Human Papillomavirus and Related Diseases Report WORLD

Transcription

1 Human Papillomavirus and Related Diseases Report WORLD Version posted on in March 20 th, 2015

2 - 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, L Hospitalet del Llobregat (Barcelona, Spain, 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 ( 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-F , HEALTH-F , 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 [Data Accessed]

3 - 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

4 - 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 Burden of cervical cancer Annual number of new cervical cancer cases 527, ,546 83,078 Standardized incidence rates per 100,000 population in cervical cancer Annual number of cervical cancer deaths 265, ,158 35,495 Standardized mortality rates per 100,000 population in cervical cancer 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 Low-grade cervical lesions (LSIL/CIN-1) High-grade cervical lesions (HSIL/ CIN-2 / CIN-3 / CIS) LSIL, low-grade intraepithelial lesions; HSIL, high-grade intraepithelial lesions; CIN, cervical intraepithelial neoplasia; CIS, carcinoma in-situ. Cervical cancer

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 Cervical cancer Incidence (last update 22 Jul 2014) Mortality (last update 14 Jul 2014) Comparison of incidence and mortality (last update 14 Jul 2014) Anogenital cancers other than the cervix Anal cancer (last update 22 Jul 2014) Vulvar cancer (last update 22 Jul 2014) Vaginal cancer (last update 22 Jul 2014) Penile cancer (last update 22 Jul 2014) Head and neck cancers Pharyngeal cancer (excluding nasopharynx) (last update 15 Jan 2014) HPV related statistics HPV burden in women with normal cytology, precancerous cervical lesions or invasive cervical cancer HPV prevalence in women with normal cytology HPV type distribution among women with normal cytology, precancerous cervical lesions and cervical cancer Terminology HPV burden in anogenital cancers other than the cervix Anal cancer and precancerous anal lesions Vulvar cancer and precancerous vulvar lesions Vaginal cancer and precancerous vaginal lesions Penile cancer and precancerous penile lesions HPV burden in men HPV burden in head and neck Burden of oral HPV infection in healthy population HPV burden in head and neck cancers Factors contributing to cervical cancer (last update 08 Aug 2013) Reproductive and sexual behaviour (last update 08 Aug 2013) HPV preventive strategies Cervical cancer screening practices (last update 30 Jul 2013) HPV vaccination HPV vaccine licensure and introduction (last update 26 Nov 2013) Protective factors for cervical cancer (last update 30 Sep 2013) References 210

6 LIST OF FIGURES - vi - List of Figures 1 World s geographical regions Population pyramid estimates of the World compared to developing and developed regions for for Population trends of four selected age groups in the World compared to developing and developed regions for Age-standardized incidence rates of cervical cancer in World (estimations for 2012) Ranking of cervical cancer to others cancers among all women and women ages years, according to incidence rates in World (estimations for 2012) World age-standarized incidence rates compared to regions and sub-regions (estimations for 2012) Ten most frequent cancer in all women in the World compared to developing and developed regions (estimations for 2012) Ten most frequent cancer in all women in the World compared to the continents (estimations for 2012) Ten most frequent cancers in women ages yrs in the World compared to developing and developed regions (estimations for 2012) Ten most frequent cancers in women ages yrs in the World compared to the continents (estimations for 2012) Age-specific incidence of cervical cancer in World and its regions (estimations for 2012) Annual number of new cases of cervical cancer by age group in developed and developing regions and five continents (estimations for 2012) Annual number of cases and age-specific incidence rates of cervical cancer in World and its regions (estimations for 2012) Annual number of cases and age-specific incidence rates of cervical cancer in World and its regions (estimations for 2012) (Continued) Age-standardized mortality rates of cervical cancer in World (estimations for 2012) World age-standardized mortality rates of cervical cancer compared to regions and sub-regions (estimations for 2012) Ranking of cervical cancer to others cancers among all women and women ages years, according to mortality rates in World (estimations for 2012) Age-specific mortality of cervical cancer in World and its regions (estimations for 2012) Annual number of deaths of cervical cancer by age group in developed and developing regions and five continents (estimations for 2012) Annual number of deaths and age-specific mortality rates of cervical cancer in World and its regions (estimations for 2012) Annual number of deaths and age-specific mortality rates of cervical cancer in World and its regions (estimations for 2012) (Continued) Age-specific incidence and mortality rates of cervical cancer in World and its regions (estimations for 2012) 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) 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) 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) Prevalence of HPV among women with normal cytology in the World Crude age-specific HPV prevalence (%) and 95% confidence interval (grey shadow) in women with normal cytology in the World Prevalence of HPV among women with normal cytology in Africa by country and study Prevalence of HPV among women with normal cytology in Africa by country and study (continued) Prevalence of HPV among women with normal cytology in Africa by country and study (continued) Prevalence of HPV among women with normal cytology in Americas by country and study Prevalence of HPV among women with normal cytology in Americas by country and study (continued) Prevalence of HPV among women with normal cytology in Americas by country and study (continued) Prevalence of HPV among women with normal cytology in Americas by country and study (continued) Prevalence of HPV among women with normal cytology in Asia by country and study Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Prevalence of HPV among women with normal cytology in Asia by country and study (continued) Prevalence of HPV among women with normal cytology in Europe by country and study Prevalence of HPV among women with normal cytology in Europe by country and study (continued) Prevalence of HPV among women with normal cytology in Europe by country and study (continued) Prevalence of HPV among women with normal cytology in Europe by country and study (continued) Prevalence of HPV among women with normal cytology in Europe by country and study (continued) Prevalence of HPV among women with normal cytology in Oceania by country and study

7 LIST OF FIGURES - vii - 48 Prevalence of HPV 16 among women with normal cytology in Africa by country and study Prevalence of HPV 16 among women with normal cytology in Americas by country and study Prevalence of HPV 16 among women with normal cytology in Americas by country and study (continued) Prevalence of HPV 16 among women with normal cytology in Asia by country and study Prevalence of HPV 16 among women with normal cytology in Asia by country and study (continued) Prevalence of HPV 16 among women with normal cytology in Europe by country and study Prevalence of HPV 16 among women with normal cytology in Europe by country and study (continued) Prevalence of HPV 16 among women with normal cytology in Oceania by country and study Prevalence of HPV 16 among women with low-grade cervical lesions in Africa by country and study Prevalence of HPV 16 among women with low-grade cervical lesions in Americas by country and study Prevalence of HPV 16 among women with low-grade cervical lesions in Americas by country and study (continued) Prevalence of HPV 16 among women with low-grade cervical lesions in Asia by country and study Prevalence of HPV 16 among women with low-grade cervical lesions in Asia by country and study (continued) Prevalence of HPV 16 among women with low-grade cervical lesions in Europe by country and study Prevalence of HPV 16 among women with low-grade cervical lesions in Europe by country and study (continued) Prevalence of HPV 16 among women with low-grade cervical lesions in Oceania by country and study Prevalence of HPV 16 among women with High-grade cervical lesions in Africa by country and study Prevalence of HPV 16 among women with High-grade cervical lesions in Americas by country and study Prevalence of HPV 16 among women with High-grade cervical lesions in Americas by country and study (continued) Prevalence of HPV 16 among women with High-grade cervical lesions in Asia by country and study Prevalence of HPV 16 among women with High-grade cervical lesions in Asia by country and study (continued) Prevalence of HPV 16 among women with High-grade cervical lesions in Europe by country and study Prevalence of HPV 16 among women with High-grade cervical lesions in Europe by country and study (continued) Prevalence of HPV 16 among women with High-grade cervical lesions in Oceania by country and study Prevalence of HPV 16 among women with invasive cervical cancer in Africa by country and study Prevalence of HPV 16 among women with invasive cervical cancer in Americas by country and study (continued) Prevalence of HPV 16 among women with invasive cervical cancer in Americas by country and study (continued) Prevalence of HPV 16 among women with invasive cervical cancer in Asia by country and study (continued) Prevalence of HPV 16 among women with invasive cervical cancer in Asia by country and study (continued) Prevalence of HPV 16 among women with invasive cervical cancer in Asia by country and study (continued) Prevalence of HPV 16 among women with invasive cervical cancer in Europe by country and study (continued) Prevalence of HPV 16 among women with invasive cervical cancer in Europe by country and study (continued) Prevalence of HPV 16 among women with invasive cervical cancer in Europe by country and study (continued) Prevalence of HPV 16 among women with invasive cervical cancer in Oceania by country and study Ten most frequent HPV oncogenic types among women with and without cervical lesions in World compared to developing and developed regions Ten most frequent HPV types among women with invasive cervical cancer by histology in the World compared to developing and developed regions Ten most frequent HPV types among cases of anal cancer in Africa compared to the World Ten most frequent HPV types among cases of anal cancer in Americas compared to the World Ten most frequent HPV types among cases of anal cancer in Asia compared to the World Ten most frequent HPV types among cases of anal cancer in Europe compared to the World Ten most frequent HPV types among cases of anal cancer in Oceania compared to the World Ten most frequent HPV types among cases of AIN 2/3 in Africa compared to the World Ten most frequent HPV types among cases of AIN 2/3 in Americas compared to the World Ten most frequent HPV types among cases of AIN 2/3 in Asia compared to the World Ten most frequent HPV types among cases of AIN 2/3 in Europe compared to the World Ten most frequent HPV types among cases of AIN 2/3 in Oceania compared to the World Ten most frequent HPV types among cases of vulvar cancer in Africa compared to the World Ten most frequent HPV types among cases of vulvar cancer in Americas compared to the World Ten most frequent HPV types among cases of vulvar cancer in Asia compared to the World Ten most frequent HPV types among cases of vulvar cancer in Europe compared to the World Ten most frequent HPV types among cases of vulvar cancer in Oceania compared to the World Ten most frequent HPV types among cases of VIN 2/3 in Africa compared to the World Ten most frequent HPV types among cases of VIN 2/3 in Americas compared to the World Ten most frequent HPV types among cases of VIN 2/3 in Asia compared to the World Ten most frequent HPV types among cases of VIN 2/3 in Europe compared to the World Ten most frequent HPV types among cases of VIN 2/3 in Oceania compared to the World Ten most frequent HPV types among cases of vaginal cancer in Africa compared to the World Ten most frequent HPV types among cases of vaginal cancer in Americas compared to the World Ten most frequent HPV types among cases of vaginal cancer in Asia compared to the World Ten most frequent HPV types among cases of vaginal cancer in Europe compared to the World Ten most frequent HPV types among cases of vaginal cancer in Oceania compared to the World Ten most frequent HPV types among cases of VaIN 2/3 in Africa compared to the World

8 LIST OF FIGURES - viii Ten most frequent HPV types among cases of VaIN 2/3 in Americas compared to the World Ten most frequent HPV types among cases of VaIN 2/3 in Asia compared to the World Ten most frequent HPV types among cases of VaIN 2/3 in Europe compared to the World Ten most frequent HPV types among cases of VaIN 2/3 in Oceania compared to the World Prevalence of female tobacco smoking worldwide Total fertility rates worldwide Prevalence of oral contraceptive use worldwide Prevalence of HIV worldwide Proportion of young women (15-24 years) who have had sex before the age of 15 worldwide Licensure status of current HPV vaccines worldwide Status of HPV vaccination programs worldwide Prevalence of male circumcision worldwide Prevalence of condom use worldwide

9 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 Sociodemographic indicators in the World for Incidence of cervical cancer by regions and sub-regions in the World (estimations for 2012) Cervical cancer mortality in regions and sub-regions in the World (estimations for 2012) Incidence of anal cancer by cancer registry and sex Incidence of vulvar cancer by cancer registry Incidence of vaginal cancer by cancer registry Incidence of penile cancer by cancer registry 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) 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) 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 Type-specific HPV prevalence in women with normal cytology, precancerous cervical lesions and invasive cervical cancer in the World Type-specific HPV prevalence among invasive cervical cancer cases by histology in the World Studies on HPV prevalence among cases of anal cancer in the World Studies on HPV prevalence among cases of AIN 2/3 in the World Studies on HPV prevalence among cases of vulvar cancer in the World Studies on HPV prevalence among cases of VIN 2/3 in the World Studies on HPV prevalence among cases of vaginal cancer in the World Studies on HPV prevalence among cases of VAIN 2/3 in the World Studies on HPV prevalence among cases of penile cancer in the World Studies on HPV prevalence among cases of PeIN 2/3 in the World Studies on anogenital HPV prevalence among men in the World Studies on anogenital HPV prevalence among men from special subgroups in the World Studies on oral HPV prevalence among healthy populations in the World Studies on HPV prevalence among cases of oral cavity cancer in the World Studies on HPV prevalence among cases of oropharyngeal cancer in the World Studies on HPV prevalence among cases of hypopharyngeal or laryngeal cancer in the World Cervical cancer screening policy in the World HPV vaccination policy in female population in the World References of studies included

10 1 INTRODUCTION 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-

11 1 INTRODUCTION 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.

