital complaints Heterosexual men for routine HPV testing 19-46 128 22.7 (15.7-30.9) 16-79 530 5.8 (4.0-8.2) Mean 46.9 30 26.7 (12.3-45.9) 27-79 46 8.7 (2.4-20.8) 18-68 378 40.5 (35.5-45.6) HC2 HR, LR University students 18-35 75 1.3 (0.0-7.2) PCR-PGMY09/MY11 and HMB01 PCR-GP5+/6+ Men working in the fishing industry Men screened to participate in an RCT of male circumcision 18-63 250 57.6 (51.2-63.8) 17-28 2705 51.1 (49.2-53.0) PCR-SPF10 Male students Median 22 381 8.7 (6.0-11.9) (Continued on next page)

- 163 - ( Table 24 continued from previous page) Anatomic sites HPV detection Age HPV prevalence Country Study samples method Population (years) No % (95% CI) Mexico Nyitray 2011 Mexico Lajous 2005 Corona, shaft, upper third of the scrotum, urethral meatus, urethra Mexico Sánchez- Alemán 2002 Anal canal PCR-PGMY09/11 HIV- MSM from organized health care systems, factories and military Glans and prepuce Mexico Lajous 2005 Corona, shaft, upper third of the scrotum, urethral meatus, urethra Mexico Mexico Mexico Mexico Mexico Mexico Mexico Mexico Mexico Mexico Philippines Rwanda Rwanda Giuliano 2008b Vaccarella 2006 Nyitray 2011 Sánchez- Alemán 2002 Nyitray 2011 Nyitray 2011 Lazcano- Ponce 2001 Giuliano 2008b Lazcano- Ponce 2001 Vaccarella 2006 Franceschi 2002 Veldhuijzen 2012 Veldhuijzen 2012 Corona sulcus, glans, shaft and scrotum Scrotum, coronal sulcus, the glans and the opening of the meatus PCR-BGH 20 and BPCO4 18-70 176 47.2 (39.6-54.8) Military conscripts 16-40 1030 44.6 (41.5-47.7) HC2 HR University students >=18 71 8.5 (3.2-17.5) PCR-BGH 20 and BPCO4 PCR-PGMY09/11 and GP5/6+ PCR-PGMY09/11 Military conscripts 16-40 1030 44.6 (41.5-47.7) General population and organized health care systems Men who requested a vasectomy Anal canal PCR-PGMY09/11 HIV- MSW from organized health care systems, factories and military Glans and prepuce 18-70 362 61.9 (56.7-66.9) Mean 34 779 8.7 (6.8-10.9) 18-70 1305 12.2 (10.5-14.1) HC2 HR University students >=18 71 8.5 (3.2-17.5) Anal canal PCR-PGMY09/11 HIV- MSW from organized health care systems, factories and military Anal canal PCR-PGMY09/11 HIV- MSM from organized health care systems, factories and military Corona, urethra PCR-GP5+/6+ Sexually active college students and industry workers Corona sulcus, glans, shaft and scrotum PCR-PGMY09/11 and GP5/6+ General population and organized health care systems Corona, urethra PCR-GP5+/6+ Sexually active college students and industry workers Scrotum, coronal sulcus, the glans and the opening of the meatus Glans, corona, urethra Shaft, scrotum, glans/sulcus corona, and foreskin in uncircumcised men Shaft, scrotum, glans/sulcus corona, and foreskin in uncircumcised men PCR-PGMY09/11 PCR-GP5+/6+ PCR-Roche Linear Array HPV Genotyping test (LR-HPV types) PCR-Roche Linear Array HPV Genotyping test (HR-HPV types) Men who requested a vasectomy Husbands of control women Men participating in a case control study assessing risk factors for infertility Men participating in a case control study assessing risk factors for infertility 18-70 1305 12.2 (10.5-14.1) 18-70 176 47.2 (39.6-54.8) 14-55 96 42.7 (32.7-53.2) 18-70 362 61.9 (56.7-66.9) 14-55 96 42.7 (32.7-53.2) Mean 34 779 8.7 (6.8-10.9) 19-71 106 4.7 (1.5-10.7) Median 31 (IQR=27-38) Median 31 (IQR=27-38) 166 31.3 (24.4-39.0) 166 26.5 (20.0-33.9) (Continued on next page)

- 164 - ( Table 24 continued from previous page) Anatomic sites HPV detection Age HPV prevalence Country Study samples method Population (years) No % (95% CI) South Africa Auvert 2010 Urethra PCR-Roche Amplicor HPV test Spain Sweden Sweden Franceschi 2002 Forslund 1993 Kataoka 1991 Glans, corona, urethra Urethra Urethra Tanzania Olesen 2013 Glans, preputial cavity (uncircumcised men), coronal sulcus (circumcised men), shaft, corpus Thailand United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America Franceschi 2002 Weaver 2004 Giuliano 2008a Nyitray 2011 Giuliano 2008b Hernandez 2008 Nielson 2007 Nyitray 2011 Partridge 2007 Glans, corona, urethra Glans, prepuce, shaft, scrotum Corona sulcus, glans, shaft and scrotum PCR-GP5+/6+ PCR-TS (6,11,16,18,31,33,35) and unespecified consensus primer PCR-TS 6,11,16,18,33 PCR-LIPA and HC2 PCR-GP5+/6+ PCR-MY09/11 HMB 01 Men recruited from the general population for an RCT of male circumcision Husbands of control women IQR=19-22 1683 19.1 (17.2-21.0) 24-78 168 3.6 (1.3-7.6) Military conscripts 20-23 138 8.7 (4.6-14.7) Army conscripts with normal epithelium Men from the general population Husbands of control women 18-23 66 12.1 (5.4-22.5) Mean 34.2 1813 20.5 (18.7-22.5) 28-78 75 17.3 (9.6-27.8) University students 18-25 283 35.0 (29.4-40.9) PCR-PGMY09/11 General population 18-44 290 30.0 (24.8-35.6) Anal canal PCR-PGMY09/11 HIV- MSW from general population and population from University Corona sulcus, glans, shaft and scrotum Glans, corona sulcus, penile shaft, scrotum Glans, corona sulcus, penile shaft and scrotum, perianal area, anus PCR-PGMY09/11 and GP5/6+ General population and population from University 18-70 1305 12.2 (10.5-14.1) 18-70 416 61.3 (56.4-66.0) PCR-PGMY09/11 University population Mean 29 300 35.3 (29.9-41.0) PCR-PGMY09/11 General population volunteers and STD clinic attendees Anal canal PCR-PGMY09/11 HIV- MSM from general population and population from University Glans, urethral meatus, penile shaft and scrotum PCR-MY09/11 HMB 01 Heterosexual university students 18-40 463 65.4 (60.9-69.8) 18-70 176 47.2 (39.6-54.8) 18-20 240 25.8 (20.4-31.9) Data updated at 15 Dec 2014 (data as of 15 Sep 2014). HC2: Hybrid Capture 2; ISH: In Situ Hybridization; PCR: Polymerase Chain Reaction; SPF: Short Primer Fragment; TS: Type Specific; Data sources: Based on published systematic reviews, the has updated data until September 2014. Reference publications: 1) Dunne EF, J Infect Dis 2006; 194: 1044 2) Smith JS, J Adolesc Health 2011; 48: 540 3) Olesen TB, Sex Transm Infect 2014; 90: 455 4) Hebnes JB, J Sex Med 2014; 11: 2630. Auvert B, J Acquir Immune Defic Syndr 2010; 53: 111 Forslund O, J Clin Microbiol 1993; 31: 1975 Franceschi S, Br J Cancer 2002; 86: 705 Giuliano AR, J Infect Dis 2008; 198: 827 Giuliano AR, Cancer Epidemiol Biomarkers Prev 2008; 17: 2036 Grce M, Anticancer Res 1996; 16: 1039 Grussendorf-Conen EI, Arch Dermatol Res 1987; 279 Suppl: S73 Gupta A, J Clin Virol 2006; 37: 190 Guzmán P, Rev Med Chil 2008; 136: 1381 Hernandez BY, J Infect Dis 2008; 197: 787 Hippeläinen M, Sex Transm Dis 1993; 20: 321 Kataoka A, J Med Virol 1991; 33: 159 Kero K, J Sex Med 2011; 8: 2522 Kjaer SK, Cancer Epidemiol Biomarkers Prev 2005; 14: 1528 Lajous M, Cancer Epidemiol Biomarkers Prev 2005; 14: 1710 Lazcano-Ponce E, Sex Transm Dis 2001; 28: 277 Liu M, Cancer Epidemiol Biomarkers Prev 2014 Lorenzon L, J Clin Virol 2014; 60: 264 Nasca MR, Int J Dermatol 2006; 45: 681 Ng ayo MO, Sex Transm Infect 2008; 84: 62 Nielson CM, Cancer Epidemiol Biomarkers Prev 2007; 16: 1107 Nyitray AG, J Infect Dis 2011; 203: 49 Olesen TB, Sex Transm Dis 2013; 40: 592 Partridge JM, J Infect Dis 2007; 196: 1128 Rosenblatt C, Int J Gynaecol Obstet 2004; 84: 156 Sánchez-Alemán MA, Salud Publica Mex 2002; 44: 442 Shin HR, J Infect Dis 2004; 190: 468 Smith JS, Int J Cancer 2010; 126: 572 Takahashi S, Sex Transm Dis 2003; 30: 629 Vaccarella S, Int J Cancer 2006; 119: 1934 Veldhuijzen NJ, Sex Transm Dis 2012; 39: 128 Weaver BA, J Infect Dis 2004; 189: 677

- 165 - Table 25: Studies on anogenital HPV prevalence among men from special subgroups in the World Anatomic sites HPV detection Age HPV prev Country Study samples method Population (years) No % (95% CI) Australia Vajdic 2009 Anal canal HC2 HIV- MSM IQR=36-48 Australia Australia Goldstone 2011 Goldstone 2011 Anus Penis RT-PCR-Multiplex or Biplex RT-PCR-Multiplex or Biplex Australia Vardas 2011 Penis RT-PCR-Multiplex or Biplex Australia Anderson 2008 HIV- MSM Median 22 (16-27) HIV- MSM Median 22 (16-27) Heterosexual men Median 20 (15-24) Anal canal HC2 HR HIV+ MSM Median 45 (28-59) Australia Vajdic 2009 Anal canal HC2 HIV+ MSM IQR=37-49 Brazil Brazil Brazil Rombaldi 2006 Nyitray 2011 Nicolau 2005 Prepuce, preglans, shaft, urethral canal PCR-L1, MY09/11 Partners of women with CIN Anal canal PCR-PGMY09/11 HIV- MSM from general population and population from a STD clinic Glans, urethra, internal and external prepuce, scrotum, anus HC2 HR, LR Brazil Vardas 2011 Penis RT-PCR-Multiplex or Biplex Brazil Brazil Rosenblatt 2004 Franceschi 2002 Brazil de Lima Rocha 2012 Shaft, dorsal and prebalanic area, prepuce, urethral meatus Glans, corona, urethra Coronal sulcus, glans, and prepuce Brazil Freire 2014 Shaft, glans, balanopreputial sulcus and urethral Brazil Brazil Brazil Canada Guimarães 2011 Goldstone 2011 Goldstone 2011 Goldstone 2011 Canada de Pokomandy 2009 HC2 HR PCR-GP5+/6+ PCR-GP5+/6+ PCR-Papillocheck Partners of women with HPV Heterosexual men Median 20 (15-24) Partners of women with CIN Husbands of women with invasive cervical cancer Sexual partners of women with cervical HPV infection Men referred to the Urological Division 193 69.9 (62.9-76.3) 602 42.4 (38.4-46.4) 602 18.4 (15.4-21.8) 3132 21.2 (19.8-22.7) 123 86.2 (78.8-91.7) 123 94.3 (88.6-97.7) 18-56 99 54.5 (44.2-64.6) 18-70 176 47.2 (39.6-54.8) 19-53 50 70.0 (55.4-82.1) 3132 21.2 (19.8-22.7) - 30 76.7 (57.7-90.1) 27-79 53 35.8 (23.1-50.2) 18-60 43 51.2 (35.5-66.7) 18-81 355 72.1 (67.1-76.7) Anus PCR-DBH HIV+ >=18 445 65.6 (61.0-70.0) Penis Anus Penis RT-PCR-Multiplex or Biplex RT-PCR-Multiplex or Biplex RT-PCR-Multiplex or Biplex HIV- MSM Median 22 (16-27) HIV- MSM Median 22 (16-27) HIV- MSM Median 22 (16-27) Anal canal PCR-PGMY09/11 HIV+ MSM Median 43 (21-66) Canada Ogilvie 2009 Shaft, scrotum PCR-Roche Amplicor HPV test Heterosexual men attending provincial STD clinic Canada Salit 2010 Anal canal HC2 HIV+ MSM Median 44.4 (IQR=39.4-50.6) Canada Vardas 2011 Penis RT-PCR-Multiplex or Biplex Canada Salit 2009 Anus PCR-PGMY09/11 HIV+ MSM participants in TRACE study Heterosexual men Median 20 (15-24) 602 18.4 (15.4-21.8) 602 42.4 (38.4-46.4) 602 18.4 (15.4-21.8) 241 97.9 (95.2-99.3) 16-69 262 69.8 (63.9-75.3) 400 93.0 (90.0-95.3) 3132 21.2 (19.8-22.7) 38-50 224 93.3 (89.2-96.2) (Continued on next page)

- 166 - ( Table 25 continued from previous page) Anatomic sites HPV detection Age HPV prevalence Country Study samples method Population (years) No % (95% CI) Canada Goldstone 2011 Anus RT-PCR-Multiplex or Biplex HIV- MSM Median 22 (16-27) 602 42.4 (38.4-46.4) China Tang 2006 Urethral meatus PCR-MY09/11 STD clinic attendees 18-70 305 13.8 (10.1-18.2) China Zhang 2014 Anus PCR-GenoArray HIV+ MSM STD clinic attendees China Yang 2012 Anus PCR-TellgenplexTM HPV DNA Test China Gao 2010 Anal canal PCR-TellgenplexTM HPV DNA Test China Gao 2010 Anal canal PCR-TellgenplexTM HPV DNA Test China Zhang 2014 Anus PCR-GenoArray HIV- MSM, STD clinic attendees Colombia Colombia Franceschi 2002 Franceschi 2002 Glans, corona, urethra Glans, corona, urethra PCR-GP5+/6+ PCR-GP5+/6+ Croatia Vardas 2011 Penis RT-PCR-Multiplex or Biplex Croatia Croatia Goldstone 2011 Goldstone 2011 Penis Anus Denmark Svare 2002 Coronal sulcus, glans, perianal area, scrotum, and shaft France France France France Germany Aynaud 2003 Aynaud 2003 Piketty 2004 Damay 2010 Goldstone 2011 Meatal urethra Meatal urethra RT-PCR-Multiplex or Biplex RT-PCR-Multiplex or Biplex PCR-GP5+/6+ and TS 6,11,16,18,31,33 PCR-TS 6,11,42,16,18,33 PCR-TS 6,11,42,16,18,33 IQR=25-34.8 28 71.4 (51.3-86.8) HIV+ MSM >=18 91 70.3 (59.8-79.5) HIV+ MSM >=18 (70% <30 years) HIV- MSM >=18 (70% <30 years) Husbands of women with invasive cervical cancer Husbands of women with cervical carcinoma in situ IQR=25-34.8 Heterosexual men Median 20 (15-24) HIV- MSM Median 22 (16-27) HIV- MSM Median 22 (16-27) 50 96.0 (86.3-99.5) 528 58.9 (54.6-63.1) 380 33.7 (28.9-38.7) 24-79 50 32.0 (19.5-46.7) 23-76 63 20.6 (11.5-32.7) 3132 21.2 (19.8-22.7) 602 18.4 (15.4-21.8) 602 42.4 (38.4-46.4) STD clinic attendees >=18 198 44.9 (37.9-52.2) Men with penile and urethral lesions whose female partners have genital HPV lesions Men with normal peniscopy whose female partners have genital HPV lesions Mean 29 55 87.3 (75.5-94.7) Mean 30 34 2.9 (0.1-15.3) Anal canal PCR-MY09/11 HIV+ MSM 27-62 45 80.0 (65.4-90.4) Anal canal PCR-PapilloCheck HIV+ MSM Median 45 (39-49.5) Penis RT-PCR-Multiplex or Biplex Germany Vardas 2011 Penis RT-PCR-Multiplex or Biplex Germany Germany Greece Schneider 1988 Goldstone 2011 Hadjivassiliou 2007 Glans, prepuce, fossa navicularis, shaft Anus India Gupta 2006 Coronal sulcus, distal and intrameatal urethra and glans Filter hybridization DNA/DNA RT-PCR-Multiplex or Biplex HIV- MSM Median 22 (16-27) Heterosexual men Median 20 (15-24) Sexual partners of women with HPV associated lesions of the cervix HIV- MSM Median 22 (16-27) Urethra HC2 HR, LR HIV- STD clinic attendees without genital warts and sexual partners of women with genital warts PCR-L1 and TS 16,18 Partners of women with cervical cancer 67 74.6 (62.5-84.5) 602 18.4 (15.4-21.8) 3132 21.2 (19.8-22.7) Mean 36.5 156 39.1 (31.4-47.2) 602 42.4 (38.4-46.4) 15-65 64 20.3 (11.3-32.2) Mean 46.4 30 66.7 (47.2-82.7) (Continued on next page)

- 167 - ( Table 25 continued from previous page) Anatomic sites HPV detection Age HPV prevalence Country Study samples method Population (years) No % (95% CI) Italy Latini 2014 Anus PCR-Linear Array HIV+ MSM Median 41 (IQR=33-47) Italy Benevolo 2008 Coronal sulcus, urethra, prepuce, shaft PCR-L1 Male partners of women with CIN and/or positive HPV Italy Latini 2014 Anus PCR-Linear Array HIV- MSM Median 32 (IQR=27-39) Italy Italy Italy Italy Pierangeli 2008 Giovannelli 2007 Barzon 2010 Orlando 2008 Italy Della Torre 1992 Italy Italy Japan Japan Japan Mexico Mexico Mexico Chiarini 1998 Pierangeli 2008 Takahashi 2003 Shigehara 2010 Takahashi 2005 Nyitray 2011 Leyva- López 2003 Torres- Ibarra 2014 180 93.3 (88.6-96.5) 20-61 71 35.2 (24.2-47.5) 438 72.4 (67.9-76.5) Anal canal PCR-MY09/11 HIV+ MSM 25-65 18 94.4 (72.7-99.9) Coronal sulcus, frenulum, glans, prepuce, shaft Glans, corona, shaft, perianal area, urethra, and semen PCR-LiPA, GP5+/6+ and MY09/11 PCR-General primers for L1 (MY09/11, GP5 + /6+) Partners of women with HPV Men referred for HPV testing. Indications for testing: STD screening, HPV suspected lesions, HPV-positive partners Anus HC2 HIV+ Median 34 (IQR=30-42) Urethra PCR-TS 6,11,16,18 Partners of women with HPV Urethra PCR-Generic primers in E1 Men with symptoms of nongonococcal urethritis 23-58 47 68.1 (52.9-80.9) 20-72 947 41.7 (38.5-44.9) 233 87.1 (82.1-91.1) - 64 21.9 (12.5-34.0) - 247 31.2 (25.5-37.4) Anal canal PCR-MY09/11 HIV- MSM 28-62 9 88.9 (51.8-99.7) Coronal sulcus, glans, prepuce Coronal sulcus, glans, prepuce, urethra, and urine Glans, corona, inner surface of prepuce HC2 HR, LR PCR-HPV GenoArray Patients with urethritis Men with urethritis Mean 35.2 (19-62) 17-49 130 18.5 (12.2-26.2) 142 47.9 (39.4-56.4) HC2 HR, LR STD clinic attendees 18-35 204 5.9 (3.1-10.0) Anal canal PCR-PGMY09/11 HIV- MSM from organized health care systems, factories and military Urethral meatus PCR-L1 Partners of women with CIN 18-70 176 47.2 (39.6-54.8) 17-64 187 2.1 (0.6-5.4) Anus PCR-PGMY09/11 HIV+ MSM 18-69 446 93.0 (90.3-95.2) Mexico Vardas 2011 Penis RT-PCR-Multiplex or Biplex Mexico Mexico Mexico Goldstone 2011 Leyva- López 2003 Goldstone 2011 Anus RT-PCR-Multiplex or Biplex Heterosexual men Median 20 (15-24) HIV- MSM Median 22 (16-27) Urethral meatus PCR-L1 Partners of women with CIN Penis RT-PCR-Multiplex or Biplex Mexico Vardas 2011 Penis RT-PCR-Multiplex or Biplex Mexico Nyitray 2011 HIV- MSM Median 22 (16-27) Heterosexual men Median 20 (15-24) Anal canal PCR-PGMY09/11 HIV- MSM from organized health care systems, factories and military 3132 21.2 (19.8-22.7) 602 42.4 (38.4-46.4) 17-64 187 2.1 (0.6-5.4) 602 18.4 (15.4-21.8) 3132 21.2 (19.8-22.7) 18-70 176 47.2 (39.6-54.8) (Continued on next page)

- 168 - ( Table 25 continued from previous page) Anatomic sites HPV detection Age HPV prevalence Country Study samples method Population (years) No % (95% CI) Mexico Mexico Mexico Goldstone 2011 Goldstone 2011 Netherlands van 2014 Netherlands van 2014 Torres- Ibarra 2014 Rijn Rijn Penis Anus RT-PCR-Multiplex or Biplex RT-PCR-Multiplex or Biplex HIV- MSM Median 22 (16-27) HIV- MSM Median 22 (16-27) 602 18.4 (15.4-21.8) 602 42.4 (38.4-46.4) Anus PCR-PGMY09/11 HIV+ MSM 18-69 446 93.0 (90.3-95.2) Anal canal Penile shaft PCR-LIPA TS 16,18,31,33,45,52,58 PCR-LIPA TS 16,18,31,33,45,52,58 Netherlands Vriend 2013 Anus PCR-SPF10 primers followed by immunoassay Netherlands van 2014 Netherlands Bleeker 2005a Netherlands Bleeker 2005b Rijn Netherlands Van Doornum 1994 Netherlands Vriend 2013 Netherlands Vriend 2013 Netherlands van der Snoek 2003 Netherlands van 2014 Rijn Netherlands van der Snoek 2003 Netherlands van der Snoek 2003 Netherlands Bleeker 2002 Penile shaft Corona, frenulum, glans, inner prepuce Corona, frenulum, glans, inner prepuce Corona, urethra, anus, rectum Coronal sulcus, glans, prepuce, shaft Coronal sulcus, glans, prepuce, shaft Coronal sulcus Anal canal Coronal sulcus Perianal area Glans, corona, frenulum, prepuce PCR-LIPA TS 16,18,31,33,45,52,58 PCR-GP5+/6+ PCR-GP5+/6+ PCR-TS 6/11,16,18,33 PCR-SPF10 primers followed by immunoassay PCR-SPF10 primers followed by immunoassay PCR-TS primers and LiPA PCR-LIPA TS 16,18,31,33,45,52,58 PCR-TS primers and LiPA PCR-TS primers and LiPA PCR-GP5+/6+ Netherlands Vriend 2013 Anus PCR-SPF10 primers followed by immunoassay Netherlands van der Snoek 2003 Philippines Slovenia Slovenia Franceschi 2002 Milosevic 2010 Milosevic 2010 Perianal area Glans, corona, urethra PCR-TS primers and LiPA PCR-GP5+/6+ HIV+ MSM HIV- MSM MSW STD clinic attendees HIV+ MSM Men visiting department of dermatology for non-sti complaints Partners of women with dyskaryosis and/or CIN Median 45.6 (IQR=39.4-52.5) Median 37.6 (IQR=33.6-42.2) 306 56.9 (51.1-62.5) 441 11.1 (8.3-14.4) 16-24 56 3.6 (0.4-12.3) Median 45.6 (IQR=39.4-52.5) 306 23.2 (18.6-28.3) 22.8-73.2 83 25.3 (16.4-36.0) 22.5-57.7 181 72.9 (65.8-79.3) STD clinic attendees Mean 37 85 28.2 (19.0-39.0) MSM STD clinic attendees MSW STD clinic attendees 16-24 173 16.2 (11.0-22.5) 16-24 922 26.0 (23.2-29.0) HIV- MSM 19-76 241 15.8 (11.4-21.0) HIV- MSM Median 37.6 (IQR=33.6-42.2) 441 33.6 (29.2-38.2) HIV+ MSM 29-59 17 23.5 (6.8-49.9) HIV+ MSM 29-59 17 64.7 (38.3-85.8) Partners of women with CIN MSM STD clinic attendees 24-58 119 58.8 (49.4-67.8) 16-24 124 33.1 (24.9-42.1) HIV- MSM 19-76 241 32.8 (26.9-39.1) Husbands of women with invasive cervical cancer 22-77 149 6.0 (2.8-11.2) Anal canal PCR-Linear Array HIV- MSM 16-80 116 75.0 (66.1-82.6) Anal canal PCR-Linear Array HIV+ MSM 20-57 20 95.0 (75.1-99.9) Slovenia Golob 2014 Penis PCR-Linear Array Men from infertile couples Mean 33 299 37.1 (31.6-42.9) (Continued on next page)

- 169 - ( Table 25 continued from previous page) Anatomic sites HPV detection Age HPV prevalence Country Study samples method Population (years) No % (95% CI) South Africa Müller 2010 South Africa Vogt 2013 South Africa Müller 2010 South Africa Müller 2010 South Africa Firnhaber 2011 South Africa Mbulawa 2010 Spain Álvarez- Argüelles 2013 Glans penis, coronal sulcus and penile shaft Coronal sulcus, glans and shaft Glans penis, coronal sulcus and penile shaft Glans penis, coronal sulcus, penile shaft and anogenital warts Prepuce, penile shaft and genital wart areas of the penis Shaft and glans, and the foreskin in uncircumcised men Anus Spain Videla 2013 Coronal sulcus, glans, urethra, shaft PCR-Roche Linear Array HPV Genotyping test PCR-PGMY09/11 PCR-Roche Linear Array HPV Genotyping test PCR-Roche Linear Array HPV Genotyping test PCR-Roche Linear Array HPV Genotyping test PCR-Roche Linear Array HPV Genotyping test PCR-General primers in L1 (MY09/11, GP5 + /6+), PCR with TS primers in E6/E7 for typing PCR-TS primers in E6/E7 F-HPVTM typing (Molgentix SL, Spain) Spain Videla 2013 Anus PCR-TS primers in E6/E7 F-HPVTM typing (Molgentix SL, Spain) Spain Álvarez- Argüelles 2013 Balanopreputial PCR-General primers in L1 (MY09/11, GP5 + /6+), PCR with TS primers in E6/E7 for typing Spain Videla 2013 Anus PCR-TS primers in E6/E7 F-HPVTM typing (Molgentix SL, Spain) Spain Spain Goldstone 2011 Franceschi 2002 Penis Glans, corona, urethra RT-PCR-Multiplex or Biplex PCR-GP5+/6+ Spain Vardas 2011 Penis RT-PCR-Multiplex or Biplex Spain Spain Franceschi 2002 Goldstone 2011 Glans, corona, urethra Anus PCR-GP5+/6+ RT-PCR-Multiplex or Biplex Men with urethritis syndrome attending a sexual health clinic Heterosexual men attending an HIV testing centre Asymptomatic men attending for HIV voluntary counselling and testing a sexual health clinic Men with anogenital wart attending a sexual health clinic Men with penile warts attending a public sector antiretroviral treatment clinic Heterosexual men recruited for investigations of genital HPV transmission Mean 29.8 56 48.2 (34.7-62.0) IQR=29-37 34 58.8 (40.7-75.4) Mean 29.8 50 62.0 (47.2-75.3) Mean 29.8 108 100.0 (96.6-100.0) Mean 36.0 73 100.0 (95.1-100.0) 19-67 471 58.0 (53.4-62.5) STD clinic attendees 17-87 123 49.6 (40.5-58.8) HIV+ MSM attending an outpatient HIV clinic HIV+ Heterosexual men attending an outpatient HIV clinic 36-47 457 24.9 (21.0-29.2) 40-48 195 41.5 (34.5-48.8) STD clinic attendees 17-87 1318 36.9 (34.3-39.5) HIV+ MSM attending an outpatient HIV clinic HIV- MSM Median 22 (16-27) Husbands of women with invasive cervical cancer Heterosexual men Median 20 (15-24) Husbands of women with cervical carcinoma in situ HIV- MSM Median 22 (16-27) 36-47 538 84.2 (80.8-87.2) 602 18.4 (15.4-21.8) 25-74 84 11.9 (5.9-20.8) 3132 21.2 (19.8-22.7) 22-76 102 21.6 (14.0-30.8) 602 42.4 (38.4-46.4) (Continued on next page)

- 170 - ( Table 25 continued from previous page) Anatomic sites HPV detection Age HPV prevalence Country Study samples method Population (years) No % (95% CI) Spain Videla 2013 Coronal sulcus, glans, urethra, shaft PCR-TS primers in E6/E7 F-HPVTM typing (Molgentix SL, Spain) Spain Torres 2013 Anus PCR-Roche Linear Array HPV Genotyping test Spain Sendagorta 2014 Anus Sweden Strand 1993 Coronal sulcus, glans, preputium, and shaft Sweden Sweden Sweden Wikström 2000 Kataoka 1991 Löwhagen 1999 Corona, glans, and prepuce Urethra Sweden Voog 1997 Glans and prepuce Sweden Sweden Thailand Thailand Thailand Löwhagen 1999 Wikström 1991 Franceschi 2002 Phanuphak 2013 Phanuphak 2013 PCR-Genomic amplification PCR-MY09/11 and GP5+/6+ HIV+ Heterosexual men attending an outpatient HIV clinic HIV+ MSM HIV+ MSM/bisexual men 40-48 191 27.2 (21.0-34.1) IQR=28.2-40.1 1439 95.8 (94.6-96.7) >=18 298 93.0 (89.4-95.6) STD clinic attendees 20-53 65 29.2 (18.6-41.8) PCR-GP5+/6+ STD clinic attendees 18-54 235 13.2 (9.1-18.2) PCR-TS 6,11,16,18,33 Army conscripts with aceto-white epithelium 18-23 39 25.6 (13.0-42.1) Anus PCR-MY09/11 HIV+ MSM 27-54 17 94.1 (71.3-99.9) PCR-MY09/11 and GP5+/6+ STD clinic attendees 19-67 20 25.0 (8.7-49.1) Anus PCR-MY09/11 HIV- MSM 26-62 13 53.8 (25.1-80.8) Coronal sulcus, inner part of the prepuce, urethra Glans, corona, urethra Anus Anus Uganda Tobian 2013 Coronal sulcus and glans Uganda Tobian 2013 Coronal sulcus and glans United Kingdom United Kingdom United Kingdom United Kingdom United Kingdom United States of America United States of America Hillman 1993 PCR-TS primers followed by dot blot PCR-GP5+/6+ PCR-Roche Linear Array HPV Genotyping test PCR-Roche Linear Array HPV Genotyping test PCR-PGMY09/11 PCR-PGMY09/11 STD clinic attendees 17-58 228 53.9 (47.2-60.5) Husbands of women with invasive cervical cancer 25-77 109 22.0 (14.6-31.0) HIV- MSM >=18 123 58.5 (49.3-67.3) HIV+ MSM >=18 123 85.4 (77.9-91.1) HIV+ heterosexual men HIV- heterosexual men Urethra PCR-GP5+/6+ Men infected with gonorrhea 15-49 421 90.7 (87.6-93.3) 15-49 978 60.9 (57.8-64.0) 17-55.6 100 18.0 (11.0-26.9) Lacey 1999 Anal canal PCR-GP5+/6+ HIV+ MSM 19-62 57 84.2 (72.1-92.5) Cuschieri 2011 Bissett 2011 Shaft PCR-INNO-LiPA Drop-in sexual health service attendees Glans, prepuce, shaft, scrotum PCR-General primers (GP5 + /6+), Bio-Plex array technology for typing Jalal 2007 Urethra PCR-General primers for L1 (MY09/11, GP5 + /6+) and RLH Nyitray 2011 Genitourinary clinic attendees with multiple sexual partners or diagnosis of genital warts within 6 months Genitourinary clinic attendees Anal canal PCR-PGMY09/11 HIV- MSM from general population and population from University Wilkin 2004 Anal canal HC2 HIV+ MSM 90% > 30 years 16-25 117 29.1 (21.0-38.2) - 87 49.4 (38.5-60.4) 15-77 437 20.8 (17.1-24.9) 18-70 176 47.2 (39.6-54.8) 55 78.2 (65.0-88.2) (Continued on next page)