12 2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS (LAST UPDATE 25 NOV 2013) 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 Under 5 44,862,128 73,318,461 47,910,524 61,545,144 67,885,516 79,626,349 92,674, ,444, ,858, ,594, ,112, ,137, ,877, ,866, ,770, ,271, ,972, ,301, ,485, ,427, ,036, ,933, ,560, ,586, ,471, ,981, ,020, ,040, ,160, ,073, ,123, ,574, ,685, ,926,471 Less developed regions Males Females 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, ,043, ,447, ,378, ,166, ,939, ,611, ,493, ,600, ,448, ,482, ,577, ,108, ,505, ,830, ,275, ,522, ,435, ,164, ,798, ,331, ,037, ,145, ,701, ,723,888 More developed regions Males Females 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:

13 2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS (LAST UPDATE 25 NOV 2013) 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) Women yrs Girls yrs Number of women (in millions) 5,200 4,200 3,200 2,200 1, All Women Women yrs Less developed regions Projections Number of women (in millions) Women yrs Girls yrs More developed regions Projections Projections Number of women (in millions) 5,200 4,200 3,200 2,200 1, All Women Women yrs Projections Number of women (in millions) Women yrs Girls yrs Number of women (in millions) 5,200 4,200 3,200 2,200 1, All Women Women yrs 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:

14 2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS (LAST UPDATE 25 NOV 2013) Table 3: Population (in millions) estimates in the World for 2013 Region / Country Male Female years 15+ years Total years 15+ years Total World Less developed regions More developed regions Africa Eastern Africa Middle Africa Northern Africa Southern Africa Western Africa Americas Caribbean Central America Northern America South America Asia Central Asia Eastern Asia South-Eastern Asia Southern Asia Western Asia Europe Eastern Europe Northern Europe Southern Europe Western Europe Oceania Australia & New Zealand Melanesia Micronesia Polynesia 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: 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 (%) c Median age of the population (years) d Population living in urban areas (%) d Crude birth rate (births per 1,000 population) c Crude death rate (deaths per 1,000 population) c Life expectancy at birth (years) Adult mortality rate (probability of dying between 15 and years per 1,000 population) Under-five mortality rate (per 1,000 live births) Gross national income per capita (PPP int $) ,079 e Density of physicians (per 10,000 population) (Continued)

15 2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS (LAST UPDATE 25 NOV 2013) 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 d 89.7 d 88.8 d Net secondary school enrollment ratio 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 ; 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: 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, Washington, DC, World Bank. Available at: [Accessed on July 2013] 4 UNESCO Institute for Statistics Data Centre [online database]. Montreal, UNESCO Institute for Statistics, Available at: [Accessed on July 2013]

16 3 BURDEN OF HPV RELATED CANCERS 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 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 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; Available from: accessed on 15/01/2014.

17 3 BURDEN OF HPV RELATED CANCERS 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 yrs World 527, Less developed 444, regions More developed 83, regions Africa 99, Eastern Africa 45, Middle Africa 11, Northern Africa 5, Southern Africa 8, Western Africa 27, Americas 83, Caribbean 5, Central America 18, Northern America 14, South America 45, Asia 284, Central Asia 5, Eastern Asia 78, South-Eastern 50, Asia Southern Asia 145, Western Asia 4, Europe 58, Eastern Europe 33, Northern Europe 5, Southern Europe 9, Western Europe 9, Oceania 2, Australia & New Zealand Melanesia 1, Micronesia Polynesia 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 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; Available from: accessed on 15/01/2014.

18 3 BURDEN OF HPV RELATED CANCERS Figure 5: Ranking of cervical cancer to others cancers among all women and women ages 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; Available from: accessed on 15/01/2014. Includes anal cancer (C21).

19 3 BURDEN OF HPV RELATED CANCERS 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 South Eastern Asia 16.3 Africa Five continents 27.6 Eastern Europe Polynesia Micronesia Americas 14.9 Northern Europe Southern Europe Eastern Asia 7.9 Asia 12.7 Western Europe 7.3 Northern America 6.6 Europe 11.4 Northern Africa Australia \& New Zealand Oceania 10.2 Western Asia 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; Available from: accessed on 15/01/2014.

20 3 BURDEN OF HPV RELATED CANCERS 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 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; Available from: accessed on 15/01/2014.

21 3 BURDEN OF HPV RELATED CANCERS 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 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 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 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)

22 3 BURDEN OF HPV RELATED CANCERS ( 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; Available from: accessed on 15/01/2014. Figure 9: Ten most frequent cancers in women ages 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 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; Available from: accessed on 15/01/2014.

23 3 BURDEN OF HPV RELATED CANCERS Figure 10: Ten most frequent cancers in women ages 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 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 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 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)

24 3 BURDEN OF HPV RELATED CANCERS ( 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; Available from: 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, >=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; Available from: accessed on 15/01/2014.

25 3 BURDEN OF HPV RELATED CANCERS 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 Asia Africa FIVE CONTINENTS Americas Europe Oceania Annual number of new cases of cervical cancer 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; Available from: accessed on 15/01/2014.

26 3 BURDEN OF HPV RELATED CANCERS 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, * Annual number of cases of cervical cancer * * * * World yrs: 754 cases yrs: 6445 cases yrs: cases yrs: cases yrs: cases yrs: cases yrs: cases yrs: cases yrs: cases yrs: cases. Africa yrs: 352 cases yrs: 1091 cases yrs: 3310 cases yrs: 6198 cases yrs: 8686 cases yrs: cases yrs: cases yrs: cases yrs: cases yrs: 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; Available from: accessed on 15/01/2014.

27 3 BURDEN OF HPV RELATED CANCERS 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, Annual number of cases of cervical cancer * 22725* * 13249* Asia Oceania Age specific rates of cervical cancer per 100, * Annual number of cases of cervical cancer * * 1151* Age group (years) * Americas yrs: 180 cases yrs: 2047 cases yrs: 4668 cases yrs: 6901 cases yrs: 8883 cases yrs: 9817 cases yrs: 9862 cases yrs: 8951 cases yrs: 7771 cases yrs: 6514 cases. Asia yrs: 195 cases yrs: 2443 cases yrs: 8394 cases yrs: cases yrs: cases yrs: cases yrs: cases yrs: cases yrs: cases yrs: cases. Europe yrs: 22 cases yrs: 798 cases yrs: 2639 cases yrs: 4235 cases yrs: 5548 cases yrs: 6449 cases yrs: 7020 cases yrs: 7137 cases yrs: 6518 cases yrs: 5221 cases. Oceania yrs: 4 cases yrs: 60 cases yrs: 144 cases yrs: 208 cases yrs: 280 cases yrs: 317 cases yrs: 278 cases yrs: 235 cases yrs: 181 cases yrs: 140 cases. (Continued on next page)

28 3 BURDEN OF HPV RELATED CANCERS ( 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; Available from: accessed on 15/01/2014.

29 3 BURDEN OF HPV RELATED CANCERS NOTE. For time trends in cervical cancer incidence please refer to specific countries 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; Available from: accessed on 15/01/2014.

30 3 BURDEN OF HPV RELATED CANCERS 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 yrs World Less developed regions More developed regions Africa Eastern Africa Middle Africa Northern Africa Southern Africa Western Africa Americas Caribbean Central America Northern America South America Asia Central Asia Eastern Asia South-Eastern Asia Southern Asia Western Asia Europe Eastern Europe Northern Europe Southern Europe Western Europe Oceania Australia & New Zealand Melanesia Micronesia Polynesia 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 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; Available from: accessed on 15/01/2014.

31 3 BURDEN OF HPV RELATED CANCERS 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 Central Asia 7.7 Africa Five continents 17.5 Eastern Europe Polynesia Eastern Asia Asia 6.4 Northern Africa Micronesia Northern America 2.6 Americas 5.9 Southern Europe 2.4 Northern Europe 2.2 Oceania 4.5 Western Asia Western Europe Europe 3.8 Australia & New Zealand 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; Available from: accessed on 15/01/2014.

32 3 BURDEN OF HPV RELATED CANCERS Figure 17: Ranking of cervical cancer to others cancers among all women and women ages 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; Available from: accessed on 15/01/2014. Includes anal cancer (C21).

33 3 BURDEN OF HPV RELATED CANCERS 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, >=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; Available from: accessed on 15/01/2014.

34 3 BURDEN OF HPV RELATED CANCERS 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 Asia Africa FIVE CONTINENTS Americas Europe Oceania Annual number of cervical cancer deaths 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; Available from: accessed on 15/01/2014.

35 3 BURDEN OF HPV RELATED CANCERS 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, Annual number of deaths of cervical cancer * * * 33320* * World yrs: 314 cases yrs: 1101 cases yrs: 3654 cases yrs: 8158 cases yrs: cases yrs: cases yrs: cases yrs: cases yrs: cases yrs: cases. Africa yrs: 265 cases yrs: 553 cases yrs: 1331 cases yrs: 2360 cases yrs: 3551 cases yrs: 4707 cases yrs: 6021 cases yrs: 7190 cases yrs: 7801 cases 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; Available from: accessed on 15/01/2014.

36 3 BURDEN OF HPV RELATED CANCERS 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, Annual number of deaths of cervical cancer * 18020* * 11769* Asia Oceania Age specific rates of cervical cancer per 100, Annual number of deaths of cervical cancer * 88208* * 545* Age group (years) * Americas yrs: 12 cases yrs: 137 cases yrs: 620 cases yrs: 1325 cases yrs: 2067 cases yrs: 2852 cases yrs: 3629 cases yrs: 3997 cases yrs: 3944 cases yrs: 3598 cases. Asia yrs: 34 cases yrs: 363 cases yrs: 1333 cases yrs: 3699 cases yrs: 8138 cases yrs: cases yrs: cases yrs: cases yrs: cases yrs: cases. Europe yrs: 2 cases yrs: 32 cases yrs: 332 cases yrs: 715 cases yrs: 1131 cases yrs: 1565 cases yrs: 2088 cases yrs: 2646 cases yrs: 2846 cases yrs: 2624 cases. Oceania yrs: 1 cases yrs: 16 cases yrs: 36 cases yrs: 56 cases yrs: 80 cases yrs: 107 cases yrs: 111 cases yrs: 122 cases yrs: 105 cases yrs: 100 cases. (Continued on next page)

37 3 BURDEN OF HPV RELATED CANCERS ( 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; Available from: accessed on 15/01/2014.

38 3 BURDEN OF HPV RELATED CANCERS 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) World Americas Age specific rates of cervical cancer per 100, Europe >= >= Oceania >= >= >= Africa Asia Incidence >=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; Available from: accessed on 15/01/2014.

39 3 BURDEN OF HPV RELATED CANCERS 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) 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 Egypt Gharbiah Gambia National Libya Benghazi Malawi Blantyre Mali Bamako South Africa PROMEC Tunisia North Uganda Kyadondo county Zimbabwe Harare Argentina Argentina Bahia Blanca Cordoba Mendoza Tierra del Fuego Brazil Aracaju Canada Belo Horizonte Cuiaba Fortaleza Goiania Sao Paulo (Continued)

40 3 BURDEN OF HPV RELATED CANCERS 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 British Columbia Manitoba National New Brunswick Newfoundland and Labrador Northwest Territories Nova Scotia Ontario Prince Edward Island Quebec Saskatchewan Yukon Chile Biobio Province Region of Antofagasta Valdivia Colombia Bucaramanga Cali Manizales Pasto Costa Rica National Cuba Villa Clara Ecuador Cuenca Quito Jamaica Kingston and St Andrew Peru Trujillo United States of America NPCR Uruguay National Bahrain Bahrain National China Beijing City Cixian County Haining County Hong Kong Jiashan County Jiaxing City Macao Nangang District, Harbin City Qidong County Shanghai City (Continued)

41 3 BURDEN OF HPV RELATED CANCERS 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 Yangcheng County Yanting County Zhongshan City India Bangalore Barshi, Paranda and Bhum Bhopal Chennai Dindigul, Ambillikai Karunagappally Mizoram Mumbai New Delhi Poona Sikkim State Trivandrum Iran Golestan Province Israel National National National Japan Aichi Prefecture Fukui Prefecture Hiroshima Miyagi Prefecture Nagasaki Prefecture Niigata Prefecture Osaka Prefecture Saga Prefecture Korea, Republic of Busan Daegu Daejeon Gwangju Incheon Jejudo National Seoul Ulsan Kuwait National National National Malaysia Penang Penang Penang Penang (Continued)

42 3 BURDEN OF HPV RELATED CANCERS 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 Pakistan South Karachi Philippines Manila Rizal Qatar National Saudi Arabia Riyadh Singapore National National National National Thailand Bangkok Chiang Mai Chonburi Khon Kaen Lampang Songkhla Turkey Antalya Edirne Izmir Trabzon Viet Nam Hanoi Ho Chi Minh City Austria Austria National Tyrol Vorarlberg Belarus National Belgium National Bulgaria National Croatia National Cyprus National Czech Republic National Denmark National Estonia National Finland National France (Continued)

43 3 BURDEN OF HPV RELATED CANCERS 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 Calvados Doubs Haut-Rhin Herault Isere Loire Atlantique Manche Martinique Somme Tarn Vendee Germany Brandenburg Bremen Free State Of Saxony Hamburg Mecklenburg-Western Pomerania Munich North Rhine-Westphalia Saarland Schleswig-Holstein Iceland National Ireland National Italy Alto Adige Biella Province Brescia Province Catania and Messina Catanzaro Ferrara Province Florence and Prato Provinces Friuli-Venezia Giulia Genova Province Latina Lombardy, Como Province Lombardy, Lecco Province Lombardy, Mantova Province Lombardy, Milan Lombardy, Varese Province Modena Province Naples Nuoro Palerme Parma Province (Continued)

44 3 BURDEN OF HPV RELATED CANCERS 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 Reggio Emilia Province Romagna Region Salerno Province Sassari Province Sondrio South Lombardy Syracuse Province Torino Trapani Trento Umbria Region Veneto Region Latvia National Lithuania National Malta National Netherlands Eindhoven National Norway National Poland Cracow Kielce Lower Silesia Rzeszow Portugal Azores Russian Federation St Petersburg Serbia Central Slovakia National Slovenia National Spain Albacete Asturias Basque Country Canary Islands Ciudad Real Cuenca Girona Granada La Rioja Mallorca Murcia Navarra Tarragona (Continued)

45 3 BURDEN OF HPV RELATED CANCERS 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 Switzerland Basel Geneva Graubunden and Glarus Neuchatel St Gall-Appenzell Ticino Valais Vaud Zurich Ukraine National United Kingdom England England, East of England Region England, North Western England, Northern and Yorkshire England, Oxford Region England, South and Western Regions England, Thames England, Trent England, West Midlands Northern Ireland Scotland Wales Australia Australia Australian Capital Territory National National New South Wales Northern Territory Northern Territory Northern Territory Queensland Tasmania Victoria New Zealand National National National National 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. last accessed on 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.

46 3 BURDEN OF HPV RELATED CANCERS NOTE. For time trends in anal cancer incidence please refer to specific countries 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 Egypt 1 Gharbiah Gambia 2 National Libya 1 Benghazi Malawi 1 Blantyre Mali 2 Bamako South Africa 1 PROMEC Tunisia 1 North Uganda 1 Kyadondo county Zimbabwe 1 Harare (African) Americas Argentina 1 Bahia Blanca Cordoba Mendoza Tierra del Fuego Brazil 1 Aracaju Belo Horizonte Cuiaba Fortaleza Goiania Sao Paulo Canada 1 Alberta British Columbia Manitoba National New Brunswick Newfoundland and Labrador Northwest Territories Nova Scotia Ontario Prince Edward Island Quebec Saskatchewan Yukon (Continued)

47 3 BURDEN OF HPV RELATED CANCERS Table 8 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Chile 1 Biobio Province Region of Antofagasta Valdivia Colombia 1 Bucaramanga Cali Manizales Pasto Costa Rica 1 National Cuba 1 Villa Clara Ecuador 1 Cuenca Quito Jamaica 1 Kingston and St Andrew Peru 3 Trujillo United States of NPCR America 1 Uruguay 1 National Asia Bahrain 1 National (Bahraini) China 1 Beijing City Cixian County Haining County Hong Kong Jiashan County Jiaxing City Macao Nangang District, Harbin City Qidong County Shanghai City Wuhan City Yangcheng County Yanting County Zhongshan City India 1 Bangalore Barshi, Paranda and Bhum Bhopal Chennai Dindigul, Ambillikai Karunagappally Mizoram Mumbai New Delhi Poona Sikkim State Trivandrum Iran 1 Golestan Province Israel 1 National National (Jews) National (Non-Jews) Japan 1 Aichi Prefecture Fukui Prefecture Hiroshima Miyagi Prefecture Nagasaki Prefecture Niigata Prefecture Osaka Prefecture Saga Prefecture (Continued)

48 3 BURDEN OF HPV RELATED CANCERS Table 8 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Korea, Republic of 1 Busan Daegu Daejeon Gwangju Incheon Jejudo National Seoul Ulsan Kuwait 1 National National (Kuwaitis) National (Non-Kuwaitis) Malaysia 1 Penang Penang (Chinese) Penang (Indian) Penang (Malay) Oman 3 Omani Pakistan 3 South Karachi Philippines 1 Manila Rizal Qatar 1 National (Qatari) Saudi Arabia 1 Riyadh (Saudi) Singapore 1 National National (Chinese) National (Indian) National (Malay) Thailand 1 Bangkok Chiang Mai Chonburi Khon Kaen Lampang Songkhla Turkey 1 Antalya Edirne Izmir Trabzon Viet Nam 2 Hanoi Ho Chi Minh City Europe Austria 1 National Tyrol Vorarlberg Belarus 1 National Belgium 1 National Bulgaria 1 National Croatia 1 National Cyprus 1 National Czech Republic 1 National Denmark 1 National Estonia 1 National Finland 1 National France 1 Bas-Rhin Calvados Doubs Haut-Rhin Herault (Continued)

49 3 BURDEN OF HPV RELATED CANCERS Table 8 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Isere Loire Atlantique Manche Martinique Somme Tarn Vendee Germany 1 Brandenburg Bremen Free State Of Saxony Hamburg Mecklenburg-Western Pomerania Munich North Rhine-Westphalia Saarland Schleswig-Holstein Iceland 1 National Ireland 1 National Italy 1 Alto Adige Biella Province Brescia Province Catania and Messina Catanzaro Ferrara Province Florence and Prato Provinces Friuli-Venezia Giulia Genova Province Latina Lombardy, Como Province Lombardy, Lecco Province Lombardy, Mantova Province Lombardy, Milan Lombardy, Varese Province Modena Province Naples Nuoro Palerme Parma Province Ragusa Province Reggio Emilia Province Romagna Region Salerno Province Sassari Province Sondrio South Lombardy Syracuse Province Torino Trapani Trento Umbria Region Veneto Region Latvia 1 National Lithuania 1 National Malta 1 National Netherlands 1 Eindhoven National (Continued)

50 3 BURDEN OF HPV RELATED CANCERS Table 8 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Norway 1 National Poland 1 Cracow Kielce Lower Silesia Rzeszow Portugal 1 Azores Russian Federation 1 St Petersburg Serbia 1 Central Slovakia 1 National Slovenia 1 National Spain 1 Albacete Asturias Basque Country Canary Islands Ciudad Real Cuenca Girona Granada La Rioja Mallorca Murcia Navarra Tarragona Sweden 1 National Switzerland 1 Basel Geneva Graubunden and Glarus Neuchatel St Gall-Appenzell Ticino Valais Vaud Zurich Ukraine 1 National United Kingdom 1 England England, East of England Region England, North Western England, Northern and Yorkshire England, Oxford Region England, South and Western Regions England, Thames England, Trent England, West Midlands Northern Ireland Scotland Wales Oceania Australia 1 Australian Capital Territory National National New South Wales Northern Territory Northern Territory (Indigenous) Northern Territory (Non-Indigenous) Queensland Tasmania (Continued)

51 3 BURDEN OF HPV RELATED CANCERS Table 8 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Victoria New Zealand 1 National National (Maori) National (Other) National (Pacific Islander) 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. last accessed on 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.

52 3 BURDEN OF HPV RELATED CANCERS NOTE. For time trends in vulvar cancer incidence please refer to specific countries 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 Egypt 1 Gharbiah Gambia 2 National Libya 1 Benghazi Malawi 1 Blantyre Mali 2 Bamako South Africa 1 PROMEC Tunisia 1 North Uganda 1 Kyadondo county Zimbabwe 1 Harare (African) Americas Argentina 1 Bahia Blanca Cordoba Mendoza Tierra del Fuego Brazil 1 Aracaju Belo Horizonte Cuiaba Fortaleza Goiania Sao Paulo Canada 1 Alberta British Columbia Manitoba National New Brunswick Newfoundland and Labrador Northwest Territories Nova Scotia Ontario Prince Edward Island Quebec Saskatchewan Yukon (Continued)

53 3 BURDEN OF HPV RELATED CANCERS Table 9 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Chile 1 Biobio Province Region of Antofagasta Valdivia Colombia 1 Bucaramanga Cali Manizales Pasto Costa Rica 1 National Cuba 1 Villa Clara Ecuador 1 Cuenca Quito Jamaica 1 Kingston and St Andrew Peru 3 Trujillo United States of NPCR America 1 Uruguay 1 National Asia Bahrain 1 National (Bahraini) China 1 Beijing City Cixian County Haining County Hong Kong Jiashan County Jiaxing City Macao Nangang District, Harbin City Qidong County Shanghai City Wuhan City Yangcheng County Yanting County Zhongshan City India 1 Bangalore Barshi, Paranda and Bhum Bhopal Chennai Dindigul, Ambillikai Karunagappally Mizoram Mumbai New Delhi Poona Sikkim State Trivandrum Iran 1 Golestan Province Israel 1 National National (Jews) National (Non-Jews) Japan 1 Aichi Prefecture Fukui Prefecture Hiroshima Miyagi Prefecture Nagasaki Prefecture Niigata Prefecture Osaka Prefecture Saga Prefecture (Continued)

54 3 BURDEN OF HPV RELATED CANCERS Table 9 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Korea, Republic of 1 Busan Daegu Daejeon Gwangju Incheon Jejudo National Seoul Ulsan Kuwait 1 National National (Kuwaitis) National (Non-Kuwaitis) Malaysia 1 Penang Penang (Chinese) Penang (Indian) Penang (Malay) Oman 3 Omani Pakistan 3 South Karachi Philippines 1 Manila Rizal Qatar 1 National (Qatari) Saudi Arabia 1 Riyadh (Saudi) Singapore 1 National National (Chinese) National (Indian) National (Malay) Thailand 1 Bangkok Chiang Mai Chonburi Khon Kaen Lampang Songkhla Turkey 1 Antalya Edirne Izmir Trabzon Viet Nam 2 Hanoi Ho Chi Minh City Europe Austria 1 National Tyrol Vorarlberg Belarus 1 National Belgium 1 National Bulgaria 1 National Croatia 1 National Cyprus 1 National Czech Republic 1 National Denmark 1 National Estonia 1 National Finland 1 National France 1 Bas-Rhin Calvados Doubs Haut-Rhin Herault (Continued)

55 3 BURDEN OF HPV RELATED CANCERS Table 9 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Isere Loire Atlantique Manche Martinique Somme Tarn Vendee Germany 1 Brandenburg Bremen Free State Of Saxony Hamburg Mecklenburg-Western Pomerania Munich North Rhine-Westphalia Saarland Schleswig-Holstein Iceland 1 National Ireland 1 National Italy 1 Alto Adige Biella Province Brescia Province Catania and Messina Catanzaro Ferrara Province Florence and Prato Provinces Friuli-Venezia Giulia Genova Province Latina Lombardy, Como Province Lombardy, Lecco Province Lombardy, Mantova Province Lombardy, Milan Lombardy, Varese Province Modena Province Naples Nuoro Palerme Parma Province Ragusa Province Reggio Emilia Province Romagna Region Salerno Province Sassari Province Sondrio South Lombardy Syracuse Province Torino Trapani Trento Umbria Region Veneto Region Latvia 1 National Lithuania 1 National Malta 1 National Netherlands 1 Eindhoven National (Continued)

56 3 BURDEN OF HPV RELATED CANCERS Table 9 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Norway 1 National Poland 1 Cracow Kielce Lower Silesia Rzeszow Portugal 1 Azores Russian Federation 1 St Petersburg Serbia 1 Central Slovakia 1 National Slovenia 1 National Spain 1 Albacete Asturias Basque Country Canary Islands Ciudad Real Cuenca Girona Granada La Rioja Mallorca Murcia Navarra Tarragona Sweden 1 National Switzerland 1 Basel Geneva Graubunden and Glarus Neuchatel St Gall-Appenzell Ticino Valais Vaud Zurich Ukraine 1 National United Kingdom 1 England England, East of England Region England, North Western England, Northern and Yorkshire England, Oxford Region England, South and Western Regions England, Thames England, Trent England, West Midlands Northern Ireland Scotland Wales Oceania Australia 1 Australian Capital Territory National National New South Wales Northern Territory Northern Territory (Indigenous) Northern Territory (Non-Indigenous) Queensland Tasmania (Continued)

57 3 BURDEN OF HPV RELATED CANCERS Table 9 Continued Female Country Cancer registry Period N cases a Crude rate b ASR b Victoria New Zealand 1 National National (Maori) National (Other) National (Pacific Islander) 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. last accessed on 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.