- 171 - ( Table 25 continued from previous page) Anatomic sites HPV detection Age HPV prevalence Country Study samples method Population (years) No % (95% CI) United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America Kiviat 1993 Anal canal PCR-MY09/11 HIV- MSM/bisexual men Fife 2003 Chin-Hong 2004 Caussy 1990 Glans, corona, shaft, inguinal skin, scrotum, perineum, perianal, urine 16-50 152 78.3 (70.9-84.6) PCR-TS 6,11 STD clinic attendees 18-50 20 10.0 (1.2-31.7) Anus PCR-MY09/11 HIV- MSM in EXPLORE cohort Anus PCR-TS 6,11,16,18,31,33,35 HIV± homosexual men Kiviat 1993 Anal canal PCR-MY09/11 HIV+ MSM/bisexual men Friedman 1998 Colón-López 2014 Anal canal PCR-MY09/11, HMB01, and HC Anus PCR-MY09/11 STD clinic attendees (29.8% MSM) 18-89 1218 56.8 (54.0-59.6) Mean 40.6 105 39.0 (29.7-49.1) 16-50 241 91.7 (87.5-94.9) HIV+ MSM <40 years 135 90.4 (84.1-94.8) Conley 2010 Anal canal PCR-Linear Array HIV+ MSW Median 42 (IQR=38-48) Baken 1995 Penis PCR-MY09/11 Heterosexual partners of STD clinic attendees Baldwin 2003 Friedman 1998 Glans, corona, urethra Anal canal >=18 192 57.8 (50.5-64.9) 92 58.7 (47.9-68.9) >17 48 62.5 (47.4-76.0) PCR-PGMY09/11 STD clinic attendees 18-70 393 28.2 (23.8-33.0) PCR-MY09/11, HMB01, and HC HIV- MSM <40 years 46 69.6 (54.2-82.3) Wiley 2013 Anus PCR-PGMY09/11 HIV- MSM Mean 55 683 70.3 (66.7-73.7) Moscicki 2003 Anus PCR-MY09/11 and HMB01 High-risk adolescent boys in REACH cohort 13-18 83 44.6 (33.7-55.9) Berry 2009 Anal canal PCR-MY09/11 HIV- MSM 26-75 81 56.8 (45.3-67.8) Chin-Hong 2008 Goldstone 2011 Palefsky 1998 Anus Penis PCR- generic probe set by DBH RT-PCR-Multiplex or Biplex HIV+ homosexual or bisexual men HIV- MSM Median 22 (16-27) Anus PCR-MY09/11 HIV+ homosexual or bisexual men 24-73 38 86.8 (71.9-95.6) 602 18.4 (15.4-21.8) 24-64 289 93.1 (89.5-95.7) Wiley 2013 Anus PCR-PGMY09/11 HIV+ MSM Mean 55 579 90.7 (88.0-92.9) Critchlow 1998 Palefsky 1998 Anus PCR-MY09/11 HIV- homosexual men Anus PCR-MY09/11 HIV- homosexual or bisexual men Mean 34 284 66.5 (60.7-72.0) 26-73 200 61.0 (53.9-67.8) (Continued on next page)

- 172 - ( Table 25 continued from previous page) Anatomic sites HPV detection Age HPV prevalence Country Study samples method Population (years) No % (95% CI) United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America Chin-Hong 2008 Palefsky 1998 Palefsky 2005 Anus PCR- generic probe set by DBH HIV- homosexual or bisexual men Anus PCR-MY09/11 HIV± homosexual or bisexual men Anal canal PCR-L1 consensus primers 24-73 87 57.5 (46.4-68.0) 24-73 489 80.0 (76.1-83.4) HIV+ MSM - 323 95.4 (92.5-97.4) Berry 2009 Anal canal PCR-MY09/11 HIV+ MSM 26-75 32 90.6 (75.0-98.0) Palefsky 1997 Critchlow 1998 Anus PCR-MY09/11 HIV+ homosexual or bisexual men Anus PCR-MY09/11 HIV+ homosexual men Conley 2010 Anal canal PCR-Linear Array HIV + MSM Median 42 (IQR=36-48) Goldstone 2011 Anus RT-PCR-Multiplex or Biplex Vardas 2011 Penis RT-PCR-Multiplex or Biplex HIV- MSM Median 22 (16-27) Heterosexual men Median 20 (15-24) 24-66 118 93.2 (87.1-97.0) Mean 34 322 91.6 (88.0-94.4) 379 95.8 (93.2-97.6) 602 42.4 (38.4-46.4) 3132 21.2 (19.8-22.7) Data updated at 15 Dec 2014 (data as of 15 Sep 2014). 95% CI: 95% Confidence Interval; DBH: Dot Blot Hybridization; HC2: Hybrid Capture 2; LiPA: Line Probe Assay; PCR: Polymerase Chain Reaction; RLH: Reverse Line Hybridisation; RT-PCR: Real Time Polymerase Chain Reaction; SPF: Short Primer Fragment; TS: Type Specific; Data sources: See references in Section 9.

- 173-4.4 HPV burden in head and neck 4.4.1 Burden of oral HPV infection in healthy population Table 26: Studies on oral HPV prevalence among healthy populations in the World HPV detection Method and targeted HPV Age No. HPV prevalence Country Study types Population (years) Tested % (95% CI) MEN Denmark Eike 1995 PCR-MY09/11. Genotyping by amplification with TS primers (6, 11, 16, 18) and RFLP Finland Kero 2012 PCR-GP5+/GP6+ and MY09/MY11. Genotyping with Multimerix kit (6, 11, 16, 18, 31, 33, 39, 42, 43, 44, 45, 51, 52, 58, 59, 68, 70, 73, 82) Italy Montaldo 2007 PCR-MY09/MY11 and GP5+N. Genotyping by sequencing United Kingdom Kujan 2006 PCR-Roche master mix and HC2 digene (both able to detect the following HR types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68). No further genotyping WOMEN Eike 1995 Leimola-Virtanen 1996 Kero 2011 Oral smear taken with a wooden stick, used on the right border of the tongue and right buccal mucosa Oral smears collected from three sites of clinically healthy oral mucosa (i.e., buccal surface, palate, and tongue) with use of a sterile interdental brush Cytobrush from the buccal mucosa PCR-MY09/11. Genotyping by amplification with TS primers (6, 11, 16, 18) and RFLP PCR-GP5/GP6. No genotyping PCR-GP5+/GP6+ and MY09/MY11. Genotyping with Multimerix kit (6, 11, 16, 18, 31, 33, 39, 42, 43, 44, 45, 51, 52, 58, 59, 68, 70, 73, 82) Montaldo 2007 Saliva samples PCR-MY09/MY11 and GP5+N. Genotyping by sequencing Cañadas 2004 Kujan 2006 UNSPECIFIED Lambropoulos 1997 Migaldi 2012 Toothbrush on the oral cavity Two brushes: 1.-cervex brush into each side of buccal mucosa and 2.-cytobrush lateral border of the tongue Cytobrush from the buccal mucosa Cytobrush from the buccal mucosa PCR-MY09/MY11. Genotyping by DBH with TS probes (6, 11, 16, 18, 26, 31-33, 35, 39, 40, 45, 51-56, 58, 59, 61, 66-68, 70, 71 (AE8), 72, 73, 81 (AE7), 83 (PAP291), 84 (PAP155), 85 (AE5), AE2 (IS39), and AE6) PCR-Roche master mix and HC2 digene (both able to detect the following HR types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68). No further genotyping PCR-MY09/MY11. Genotyping by SBH with TS probes (6, 11, 16, 18, 33) PCR-GP5+/GP6+, MY09/11, LCRS/E7AS, pu-1m and pu-2r. Genotyping by sequencing Patients with unrelated disease (otosclerosis, nasal complaints)and their accompanying relatives Fathers-to-be of cohort study 20-79 31 0.0 (0.0-11.2) - 131 18.3 (12.1-26.0) Dental clinic visitors 4-77 69 14.5 (7.2-25.0) Healthy volunteers from university dental hospital. Patients with unrelated disease (otosclerosis, nasal complaints)and their accompanying relatives Post-menopausal women participating in annual mass-screening program for the detection of cervical precancerous lesions Spouses in 3rd trimestres of pregnancy of the fathers-to-be of cohort study - 26 3.9 (0.1-19.6) 20-79 30 0.0 (0.0-11.6) 55 131 10.7 (6.0-17.3) - 128 17.2 (11.1-24.9) Dental clinic visitors 4-77 95 21.1 (13.4-30.6) Female sex workers who attended a dermatology or STD clinic. Healthy volunteers from university dental hospital. Healthy population receiving routine oral examination Patients undergoing to routine oral examination Data updated at 31 Jul 2013 (data as of 29 Feb 2012). Only for European countries. 95% CI: 95% Confidence Interval; PCR: Polymerase Chain Reaction; SBH: Southern Blot Hybridization; TS: Type Specific; Data sources: See references in Section 9. - 188 8.5 (4.9-13.5) - 24 12.5 (2.7-32.4) 14-85 169 9.5 (5.5-14.9) 49-77 81 1.2 (0.0-6.7)

- 174-4.4.2 HPV burden in head and neck cancers MEN Table 27: Studies on HPV prevalence among cases of oral cavity cancer in the World HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Brazil Oliveira 2009 GP5+/GP6+ (L1) DBH (6. 11. 16. 18. 31. 33. 34. 35. 39. 40. 42. 43. 44. 45. 51. 52. 54. 56. 58) Canada Noble-Topham 1993 TS-PCR E6/E7 for 6b/11/16/18 Amplification with TS primers (6b/11. 16. 18) Canada Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) China Zhang 2004 TS-PCR E6 for 16/18 Amplification with TS primers (16. 18) Cuba Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Hungary Nemes 2006 MY09/MY11 (L1) Hybridization with TS probes (16. 18. 31. 33. 45. 51. 52. 58) India Balaram 1995 MY09/MY11 (L1). GP5+/GP6+ (L1)/GP17+/GP18+ (L1). Y1/Y2 and TS-PCR for 6/11/16/18 Sequencing India D Costa 1998 MY09/MY11 (L1) SBH (6. 11. 16. 18. 33) India Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) India Chaudhary 2010 MY09/MY11 (L1) Amplification with TS primers (16) Iran Saghravanian 2011 GP5+/GP6+ (L1) Amplification with TS primers HPV E6/7 (16. 18. 31. 33) Ireland Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Italy Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) 57 31.6 (21.0-44.5) 7 57.1 (25.0-84.2) 17 11.8 (3.3-34.3) 48 81.3 (68.1-89.8) 53 0.0 (0.0-6.8) 67 44.8 (33.5-56.6) 50 74.0 (60.4-84.1) 71 12.7 (6.8-22.4) 127 4.7 (2.2-9.9) 146 33.6 (26.4-41.6) 8 0.0 (0.0-32.4) 22 4.5 (0.8-21.8) 32 0.0 (0.0-10.7) Japan Shimizu 2004 TS-PCR L1 for 13 15.4 (4.3-42.2) 16/18/31/33/35/39/45/51/52/56/58/59/68/73/75/76/82 Sequencing Japan Tsuhako 2000 TS-PCR E6/E7 for 16/18 and E6 for 6/11 Amplification with TS primers (6.11.16.18) Japan Chiba 1996 TS-PCR E6/E7 for 6/11/16/18/31/33/52b/58 Restriction enzyme digestion (6. 11. 16. 18. 31. 33. 52b. 58) 51 52.9 (39.5-65.9) 22 27.3 (13.2-48.2) ( Table 27 continued from previous page)

- 175 - ( Table 27 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Japan Bhawal 2008 TS-PCR E6 for 16 Electrophoretic analysis using SiHa DNA as positive control for HPV-16 Korea, Republic of Shin 2002 TS-PCR E6 for 16/18/33 Amplification with TS primers (16. 18. 33) Mexico Ibieta 2005 MY09/MY11 (L1) and GP5/GP6 (L1) Amplification with TS primers (16. 18) Netherlands Cruz 1996 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers and hybridization with TS probes (2. 4. 6. 10. 11. 13. 16. 18. 25. 31. 33. 46. 51. 52) Poland Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Serbia Kozomara 2005 TS-PCR E6 for 16. L1 for 18. E4 for 31 and E1 for 33 Amplification with TS primers (16. 18. 31. 33) Slovenia Kansky 2003 PGMY09/11 (L1). GP5+/GP6+ (L1) and WD72/76/66/67/154 (E6) RFLP South Africa Boy 2006 TS-PCR E1 for 16 and E7 for 18 Hybridization with TS probes (16. 18) Spain Llamas-Martínez 2008 WD-66/67/72/76/154 (E6) RFLP (6.11.16.18.31.33.39.42.45.52) Spain Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Sudan Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Sweden Dahlgren 2004 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers (16. 18. 33) and sequencing Taiwan Chang 2003 MY09 (L1) and GP5+/GP6+ (L1) Sequencing Taiwan Chen 2002 MY09/MY11 (L1) Hybridization with TS probes (6. 11. 16. 18) United States of America Venezuela Lohavanichbutr 2009 Premoli-De-Percoco 2001 MY09/MY11 (L1) and GP5+/GP6+ (L1) Hybridization with Roche LBA (6. 11. 16. 18. 26. 31. 33. 35. 39. 40. 42. 45. 51. 52. 53. 54. 55. 56. 58. 59. 61. 62. 64. 66. 67. 68. 69. 70. 71. 72. 73. 81. 82. 83. 84. 89) TS-PCR for 6/11/16/18 Hybridization with TS probes (6. 11. 16. 18) Venezuela Miller 1994 TS-PCR E6 for 16/18 Hybridization with TS probes (16. 18) WOMEN 19 26.3 (11.8-48.8) 76 9.2 (4.5-17.8) 36 41.7 (27.1-57.8) 22 63.6 (43.0-80.3) 53 0.0 (0.0-6.8) 42 61.9 (46.8-75.0) 48 4.2 (1.2-14.0) 22 9.1 (2.5-27.8) 19 47.4 (27.3-68.3) 140 5.7 (2.9-10.9) 28 3.6 (0.6-17.7) 51 3.9 (1.1-13.2) 42 33.3 (21.0-48.4) 28 92.9 (77.4-98.0) 56 19.6 (11.3-31.8) 0 - - 14 78.6 (52.4-92.4) ( Table 27 continued from previous page)

- 176 - ( Table 27 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Brazil Oliveira 2009 GP5+/GP6+ (L1) DBH (6. 11. 16. 18. 31. 33. 34. 35. 39. 40. 42. 43. 44. 45. 51. 52. 54. 56. 58) Canada Noble-Topham 1993 TS-PCR E6/E7 for 6b/11/16/18 Amplification with TS primers (6b/11. 16. 18) Canada Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) China Zhang 2004 TS-PCR E6 for 16/18 Amplification with TS primers (16. 18) Cuba Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Hungary Nemes 2006 MY09/MY11 (L1) Hybridization with TS probes (16. 18. 31. 33. 45. 51. 52. 58) India Balaram 1995 MY09/MY11 (L1). GP5+/GP6+ (L1)/GP17+/GP18+ (L1). Y1/Y2 and TS-PCR for 6/11/16/18 Sequencing India D Costa 1998 MY09/MY11 (L1) SBH (6. 11. 16. 18. 33) India Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) India Chaudhary 2010 MY09/MY11 (L1) Amplification with TS primers (16) Iran Saghravanian 2011 GP5+/GP6+ (L1) Amplification with TS primers HPV E6/7 (16. 18. 31. 33) Ireland Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Italy Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) 31 25.8 (13.7-43.2) 13 46.2 (23.2-70.9) 11 9.1 (1.6-37.7) 25 60.0 (40.7-76.6) 25 4.0 (0.7-19.5) 12 25.0 (8.9-53.2) 41 68.3 (53.0-80.4) 5 20.0 (3.6-62.4) 135 1.5 (0.4-5.2) 76 30.3 (21.1-41.3) 13 23.1 (8.2-50.3) 8 25.0 (7.1-59.1) 21 9.5 (2.7-28.9) Japan Shimizu 2004 TS-PCR L1 for 11 18.2 (5.1-47.7) 16/18/31/33/35/39/45/51/52/56/58/59/68/73/75/76/82 Sequencing Japan Tsuhako 2000 TS-PCR E6/E7 for 16/18 and E6 for 6/11 Amplification with TS primers (6.11.16.18) Japan Chiba 1996 TS-PCR E6/E7 for 6/11/16/18/31/33/52b/58 Restriction enzyme digestion (6. 11. 16. 18. 31. 33. 52b. 58) Japan Bhawal 2008 TS-PCR E6 for 16 Electrophoretic analysis using SiHa DNA as positive control for HPV-16 21 66.7 (45.4-82.8) 1 0.0 (0.0-79.3) 9 55.6 (26.7-81.1) ( Table 27 continued from previous page)

- 177 - ( Table 27 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Korea, Republic of Shin 2002 TS-PCR E6 for 16/18/33 Amplification with TS primers (16. 18. 33) Mexico Ibieta 2005 MY09/MY11 (L1) and GP5/GP6 (L1) Amplification with TS primers (16. 18) Netherlands Cruz 1996 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers and hybridization with TS probes (2. 4. 6. 10. 11. 13. 16. 18. 25. 31. 33. 46. 51. 52) Poland Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Serbia Kozomara 2005 TS-PCR E6 for 16. L1 for 18. E4 for 31 and E1 for 33 Amplification with TS primers (16. 18. 31. 33) Slovenia Kansky 2003 PGMY09/11 (L1). GP5+/GP6+ (L1) and WD72/76/66/67/154 (E6) RFLP South Africa Boy 2006 TS-PCR E1 for 16 and E7 for 18 Hybridization with TS probes (16. 18) Spain Llamas-Martínez 2008 WD-66/67/72/76/154 (E6) RFLP (6.11.16.18.31.33.39.42.45.52) Spain Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Sudan Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Sweden Dahlgren 2004 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers (16. 18. 33) and sequencing Taiwan Chang 2003 MY09 (L1) and GP5+/GP6+ (L1) Sequencing Taiwan Chen 2002 MY09/MY11 (L1) Hybridization with TS probes (6. 11. 16. 18) United States of America Venezuela Lohavanichbutr 2009 Premoli-De-Percoco 2001 MY09/MY11 (L1) and GP5+/GP6+ (L1) Hybridization with Roche LBA (6. 11. 16. 18. 26. 31. 33. 35. 39. 40. 42. 45. 51. 52. 53. 54. 55. 56. 58. 59. 61. 62. 64. 66. 67. 68. 69. 70. 71. 72. 73. 81. 82. 83. 84. 89) TS-PCR for 6/11/16/18 Hybridization with TS probes (6. 11. 16. 18) Venezuela Miller 1994 TS-PCR E6 for 16/18 Hybridization with TS probes (16. 18) UNSPECIFIED Argentina González 2007 MY09/MY11 (L1) and GP5+/GP6+ (L1) RFLP and DBH Argentina Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) 76 5.3 (2.1-12.8) 14 42.9 (21.4-67.4) 13 38.5 (17.7-64.5) 30 0.0 (0.0-11.4) 8 75.0 (40.9-92.9) 7 14.3 (2.6-51.3) 37 13.5 (5.9-28.0) 14 35.7 (16.3-61.2) 32 6.3 (1.7-20.1) 15 0.0 (0.0-20.4) 34 0.0 (0.0-10.2) 61 60.7 (48.1-71.9) 1 100.0 (20.7-100.0) 32 21.9 (11.0-38.8) 50 60.0 (46.2-72.4) 13 53.8 (29.1-76.8) 25 60.0 (40.7-76.6) 132 0.0 (0.0-2.8) ( Table 27 continued from previous page)

- 178 - ( Table 27 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Brazil Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Brazil Rivero 2006 GP5+/GP6+ (L1) CSA-ISH (DAKO) (6. 11. 16. 18) China Wen 1997 TS-PCR E6 for 16/18 Hybridization with TS probes (HPV16.18 E6) 132 0.0 (0.0-2.8) 40 0.0 (0.0-8.8) 45 31.1 (19.5-45.7) China Tang 2003 TS-PCR E6 for 16/18/33 Sequencing 30 46.7 (30.2-63.9) Cuba Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Czech Republic Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Finland Mork 2001 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers (6. 11. 16. 18. 33) 132 0.0 (0.0-2.8) 132 0.0 (0.0-2.8) 91 7.7 (3.8-15.0) Finland Koskinen 2003 SPF10 (L1) LiPA 25 28 64.3 (45.8-79.3) Germany Klussmann 2001 A10/A5-A6/A8 (L1) and CP62/70-CP65/69a (L1) Sequencing Germany Ostwald 2003 TS-PCR E6 for 6/11/16/18 Hybridization with TS probes (6/11. 16. 18) Germany Weiss 2011 RT-PCR E6/E7 for 16 Hybridization with TS probes (16) Greece Aggelopoulou 1999 L1 consensus primers and TS-PCR E7 for 16/18 Amplification with TS primers (16. 18) Greece Romanitan 2008 GP5+/GP6+ (L1). CPI/CPIIG (E1) and TS-PCR E6/E7 for 16 Amplification with TS primers (16) Hungary Szarka 2009 MY09/MY11 (L1) and GP5+/GP6+ (L1) RFLP India Mishra 2006 MY09/MY11 (L1) Amplification with TS primers (16. 18) India Bhattacharya 2009 MY09/MY11 (L1) Amplification with TS primers (16. 18) Italy Badaracco 2000 MY09/MY11 (L1) Amplification with TS primers (6.16) and hybridization with TS probes (11.16.18.31.45.56.57) Italy Badaracco 2007 MY09/MY11 (L1) and GP5+/GP6+ (L1) Sequencing Italy Scapoli 2009 RT-PCR for 16/18/31/45 Hybridization with TS probes (16. 18. 31. 45) Italy Rittà 2009 MY09/MY11 (L1) and GP5+/GP6+ (L1) Sequencing Japan Higa 2003 TS-PCR E6/E7 for 16/18 Amplification with TS E6/E7 primers (6. 11. 16. 18) 22 18.2 (7.3-38.5) 118 43.2 (34.6-52.2) 34 2.9 (0.5-14.9) 81 49.4 (38.8-60.0) 75 1.3 (0.2-7.2) 65 47.7 (36.0-59.6) 66 27.3 (18.0-39.0) 193 62.2 (55.2-68.7) 38 26.3 (15.0-42.0) 53 11.3 (5.3-22.6) 247 1.2 (0.4-3.5) 25 36.0 (20.2-55.5) 46 80.4 (66.8-89.3) Japan Kojima 2002 TS-PCR L1 and E6 for 38 Sequencing 53 66.0 (52.6-77.3) Japan Shima 2000 TS-PCR E6/E7 for 6/11/16/18/31/33/52b/58 RFLP (16. 18) 46 73.9 (59.7-84.4) ( Table 27 continued from previous page)

- 179 - ( Table 27 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Japan Sugiyama 2003 TS-PCR E6/E7 for 16/18 Electrophoretic analysis using SiHa DNA and Hela DNA as positive controls for HPV-16 and HPV-18. respectively. 79 35.4 (25.8-46.4) Japan Tang 2003 TS-PCR E6 for 16/18/33 Sequencing 30 50.0 (33.2-66.8) Malaysia Lim 2007 GP5+/GP6+ (L1) Amplification with TS primers (16. 18) Mexico Anaya-Saavedra 2008 MY09/MY11 (L1) and GP5+GP6+ (L1) Sequencing Netherlands Braakhuis 2004 GP5+/GP6+ (L1) and TS-PCR RLBH (6. 11. 16. 18. 26. 31. 33. 34. 35. 39. 40. 42. 43. 44. 45. 51. 52. 53. 54. 55. 56. 57. 58. 59. 61. 66. 68.70.72.73. 82/MM4. 83. 84. 82/IS39. 71/CP8061. 81/CP8304. 89) Norway Matzow 1998 GP5+/GP6+ (L1). CPI/CPIIG (E1) and TS-PCR for 6/16/18/31/33 Amplification with TS primers (6. 16. 18. 31. 33) Norway Mork 2001 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers (6. 11. 16. 18. 33) Poland Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Poland Snietura 2010 Real-time High Risk HPV test (Abbott Molecular) using L1 consensus primers Amplification with TS primers (16. 18. 31. 33. 35. 39. 45. 51. 52. 56. 58. 59. 66 and 68 - the technique only differentiates 16-18-other) Romania Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Russian Federation Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Slovakia Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) South Africa Van Rensburg 1996 TS-PCR E6 for 6/11/16/18 Hybridization with TS probes (4. 16. 18) Sweden Mork 2001 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers (6. 11. 16. 18. 33) Sweden Sand 2000 MY09/MY11 (L1) Amplification with TS primers (6b/11. 16. 18) Taiwan Yang 2004 MY09/MY11 (L1) Amplification with TS primers (6.11.16.18.31.33.35.45.58) United Kingdom Lopes 2011 GP5+/GP6+ (L1) and qpcr for 16/18 Hybridization with TS probes (16. 18) United Kingdom Snijders 1996 GP5+/GP6+ (L1) Amplification with TS primers and SBH with TS probes (6. 11. 16. 18. 31. 33) 20 85.0 (64.0-94.8) 62 43.5 (31.9-55.9) 106 9.4 (5.2-16.5) 30 0.0 (0.0-11.4) 91 7.7 (3.8-15.0) 132 0.0 (0.0-2.8) 45 4.4 (1.2-14.8) 132 0.0 (0.0-2.8) 132 0.0 (0.0-2.8) 132 0.0 (0.0-2.8) 146 1.4 (0.4-4.9) 91 7.7 (3.8-15.0) 24 12.5 (4.3-31.0) 37 10.8 (4.3-24.7) 142 3.5 (1.5-8.0) 25 20.0 (8.9-39.1) ( Table 27 continued from previous page)

- 180 - ( Table 27 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) United Kingdom Yeudall 1991 TS-PCR E6/E7 for 16. E6 for 18 and specific for 4 Hybridization with TS probes (4. 16. 18) United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America Paz 1997 Harris 2011 Holladay 1993 Liang 2008 Zhao 2005 Schlecht 2011 Schwartz 1998 Smith 2004 Chuang 2008 Furniss 2007 Ha 2002 MY09/MY11 (L1) and IU/IWDO (E1) Amplification with TS primers (6. 16. 18) MY09/MY11 (L1) and GP5+GP6+ (L1) Sequencing L1 consensus primers Hybridization with TS probes (6. 11. 16. 18. 33) GP5+/GP6+ (L1) Amplification with TS primers (16) RT-PCR E6/E7 for 16 Hybridization with TS probes (16) MY09/MY11 (L1) and HMB01 (L1) DBH (40 HPV types including 16. 18. 31. 33. 35. 39. 45. 51. 52. 56. 58. 66) MY09/MY11 (L1) and TS-PCR E6 for 6/11/16/18 Hybridization with TS probes (6. 11. 16. 18. 31/33/35) MY09/MY11 (L1) and HMB01 (L1) Sequencing RT-PCR E6/E7 for 16 Hybridization with TS probes (16) TS-PCR L1 for 16 Amplification with TS primers (16) RT-PCR E6/E7 for 16 Amplification with TS primers (16) 39 46.2 (31.6-61.4) 53 13.2 (6.5-24.8) 25 8.0 (2.2-25.0) 39 17.9 (9.0-32.7) 51 2.0 (0.3-10.3) 38 15.8 (7.4-30.4) 36 13.9 (6.1-28.7) 193 21.2 (16.1-27.5) 123 10.6 (6.3-17.2) 21 0.0 (0.0-15.5) 150 25.3 (19.0-32.8) 34 2.9 (0.5-14.9) Data updated at 15 Dec 2014 (data as of 29 Feb 2012). 95% CI: 95% Confidence Interval; DBH: Dot Blot Hybridization; ISH: In Situ Hybridization; LiPA: Line Probe Assay; PCR: Polymerase Chain Reaction; RFLP: Restriction Fragment Length Polymorphism; RLBH: Reverse Line Blot Hybridization; RT-PCR: Real Time Polymerase Chain Reaction; SBH: Southern Blot Hybridization; SPF: Short Primer Fragment; TS: Type Specific; Data sources: See references in Section 9. MEN Table 28: Studies on HPV prevalence among cases of oropharyngeal cancer in the World HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) China Li 2007 GP5+/GP6+ (L1). CP65/70ct-CP66/69ct (L1). FAP59/6415 (L1). A5/A10-A6/A8 (L1) and TS-PCR E6 for 16 Sequencing Cuba Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Czech Republic Rotnáglová 2011 GP5+/GP6+ (L1) RBLH (6. 11. 16. 18. 26. 31. 33. 34. 35. 39. 40. 42. 43. 44. 45. 51. 52. 53. 54. 55. 56. 57. 58. 59. 61. 66. 68. 70. 71. 72. 73. 81. 82. 83. 84. 89) 21 14.3 (5.0-34.6) 21 19.0 (7.7-40.0) 90 64.4 (54.2-73.6) ( Table 28 continued from previous page)

- 181 - ( Table 28 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) France Charfi 2008 GP5+/GP6+ (L1) and TS-PCR for 6/11/16/18/33 Amplification with TS primers (6. 11. 16. 18. 33) Germany Hoffmann 2010 GP5+/GP6+ (L1). MY09/MY11 (L1) and TS-PCR for 6/11/16/18 Hybridization with TS probes - Multiplex luminex* Germany Reimers 2007 A10/A5-A6/A8 (L1) and CP62/70-CP65/69a (L1) Sequencing Italy Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) 36 55.6 (39.6-70.5) 31 54.8 (37.8-70.8) 83 25.3 (17.2-35.6) 30 23.3 (11.8-40.9) Norway Hannisdal 2010 GP5+/GP6+ (L1) Sequencing 99 56.6 (46.7-65.9) Spain Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Sweden Dahlgren 2004 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers (16. 18. 33) and sequencing Sweden Hammarstedt 2006 GP5+/GP6+ (L1). CPI/CPIIG (E1) and TS-PCR E6 for 16 Sequencing Sweden Attner 2010 GP5+/GP6+ (L1). CPI/IIG (E1) and TS-PCR E6/7 for 16/33 Amplification with TS primers (16. 33) and sequencing Sweden Näsman 2009 GP5+/GP6+ (L1). CPI/CPIIG (E1) and TS-PCR E6 for 16 Sequencing 40 5.0 (1.4-16.5) 18 44.4 (24.6-66.3) 145 48.3 (40.3-56.3) 65 75.4 (63.7-84.2) 76 81.6 (71.4-88.7) Switzerland Lindel 2001 SPF10 (L1) Sequencing 75 8.0 (3.7-16.4) Taiwan Kuo 2008 MY09 (L1) and GP5+/GP6+ (L1) Hybridization with HPV gene chip (6.11.16.18.26.31-33.35.37.39. 42-45.51-56.58.59.61.62.66-70. 79 70.9 (60.1-79.7) 72.74.82.CP8061.CP8304.L1AE5MM4.MM7.MM8) Taiwan Al-Swiahb 2010 MY09/MY11 (L1) and GP5/GP6 (L1) In situ hybridization with TS probes (6. 11. 16. 18. 31) and Roche LBA United States of America United States of America United States of America United States of America United States of America Tezal 2009 Posner 2011 TS-PCR E6 for 16/18 Amplification with TS primers (16. 18) TS-PCR E6/E7 for 16 Amplification with TS primers (16) Chaturvedi 2011 SPF10 (L1) Inno-LiPA (6. 11. 16. 18. 26. 31. 33. 35. 40. 43. 44. 45. 51. 52. 53. 54. 56. 58. 59. 66. 68. 69-71. 70. 73. 74. 82) Cohen 2008 Ernster 2007 GP5+/GP6+ (L1) and TS-PCR E7 for 16 Hybridization with TS probes (16) TS-PCR for 16/18 Amplification with TS primers (16. 18) 260 13.8 (10.2-18.6) 26 76.9 (57.9-89.0) 89 50.6 (40.4-60.7) 210 47.6 (41.0-54.4) 27 70.4 (51.5-84.1) 51 72.5 (59.1-82.9) ( Table 28 continued from previous page)