58 3 BURDEN OF HPV RELATED CANCERS NOTE. For time trends in vaginal cancer incidence please refer to specific countries 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 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 % 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 Egypt 1 Gharbiah Gambia 3 National Libya 1 Benghazi Malawi 1 Blantyre Mali 3 Bamako Mozambique 4 Lourenco Marques Nigeria 5 Ibadan Senegal 6 Dakar South Africa 1 PROMEC Tunisia 1 North Uganda 1 Kyadondo county Zimbabwe 1 Harare (African) Americas Argentina 1 Bahia Blanca Cordoba Mendoza Tierra del Fuego Brazil 1 Aracaju Belo Horizonte Cuiaba Fortaleza Goiania Sao Paulo Canada 1 Alberta British Columbia Manitoba National New Brunswick Newfoundland and Labrador Northwest Territories Nova Scotia (Continued)

59 3 BURDEN OF HPV RELATED CANCERS Table 10 Continued Male Country Cancer registry Period N cases a Crude rate b ASR b Ontario Prince Edward Island Quebec Saskatchewan Yukon Chile 1 Biobio Province Region of Antofagasta Valdivia Colombia 1 Bucaramanga Cali Manizales Pasto Costa Rica 1 National Cuba 1 Villa Clara Ecuador 1 Cuenca Quito Jamaica 1 Kingston and St Andrew Paraguay 2 Asuncion Region Peru 7 Trujillo United States of NPCR America 1 Uruguay 1 National Asia Bahrain 1 National (Bahraini) China 1 Beijing City Cixian County Haining County Hong Kong Jiashan County Jiaxing City Macao Nangang District, Harbin City Qidong County Shanghai City Wuhan City Yangcheng County Yanting County Zhongshan City India 1 Bangalore Barshi, Paranda and Bhum Bhopal Chennai Dindigul, Ambillikai Karunagappally Mizoram Mumbai New Delhi Poona Sikkim State Trivandrum Iran 1 Golestan Province Israel 1 National National (Jews) National (Non-Jews) Japan 1 Aichi Prefecture Fukui Prefecture (Continued)

60 3 BURDEN OF HPV RELATED CANCERS Table 10 Continued Male Country Cancer registry Period N cases a Crude rate b ASR b Hiroshima Miyagi Prefecture Nagasaki Prefecture Niigata Prefecture Osaka Prefecture Saga Prefecture Korea, Republic of 1 Busan Daegu Daejeon Gwangju Incheon Jejudo National Seoul Ulsan Kuwait 1 National National (Kuwaitis) National (Non-Kuwaitis) Kyrgyzstan 2 National Malaysia 1 Penang Penang (Chinese) Penang (Indian) Penang (Malay) Oman 7 Omani Pakistan 7 South Karachi Philippines 1 Manila Rizal Qatar 1 National (Qatari) Saudi Arabia 1 Riyadh (Saudi) Singapore 1 National National (Chinese) National (Indian) National (Malay) Thailand 1 Bangkok Chiang Mai Chonburi Khon Kaen Lampang Songkhla Turkey 1 Antalya Edirne Izmir Trabzon Viet Nam 3 Hanoi Ho Chi Minh City Europe Austria 1 National Tyrol Vorarlberg Belarus 1 National Belgium 1 National Bulgaria 1 National Croatia 1 National Cyprus 1 National Czech Republic 1 National Denmark 1 National (Continued)

61 3 BURDEN OF HPV RELATED CANCERS Table 10 Continued Male Country Cancer registry Period N cases a Crude rate b ASR b Estonia 1 National Finland 1 National France 1 Bas-Rhin Calvados Doubs Haut-Rhin Herault Isere Loire Atlantique Manche Martinique Somme Tarn Vendee Germany 1 Brandenburg Bremen Free State Of Saxony Hamburg Mecklenburg-Western Pomerania Munich North Rhine-Westphalia Saarland Schleswig-Holstein Hungary 2 County Szabolcs-Szatmar County Vas Iceland 1 National Ireland 1 National Italy 1 Alto Adige Biella Province Brescia Province Catania and Messina Catanzaro Ferrara Province Florence and Prato Provinces Friuli-Venezia Giulia Genova Province Latina Lombardy, Como Province Lombardy, Lecco Province Lombardy, Mantova Province Lombardy, Milan Lombardy, Varese Province Modena Province Naples Nuoro Palerme Parma Province Ragusa Province Reggio Emilia Province Romagna Region Salerno Province Sassari Province Sondrio South Lombardy Syracuse Province Torino (Continued)

62 3 BURDEN OF HPV RELATED CANCERS Table 10 Continued Male Country Cancer registry Period N cases a Crude rate b ASR b Trapani Trento Umbria Region Veneto Region Latvia 1 National Lithuania 1 National Malta 1 National Montenegro 3 Vojvodina Netherlands 1 Eindhoven National Norway 1 National Poland 1 Cracow Kielce Lower Silesia Rzeszow Portugal 1 Azores Romania 2 County Cluj Russian Federation 1 St Petersburg Serbia 1 Central Slovakia 1 National Slovenia 1 National Spain 1 Albacete Asturias Basque Country Canary Islands Ciudad Real Cuenca Girona Granada La Rioja Mallorca Murcia Navarra Tarragona Sweden 1 National Switzerland 1 Basel Geneva Graubunden and Glarus Neuchatel St Gall-Appenzell Ticino Valais Vaud Zurich Ukraine 1 National United Kingdom 1 England England, East of England Region England, North Western England, Northern and Yorkshire England, Oxford Region England, South and Western Regions England, Thames England, Trent England, West Midlands Northern Ireland Scotland (Continued)

63 3 BURDEN OF HPV RELATED CANCERS Table 10 Continued Male Country Cancer registry Period N cases a Crude rate b ASR b Wales Oceania Australia 1 Australian Capital Territory National National New South Wales Northern Territory Northern Territory (Indigenous) Northern Territory (Non-Indigenous) Queensland Tasmania Victoria New Zealand 1 National National (Maori) National (Other) National (Pacific Islander) 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. last accessed on 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

64 3 BURDEN OF HPV RELATED CANCERS 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) 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 World Less developed regions More developed regions Africa Eastern Africa Middle Africa Northern Africa Southern Africa Western Africa Americas Caribbean Central America Northern America South America Asia Central Asia Eastern Asia South-Eastern Asia Southern Asia Western Asia Europe Eastern Europe Northern Europe Southern Europe Western Europe Oceania Australia & New Zealand Melanesia Micronesia Polynesia 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; Available from: 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 World (Continued)

65 3 BURDEN OF HPV RELATED CANCERS 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 Less developed regions More developed regions Africa Eastern Africa Middle Africa Northern Africa Southern Africa Western Africa Americas Caribbean Central America Northern America South America Asia Central Asia Eastern Asia South-Eastern Asia Southern Asia Western Asia Europe Eastern Europe Northern Europe Southern Europe Western Europe Oceania Australia & New Zealand Melanesia Micronesia Polynesia 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; Available from: accessed on 15/01/2014.

66 3 BURDEN OF HPV RELATED CANCERS 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 Age specific rates of pharyngeal cancer (excluding nasopharynx) per 100, World >= FEMALE 25 Less developed regions >= More developed regions >= >=75 Incidence >= Mortality >=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; Available from: accessed on 15/01/2014.

67 3 BURDEN OF HPV RELATED CANCERS 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 Asia Age specific rates of pharyngeal cancer (excluding nasopharynx) per 100, Africa Americas >= >= Europe Oceania >= >= >=75 Incidence Mortality >=75 Age group (years) Rates per 100,000 men per year. Data sources: (Continued on next page)

68 3 BURDEN OF HPV RELATED CANCERS ( 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; Available from: accessed on 15/01/2014.

69 3 BURDEN OF HPV RELATED CANCERS 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 Age specific rates of pharyngeal cancer (excluding nasopharynx) per 100, Africa Americas >= >= Europe Oceania >= >= >=75 Incidence Mortality >=75 Age group (years) Rates per 100,000 women per year. Data sources: (Continued on next page)

70 3 BURDEN OF HPV RELATED CANCERS ( 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; Available from: accessed on 15/01/2014.

71 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.

72 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.

73 Figure 27: Crude age-specific HPV prevalence (%) and 95% confidence interval (grey shadow) in women with normal cytology in the World HPV prevalence (%) Europe Oceania < < HPV prevalence (%) Africa Asia < < HPV prevalence (%) Americas World < < Age group (years) Data updated at 15 Dec 2014 (data as of 31 Oct 2014). Data sources: See references in Section 9.

74 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) (52.7) yrs yrs yrs (44.0) yrs >=30 yrs (27.9) yrs (30.0) yrs (43.5) yrs (37.3) yrs (34.0) yrs yrs (26.4) yrs (33.0) yrs (35.0) yrs (29.7) yrs (35.7) yrs (29.9) yrs >=15 yrs (35.3) yrs (34.2) yrs (33.8) yrs (40.7) yrs (38.0) yrs (42.5) yrs (40.0) yrs (36.0) yrs >=25 (33.0) yrs >=15 yrs (37.6) yrs HPV prevalence (%) N ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 306 % (95% CI) 5.3 ( ) 8.7 ( ) 4.2 ( ) ( ) ( ) ( ) ( ) ( ) ( ) (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.

75 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) (43.7) yrs >=15 yrs (36.2) yrs >=25 (42.0) yrs (34.0) yrs >=15 (31.9) yrs (42.7) yrs (43.0) yrs (41.8) yrs (41.8) yrs (42.1) yrs (41.8) yrs (39.0) yrs (43.3) yrs >=18 yrs (44.0) yrs yrs (39.0) yrs >=18 (40.3) yrs (18.0) yrs (38.0) yrs (35.0) yrs (30.0) yrs (30.0) yrs (20.0) yrs yrs (41.0) yrs (36.8) yrs yrs HPV prevalence (%) N % (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) (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.

76 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) (32.4) yrs (40.5) yrs (31.0) yrs (31.6) yrs (31.2) yrs (39.6) yrs (36.0) yrs (33.0) yrs (52.2) yrs (36.5) yrs (36.6) yrs (27.2) yrs (31.0) yrs yrs (33.0) yrs (33.0) yrs yrs yrs (19.6) yrs >=13 (36.9) yrs >=13 (34.1) yrs (20.0) yrs yrs (17.2) yrs yrs (36.4) yrs (38.4) yrs (42.7) yrs (33.3) yrs HPV prevalence (%) N ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 338 % (95% CI) 5.9 ( ) 6.9 ( ) 2.3 ( ) 8.0 ( ) ( ) ( ) 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.

77 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) (32.4) yrs (40.5) yrs (31.0) yrs (31.6) yrs (31.2) yrs (39.6) yrs (36.0) yrs (33.0) yrs (52.2) yrs (36.5) yrs (36.6) yrs (27.2) yrs (31.0) yrs yrs (33.0) yrs (33.0) yrs yrs yrs (19.6) yrs >=13 (36.9) yrs >=13 (34.1) yrs (20.0) yrs yrs (17.2) yrs yrs (36.4) yrs (38.4) yrs (42.7) yrs (33.3) yrs HPV prevalence (%) N ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 338 % (95% CI) 5.9 ( ) 6.9 ( ) 2.3 ( ) 8.0 ( ) ( ) ( ) (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.