- 182 - ( Table 28 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) United States of America WOMEN Lohavanichbutr 2009 MY09/MY11 (L1) and GP5+/GP6+ (L1) Hybridization with Roche LBA (6. 11. 16. 18. 26. 31. 33. 35. 39. 40. 42. 45. 51. 52. 53. 54. 55. 56. 58. 59. 61. 62. 64. 66. 67. 68. 69. 70. 71. 72. 73. 81. 82. 83. 84. 89) China Li 2007 GP5+/GP6+ (L1). CP65/70ct-CP66/69ct (L1). FAP59/6415 (L1). A5/A10-A6/A8 (L1) and TS-PCR E6 for 16 Sequencing Cuba Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Czech Republic Rotnáglová 2011 GP5+/GP6+ (L1) RBLH (6. 11. 16. 18. 26. 31. 33. 34. 35. 39. 40. 42. 43. 44. 45. 51. 52. 53. 54. 55. 56. 57. 58. 59. 61. 66. 68. 70. 71. 72. 73. 81. 82. 83. 84. 89) France Charfi 2008 GP5+/GP6+ (L1) and TS-PCR for 6/11/16/18/33 Amplification with TS primers (6. 11. 16. 18. 33) Germany Hoffmann 2010 GP5+/GP6+ (L1). MY09/MY11 (L1) and TS-PCR for 6/11/16/18 Hybridization with TS probes - Multiplex luminex* Germany Reimers 2007 A10/A5-A6/A8 (L1) and CP62/70-CP65/69a (L1) Sequencing Italy Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) 28 82.1 (64.4-92.1) 10 60.0 (31.3-83.2) 5 0.0 (0.0-43.4) 19 68.4 (46.0-84.6) 16 75.0 (50.5-89.8) 8 50.0 (21.5-78.5) 23 39.1 (22.2-59.2) 6 0.0 (0.0-39.0) Norway Hannisdal 2010 GP5+/GP6+ (L1) Sequencing 38 39.5 (25.6-55.3) Spain Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes (2. 6. 11. 16. 18. 31. 33. 35. 39. 40. 42. 43. 44. 45. 51. 52. 56. 58. 59. 66. 68) Sweden Dahlgren 2004 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers (16. 18. 33) and sequencing Sweden Hammarstedt 2006 GP5+/GP6+ (L1). CPI/CPIIG (E1) and TS-PCR E6 for 16 Sequencing Sweden Attner 2010 GP5+/GP6+ (L1). CPI/IIG (E1) and TS-PCR E6/7 for 16/33 Amplification with TS primers (16. 33) and sequencing Sweden Näsman 2009 GP5+/GP6+ (L1). CPI/CPIIG (E1) and TS-PCR E6 for 16 Sequencing 4 50.0 (15.0-85.0) 7 28.6 (8.2-64.1) 58 50.0 (37.5-62.5) 30 73.3 (55.6-85.8) 22 95.5 (78.2-99.2) Switzerland Lindel 2001 SPF10 (L1) Sequencing 24 33.3 (18.0-53.3) ( Table 28 continued from previous page)

- 183 - ( Table 28 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Taiwan Kuo 2008 MY09 (L1) and GP5+/GP6+ (L1) Hybridization with HPV gene chip (6.11.16.18.26.31-33.35.37.39. 42-45.51-56.58.59.61.62.66-70. 13 100.0 (77.2-100.0) 72.74.82.CP8061.CP8304.L1AE5MM4.MM7.MM8) Taiwan Al-Swiahb 2010 MY09/MY11 (L1) and GP5/GP6 (L1) In situ hybridization with TS probes (6. 11. 16. 18. 31) and Roche LBA United States of America United States of America United States of America United States of America United States of America United States of America UNSPECIFIED Tezal 2009 Posner 2011 TS-PCR E6 for 16/18 Amplification with TS primers (16. 18) TS-PCR E6/E7 for 16 Amplification with TS primers (16) Chaturvedi 2011 SPF10 (L1) Inno-LiPA (6. 11. 16. 18. 26. 31. 33. 35. 40. 43. 44. 45. 51. 52. 53. 54. 56. 58. 59. 66. 68. 69-71. 70. 73. 74. 82) Cohen 2008 Ernster 2007 Lohavanichbutr 2009 GP5+/GP6+ (L1) and TS-PCR E7 for 16 Hybridization with TS probes (16) TS-PCR for 16/18 Amplification with TS primers (16. 18) MY09/MY11 (L1) and GP5+/GP6+ (L1) Hybridization with Roche LBA (6. 11. 16. 18. 26. 31. 33. 35. 39. 40. 42. 45. 51. 52. 53. 54. 55. 56. 58. 59. 61. 62. 64. 66. 67. 68. 69. 70. 71. 72. 73. 81. 82. 83. 84. 89) Argentina Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Australia Hong 2010 E6-based MT-PCR Amplification with MT-PCR kit (6. 11. 16. 18. 26. 31. 33. 35. 39. 45. 51. 52. 53. 56. 58. 59. 66. 68. 70. 73. 82) Brazil Cortezzi 2004 GP5+/GP6+ (L1) DBH (6. 11. 16. 18. 31. 33. 34. 39. 42. 45. 51. 52. 54. 56) Brazil Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Cuba Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Czech Republic Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Czech Republic Klozar 2008 GP5+/GP6+ (L1) RLBH (6. 11. 16. 18. 26. 31. 33. 34. 35. 39. 40. 42. 43. 44. 45. 51. 52. 53. 54. 55. 56. 57. 58. 59. 61. 66. 68. 70. 71. 72. 73. 81. 82. 83. 84. 89) France Fouret 1997 TS-PCR E6 for 16/18/31/33/45 Hybridization with TS probes (16. 18. 31. 33. 45) Germany Andl 1998 TS-PCR for 6/11/16/18 Hybridization with TS probes (6. 11. 16. 18) and cycle sequencing system of BRL 14 64.3 (38.8-83.7) 4 25.0 (4.6-69.9) 22 50.0 (30.7-69.3) 53 30.2 (19.5-43.5) 8 62.5 (30.6-86.3) 21 61.9 (40.9-79.2) 3 0.0 (0.0-56.1) 136 0.7 (0.1-4.0) 302 47.7 (42.1-53.3) 21 14.3 (5.0-34.6) 136 0.7 (0.1-4.0) 136 0.7 (0.1-4.0) 136 0.7 (0.1-4.0) 20 45.0 (25.8-65.8) 58 17.2 (9.6-28.9) 21 52.4 (32.4-71.7) ( Table 28 continued from previous page)

- 184 - ( Table 28 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Germany Hoffmann 1998 MY09/MY11 (L1) and TS-PCR for 6/11/16/18/33 SBH (6. 11. 16. 18. 31. 33. 45) Germany Weiss 2011 RT-PCR E6/E7 for 16 Hybridization with TS probes (16) Germany Wittekindt 2005 A10/A5-A6/A8 (L1) and (L1) Sequencing Germany Klussmann 2001 A10/A5-A6/A8 (L1) and CP62/70-CP65/69a (L1) Sequencing Greece Romanitan 2008 GP5+/GP6+ (L1). CPI/CPIIG (E1) and TS-PCR E6/E7 for 16 Amplification with TS primers (16) Italy Boscolo-Rizzo 2009 MY09/MY11 (L1) RFLP* and amplification with TS primers E6/E2 for 16 Italy Licitra 2006 RT-PCR E1 for 16/18 Hybridization with TS probes (16. 18) Italy Rittà 2009 MY09/MY11 (L1) and GP5+/GP6+ (L1) Sequencing Korea, Republic of Korea, Republic of Oh 2004 Kim 2007 MY09/MY11 (L1) and HMB01 (L1) Microarray hybridization (6. 11. 16. 18. 31. 33. 34. 35. 39. 40. 42. 43. 44. 45. 51. 52. 54. 56. 58. 59. 62. 66. 67. 68. 69. 70. 72) RT-PCR E2/E6 for 16 Hybridization with HPV genotyping DNA chip arrayed by multiple oligonucleotide probes (6.11.16.18.31.33.34.35.39.40.42. 43.44.45.51.52.56.58.59.66.68.69) Netherlands Braakhuis 2004 GP5+/GP6+ (L1) and TS-PCR RLBH (6. 11. 16. 18. 26. 31. 33. 34. 35. 39. 40. 42. 43. 44. 45. 51. 52. 53. 54. 55. 56. 57. 58. 59. 61. 66. 68.70.72.73. 82/MM4. 83. 84. 82/IS39. 71/CP8061. 81/CP8304. 89) Poland Szkaradkiewicz 2002 MY09/MY11 (L1) Amplification with TS primers (16. 18) Poland Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Poland Snietura 2010 Real-time High Risk HPV test (Abbott Molecular) using L1 consensus primers Amplification with TS primers (16. 18. 31. 33. 35. 39. 45. 51. 52. 56. 58. 59. 66 and 68 - the technique only differentiates 16-18-other) Romania Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Russian Federation Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Slovakia Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) 23 26.1 (12.5-46.5) 86 38.4 (28.8-48.9) 34 52.9 (36.7-68.5) 33 45.5 (29.8-62.0) 28 42.9 (26.5-60.9) 22 18.2 (7.3-38.5) 90 18.9 (12.1-28.2) 22 50.0 (30.7-69.3) 39 64.1 (48.4-77.3) 52 73.1 (59.7-83.2) 37 37.8 (24.1-53.9) 28 10.7 (3.7-27.2) 136 0.7 (0.1-4.0) 14 50.0 (26.8-73.2) 136 0.7 (0.1-4.0) 136 0.7 (0.1-4.0) 136 0.7 (0.1-4.0) ( Table 28 continued from previous page)

- 185 - ( Table 28 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Sweden Lindquist 2012 GP5+/GP6+ (L1) and CPI/CPIIG (E1) Amplification with TS primers (16) and Multiplex Luminex (6. 11. 16. 18. 26. 31. 33. 35. 39. 42. 43. 44. 45. 51. 52. 53. 56. 58. 59. 66. 68. 70. 73. 82) United Kingdom Thavaraj 2011 GP5+/GP6+ (L1) Luminex 200 IS (16. 18. 26. 31. 33. 35. 39. 45. 51. 52. 53. 56. 58. 59. 66. 68. 73. 82) United Kingdom Schache 2011 TS-PCR E6 for 16 Amplification with TS primers (16) United Kingdom Anderson 2007 GP5+/GP6+ (L1) Hybridization with Roche LBA (6. 11. 16. 18. 26. 31. 33. 35. 39. 40. 42. 45. 51. 52. 53. 54. 55. 56. 58. 59. 61. 62. 64. 66. 67. 68. 69. 70. 71. 72. 73. 81. 82. 83. 84. 89) United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America United States of America Agoston 2010 D Souza 2007 Kong 2009 Schlecht 2011 Furniss 2007 Generic L1 primers from Access Genetics and TS-PCR E7 for 16 RFLP MY09/MY11 (L1) Hybridization with Roche LBA (6. 11. 16. 18. 26. 31. 33. 35. 39. 40. 42. 45. 51. 52. 53. 54. 55. 56. 58. 59. 61. 62. 64. 66. 67. 68. 69. 70. 71. 72. 73. 81. 82. 83. 84. 89) GP5+/GP6+ (L1) and TS-PCR Sequencing MY09/MY11 (L1) and HMB01 (L1) DBH (40 HPV types including 16. 18. 31. 33. 35. 39. 45. 51. 52. 56. 58. 66) TS-PCR L1 for 16 Amplification with TS primers (16) Kingma 2010 PGMY09/11 (L1) Inno-LiPA (6. 11. 16. 18. 26. 31. 33. 35. 40. 43. 44. 45. 51. 52. 53. 54. 56. 58. 59. 66. 68. 69-71. 70. 73. 74. 82) Strome 2002 Zhao 2005 Schwartz 1998 Smith 2004 MY09/MY11 (L1) and TS-PCR E6 for 6/11/16/18 Sequencing RT-PCR E6/E7 for 16 Hybridization with TS probes (16) MY09/MY11 (L1) and TS-PCR E6 for 6/11/16/18 Hybridization with TS probes (6. 11. 16. 18. 31/33/35) MY09/MY11 (L1) and HMB01 (L1) Sequencing 56 64.3 (51.2-75.5) 142 70.4 (62.5-77.3) 98 40.8 (31.6-50.7) 36 22.2 (11.7-38.1) 102 90.2 (82.9-94.6) 60 63.3 (50.7-74.4) 49 67.3 (53.4-78.8) 30 50.0 (33.2-66.8) 43 34.9 (22.4-49.8) 61 86.9 (76.2-93.2) 52 46.2 (33.3-59.5) 26 57.7 (38.9-74.5) 55 41.8 (29.7-55.0) 62 40.3 (29.0-52.7) Data updated at 15 Dec 2014 (data as of 29 Feb 2012). 95% CI: 95% Confidence Interval; DBH: Dot Blot Hybridization; LBA: Line-Blot Assay; LiPA: Line Probe Assay; PCR: Polymerase Chain Reaction; RFLP: Restriction Fragment Length Polymorphism; RLBH: Reverse Line Blot Hybridization; RT-PCR: Real Time Polymerase Chain Reaction; SBH: Southern Blot Hybridization; TS: Type Specific; Data sources: See references in Section 9. Table 29: Studies on HPV prevalence among cases of hypopharyngeal or laryngeal cancer in the World HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) ( Table 29 continued from previous page)

- 186 - MEN ( Table 29 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Canada Fliss 1994 TS-PCR E6/E7 for 6b/11/16/18 Amplification with TS primers (6b/11. 16. 18) 28 46.4 (29.5-64.2) Chile Torrente 2005 MY09/MY11 (L1) RFLP 25 36.0 (20.2-55.5) China Liu 2010 GP5+/GP6+ (L1) and TS-PCR E6/E7 for 16 and E6 for 18 Amplification with TS primers (16. 18) Germany Hoffmann 2006 MY09/MY11 (L1) and TS-PCR for 6/11/16/18/33 Hybridization with TS and consensus probes and further confirmation by SBH with TS and consensus probes (6. 11. 16. 18. 31. 33. 45) Germany Hoffmann 2009 MY09/MY11 (L1) and TS-PCR for 6/11/16/18 Hybridization with TS and consensus probes and further confirmation by SBH with TS and consensus probes (6. 11. 16. 18. 31. 33. 45) Italy Cattani 1998 MY09/MY11 (L1) and TS-PCR for 33 Hybridization with TS probes (6.11.16.18.31) and amplification with TS primer (33) Italy Gallo 2009 MY09/MY11 (L1). LCRF1. LCRF2. LCRF3. LCRF4. E7R1. E7R2. E7R3. E7R4 (E6) and TS-PCR E1 for 6/11/16/18-31/33 Sequencing 61 37.7 (26.6-50.3) 17 23.5 (9.6-47.3) 21 33.3 (17.2-54.6) 70 30.0 (20.5-41.5) 36 0.0 (0.0-9.6) Italy Azzimonti 2004 GP5+/GP6+ (L1) Sequencing 23 56.5 (36.8-74.4) Japan Anwar 1993 TS-PCR for 16/18/33 Hybridization with TS probes (4. 16. 18) Japan Shidara 1994 L1C1/L1C2 RFLP (6. 11. 16. 18. 31. 33. 42. 52. 58) Norway Lie 1996 CP (E1). MY09/MY11 (L1) and GP5+/GP6+ (L1) Amplification with TS primers (6.11.16.18.31.33.35) 26 38.5 (22.4-57.5) 40 20.0 (10.5-34.8) 38 7.9 (2.7-20.8) Poland Morshed 2008 SPF10 (L1) LiPA 25 78 34.6 (25.0-45.7) Turkey Bozdayi 2009 MY09/MY11 (L1) Amplification with GP5+/6+ and TS primers for HPV16 positive; For HPV16 negative cases. sequencing was performed Turkey Dönmez 2000 MY09/MY11 (L1) RFLP (6. 11. 16. 18. 31. 33. 35. 39. 42. 51. 58) WOMEN Canada Fliss 1994 TS-PCR E6/E7 for 6b/11/16/18 Amplification with TS primers (6b/11. 16. 18) 62 43.5 (31.9-55.9) 55 12.7 (6.3-24.0) 1 0.0 (0.0-79.3) Chile Torrente 2005 MY09/MY11 (L1) RFLP 6 16.7 (3.0-56.4) China Liu 2010 GP5+/GP6+ (L1) and TS-PCR E6/E7 for 16 and E6 for 18 Amplification with TS primers (16. 18) 23 34.8 (18.8-55.1) ( Table 29 continued from previous page)

- 187 - ( Table 29 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Germany Hoffmann 2006 MY09/MY11 (L1) and TS-PCR for 6/11/16/18/33 Hybridization with TS and consensus probes and further confirmation by SBH with TS and consensus probes (6. 11. 16. 18. 31. 33. 45) Germany Hoffmann 2009 MY09/MY11 (L1) and TS-PCR for 6/11/16/18 Hybridization with TS and consensus probes and further confirmation by SBH with TS and consensus probes (6. 11. 16. 18. 31. 33. 45) Italy Cattani 1998 MY09/MY11 (L1) and TS-PCR for 33 Hybridization with TS probes (6.11.16.18.31) and amplification with TS primer (33) Italy Gallo 2009 MY09/MY11 (L1). LCRF1. LCRF2. LCRF3. LCRF4. E7R1. E7R2. E7R3. E7R4 (E6) and TS-PCR E1 for 6/11/16/18-31/33 Sequencing 3 33.3 (6.1-79.2) 6 16.7 (3.0-56.4) 28 21.4 (10.2-39.5) 4 0.0 (0.0-49.0) Italy Azzimonti 2004 GP5+/GP6+ (L1) Sequencing 2 50.0 (9.5-90.5) Japan Anwar 1993 TS-PCR for 16/18/33 Hybridization with TS probes (4. 16. 18) Japan Shidara 1994 L1C1/L1C2 RFLP (6. 11. 16. 18. 31. 33. 42. 52. 58) Norway Lie 1996 CP (E1). MY09/MY11 (L1) and GP5+/GP6+ (L1) Amplification with TS primers (6.11.16.18.31.33.35) 4 25.0 (4.6-69.9) 5 60.0 (23.1-88.2) 10 0.0 (0.0-27.8) Poland Morshed 2008 SPF10 (L1) LiPA 25 15 40.0 (19.8-64.3) Turkey Bozdayi 2009 MY09/MY11 (L1) Amplification with GP5+/6+ and TS primers for HPV16 positive; For HPV16 negative cases. sequencing was performed Turkey Dönmez 2000 MY09/MY11 (L1) RFLP (6. 11. 16. 18. 31. 33. 35. 39. 42. 51. 58) UNSPECIFIED Argentina Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Belgium Duray 2011 GP5+/GP6+ (L1) and RT-PCR E6/E7 for 6. 11. 16. 18. 31. 33. 35. 39. 45. 51. 52. 53. 56. 58. 59. 66. 67-L1. 68 TS real-time and consensus PCR E6/E7 (6. 11. 16. 18. 31. 33. 35. 39. 45. 51. 52. 53. 56. 58. 59. 66. 67-L1. 68) Brazil Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Brazil Miranda 2009 GP5+/GP6+ (L1) Amplification with TS primers (16. 18. 33) and sequencing China Ma 1998 TS-PCR E6/E7 for 6/11/16/18/31/33/52b/58 SBH (6. 11. 16. 18. 31. 33. 52b. 58) 3 0.0 (0.0-56.1) 0 - - 239 0.8 (0.2-3.0) 59 79.7 (67.7-88.0) 239 0.8 (0.2-3.0) 27 7.4 (2.1-23.4) 102 58.8 (49.1-67.9) ( Table 29 continued from previous page)

- 188 - ( Table 29 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Cuba Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Cuba García-Milián 1998 MY09/MY11 (L1) and TS-PCR E6 for 6/11/16/18 SBH (6. 11. 16. 18) Czech Republic Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Denmark Lindeberg 1999 MY09/MY11 (L1). GP5+/GP6+ (L1) and CPII/II (L1) Hybridization with TS probes (6.11.16.18.30.31.33.35) Finland Koskinen 2007 MY09/MY11 (L1). GP5+/GP6+ (L1) and SPF10 (L1) LiPA 25 Finland Mork 2001 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers (6. 11. 16. 18. 33) 239 0.8 (0.2-3.0) 33 48.5 (32.5-64.8) 239 0.8 (0.2-3.0) 30 3.3 (0.6-16.7) 69 4.3 (1.5-12.0) 40 2.5 (0.4-12.9) Finland Koskinen 2003 SPF10 (L1) LiPA 25 28 50.0 (32.6-67.4) France Fouret 1997 TS-PCR E6 for 16/18/31/33/45 Hybridization with TS probes (16. 18. 31. 33. 45) 103 6.8 (3.3-13.4) Germany Fischer 2003 L1-CP65F. 66F. 69F. 70F Sequencing 47 34.0 (22.2-48.3) Germany Kleist 2000 MY09/MY11 (L1) Amplification with TS primers (16. 18) Germany Klussmann 2001 A10/A5-A6/A8 (L1) and CP62/70-CP65/69a (L1) Sequencing Germany Hoffmann 1998 MY09/MY11 (L1) and TS-PCR for 6/11/16/18/33 SBH (6. 11. 16. 18. 31. 33. 45) Greece Gorgoulis 1999 MY09/MY11 (L1) and GP5/GP6 (L1) Amplification with TS primers (6. 11. 16. 18. 31. 33. 35) and confirmation by DBH with TS probes (6.11.16.18. 31.33.35). Greece Vlachtsis 2005 TS-PCR for 16/18 Amplification with TS primers (16. 18) Hungary Major 2005 MY09/MY11 (L1) and GP5+/GP6+ (L1) RFLP (6. 11. 16. 18) India Jacob 2002 TS-PCR E1 for 6/11/18 and L1 for 16 SBH with TS probes (6. 11. 16. 18) Italy Badaracco 2000 MY09/MY11 (L1) Amplification with TS primers (6.16) and hybridization with TS probes (11.16.18.31.45.56.57) Italy Badaracco 2007 MY09/MY11 (L1) and GP5+/GP6+ (L1) Sequencing Italy Boscolo-Rizzo 2009 MY09/MY11 (L1) RFLP* and amplification with TS primers E6/E2 for 16 Japan Mineta 1998 TS-PCR E7 for 16/18 Amplification with TS primers (16. 18) Japan Ogura 1991 TS-PCR E6 for 16/18 Hybridization with TS probes (16. 18) Lithuania Gudleviciene 2009 Consensus primers from Master Mix Amplification with TS primers (16. 18) 35 20.0 (10.0-35.9) 30 16.7 (7.3-33.6) 51 21.6 (12.5-34.6) 91 20.9 (13.8-30.3) 90 40.0 (30.5-50.3) 22 54.5 (34.7-73.1) 44 34.1 (21.9-48.9) 22 50.0 (30.7-69.3) 30 16.7 (7.3-33.6) 45 4.4 (1.2-14.8) 42 31.0 (19.1-46.0) 28 10.7 (3.7-27.2) 25 32.0 (17.2-51.6) ( Table 29 continued from previous page)

- 189 - ( Table 29 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) Norway Mork 2001 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers (6. 11. 16. 18. 33) Norway Koskinen 2007 MY09/MY11 (L1). GP5+/GP6+ (L1) and SPF10 (L1) LiPA 25 Poland Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Poland Snietura 2011 Real-time High Risk HPV test (Abbott Molecular) using L1 consensus primers RT-PCR (16. 18. 31. 33. 35. 39. 45. 51. 52. 56. 58. 59. 66. 68) Romania Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Russian Federation Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Slovakia Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Slovenia Poljak 1997 PGMY09/11 (L1). GP5+/GP6+ (L1) and WD72/76/66/67/154 (E6) Amplification with TS primers (6.11.16.18.31.33.51) Spain Alvarez Alvarez 1997 TS-PCR E6 and L1 for 6b/16/18 Amplification with TS primers (6b. 16. 18) Spain Pérez-Ayala 1990 TS-PCR E6 for 6/11 Hybridization with TS probes (11.16) Sweden Koskinen 2007 MY09/MY11 (L1). GP5+/GP6+ (L1) and SPF10 (L1) LiPA 25 Sweden Mork 2001 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers (6. 11. 16. 18. 33) Switzerland Adams 1999 MY09/MY11 (L1) RFLP (6.11.16.18.31.33.35.51.53.56) Turkey Gungor 2007 SP10296 (L1) Amplification with mpcr kit (6. 11. 16. 18. 31. 33. 52. 58) United Kingdom Salam 1995 MY09/MY11 (L1) RFLP (6. 11. 16. 18. 33) United Kingdom Snijders 1996 GP5+/GP6+ (L1) Amplification with TS primers and SBH with TS probes (6. 11. 16. 18. 31. 33) United Kingdom Anderson 2007 GP5+/GP6+ (L1) Hybridization with Roche LBA (6. 11. 16. 18. 26. 31. 33. 35. 39. 40. 42. 45. 51. 52. 53. 54. 55. 56. 58. 59. 61. 62. 64. 66. 67. 68. 69. 70. 71. 72. 73. 81. 82. 83. 84. 89) United States of America United States of America Brandwein 1993 Furniss 2007 Perkin Census L1 consensus primers Hybridization with TS probes (6. 11. 16. 18. 31. 35. 51) TS-PCR L1 for 16 Amplification with TS primers (16) 40 2.5 (0.4-12.9) 69 4.3 (1.5-12.0) 239 0.8 (0.2-3.0) 65 0.0 (0.0-5.6) 239 0.8 (0.2-3.0) 239 0.8 (0.2-3.0) 239 0.8 (0.2-3.0) 30 3.3 (0.6-16.7) 35 25.7 (14.2-42.1) 51 56.9 (43.3-69.5) 69 4.3 (1.5-12.0) 40 2.5 (0.4-12.9) 36 16.7 (7.9-31.9) 95 7.4 (3.6-14.4) 36 22.2 (11.7-38.1) 31 19.4 (9.2-36.3) 64 0.0 (0.0-5.7) 40 7.5 (2.6-19.9) 63 31.7 (21.6-44.0) ( Table 29 continued from previous page)

- 190 - ( Table 29 continued from previous page) HPV detection method and targeted HPV prevalence Country Study HPV types No. Tested % (95% CI) United States of America United States of America United States of America United States of America Schlecht 2011 Shen 1996 Zhao 2005 Paz 1997 MY09/MY11 (L1) and HMB01 (L1) DBH (40 HPV types including 16. 18. 31. 33. 35. 39. 45. 51. 52. 56. 58. 66) MY09/MY11 (L1) and TS-PCR E7 for 16/18 RFLP* RT-PCR E6/E7 for 16 Hybridization with TS probes (16) MY09/MY11 (L1) and IU/IWDO (E1) Amplification with TS primers (6. 16. 18) 40 27.5 (16.1-42.8) 32 9.4 (3.2-24.2) 22 18.2 (7.3-38.5) 43 4.7 (1.3-15.5) Data updated at 15 Dec 2014 (data as of 29 Feb 2012). 95% CI: 95% Confidence Interval; DBH: Dot Blot Hybridization; LBA: Line-Blot Assay; LiPA: Line Probe Assay; PCR: Polymerase Chain Reaction; RFLP: Restriction Fragment Length Polymorphism; RT-PCR: Real Time Polymerase Chain Reaction; SBH: Southern Blot Hybridization; SPF: Short Primer Fragment; TS: Type Specific; Data sources: See references in Section 9.

5 FACTORS CONTRIBUTING TO CERVICAL CANCER (LAST UPDATE 08 AUG 2013) - 191-5 Factors contributing to cervical cancer (last update 08 Aug 2013) HPV is a necessary cause of cervical cancer, but it is not a sufficient cause. Other cofactors are necessary for progression from cervical HPV infection to cancer. Tobacco smoking, high parity, long-term hormonal contraceptive use, and co-infection with HIV have been identified as established cofactors. Co-infection with Chlamydia trachomatis and herpes simplex virus type-2, immunosuppression, and certain dietary deficiencies are other probable cofactors. Genetic and immunological host factors and viral factors other than type, such as variants of type, viral load and viral integration, are likely to be important but have not been clearly identified. (Muñoz N, Vaccine 2006; 24(S3): 1-10). In this section, the prevalence of smoking, parity (fertility), oral contraceptive use, and HIV in World are presented. Figure 114: Prevalence of female tobacco smoking worldwide Adjusted and age-standardized prevalence estimates of tobacco use by country, for the year 2011. These rates are constructed solely for the purpose of comparing tobacco use prevalence estimates across countries, and should not be used to estimate the number of smokers in the population. Smoking any form of tobacco, including cigarettes, cigars, pipes, etc. and excluding smokeless tobacco. ; Smoking at the time of the survey, including daily and non-daily smoking. For Palestine the note is: Refers to a territory. WHO report on the global tobacco epidemic, 2013: The MPOWER package. Geneva, World Health Organization, 2013. <BR> Available at http://www.who.int/tobacco/global_report/2013/en/index.html

5 FACTORS CONTRIBUTING TO CERVICAL CANCER (LAST UPDATE 08 AUG 2013) - 192 - Figure 115: Total fertility rates worldwide For Morocco and Mozambique the note is: Data pertain to nationals of the country. Fertility rate estimates by country are presented as a proxy measure of parity. Parity is the number of times a woman has given birth, while fertility rate is the average number of live births per woman, assuming the age-specific fertility rate observed in a given year or period. For Bahrain, Bosnia & Herzegovina, Canada, Costa Rica, Cuba, Egypt, El Salvador, Fiji, Guatemala, Israel, Jamaica, Japan, Korea, Republic of, Kuwait, Kyrgyzstan, Malaysia, Marshall Islands, Mauritius, Mexico, Micronesia, Mongolia, New Zealand, Qatar, Republic of Moldova, Singapore, St Vincent & The Grenadines, Suriname, Thailand, Tunisia, Tuvalu and United States of America the note is: The number of women by age is estimated by the United Nations Population Division and published in the World Population Prospects Revision 2006. For Saudi Arabia the note is: Data pertain to Saudi women only. For South Sudan and Sudan the note is: Data pertain to Northern Sudan and urban areas of Southern Sudan. For Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Macedonia, TFYR, Malta, Montenegro, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and United Kingdom the source is: Eurostat - Statistical office of the European Comission [web site]. Luxembourg: European Commission; 2013. <BR> Available at: http://epp.eurostat.ec.europa.eu/portal/page/portal/eurostat/home/ [Accessed on July 2013] For Afghanistan, Albania, Algeria, Andorra, Angola, Antigua & Barbuda, Argentina, Armenia, Australia, Azerbaijan, Bahamas, Bahrain, Bangladesh, Barbados, Belarus, Belize, Benin, Bhutan, Bolivia, Bosnia & Herzegovina, Botswana, Brazil, Brunei, Burkina Faso, Burundi, Cambodia, Cameroon, Canada, Cape Verde, Central African Republic, Chad, Chile, China, Colombia, Comoros, Congo, Congo, DR, Cook Islands, Costa Rica, Côte d Ivoire, Cuba, Djibouti, Dominica, Dominican Republic, Ecuador, Egypt, El Salvador, Equatorial Guinea, Eritrea, Ethiopia, Fiji, Gabon, Gambia, Georgia, Ghana, Grenada, Guatemala, Guinea, Guinea- Bissau, Guyana, Haiti, Honduras, India, Indonesia, Iran, Iraq, Israel, Jamaica, Japan, Jordan, Kazakhstan, Kenya, Kiribati, Korea, DPR, Korea, Republic of, Kuwait, Kyrgyzstan, Laos, Lebanon, Lesotho, Liberia, Libya, Madagascar, Malawi, Malaysia, Maldives, Mali, Marshall Islands, Mauritania, Mauritius, Mexico, Micronesia, Mongolia, Morocco, Mozambique, Myanmar, Namibia, Nauru, Nepal, New Zealand, Nicaragua, Niger, Nigeria, Niue, Oman, Pakistan, Palau, Palestine, Panama, Papua New Guinea, Paraguay, Peru, Philippines, Qatar, Republic of Moldova, Rwanda, Samoa, San Marino, Sao Tome & Principe, Saudi Arabia, Senegal, Seychelles, Sierra Leone, Singapore, Solomon Islands, Somalia, South Africa, South Sudan, Sri Lanka, St Kitts & Nevis, St Lucia, St Vincent & The Grenadines, Sudan, Suriname, Swaziland, Syria, Tajikistan, Tanzania, Thailand, Timor-Leste, Togo, Tonga, Trinidad & Tobago, Tunisia, Turkmenistan, Tuvalu, Uganda, Ukraine, United Arab Emirates, United States of America, Uruguay, Uzbekistan, Vanuatu, Venezuela, Viet Nam, Yemen, Zambia and Zimbabwe the source is: United Nations, Department of Economic and Social Affairs, Population Division. World Fertility Data 2008. (POP/DB/Fert/Rev2008).<BR> Available at: http://www.un.org/esa/population/publications/wfd%202008/main.html [Accessed on July 2013]