78 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) (32.9) yrs (33.0) yrs (42.8) yrs (41.0) yrs N % (95% CI) ( ) ( ) ( ) ( ) 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 yrs (23.0) yrs (43.0) yrs ( ) ( ) ( ) ( ) ( ) ( ) Kapala 2007 Ontario Moore 2009 British Columbia Roteli Martins 2011 >=15 (40.0) yrs (21.1) yrs ( ) ( ) ( ) Demers 2012 Manitoba Jiang 2013(H) >=18 (43.0) yrs (38.0) yrs ( ) ( ) Chile Ogilvie 2013(a) British Columbia Louvanto 2014(a) Montreal Ferreccio 2004 Santiago Ferreccio 2008(a) yrs (43.4) yrs (41.9) yrs ( ) ( ) ( ) ( ) Colombia Montalvo 2011 Arica Ferreccio 2013 Santiago Muñoz 1996 Cali Molano 2002 Bogota Leon 2009 Girardot Soto De Leon 2011(I) (21.6) yrs (42.2) yrs (42.8) yrs (33.0) yrs (41.6) yrs (39.0) yrs ( ) ( ) ( ) ( ) ( ) ( ) Costa Rica Cuba Ecuador Guatemala Guyana Herrero 2005 Guanacaste Safaeian 2007 Guanacaste Soto 2014 La Havana Brown 2009 Guayas Vallès 2009 Escuintla Kightlinger (41.0) yrs (21.0) yrs (40.0) yrs (37.7) yrs (29.7) yrs (36.9) yrs ( ) ( ) ( ) ( ) ( ) ( ) 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.

79 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) (36.9) yrs (40.4) yrs (24.0) yrs yrs (35.0) yrs (32.0) yrs (44.3) yrs (34.3) yrs (41.6) yrs (42.5) yrs (51.2) yrs yrs (36.5) yrs (39.0) yrs (36.0) yrs (50.2) yrs (36.2) yrs yrs (33.3) yrs (37.7) yrs yrs (37.9) yrs (45.1) yrs (34.0) yrs (35.0) yrs (49.2) yrs (35.4) yrs (35.0) yrs yrs HPV prevalence (%) N ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 501 % (95% CI) 8.8 ( ) 7.8 ( ) 7.0 ( ) 4.1 ( ) 8.0 ( ) 7.9 ( ) 9.8 ( ) 3.8 ( ) 7.5 ( ) ( ) ( ) (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.

80 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) (37.0) yrs (32.0) yrs yrs (39.1) yrs N % (95% CI) ( ) ( ) ( ) ( ) Chan 2002 Hong Kong Belinson 2003(B) (43.8) yrs (40.9) yrs ( ) ( ) Dai 2006 Shanxi Li 2006 Shenyang He 2008 Hangzhou Lin 2008(a) Guandong Chan 2009(a) Hong Kong Jin 2010(C) (40.4) yrs (41.2) yrs (40.0) yrs (39.0) yrs (43.3) yrs (38.1) yrs ( ) ( ) ( ) ( ) ( ) ( ) Li 2010 Beijing Moy 2010(D) (39.6) yrs (39.0) yrs ( ) 9.5 ( ) 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) (38.9) yrs (23.2) yrs yrs (38.0) yrs yrs (38.0) yrs ( ) ( ) ( ) ( ) ( ) ( ) ( ) Wang 2012(F)(a) yrs ( ) Bian 2013 Beijing Chen 2013(a) Urumqi Li 2013 Hunan Province Sui 2013(G)(a) (39.0) yrs (39.6) yrs (41.5) yrs (36.3) yrs ( ) ( ) ( ) ( ) Wang 2013(a) Huzhou Wang 2013 Shenzhen Ding 2014 Beijing Mai 2014(H) (29.0) yrs >=15 yrs (36.5) yrs >=18 (36.4) yrs ( ) ( ) ( ) ( ) 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.

81 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) (37.0) yrs (32.0) yrs yrs (39.1) yrs N % (95% CI) ( ) ( ) ( ) ( ) Chan 2002 Hong Kong Belinson 2003(B) (43.8) yrs (40.9) yrs ( ) ( ) Dai 2006 Shanxi Li 2006 Shenyang He 2008 Hangzhou Lin 2008(a) Guandong Chan 2009(a) Hong Kong Jin 2010(C) (40.4) yrs (41.2) yrs (40.0) yrs (39.0) yrs (43.3) yrs (38.1) yrs ( ) ( ) ( ) ( ) ( ) ( ) Li 2010 Beijing Moy 2010(D) (39.6) yrs (39.0) yrs ( ) 9.5 ( ) 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) (38.9) yrs (23.2) yrs yrs (38.0) yrs yrs (38.0) yrs ( ) ( ) ( ) ( ) ( ) ( ) ( ) Wang 2012(F)(a) yrs ( ) Bian 2013 Beijing Chen 2013(a) Urumqi Li 2013 Hunan Province Sui 2013(G)(a) (39.0) yrs (39.6) yrs (41.5) yrs (36.3) yrs ( ) ( ) ( ) ( ) Wang 2013(a) Huzhou Wang 2013 Shenzhen Ding 2014 Beijing Mai 2014(H) (29.0) yrs >=15 yrs (36.5) yrs >=18 (36.4) yrs ( ) ( ) ( ) ( ) 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.

82 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 (35.0) yrs (34.3) yrs (40.5) yrs (35.9) yrs yrs (39.7) yrs yrs yrs yrs >=15 yrs (37.4) yrs yrs (41.0) yrs yrs yrs yrs (23.0) yrs yrs (35.8) yrs (32.4) yrs (37.5) yrs (37.6) yrs (28.7) yrs yrs >=25 (37.4) yrs (36.8) yrs yrs yrs (36.3) yrs (37.9) yrs HPV prevalence (%) N ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) % (95% CI) 8.8 ( ) 9.6 ( ) 8.9 ( ) 1.7 ( ) 7.6 ( ) 9.2 ( ) 5.8 ( ) 5.8 ( ) 4.4 ( ) 2.3 ( ) (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.

83 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) (35.0) yrs Sankaranarayanan 2004 Mumbai (40.0) yrs Sankaranarayanan 2004 Trivandrum (42.0) yrs Sankaranarayanan 2004 Kolkata (2) (35.0) yrs Sankaranarayanan 2005(a) (39.3) yrs Osnamabad Laikangbam 2007 West Bengal (30.7) yrs Laikangbam 2007 Sikkim (36.6) yrs Laikangbam 2007 Manipur (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 (35.5) yrs Srivastava 2012(a) Varanasi yrs Vinodhini 2012 Tamil Nadu (47.2) yrs Kashyap 2013(c) 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 yrs (44.2) yrs (40.0) yrs (39.0) yrs (40.0) yrs (39.9) yrs yrs (35.2) yrs (37.5) yrs (36.0) yrs yrs (52.4) yrs (36.0) yrs HPV prevalence (%) N ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 791 % (95% CI) 7.8 ( ) 6.3 ( ) 4.8 ( ) 5.2 ( ) 6.7 ( ) 8.1 ( ) 9.1 ( ) 9.7 ( ) 5.8 ( ) 4.6 ( ) 8.8 ( ) 5.7 ( ) 5.5 ( ) 5.5 ( ) 0.6 ( ) 6.6 ( ) ( ) 6.6 ( ) ( ) (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.

84 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) (40.9) yrs (40.0) yrs <=55 (40.7) yrs yrs (35.0) yrs (46.0) yrs (53.0) yrs (29.0) yrs (36.0) yrs (38.7) yrs (35.0) yrs (22.5) yrs (44.4) yrs (41.9) yrs yrs (42.0) yrs (42.9) yrs yrs (30.0) yrs yrs yrs (42.0) yrs (48.0) yrs yrs (40.1) yrs (48.2) yrs (46.7) yrs (12.5) yrs HPV prevalence (%) N ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 206 % (95% CI) 6.6 ( ) 4.5 ( ) 9.7 ( ) 6.6 ( ) 9.4 ( ) 6.5 ( ) 6.2 ( ) 4.9 ( ) 8.3 ( ) ( ) ( ) ( ) ( ) (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.

85 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) (45.0) yrs (49.0) yrs (45.4) yrs (19.0) yrs yrs (37.9) yrs N % (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Um ( ) Lee 2012(a) (44.0) yrs ( ) Lee 2012 Suwon Kim 2014(a) Busan Kim 2014 Cheonan Kim 2014 Gangnam (Seoul) Lee 2014(V)(a) (12.5) yrs (39.9) yrs (49.6) yrs yrs ( ) ( ) ( ) ( ) ( ) Park 2014(a) (50.0) yrs ( ) Kuwait Al Awadhi (41.0) yrs ( ) Lebanon Mroueh (41.0) yrs ( ) Malaysia Mongolia Karam 2005 Tay 2009 Johor and Singapore Chong 2010(a) Southern Selangor Othman 2014(W) Chimeddorj 2008(b) (39.6) yrs (42.0) yrs (39.0) yrs (43.0) yrs ( ) ( ) ( ) ( ) ( ) Nepal Dondog 2008 Ulaanbaatar Sherpa 2010(X) (36.4) yrs yrs ( ) ( ) Johnson 2014(Y) (33.8) yrs ( ) Pakistan Philippines Saudi Arabia Taiwan Raza 2010 Karachi Ngelangel 1998 Manila Al Ahdal 2014 Riyadh Jeng 2005 Taipei Huang yrs (46.8) yrs (37.0) yrs (40.0) yrs (43.0) yrs ( ) ( ) ( ) ( ) ( ) Chen 2011(Z) (46.3) yrs ( ) 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.

86 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) (43.0) yrs (40.0) yrs >=20 (46.2) yrs (40.0) yrs (41.0) yrs (46.7) yrs (32.0) yrs (49.7) yrs (43.9) yrs (47.8) yrs (46.3) yrs yrs (28.9) yrs >=35 (54.5) yrs (44.0) yrs (43.4) yrs (36.0) yrs (46.4) yrs (29.6) yrs yrs >=20 (39.0) yrs (47.8) yrs (46.6) yrs yrs (33.6) yrs (36.8) yrs (34.9) yrs HPV prevalence (%) N ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 410 % (95% CI) 9.2 ( ) 4.9 ( ) 6.9 ( ) 3.3 ( ) 5.9 ( ) 4.7 ( ) 7.8 ( ) 6.2 ( ) 6.7 ( ) 4.0 ( ) 4.3 ( ) 5.2 ( ) 8.5 ( ) (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.

87 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) (28.2) yrs (39.4) yrs (40.1) yrs (35.8) yrs (42.0) yrs yrs (45.0) yrs (39.0) yrs >=20 (41.0) yrs 4 18 (16.9) yrs (29.7) yrs (40.0) yrs (33.5) yrs (30.0) yrs (45.0) yrs (25.0) yrs (37.0) yrs (37.3) yrs (37.0) yrs (26.9) yrs (19.7) yrs (24.0) yrs (47.0) yrs (34.0) yrs (35.7) yrs (44.0) yrs (38.9) yrs (39.6) yrs (40.1) yrs (21.1) yrs HPV prevalence (%) N ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 613 % (95% CI) 6.9 ( ) 8.2 ( ) 4.4 ( ) 6.3 ( ) 7.5 ( ) 5.2 ( ) ( ) ( ) ( ) ( ) 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.

88 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) (28.2) yrs (39.4) yrs (40.1) yrs (35.8) yrs (42.0) yrs yrs (45.0) yrs (39.0) yrs >=20 (41.0) yrs 4 18 (16.9) yrs (29.7) yrs (40.0) yrs (33.5) yrs (30.0) yrs (45.0) yrs (25.0) yrs (37.0) yrs (37.3) yrs (37.0) yrs (26.9) yrs (19.7) yrs (24.0) yrs (47.0) yrs (34.0) yrs (35.7) yrs (44.0) yrs (38.9) yrs (39.6) yrs (40.1) yrs (21.1) yrs HPV prevalence (%) N ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 613 % (95% CI) 6.9 ( ) 8.2 ( ) 4.4 ( ) 6.3 ( ) 7.5 ( ) 5.2 ( ) ( ) ( ) ( ) ( ) (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.