5 FACTORS CONTRIBUTING TO CERVICAL CANCER (LAST UPDATE 08 AUG 2013) - 193 - Figure 116: Prevalence of oral contraceptive use worldwide For Austria, Bulgaria, Cook Islands, Denmark, Estonia, Greece, Grenada, Guam, Hungary, Italy, Korea, DPR, Latvia, Lithuania, Mauritania, Mauritius, New Zealand, Pakistan, Poland, Puerto Rico, Reunion, Singapore, Slovenia, Tunisia and Turkmenistan the note is: Adjusted. For Argentina, Belgium, Denmark and Greece the note is: Data pertain to sexually active women of reproductive age. For Belgium the note is: Data pertain to methods used during the last 12 months. For Anguilla, Cook Islands, Croatia, Guadeloupe, Kiribati, Martinique, N Mariana Islands, Palau, Reunion and Uruguay the note is: Data pertain to all women of reproductive age, irrespective of marital status. For Anguilla and Croatia the note is: Data pertain to methods used during the last two months. For Estonia, Guam, Portugal, Puerto Rico and US Virgin Islands the note is: Data pertain to sexually active, non-pregnant women. For Estonia the note is: Data pertain to methods used during the last month. For Israel the note is: Data pertain to the Jewish population. For Malta the note is: Data pertain to married women who visited a practitioner belonging to the Malta College of Family Doctors. For Norway the note is: Data pertain to women who were sexually active during the three months prior to the interview. For Poland the note is: Data pertain to women who were sexually active during the month prior to the interview. For Australia and Slovakia the note is: Data pertain to women exposed to the risk of pregnancy. For Canada and Sweden the note is: Data pertain to women who have ever had sex. For Sweden the note is: Data pertain to methods used at last sex. For United Kingdom the note is: Excluding Northern Ireland. For Jamaica and United Kingdom the note is: Including emergency contraception. For Uruguay the note is: Data pertain to men and women of reproductive age who are married or in a union. For Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and United Arab Emirates the note is: Data pertain to nationals of the country. For Chile the note is: Data pertain to men and women of reproductive age. For Guyana, Lesotho, Maldives, Nauru, Sri Lanka, Tanzania and Timor-Leste the note is: Preliminary data. For Malaysia the note is: Data pertain to Peninsular Malaysia. For Korea, Republic of and Uruguay the note is: Estimate. For Sri Lanka the note is: Excluding the Northern Province. For South Sudan and Sudan the note is: Including data for Sudan and South Sudan (Sudan presecession). Proportion of women using hormonal contraception among those of reproductive age (15-49 years) who are married or in union. For Iran and Kuwait the note is: Data pertain to non-pregnant women. United Nations, Department of Economic and Social Affairs, Population Division (2011). World Contraceptive Use 2010 (POP/DB/CP/Rev2010) <BR> (http://www.un.org/esa/population/publications/wcu2010/main.html)

5 FACTORS CONTRIBUTING TO CERVICAL CANCER (LAST UPDATE 08 AUG 2013) - 194 - Figure 117: Prevalence of HIV worldwide Estimates include all people with HIV infection, regardless of whether they have developed symptoms of AIDS. For Afghanistan, Algeria, Angola, Argentina, Armenia, Australia, Austria, Azerbaijan, Bahamas, Bangladesh, Barbados, Belarus, Belgium, Belize, Benin, Bhutan, Bolivia, Botswana, Brazil, Bulgaria, Burkina Faso, Burundi, Cambodia, Cameroon, Canada, Cape Verde, Central African Republic, Chad, Chile, China, Colombia, Comoros, Congo, Costa Rica, Côte d Ivoire, Croatia, Cuba, Czech Republic, Denmark, Djibouti, Dominican Republic, Ecuador, Egypt, El Salvador, Equatorial Guinea, Eritrea, Estonia, Ethiopia, Fiji, Finland, France, Gabon, Gambia, Georgia, Germany, Ghana, Greece, Guatemala, Guinea, Guinea-Bissau, Guyana, Haiti, Honduras, Hungary, Iceland, Indonesia, Iran, Ireland, Israel, Italy, Jamaica, Japan, Kazakhstan, Kenya, Korea, Republic of, Kyrgyzstan, Laos, Latvia, Lebanon, Lesotho, Liberia, Lithuania, Luxembourg, Madagascar, Malawi, Malaysia, Maldives, Mali, Malta, Mauritania, Mauritius, Mexico, Mongolia, Morocco, Mozambique, Myanmar, Namibia, Nepal, Netherlands, New Zealand, Nicaragua, Niger, Nigeria, Norway, Pakistan, Panama, Papua New Guinea, Paraguay, Peru, Philippines, Poland, Portugal, Republic of Moldova, Romania, Russian Federation, Rwanda, Sao Tome & Principe, Senegal, Serbia, Sierra Leone, Singapore, Slovakia, Slovenia, Somalia, South Africa, South Sudan, Spain, Sri Lanka, Sudan, Suriname, Swaziland, Sweden, Switzerland, Tajikistan, Tanzania, Thailand, Togo, Trinidad & Tobago, Tunisia, Turkey, Uganda, Ukraine, United Kingdom, United States of America, Uruguay, Venezuela, Viet Nam, Yemen, Zambia and Zimbabwe the source is: 2012 UNAIDS Report on the Global AIDS Epidemic (http://www.unaids.org/en/resources/campaigns/20121120_globalreport2012/globalreport/) For Albania, Bosnia & Herzegovina, Cyprus, Jordan, Libya, Macedonia, TFYR, Qatar, Saudi Arabia, Syria, Turkmenistan and United Arab Emirates the source is: Global report: UNAIDS report on the global AIDS epidemic 2008: Annex 1: HIV and AIDS estimates and data, 2007 and 2001. Available at: http://www.unaids.org/en/media/unaids/contentassets/dataimport/pub/globalreport/2008/jc1510_2008globalreport_en.pdf

6 REPRODUCTIVE AND SEXUAL BEHAVIOUR (LAST UPDATE 08 AUG 2013) - 195-6 Reproductive and sexual behaviour (last update 08 Aug 2013) Sexual intercourse is the primary route of transmission of genital HPV infection. Information about sexual and reproductive health behaviours is essential to the design of effective preventive strategies against anogenital cancers. In this section, we describe sexual and reproductive health indicators that may be used as proxy measures of risk for HPV infection and anogenital cancers. Several studies have reported that earlier sexual debut is a risk factor for HPV infection, although the reason for this relationship is still unclear. In this section, information on sexual and reproductive health behavior in World is presented. Figure 118: Proportion of young women (15-24 years) who have had sex before the age of 15 worldwide

7 HPV PREVENTIVE STRATEGIES - 196-7 HPV preventive strategies It is established that well-organised cervical screening programmes or widespread good quality cytology can reduce cervical cancer incidence and mortality. The introduction of HPV vaccination could also effectively reduce the burden of cervical cancer in the coming decades. This section presents indicators on basic characteristics and performance of cervical cancer screening, status of HPV vaccine licensure, introduction in World. 7.1 Cervical cancer screening practices (last update 30 Jul 2013) Screening strategies differ between countries. Some countries have population-based programmes, where in each round of screening women in the target population are individually identified and invited to attend screening. This type of programme can be implemented nationwide or only in specific regions of the country. In opportunistic screening, invitations depend on the individual s decision or on encounters with health-care providers. The most frequent method for cervical cancer screening is cytology, and there are alternative methods such as HPV DNA tests and Visual inspection with acetic acid (VIA). VIA is an alternative to cytology-based screening in low-resource settings ( see and treat approach). HPV DNA testing is being introduced into some countries as an adjunct to cytology screening ( co-testing ) or as the primary screening test to be followed by a secondary, more specific test, such as cytology. Table 30: Cervical cancer screening policy in the World Screening Screening Screening HPV Country name type ages (years) interval VIA DNA test (years) Africa - - - - - Algeria - - - No visual inspection program 1 No HPV DNA Angola - - - Pilot program 1 No HPV DNA Benin - - - Pilot program 1 No HPV DNA Botswana - - - Pilot program 1 No HPV DNA Burkina Faso - - - Pilot program 1 No HPV DNA Burundi - - - No visual inspection program 1 No HPV DNA Cameroon - - - Pilot program 1 No HPV DNA Cape Verde - - - No visual inspection program 1 Central African Republic - - - No visual inspection program 1 Chad - - - No visual inspection program 1 Comoros - - - No visual inspection program 1 No HPV DNA No HPV DNA No HPV DNA No HPV DNA Congo - - - Pilot program 1 No HPV DNA Congo, DR - - - No visual inspection program 1 No HPV DNA Côte d Ivoire - - - Pilot program 1 No HPV DNA Djibouti - - - No visual inspection program 1 Egypt - - - No visual inspection program 1 Equatorial Guinea - - - No visual inspection program 1 Eritrea - - - No visual inspection program 1 No HPV DNA No HPV DNA No HPV DNA No HPV DNA Ethiopia - - - Pilot program 1 No HPV DNA (Continued)

7 HPV PREVENTIVE STRATEGIES - 197 - Table 30 Continued Screening Screening Screening HPV Country name type ages (years) interval (years) VIA Gabon - - - No visual inspection program 1 DNA test No HPV DNA Gambia - - - Pilot program 1 No HPV DNA Ghana - - - Pilot program 1 No HPV DNA Guinea - - - Pilot program 1 No HPV DNA Guinea-Bissau - - - No visual inspection program 1 No HPV DNA Kenya - - - National program 1 No HPV DNA Lesotho - - - Pilot program 1 No HPV DNA Liberia - - - No visual inspection program 1 Libya - - - No visual inspection program 1 Madagascar Malawi No HPV DNA No HPV DNA - - Pilot program 1 No HPV DNA - - National program 1 No HPV DNA Mali - - - Pilot program 1 No HPV DNA Mauritania - - - Pilot program 1 No HPV DNA Mauritius - - - No visual inspection program 1 No HPV DNA Swaziland - - - No visual inspection program 1 Tanzania No HPV DNA - - National program 1 No HPV DNA Zambia Non-populationbased Non-populationbased Morocco - - - National program 1 No HPV DNA Mozambique - - - National program 1 No HPV DNA Namibia - - - Pilot program 1 No HPV DNA Niger - - - Pilot program 1 No HPV DNA Nigeria Non-populationbased - - Pilot program 1 No HPV DNA Rwanda - - - National program 1 Pilot program 1 Sao Tome & Principe - - - No visual inspection program 1 No HPV DNA Senegal - - - Pilot program 1 No HPV DNA Seychelles - - - No visual inspection program 1 No HPV DNA Sierra Leone - - - Pilot program 1 No HPV DNA Somalia - - - No visual inspection program 1 No HPV DNA South Africa Non-populationbased >=30 8 10 8 Pilot program 1 No HPV DNA South Sudan - - - No visual inspection program 1 No HPV DNA Sudan - - - Pilot program 1 No HPV DNA Non-populationbased Togo - - - Pilot program 1 No HPV DNA Tunisia - - - No visual inspection program 1 No HPV DNA Uganda Non-populationbased - - National program 1 Pilot program 1 Non-populationbased - - National program 1 No HPV DNA (Continued)

7 HPV PREVENTIVE STRATEGIES - 198 - Table 30 Continued Screening Screening Screening HPV Country name type ages (years) interval VIA DNA test (years) Zimbabwe - - - Pilot program 1 No HPV DNA Americas - - - - - Antigua & Barbuda - - - No visual inspection program 1 Argentina 35-64 3 Every 3 years after 2 consecutive annual negative smears (1-1-3) 3 No HPV DNA No visual inspection program 1 Pilot program 4 Bahamas - - - No visual inspection program 1 Pilot program 4 Barbados - - - No visual inspection program 1 Belize - - - No visual inspection program 1 Bolivia Brazil Non-populationbased Non-populationbased Non-populationbased Canada Population-based >=18 (Northwest Territories, Yukon, Nunavut, Newfoundland, Nova Scotia);18-69 (Quebec, Alberta, British Columbia);20-69 (Prince Edward Island, Ontario) 8 Chile Colombia Costa Rica Cuba Non-populationbased (organized in some regions) Non-populationbased Non-populationbased Non-populationbased 25-49 3 Every 3 years after 2 consecutive annual negative smears (1-1-3) 3 National program 1 No HPV DNA No HPV DNA No HPV DNA 25-60 3 3 3 No visual inspection program 1 Pilot program 4 Every 2 years after 3 normal annual smears; Annual if at high-risk; Annual in Alberta 8 No visual inspection program 1 Pilot program 9 25-64 3 3 3 No visual inspection program 1 Pilot program 4 25-69 3 3 3 National program 1 Pilot program 1 20-59 3 2 3 No visual inspection program 1 No HPV DNA 25-59 3 3 3 National program 4 No HPV DNA Dominica - - - No visual inspection program 1 Dominican Republic Ecuador El Salvador 25-59 3 6-6-12 (months) 3 No visual inspection program 1 No HPV DNA No HPV DNA Pilot program 4 35-64 3 5 3 No visual inspection program 1 30-59 3 2 3 National program 1 Pilot program 1 Haiti Honduras Non-populationbased Non-populationbased Non-populationbased Grenada - - - Pilot program 1 No HPV DNA Guatemala Non-populationbased 25-59 3 5 3 National program 1 No HPV DNA Guyana - - - National program 1 No HPV DNA Non-populationbased Non-populationbased - - Pilot program 1 No HPV DNA 25-59 3 1 3 Pilot program 1 No HPV DNA (Continued)

7 HPV PREVENTIVE STRATEGIES - 199 - Table 30 Continued Screening Screening Screening HPV Mexico Nicaragua Panama Paraguay >=25 3 Every 3 years after 2 consecutive annual negative smears (1-1-3) 6 25-59 3 Every 3 years after 3 consecutive annual negative smears (1-1-1-3) 3 No visual inspection program 1 DNA test No HPV DNA National program 1 National program 1 Pilot program 1 >=15 3 3 3 National program 1 No HPV DNA 25-69 3 Every 3 years National program 1 Pilot program 1 after 3 consecutive annual negative smears (1-1-1-3) 3 25-59 3 3 3 National program 1 Pilot program 1 No HPV DNA St Lucia - - - Pilot program 1 No HPV DNA St Vincent & The Grenadines - - - No visual inspection program 1 No HPV DNA Suriname - - - National program 1 No HPV DNA Trinidad & Tobago United States of America Uruguay Venezuela 20-59 3 Every 3 years after 2 consecutive annual negative smears (1-1-3) 3 No visual inspection program 1 21-65 8 3 8 No visual inspection program 1 No HPV DNA National program 1 >18 3 3 3 No visual inspection Pilot program 4 program 1 25-64 3 3 3 No visual inspection Pilot program 4 program 1 Asia - - - - - No HPV DNA No HPV DNA No HPV DNA No HPV DNA Bangladesh - - - National program 1 No HPV DNA Bhutan - - - Pilot program 1 No HPV DNA Brunei - - - No visual inspection program 1 No HPV DNA Cambodia - - - National program 1 No HPV DNA China - - - National program 1 Pilot program 1 Georgia Country name type ages (years) interval (years) VIA Jamaica Non-populationbased - - No visual inspection program 1 Non-populationbased Non-populationbased Non-populationbased Non-populationbased Peru Non-populationbased St Kitts & Nevis - - - No visual inspection program 1 Non-populationbased Non-populationbased Non-populationbased Non-populationbased Afghanistan - - - No visual inspection program 1 Armenia Non-populationbased 30-60 5 3 5 No visual inspection program 1 Azerbaijan No programme - - No visual inspection program 1 Bahrain - - - No visual inspection program 1 Non-populationbased (organized in 1 region) 25-60 2 3 2 No visual inspection program 1 Pilot program 1 (Continued)