89 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) (36.2) yrs (39.4) yrs (41.6) yrs yrs (38.5) yrs (40.1) yrs (35.0) yrs (42.7) yrs N % (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Luyten 2009 Wolfsburg Iftner 2010 >=30 (47.7) yrs (21.5) yrs ( ) ( ) de Jonge 2013(H) >=20 (39.6) yrs ( ) Greece Paraskevaidis 2001 Ioannina Agorastos 2004(I) (38.0) yrs (43.0) yrs ( ) 2.0 ( ) Panotopoulou 2007 Athens Agorastos 2009(a) (32.2) yrs ( ) ( ) Tsiodras 2010 Athens Tsiodras (34.2) yrs (41.9) yrs ( ) ( ) Hungary Argyri 2013 Athens Nyári (34.2) yrs (31.1) yrs ( ) ( ) 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 (35.0) yrs (39.0) yrs (37.7) yrs (36.0) yrs (51.0) yrs (21.6) yrs >=20 (37.0) yrs (38.4) yrs ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Masia 2009 Sardinia Giorgi Rossi 2011(J) yrs yrs ( ) ( ) Giambi 2013(K) (23.8) yrs ( ) Panatto 2013(L) (19.7) yrs ( ) 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.

90 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) (29.0) yrs (46.8) yrs (30.0) yrs N % (95% CI) ( ) ( ) ( ) Ronco 2006(N) (45.0) yrs ( ) Tornesello 2006 Milan, Naples Tornesello 2008 Naples Verteramo 2009 Rome Zappacosta 2009 Molise Piana 2011 North Sardinia Panatto 2013(O) (41.0) yrs (32.5) yrs (32.7) yrs (38.1) yrs (37.0) yrs (19.7) yrs ( ) ( ) ( ) ( ) ( ) ( ) Latvia Sammarco 2013 Molise Silins 2004(a) yrs (50.8) yrs ( ) ( ) Lithuania Gudleviciene 2005 Vilnius Kliucinskas 2006(a) (29.8) yrs (30.0) yrs ( ) ( ) Netherlands Simanaviciene 2014 Vilnius Jacobs 2000 Amsterdam Rozendaal 2000 Amsterdam Zielinski 2001 Zeeland Bulkmans 2004 Amsterdam Lenselink 2008(P)(a) (40.4) yrs (45.3) yrs (43.0) yrs (43.0) yrs (42.8) yrs (23.4) yrs ( ) ( ) ( ) ( ) ( ) ( ) Rijkaart (40.0) yrs ( ) Norway Rijkaart 2012 Utrecht Hesselink 2013 Utrecht region Boers 2014 Gjøoen 1996 Oslo Molden 2005 Oslo Molden 2006 Oslo Skjeldestad 2008(Q)(a) (44.0) yrs (41.0) yrs yrs (32.7) yrs (48.9) yrs <=30 (26.9) yrs (21.2) yrs ( ) ( ) ( ) ( ) ( ) ( ) ( ) Poland Portugal Bardin 2008 Warsaw Dutra 2008(a) Açores Pista 2011(R) (38.0) yrs (41.0) yrs (34.3) yrs ( ) ( ) ( ) 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.

91 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) (34.3) yrs (32.4) yrs (39.0) yrs (32.7) yrs (30.2) yrs yrs (32.1) yrs (45.0) yrs (22.0) yrs (39.5) yrs yrs (35.6) yrs yrs (36.5) yrs (42.7) yrs (43.0) yrs (32.7) yrs (34.0) yrs (36.0) yrs (37.9) yrs yrs yrs (40.0) yrs (26.0) yrs (35.1) yrs (41.0) yrs yrs (44.4) yrs (36.6) yrs HPV prevalence (%) N ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) % (95% CI) 9.9 ( ) 8.8 ( ) 5.2 ( ) 1.3 ( ) 7.8 ( ) 7.3 ( ) 4.1 ( ) 5.8 ( ) 5.5 ( ) 9.7 ( ) 6.3 ( ) ( ) (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.

92 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) (16.8) yrs N % (95% CI) ( ) Tabrizi 2012(B)(b) (21.1) yrs ( ) Tabrizi (32.0) yrs ( ) Fiji Foliaki 2014(a) (36.9) yrs ( ) Suva Vanuatu McAdam 2010(C) (39.3) yrs ( ) Aruhuri 2012(D) yrs ( ) 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.

93 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) (16.8) yrs N % (95% CI) ( ) Tabrizi 2012(B)(b) (21.1) yrs ( ) Tabrizi (32.0) yrs ( ) Fiji Foliaki 2014(a) (36.9) yrs ( ) Suva Vanuatu McAdam 2010(C) (39.3) yrs ( ) Aruhuri 2012(D) yrs ( ) 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.

94 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, ( ) 43, ( ) 44, ( ) 53, ( ) Less developed regions 168, ( ) 10, ( ) 11, ( ) 21, ( ) More developed regions 282, ( ) 33, ( ) 29, ( ) 23, ( ) Africa 19, ( ) ( ) ( ) 3, ( ) Eastern Africa 4, ( ) ( ) ( ) 1, ( ) Middle Africa ( ) ( ) Northern Africa 2, ( ) ( ) ( ) ( ) Southern Africa 8, ( ) ( ) ( ) ( ) Western Africa 4, ( ) ( ) ( ) ( ) Americas 105, ( ) 13, ( ) 11, ( ) 8, ( ) Caribbean ( ) ( ) ( ) ( ) Central America 16, ( ) 1, ( ) ( ) 1, ( ) Northern America 77, ( ) 9, ( ) 8, ( ) 3, ( ) South America 10, ( ) 2, ( ) 2, ( ) 6, ( ) Asia 142, ( ) 7, ( ) 11, ( ) 18, ( ) Central Asia Eastern Asia 111, ( ) 6, ( ) 9, ( ) 13, ( ) South-Eastern Asia 8, ( ) ( ) ( ) 3, ( ) Southern Asia 14, ( ) ( ) ( ) 2, ( ) Western Asia 7, ( ) ( ) ( ) ( ) Europe 180, ( ) 20, ( ) 19, ( ) 16, ( ) Eastern Europe 7, ( ) ( ) ( ) 1, ( ) Northern Europe 86, ( ) 4, ( ) 6, ( ) 4, ( ) Southern Europe 31, ( ) 10, ( ) 5, ( ) 3, ( ) Western Europe 56, ( ) 4, ( ) 3, ( ) 3, ( ) Oceania 2, ( ) ( ) 1, ( ) ( ) Australia & New Zealand 2, ( ) ( ) 1, ( ) ( ) Melanesia ( ) ( ) ( ) 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.

95 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 ( ) 0.5 ( ) 4.3 ( ) 6.6 ( ) 3.5 ( ) 7.5 ( ) 4.1 ( ) 1.3 ( ) 2.2 ( ) 4.8 ( ) 3.0 ( ) 1.5 ( ) 5.7 ( ) 1.0 ( ) 1.6 ( ) 2.0 ( ) 2.0 ( ) % (95% CI) ( ) ( ) 5.2 ( ) 2.8 ( ) 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.

96 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 % (95% CI) 15.1 ( ) 3.2 ( ) 6.5 ( ) 8.3 ( ) 1.2 ( ) 5.2 ( ) 7.0 ( ) 0.5 ( ) 5.0 ( ) 1.2 ( ) 1.4 ( ) 14.5 ( ) 9.6 ( ) 8.9 ( ) 9.2 ( ) 8.7 ( ) 1.9 ( ) 3.6 ( ) 2.1 ( ) 5.5 ( ) 3.3 ( ) 2.2 ( ) 35.1 ( ) 21.2 ( ) 3.3 ( ) 11.0 ( ) 6.0 ( ) 1.2 ( ) 1.7 ( ) 0.8 ( ) 3.8 ( ) 2.9 ( ) 9.0 ( ) 11.3 ( ) 2.3 ( ) 1.1 ( ) 9.0 ( ) 1.0 ( ) 5.5 ( ) 4.5 ( ) 4.0 ( ) 2.4 ( ) 12.3 ( ) 2.4 ( ) 2.6 ( ) 1.6 ( ) 1.2 ( ) 9.7 ( ) 0.5 ( ) 4.7 ( ) 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.

97 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 ( ) Berois ( ) USA Wideroff ( ) Swan ( ) Moscicki ( ) Hernandez ( ) Insinga ( ) Schiffman ( ) Wheeler ( ) 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.

98 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 HPV prevalence (%) N ( ) 3.4 ( ) ( ) 9.4 ( ) 2.8 ( ) 3.6 ( ) 4.7 ( ) 2.2 ( ) 10.1 ( ) 8.3 ( ) 1.5 ( ) 0.5 ( ) 8.9 ( ) 2.0 ( ) 2.0 ( ) 4.0 ( ) 1.8 ( ) 1.0 ( ) 0.8 ( ) 1.3 ( ) 0.5 ( ) 0.3 ( ) 1.2 ( ) 4.5 ( ) 2.6 ( ) 4.1 ( ) 1.5 ( ) % (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 0.2 ( ) 3.0 ( ) (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.

99 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 ( ) 0.9 ( ) 4.8 ( ) 1.4 ( ) 0.9 ( ) 0.5 ( ) 1.3 ( ) 3.1 ( ) 2.9 ( ) 1.1 ( ) 1.4 ( ) 0.2 ( ) % (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 7.1 ( ) 1.7 ( ) 2.6 ( ) 3.6 ( ) 1.4 ( ) 4.2 ( ) 1.5 ( ) 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.

100 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 ( ) 2.8 ( ) 4.2 ( ) 2.1 ( ) 2.3 ( ) 5.6 ( ) 2.1 ( ) 15.6 ( ) 4.8 ( ) 8.4 ( ) 4.8 ( ) 4.0 ( ) 5.3 ( ) % (95% CI) ( ) ( ) ( ) ( ) ( ) 1.1 ( ) 6.6 ( ) 4.9 ( ) 0.4 ( ) 0.5 ( ) 0.0 ( ) 4.0 ( ) 2.6 ( ) 1.7 ( ) 3.2 ( ) 5.1 ( ) 8.8 ( ) 2.7 ( ) 8.7 ( ) 2.8 ( ) 3.0 ( ) 2.1 ( ) 2.8 ( ) 6.6 ( ) 6.9 ( ) 4.3 ( ) 0.9 ( ) 2.7 ( ) 1.8 ( ) 1.0 ( ) 6.3 ( ) 1.3 ( ) 2.8 ( ) 5.2 ( ) 7.5 ( ) 7.4 ( ) 24.1 ( ) 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.

101 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 % (95% CI) 24.1 ( ) 2.7 ( ) 7.1 ( ) Slovenia Ucakar ( ) Spain Muñoz 1996 de Sanjose 2003 González 2006 Dillner 2008 Castellsagué ( ) 0.4 ( ) 1.3 ( ) 3.1 ( ) 2.5 ( ) Sweden Kjellberg 1998 Ylitalo 2000 Naucler ( ) 5.8 ( ) 1.7 ( ) UK Cuzick 1995 Cuzick 1999 Cuschieri 2004 Grainge 2005 Hibbitts 2006 Sargent 2008 Hibbitts ( ) 0.1 ( ) 4.4 ( ) 1.4 ( ) 1.4 ( ) 1.5 ( ) 4.3 ( ) 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.

102 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 ( ) Vanuatu Aruhuri ( ) 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.

103 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 HPV prevalence (%) N ( ) ( ) 0.0 ( ) 10.6 ( ) 18.8 ( ) 13.3 ( ) 8.3 ( ) 0.0 ( ) 16.7 ( ) 5.9 ( ) 6.3 ( ) 0.0 ( ) % (95% CI) ( ) ( ) ( ) ( ) 12.5 ( ) 19.6 ( ) 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.

104 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 ( ) ( ) 34.5 ( ) 11.5 ( ) 11.4 ( ) 6.5 ( ) 4.3 ( ) ( ) 74.5 ( ) 19.5 ( ) 22.7 ( ) % (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 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.

105 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 HPV prevalence (%) N % (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 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.

106 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 HPV prevalence (%) N ( ) ( ) 39.1 ( ) 0.0 ( ) % (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 18.3 ( ) 18.3 ( ) 26.1 ( ) 60.0 ( ) ( ) (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.

107 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) ( ) Taiwan Chao 2008 Ding 2008 Huang ( ) 6.1 ( ) 0.0 ( ) Thailand Turkey Ekalaksananan 2001 Bhattarakosol 2002 Chaiwongkot 2007 Suwannarurk 2009 Chansaenroj 2010 Chansaenroj 2014 Ergünay 2008 Ozgul 2008 Sahiner 2012 Yuce 2012 Tezcan 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.

108 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 ( ) ( ) 11.6 ( ) 8.3 ( ) 28.4 ( ) % (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 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.

109 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 ( ) 6.7 ( ) ( ) ( ) 5.6 ( ) 23.2 ( ) 35.1 ( ) 26.1 ( ) ( ) % (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 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.

110 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 ( ) Stevens ( ) Garland ( ) 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.

111 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 HPV prevalence (%) N % (95% CI) 33.3 ( ) 16.7 ( ) 31.3 ( ) 30.6 ( ) 18.8 ( ) 61.5 ( ) 20.0 ( ) 34.5 ( ) 28.6 ( ) 50.0 ( ) 14.3 ( ) 22.2 ( ) 21.9 ( ) 0.0 ( ) 43.5 ( ) 19.7 ( ) 18.9 ( ) 12.5 ( ) 55.6 ( ) 22.7 ( ) 30.2 ( ) 9.1 ( ) 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.

112 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 % (95% CI) 48.8 ( ) 54.0 ( ) 60.0 ( ) 58.3 ( ) 46.7 ( ) 56.7 ( ) 30.5 ( ) 66.7 ( ) 40.0 ( ) 69.7 ( ) 25.0 ( ) 53.6 ( ) 61.8 ( ) 51.8 ( ) 59.9 ( ) 48.2 ( ) 48.9 ( ) 46.9 ( ) 52.4 ( ) 65.5 ( ) 55.5 ( ) 34.8 ( ) 32.8 ( ) 91.8 ( ) 45.4 ( ) 31.1 ( ) 26.3 ( ) 35.8 ( ) 24.2 ( ) 23.5 ( ) 58.3 ( ) 27.3 ( ) 42.4 ( ) 13.7 ( ) 27.5 ( ) 26.9 ( ) 41.9 ( ) 50.0 ( ) 51.0 ( ) 12.5 ( ) 68.2 ( ) 40.2 ( ) 49.2 ( ) 40.0 ( ) 41.2 ( ) 36.1 ( ) 59.9 ( ) 44.4 ( ) 47.2 ( ) 48.9 ( ) 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.

113 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 % (95% CI) 40.2 ( ) 47.7 ( ) 50.0 ( ) 43.4 ( ) 47.5 ( ) 60.0 ( ) 61.5 ( ) 58.8 ( ) 56.3 ( ) 51.2 ( ) 46.8 ( ) 29.5 ( ) Venezuela Sánchez Lander ( ) 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.

114 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 HPV prevalence (%) N % (95% CI) 66.7 ( ) 35.3 ( ) 24.4 ( ) 25.8 ( ) 35.7 ( ) 39.9 ( ) 36.4 ( ) 32.1 ( ) 35.3 ( ) 15.2 ( ) 34.9 ( ) 47.5 ( ) 35.8 ( ) 44.6 ( ) 42.9 ( ) 59.7 ( ) 64.7 ( ) 44.0 ( ) 63.0 ( ) 48.0 ( ) 35.0 ( ) 45.2 ( ) 65.1 ( ) 71.4 ( ) 63.2 ( ) 50.0 ( ) 71.9 ( ) 37.9 ( ) 35.8 ( ) 41.9 ( ) 36.4 ( ) 11.5 ( ) 33.3 ( ) 33.7 ( ) 28.8 ( ) 36.9 ( ) 22.8 ( ) 57.1 ( ) 15.4 ( ) 28.1 ( ) 43.8 ( ) 39.8 ( ) 40.5 ( ) 51.4 ( ) 24.7 ( ) 39.7 ( ) 36.0 ( ) 45.0 ( ) 33.3 ( ) 41.1 ( ) (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.

115 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 HPV prevalence (%) N % (95% CI) 41.1 ( ) 50.0 ( ) 50.0 ( ) 0.0 ( ) 39.6 ( ) 27.5 ( ) 50.0 ( ) 18.6 ( ) 35.0 ( ) 17.5 ( ) 24.1 ( ) 33.3 ( ) 33.3 ( ) 25.0 ( ) 33.7 ( ) 12.4 ( ) 27.0 ( ) 60.0 ( ) 25.0 ( ) 25.3 ( ) 25.0 ( ) 34.1 ( ) 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.

116 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 % (95% CI) 55.9 ( ) 56.0 ( ) 56.7 ( ) 50.0 ( ) 43.1 ( ) 34.9 ( ) 17.1 ( ) 20.3 ( ) 58.2 ( ) 85.3 ( ) 50.0 ( ) 48.0 ( ) 46.2 ( ) 49.0 ( ) 47.2 ( ) 33.3 ( ) 62.3 ( ) 42.6 ( ) 49.2 ( ) 36.5 ( ) 61.4 ( ) 56.9 ( ) 46.2 ( ) 54.3 ( ) 34.4 ( ) 36.0 ( ) 35.7 ( ) 58.1 ( ) 51.7 ( ) 50.0 ( ) 36.7 ( ) 50.0 ( ) 57.3 ( ) 51.2 ( ) 95.0 ( ) 70.4 ( ) 78.1 ( ) 75.7 ( ) 50.0 ( ) 50.6 ( ) 47.7 ( ) 38.8 ( ) 42.9 ( ) 60.7 ( ) 53.4 ( ) 73.7 ( ) 62.9 ( ) 37.5 ( ) 45.9 ( ) 56.0 ( ) 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.

117 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 % (95% CI) 56.0 ( ) 48.3 ( ) 52.8 ( ) 56.9 ( ) 65.0 ( ) 60.6 ( ) 51.2 ( ) 70.8 ( ) 49.3 ( ) 28.0 ( ) 44.1 ( ) 20.6 ( ) 74.2 ( ) 32.4 ( ) 27.7 ( ) 55.6 ( ) 48.9 ( ) 48.1 ( ) 31.7 ( ) 31.4 ( ) 56.0 ( ) 62.5 ( ) 41.9 ( ) 51.0 ( ) 49.0 ( ) 33.3 ( ) 36.0 ( ) 75.0 ( ) 28.8 ( ) 48.8 ( ) 69.1 ( ) 50.5 ( ) 35.4 ( ) 37.1 ( ) 57.6 ( ) 50.0 ( ) 63.0 ( ) 57.9 ( ) 61.5 ( ) 48.9 ( ) 40.9 ( ) 46.8 ( ) 49.0 ( ) 54.1 ( ) 56.9 ( ) 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.

118 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 % (95% CI) ( ) ( ) ( ) ( ) Fiji Tabrizi ( ) New Zealand Simonella ( ) 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.

119 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 HPV prevalence (%) N % (95% CI) 38.4 ( ) 33.3 ( ) 61.4 ( ) 50.0 ( ) 32.5 ( ) 71.8 ( ) 86.0 ( ) 55.4 ( ) 38.9 ( ) 42.4 ( ) 43.8 ( ) 34.5 ( ) 47.7 ( ) 58.6 ( ) 56.6 ( ) 55.6 ( ) 52.4 ( ) 37.3 ( ) 35.0 ( ) 44.8 ( ) 46.8 ( ) 82.0 ( ) 47.5 ( ) 77.4 ( ) 37.7 ( ) 44.9 ( ) 52.4 ( ) 48.2 ( ) 61.2 ( ) 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.

120 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 % (95% CI) 59.6 ( ) 61.9 ( ) 56.4 ( ) 68.6 ( ) 34.0 ( ) 58.6 ( ) 52.2 ( ) 59.3 ( ) 56.6 ( ) 27.1 ( ) 53.8 ( ) 58.7 ( ) 76.7 ( ) 51.7 ( ) 60.0 ( ) 35.5 ( ) 54.0 ( ) 45.0 ( ) 76.8 ( ) 61.1 ( ) 54.1 ( ) 52.6 ( ) 57.6 ( ) 51.2 ( ) 45.7 ( ) 57.8 ( ) 81.3 ( ) 43.3 ( ) 21.4 ( ) 43.3 ( ) 43.9 ( ) 26.7 ( ) 72.2 ( ) 66.7 ( ) 66.9 ( ) 47.9 ( ) 52.6 ( ) 46.5 ( ) 59.3 ( ) 48.0 ( ) 56.1 ( ) 50.9 ( ) 35.3 ( ) 43.5 ( ) 70.0 ( ) 54.5 ( ) 51.4 ( ) 25.9 ( ) 58.3 ( ) 69.0 ( ) HPV prevalence (%) (Continued on next page) Data updated at 15 Dec 2014 (data as of 30 Jun 2014). (Continued on next page)

121 ( 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.

122 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 ( ) USA Resnick ( ) Paquette ( ) Wistuba ( ) Pirog ( ) Sebbelov ( ) Schwartz ( ) Guo ( ) Zuna ( ) Patel ( ) Quint ( ) Wentzensen ( ) Wheeler ( ) de Sanjose ( ) Hariri ( ) Hopenhayn ( ) Venezuela Sánchez Lander ( ) 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.

123 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 HPV prevalence (%) N % (95% CI) 58.0 ( ) 31.7 ( ) 27.5 ( ) 48.1 ( ) 58.1 ( ) 48.8 ( ) 66.9 ( ) 40.0 ( ) 70.0 ( ) 50.0 ( ) 66.0 ( ) 55.6 ( ) 78.6 ( ) 81.8 ( ) 65.2 ( ) 45.8 ( ) 73.7 ( ) 68.7 ( ) 52.0 ( ) 81.3 ( ) 56.1 ( ) 76.7 ( ) 66.7 ( ) 83.1 ( ) 73.1 ( ) 65.2 ( ) 59.0 ( ) 53.8 ( ) 58.2 ( ) 53.5 ( ) 69.1 ( ) 60.6 ( ) 62.8 ( ) 58.5 ( ) 73.6 ( ) 60.5 ( ) 86.7 ( ) 65.9 ( ) 81.7 ( ) 65.1 ( ) 72.7 ( ) 78.6 ( ) 76.1 ( ) 31.9 ( ) 41.9 ( ) 33.8 ( ) 90.0 ( ) 85.7 ( ) 54.3 ( ) 28.4 ( ) (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.

124 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 % (95% CI) 28.6 ( ) 73.9 ( ) 60.0 ( ) 28.4 ( ) 60.5 ( ) 48.7 ( ) 44.8 ( ) 42.9 ( ) 32.8 ( ) 73.9 ( ) 37.7 ( ) 34.8 ( ) 53.8 ( ) 42.9 ( ) 26.2 ( ) 39.3 ( ) 28.3 ( ) 37.1 ( ) 32.0 ( ) 33.3 ( ) 29.0 ( ) 33.3 ( ) 48.8 ( ) 37.9 ( ) 35.0 ( ) 41.9 ( ) 83.3 ( ) 42.3 ( ) 12.5 ( ) 48.3 ( ) 68.3 ( ) 53.3 ( ) 37.5 ( ) 64.0 ( ) 61.2 ( ) 52.8 ( ) 44.4 ( ) 51.9 ( ) 65.5 ( ) 51.5 ( ) 65.7 ( ) 39.8 ( ) 58.8 ( ) 73.9 ( ) 72.7 ( ) 15.4 ( ) 36.6 ( ) 57.5 ( ) 48.3 ( ) 60.7 ( ) 95.0 ( ) 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.

125 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 % (95% CI) 95.0 ( ) 75.8 ( ) 45.8 ( ) 38.8 ( ) 31.1 ( ) 63.3 ( ) 67.0 ( ) 64.0 ( ) 36.9 ( ) 77.8 ( ) 68.4 ( ) 47.7 ( ) 46.5 ( ) 46.0 ( ) 64.2 ( ) 51.6 ( ) 98.7 ( ) 65.8 ( ) 36.0 ( ) 30.9 ( ) 53.6 ( ) 50.3 ( ) 58.4 ( ) 43.7 ( ) 72.0 ( ) 59.3 ( ) 35.0 ( ) 56.5 ( ) 54.6 ( ) 61.1 ( ) 77.8 ( ) 75.0 ( ) 51.0 ( ) 48.0 ( ) 29.3 ( ) 51.0 ( ) 52.2 ( ) 55.4 ( ) 48.5 ( ) 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.