7 HPV PREVENTIVE STRATEGIES - 200 - Table 30 Continued Screening Screening Screening HPV Iran - - - No visual inspection program 1 Iraq - - - No visual inspection program 1 Israel - 35-54 8 3 8 No visual inspection program 1 Japan Population-based >=20 6 1 6 No visual inspection program 1 Jordan - - - No visual inspection program 1 Kazakhstan Country name type ages (years) interval VIA DNA test (years) India Non-populationbased 18-69 6 3 6 Pilot program 1 Pilot program 1 Indonesia - - - National program 1 No HPV DNA Non-populationbased (call-recall system in few regions on unregular basis) 30-60 5 5 5 No visual inspection program 1 Korea, DPR - - - No visual inspection program 1 Korea, Republic of National Health insurance Corp. (NHIC) >=30 6 2 6 No visual inspection program 1 Kuwait - - - No visual inspection program 1 Kyrgyzstan - - - No visual inspection program 1 Laos - - - No visual inspection program 1 Lebanon - - - No visual inspection program 1 Malaysia 20-65 6 3 11 No visual inspection program 1 No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA Maldives - - - Pilot program 1 No HPV DNA Mongolia - - - No visual inspection program 1 No HPV DNA Myanmar - - - Pilot program 1 No HPV DNA Nepal - - - Pilot program 1 No HPV DNA Oman - - - No visual inspection program 1 Pakistan - - - No visual inspection program 1 No HPV DNA No HPV DNA Philippines - - - National program 1 No HPV DNA Qatar - - - No visual inspection program 1 Saudi Arabia - - - No visual inspection program 1 Singapore - 25-69 12 Every 3 years after 2 consecutive annual negative smears (1-1-3) 12 No visual inspection program 1 Sri Lanka - - - No visual inspection program 1 Syria - - - No visual inspection program 1 Tajikistan Thailand Non-populationbased Non-populationbased Non-populationbased 20+ 5 - No visual inspection program 1 No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA 30-65 6 5 6 National program 1 No HPV DNA (Continued)

7 HPV PREVENTIVE STRATEGIES - 201 - Table 30 Continued Screening Screening Screening HPV United Arab Emirates - - - No visual inspection program 1 Uzbekistan Country name type ages (years) interval VIA DNA test (years) Timor-Leste - - - No visual inspection program 1 No HPV DNA Turkey Non-populationbased 18 to no limit 2 1 2 Pilot program 1 Pilot program 9 Turkmenistan Non-populationbased 20+ 5 1 5 No visual inspection program 1 No HPV DNA Non-populationbased (organized in some pilot regions) 25-49 5 - No visual inspection program 1 No HPV DNA No HPV DNA Viet Nam - - - National program 1 No HPV DNA Yemen - - - No visual inspection program 1 No HPV DNA Europe - - - - - Albania - - - No visual inspection program 1 Andorra Austria Belarus Belgium Bosnia & Herzegovina - - No visual inspection program 1 18 to not 1 2 No visual inspection specified 2 program 1 18 to no limit 5 1 5 No visual inspection program 1 25-64 7 3 7 No visual inspection program 1 20 to no limit 2 Every 3 years after 3 consecutive annual negative smears (1-1-1-3) 2 No visual inspection program 1 Finland Population-based 30-60 (some counties 25-65) 10 France Germany Non-populationbased Non-populationbased Non-populationbased Non-populationbased Non-populationbased Bulgaria Non-populationbased 30-59 2 3 2 No visual inspection program 1 Croatia Non-populationbased 25-64 2 3 2 No visual inspection program 1 Cyprus Non-populationbased - - No visual inspection program 1 Czech Republic Population-based 25-60 2 1 2 No visual inspection program 1 Denmark Population-based 23-65 2 23-49 age: 3, No visual inspection 50-65 age: 5 2 program 1 Estonia Population-based 30-59 2 3 2 No visual inspection program 1 Non-populationbased (organized in some regions) Non-populationbased Non-populationbased Regional variation: From (20) 25 to not specified 2 5 2 No visual inspection program 1 3 2 No visual inspection program 1 No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA 20 to not 1 2 No visual inspection Pilot program 1 specified 2 program 1 1 2 No visual inspection Greece 20 to not specified 2 program 1 Hungary Population-based 25-65 2 3 2 No visual inspection program 1 Iceland Population-based 20-69 2 20-39 age: 2, 40-65(69) age: 4 2 Ireland Population-based (regional but nationwide planned) No visual inspection program 1 25-65 2 3 in age 25-44 No visual inspection (5 for 45+ age) 2 program 1 (Continued) No HPV DNA No HPV DNA No HPV DNA No HPV DNA

7 HPV PREVENTIVE STRATEGIES - 202 - Table 30 Continued Screening Screening Screening HPV Country name type ages (years) interval VIA DNA test (years) Italy Population-based 25-64 2 3 2 No visual inspection program 1 Pilot program 1 Portugal Republic of Moldova Romania Russian Federation Russian Federation Latvia Population-based 25-70 2 3 2 No visual inspection program 1 Lithuania Population-based 25-60 2 3 2 No visual inspection program 1 Luxembourg Non-populationbased 15 to not 1 2 No visual inspection specified 2 program 1 Macedonia, TFYR Non-populationbased 30-55 2 3 2 No visual inspection program 1 Malta Non-populationbased - - No visual inspection program 1 Monaco - - - No visual inspection program 1 Montenegro Non-populationbased 25-64 2 3 2 No visual inspection program 1 Netherlands Population-based 30-60 2 5 2 No visual inspection program 1 Norway Population-based 25-69 2 3 2 No visual inspection program 1 Poland Population-based 25-59 2 3 2 No visual inspection program 1 Population-based (some regions) Non-populationbased Non-populationbased (organized pilot in one region) Non-populationbased (call-recall system in few regions on unregular basis) Non-populationbased (call-recall system in few regions on unregular basis) 25-64 2 3 2 No visual inspection program 1 20 to no limit 2 2 2 No visual inspection program 1 25-64 2 3 2 No visual inspection program 1 35-69 5 3 5 No visual inspection program 1 18 to no limit 5 1 5 No visual inspection program 1 San Marino - - - No visual inspection program 1 Serbia Non-populationbased (organized in process of implementation) Non-populationbased 25-65 (69) 2 3 2 No visual inspection program 1 Slovakia 23-64 2 3 2 No visual inspection program 1 Slovenia Population-based 20-64 2 3 2 No visual inspection program 1 Spain Non-populationbased (organized in some regions) mainly 25-65, but variable by region 2 mainly 3, but variable by region 2 No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA National program 1 No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No visual inspection program 1 Pilot program 1 Sweden Population-based 23-60 2 23-50 age: 3, No visual inspection Pilot program 9 51-60 age: 5 10 program 1 Switzerland Ukraine Non-populationbased Non-populationbased United Kingdom Population-based Regional variation: From (20) 25 to (60) 64 2 20 to no limit 2 3 2 No visual inspection program 1 18-65 5 1 5 No visual inspection program 1 3 2 No visual inspection program 1 No HPV DNA No HPV DNA No HPV DNA Oceania - - - - - Australia Population-based 18-69 6 2 (under review) 6 No visual inspection program 1 Fiji - - - No visual inspection program 1 (Continued) No HPV DNA No HPV DNA

7 HPV PREVENTIVE STRATEGIES - 203 - Table 30 Continued Screening Screening Screening HPV Country name type ages (years) interval (years) VIA Kiribati - - - No visual inspection program 1 Marshall Islands - - - No visual inspection program 1 Micronesia - - - No visual inspection program 1 Nauru - - - No visual inspection program 1 New Zealand Population-based 20-69 6 3 8 No visual inspection program 1 Palau - - - No visual inspection program 1 Papua New Guinea - - - No visual inspection program 1 Samoa - - - No visual inspection program 1 Solomon Islands - - - No visual inspection program 1 Tonga - - - No visual inspection program 1 Tuvalu - - - No visual inspection program 1 DNA test No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA Vanuatu - - - Pilot program 1 No HPV DNA Data sources: 1 Cervical Cancer Action: a global Coalition to stop Cervical Cancer (CCa). Progress In Cervical Cancer Prevention: The CCA Report card. Update June 2013 [Accessed on July 2013], avaiable at http://www.cervicalcanceraction.org/pubs/pubs.php. The information represented there has been collected through interviews with individuals and organizations involved with the countries represented and has not been verified with individual Ministries of Health. Any versights or inaccuracies are unintentional. 2 Kesic V, Poljak M, Rogovskaya S.Cervical cancer burden and prevention activities in Europe. Cancer Epidemiol Biomarkers Prev. 2012 Sep;21(9):1423-33. 3 Murillo R, Almonte M, Pereira A, Ferrer E, Gamboa OA, Jerónimo J, Lazcano-Ponce E. Cervical cancer screening programs in Latin America and the Caribbean. Vaccine. 2008;26 Suppl 11:L37-48. 4 Luciani S, Cabanes A, Prieto-Lara E, Gawryszewski V. Cervical and female breast cancers in the Americas: current situation and opportunities for action.bull World Health Organ. 2013;91(9):640-649. 5 Rogovskaya SI, et al. Human papillomavirus prevalence and type-distribution, cervical cancer screening practices and current status of vaccination implementation in Russian Federation, the Western countries of the former Soviet Union, Caucasus Region and Central Asia. Vaccine (2013), http://dx.doi.org/10.1016/j.vaccine.2013.06.043 6 Garland, S.M., Bhatla, N., Ngan, H.Y.S. Cervical cancer burden and prevention strategies: Asia oceania perspective (2012) Cancer Epidemiology Biomarkers and Prevention, 21 (9), pp. 1414-1422. 7 Anttila A, von Karsa L, Aasmaa A, Fender M, Patnick J, Rebolj M, et al. Cervical cancer screening policies and coverage in Europe. Eur. J. Cancer. 2009 Oct;45(15):2649-2658. 8 IARC Handbooks of Cancer Prevention Vol. 10: Cervix Cancer Screening. IARC Press. Lyon, 2005. 9 Castle PE, de Sanjosé S, Qiao YL, Belinson JL, Lazcano-Ponce E, Kinney W. Introduction of human papillomavirus DNA screening in the world: 15 years of experience. Vaccine. 2012 Nov 20;30 Suppl 5:F117-22 10 Sander BB, Rebolj M, Valentiner-Branth P, Lynge E. Introduction of human papillomavirus vaccination in Nordic countries (2012) Vaccine, 30 (8):1425-1433. 11 Abdullah F, Su TT. Enhancement of the cervical cancer screening program in Malaysia: a qualitative study. Asian Pac J Cancer Prev. 2010;11(5):1359-66. 12 Lee VJ, Tay SK, Teoh YL, Tok MY. Cost-effectiveness of different human papillomavirus vaccines in Singapore (2011) BMC Public Health, 11, art. no. 203.

7 HPV PREVENTIVE STRATEGIES - 204-7.2 HPV vaccination 7.2.1 HPV vaccine licensure and introduction (last update 26 Nov 2013) Figure 119: Licensure status of current HPV vaccines worldwide Data sources: For Afghanistan, Albania, Algeria, Andorra, Angola, Antigua & Barbuda, Argentina, Australia, Austria, Bahamas, Bahrain, Bangladesh, Barbados, Belgium, Belize, Benin, Bermuda, Bolivia, Bosnia & Herzegovina, Botswana, Brazil, Bulgaria, Burkina Faso, Burundi, Cambodia, Cameroon, Canada, Cape Verde, Cayman Islands, Central African Republic, Chad, Chile, China, Colombia, Comoros, Congo, Congo, DR, Cook Islands, Costa Rica, Côte d Ivoire, Croatia, Cuba, Cyprus, Czech Republic, Denmark, Djibouti, Dominica, Dominican Republic, Ecuador, Egypt, El Salvador, Equatorial Guinea, Eritrea, Estonia, Ethiopia, Finland, France, Gabon, Gambia, Germany, Gibraltar, Greece, Grenada, Guatemala, Guinea-Bissau, Guyana, Haiti, Honduras, Hong Kong SAR, Hungary, Iceland, India, Indonesia, Iran, Iraq, Ireland, Israel, Italy, Jamaica, Jordan, Kenya, Kiribati, Korea, DPR, Kuwait, Laos, Latvia, Lesotho, Liberia, Libya, Liechtenstein, Lithuania, Luxembourg, Macao SAR, Macedonia, TFYR, Madagascar, Malawi, Malaysia, Maldives, Malta, Marshall Islands, Mauritania, Mauritius, Mexico, Micronesia, Monaco, Mongolia, Montenegro, Morocco, Mozambique, Myanmar, Nauru, Nepal, Netherlands, New Zealand, Nicaragua, Niue, Norway, Oman, Pakistan, Palau, Panama, Papua New Guinea, Peru, Philippines, Poland, Portugal, Puerto Rico, Romania, Samoa, San Marino, Sao Tome & Principe, Saudi Arabia, Senegal, Serbia, Seychelles, Sierra Leone, Singapore, Slovakia, Slovenia, Solomon Islands, Somalia, South Africa, Spain, St Kitts & Nevis, St Lucia, St Vincent & The Grenadines, Sudan, Suriname, Swaziland, Sweden, Switzerland, Syria, Tanzania, Thailand, Timor-Leste, Togo, Tonga, Trinidad & Tobago, Turkey, Tuvalu, Uganda, United Arab Emirates, United Kingdom, United States of America, Uruguay, Vanuatu, Venezuela, Viet Nam, Yemen and Zimbabwe the source is: PATH, January 2011 [accessed on 2009]. For Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Republic of Moldova, Russian Federation, Tajikistan, Turkmenistan, Ukraine and Uzbekistan the source is: Rogovskaya SI, et al. Human papillomavirus prevalence and type-distribution, cervical cancer screening practices and current status of vaccination implementation in Russian Federation, the Western countries of the former Soviet Union, Caucasus Region and Central Asia. Vaccine (2013), http://dx.doi.org/10.1016/j.vaccine.2013.06.043 For Albania, Argentina, Australia, Austria, Bahamas, Bahrain, Barbados, Belgium, Bermuda, Bolivia, Bosnia & Herzegovina, Botswana, Brazil, Bulgaria, Burkina Faso, Cameroon, Canada, Cayman Islands, Central African Republic, Chad, Chile, Colombia, Congo, Congo, DR, Costa Rica, Côte d Ivoire, Croatia, Cyprus, Czech Republic, Denmark, Dominican Republic, Ecuador, Egypt, El Salvador, Equatorial Guinea, Estonia, Ethiopia, Finland, France, Gabon, Germany, Gibraltar, Greece, Guatemala, Honduras, Hong Kong SAR, Hungary, Iceland, India, Indonesia, Ireland, Israel, Italy, Jamaica, Jordan, Kenya, Korea, DPR, Kuwait, Latvia, Liechtenstein, Lithuania, Luxembourg, Macao SAR, Macedonia, TFYR, Malawi, Malaysia, Malta, Mauritania, Mauritius, Mexico, Montenegro, Morocco, Netherlands, New Zealand, Nicaragua, Norway, Pakistan, Panama, Peru, Philippines, Poland, Portugal, Puerto Rico, Romania, Saudi Arabia, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, Togo, Trinidad & Tobago, Turkey, Uganda, United Arab Emirates, United Kingdom, United States of America, Uruguay and Viet Nam the source is: Quadrivalent: Merck & Co., Inc., Whitehouse Station, NJ, USA, March 2009 For Japan the source is: Garland, S.M., Bhatla, N., Ngan, H.Y.S. Cervical cancer burden and prevention strategies: Asia oceania perspective (2012) Cancer Epidemiology Biomarkers and Prevention, 21 (9), pp. 1414-1422. For Aruba, Australia & New Zealand, Bhutan, Brunei, Curaçao, Fiji, French Guiana, French Polynesia, Ghana, Guadeloupe, Guinea, Haiti, Japan, Korea, Republic of, Lebanon, Mali, Martinique, Mayotte, Namibia, New Caledonia, Niger, Nigeria, Paraguay, Qatar, Reunion, Rwanda, Sri Lanka, St-Martin (French part), St Pierre and Miquelon, Tunisia, Wallis & Futuna Islands and Zambia the source is: Gardasil (HPV Recombinant, Quadrivalent), Registrations status June 2013. Available at http://www.merckresponsibility.com/wpcontent/uploads/2013/07/gardasil-registration-status-june-2013.pdf