126 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 ( ) 75.5 ( ) 65.4 ( ) 68.5 ( ) 33.3 ( ) 70.9 ( ) 30.3 ( ) 62.7 ( ) 59.2 ( ) 61.2 ( ) 73.3 ( ) 18.0 ( ) 70.6 ( ) 33.3 ( ) 60.8 ( ) 40.7 ( ) 57.4 ( ) 55.9 ( ) 63.5 ( ) 54.7 ( ) 50.5 ( ) 72.9 ( ) 55.5 ( ) 54.0 ( ) % (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 56.8 ( ) 57.1 ( ) 80.0 ( ) 23.7 ( ) 93.1 ( ) 80.0 ( ) 50.0 ( ) 57.8 ( ) 71.1 ( ) 60.0 ( ) 61.3 ( ) 61.5 ( ) 66.7 ( ) 63.4 ( ) 67.9 ( ) 58.5 ( ) 54.5 ( ) 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)

127 ( 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.

128 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 % (95% CI) 71.0 ( ) 50.0 ( ) 58.5 ( ) 60.6 ( ) 65.4 ( ) 56.5 ( ) 79.3 ( ) 75.8 ( ) 84.0 ( ) 61.7 ( ) 58.6 ( ) 32.5 ( ) 62.5 ( ) 43.8 ( ) 54.2 ( ) 63.5 ( ) 32.7 ( ) 68.4 ( ) 52.8 ( ) 78.3 ( ) 36.6 ( ) 47.2 ( ) 73.9 ( ) 85.8 ( ) 58.4 ( ) 80.0 ( ) 80.0 ( ) 61.4 ( ) 70.3 ( ) 64.4 ( ) 65.4 ( ) 65.2 ( ) 54.1 ( ) 54.3 ( ) 61.1 ( ) 52.4 ( ) 79.2 ( ) 47.9 ( ) 43.2 ( ) 38.0 ( ) 53.3 ( ) 23.7 ( ) 47.1 ( ) 23.7 ( ) 34.1 ( ) 79.1 ( ) 66.7 ( ) 58.4 ( ) 71.4 ( ) 53.2 ( ) 56.5 ( ) 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.

129 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 ( ) Cuzick ( ) Tawfik El Mansi ( ) Sargent ( ) Powell ( ) Cuschieri ( ) Howell Jones ( ) 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.

130 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 ( ) Chen ( ) Plunkett ( ) Liu ( ) Brestovac ( ) Stevens ( ) de Sanjose ( ) Papua N. Guinea Tabone ( ) 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.

131 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 Low grade lesions HPV type High grade lesions HPV type Cervical Cancer HPV type Prevalence (%) Prevalence (%) 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.

132 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 Squamous cell carcinoma HPV type Adenocarcinoma HPV type Unespecified HPV type Prevalence (%) Prevalence (%) 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.

133 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 , ( ) 43, ( ) 44, ( ) 53, ( ) , ( ) 42, ( ) 43, ( ) 52, ( ) , ( ) 40, ( ) 42, ( ) 46, ( ) , ( ) 40, ( ) 42, ( ) 47, ( ) , ( ) 35, ( ) 39, ( ) 43, ( ) , ( ) 33, ( ) 38, ( ) 40, ( ) , ( ) 35, ( ) 39, ( ) 42, ( ) , ( ) 31, ( ) 38, ( ) 39, ( ) , ( ) 33, ( ) 39, ( ) 44, ( ) , ( ) 33, ( ) 37, ( ) 39, ( ) , ( ) 36, ( ) 39, ( ) 44, ( ) , ( ) 33, ( ) 36, ( ) 40, ( ) , ( ) 31, ( ) 32, ( ) 36, ( ) , ( ) 17, ( ) 20, ( ) 28, ( ) , ( ) 24, ( ) 29, ( ) 31, ( ) , ( ) 31, ( ) 35, ( ) 37, ( ) , ( ) 14, ( ) 16, ( ) 21, ( ) , ( ) 23, ( ) 23, ( ) 30, ( ) , ( ) 22, ( ) 21, ( ) 26, ( ) , ( ) 22, ( ) 23, ( ) 28, ( ) NON-ONCOGENIC HPV TYPES 6 418, ( ) 31, ( ) 31, ( ) 35, ( ) , ( ) 31, ( ) 30, ( ) 35, ( ) 30 56, ( ) 3, ( ) 1, ( ) 14, ( ) , ( ) 6, ( ) 8, ( ) 20, ( ) , ( ) 10, ( ) 9, ( ) 21, ( ) , ( ) 9, ( ) 6, ( ) 23, ( ) , ( ) 5, ( ) 3, ( ) 19, ( ) , ( ) 5, ( ) 9, ( ) 20, ( ) , ( ) 8, ( ) 8, ( ) 23, ( ) , ( ) 6, ( ) 7, ( ) 20, ( ) , ( ) 5, ( ) 6, ( ) 5, ( ) , ( ) 15, ( ) 16, ( ) 17, ( ) , ( ) 6, ( ) 6, ( ) 7, ( ) , ( ) 5, ( ) 6, ( ) 8, ( ) , ( ) 2, ( ) 1, ( ) 15, ( ) , ( ) 6, ( ) 6, ( ) 7, ( ) , ( ) 5, ( ) 6, ( ) 8, ( ) , ( ) 6, ( ) 6, ( ) 6, ( ) , ( ) 4, ( ) 5, ( ) 6, ( ) 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.

134 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, ( ) 36, ( ) 6, ( ) 11, ( ) 18 52, ( ) 36, ( ) 6, ( ) 11, ( ) 31 46, ( ) 32, ( ) 5, ( ) 9, ( ) 33 47, ( ) 33, ( ) 5, ( ) 10, ( ) 35 43, ( ) 30, ( ) 4, ( ) 8, ( ) 39 40, ( ) 29, ( ) 4, ( ) 7, ( ) 45 42, ( ) 30, ( ) 4, ( ) 8, ( ) 51 39, ( ) 29, ( ) 4, ( ) 7, ( ) 52 44, ( ) 31, ( ) 4, ( ) 8, ( ) 56 39, ( ) 28, ( ) 4, ( ) 7, ( ) 58 44, ( ) 32, ( ) 4, ( ) 9, ( ) 59 40, ( ) 29, ( ) 4, ( ) 7, ( ) 68 36, ( ) 26, ( ) 4, ( ) 5, ( ) 53 31, ( ) 23, ( ) 3, ( ) 5, ( ) 66 37, ( ) 28, ( ) 4, ( ) 6, ( ) 67 21, ( ) 16, ( ) 1, ( ) 3, ( ) 70 30, ( ) 23, ( ) 2, ( ) 5, ( ) 73 26, ( ) 20, ( ) 2, ( ) 4, ( ) 82 28, ( ) 21, ( ) 2, ( ) 4, ( ) NON-ONCOGENIC HPV TYPES 6 35, ( ) 12, ( ) 1, ( ) ( ) 11 35, ( ) 27, ( ) 3, ( ) 5, ( ) 30 14, ( ) 11, ( ) 1, ( ) 1, ( ) 34 20, ( ) 15, ( ) 2, ( ) 2, ( ) 42 23, ( ) 18, ( ) 2, ( ) 3, ( ) 44 20, ( ) 17, ( ) 2, ( ) 2, ( ) 54 23, ( ) 18, ( ) 2, ( ) 3, ( ) 62 5, ( ) 2, ( ) ( ) 2, ( ) 69 17, ( ) 14, ( ) 1, ( ) 2, ( ) 71 7, ( ) 4, ( ) ( ) 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.

135 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.

136 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 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: ). 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) ( ) HPV 16 (67.3%) HPV 18 (3.8%) HPV 35 (3.8%) HPV 56 (1.9%) HPV 58 (1.9%) ( ) HPV 16 (77.1%) HPV 52 (13.3%) HPV 6 (10.5%) HPV 54 (9.5%) HPV 11 (5.7%) ( ) HPV 16 (82.3%) HPV 6 (3.1%) HPV 33 (3.1%) HPV 18 (2.1%) HPV 58 (2.1%) ( ) ( ) HPV 16 (81.8%) ( ) HPV 16 (81.0%) HPV 33 (5.1%) HPV 18 (2.2%) HPV 58 (0.7%) (Continued on next page)

137 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, ( ) 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) ( ) HPV 16 (75.4%) HPV 11 (7.4%) HPV 6 (6.0%) HPV 18 (6.0%) HPV 52 (5.2%) ( ) HPV 16 (89.0%) HPV 39 (4.1%) HPV 33 (2.7%) HPV 6 (1.4%) HPV 11 (1.4%) ( ) HPV 16 (63.0%) HPV 18 (7.4%) ( ) HPV 16 (90.9%) HPV 31 (54.5%) HPV 44 (36.4%) HPV 52 (36.4%) HPV 58 (36.4%) ( ) HPV 16 (94.5%) HPV 11 (2.2%) HPV 31 (2.2%) HPV 35 (2.2%) HPV 18 (1.1%) ( ) HPV 16 (74.5%) HPV 33 (6.4%) HPV 18 (2.1%) HPV 31 (2.1%) HPV 45 (2.1%) ( ) HPV 16 (42.9%) ( ) HPV 16 (66.0%) HPV 58 (6.4%) HPV 35 (2.1%) ( ) HPV 16 (70.1%) HPV 33 (5.7%) HPV 58 (3.2%) HPV 18 (2.5%) HPV 31 (1.9%) ( ) ( ) HPV 16 (69.4%) HPV 18 (34.7%) HPV 33 (2.8%) ( ) - Crook 1991 (UK) SBH, PCR-TS (HPV 16,18) ( ) HPV 16 (76.0%) HPV 18 (8.0%) Ogunbiyi 1993 PCR- E6/E7, TS (HPV 16) ( ) HPV 16 (73.9%) (UK) (Continued on next page)

138 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) ( ) 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, ( ) - (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) ( ) 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, ( ) - (USA) Palefsky 1991 PCR primers for 6/11, 16, 18, 31, ( ) - (USA) 33 and 35 Shroyer 1995 PCR MY09/11 and SBH (HPV6, ( ) - (USA) 11, 16, 18, 31 and 33) Zaki 1992 (USA) PCR primers for 6, 11, 16, 18 and ( ) - 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) ( ) 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) ( ) HPV 16 (33.3%) HPV 31 (19.0%) HPV 18 (4.8%) PCR ( ) - 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) ( ) HPV 16 (35.5%) HPV 18 (16.1%) HPV 58 (16.1%) HPV 42 (9.7%) HPV 45 (9.7%) ( ) HPV 16 (52.7%) HPV 18 (32.4%) HPV 31 (31.1%) HPV 6 (28.4%) HPV 52 (27.0%) (Continued on next page)

139 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, ( ) 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) ( ) HPV 16 (79.2%) HPV 6 (8.3%) HPV 33 (8.3%) HPV 31 (4.2%) HPV 40 (4.2%) ( ) HPV 16 (67.9%) ( ) HPV 16 (69.0%) HPV 18 (23.8%) HPV 68 (11.9%) HPV 73 (11.9%) HPV 26 (9.5%) ( ) HPV 16 (70.8%) HPV 11 (12.5%) HPV 6 (8.3%) HPV 58 (4.2%) ( ) 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 ( ) 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) ( ) ( ) HPV 16 (58.8%) HPV 31 (17.6%) HPV 18 (11.8%) HPV 53 (11.8%) HPV 58 (11.8%) ( ) HPV 16 (43.3%) HPV 33 (36.7%) HPV 51 (36.7%) HPV 58 (36.7%) HPV 6 (33.3%) ( ) HPV 16 (50.0%) HPV 58 (35.0%) HPV 6 (30.0%) HPV 31 (30.0%) HPV 43 (30.0%) (Continued on next page)

140 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) ( ) HPV 16 (39.3%) HPV 6 (25.0%) HPV 11 (21.4%) HPV 18 (21.4%) HPV 51 (21.4%) ( ) HPV 16 (55.1%) HPV 58 (34.8%) HPV 33 (29.0%) HPV 51 (23.2%) HPV 18 (21.7%) ( ) HPV 16 (59.1%) HPV 6 (34.1%) HPV 66 (31.8%) HPV 52 (29.5%) HPV 53 (29.5%) ( ) HPV 16/18 (23.5%) ( ) 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) ( ) HPV 16 (66.7%) PCR- E6/E7,TS (HPV 16) ( ) 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) ( ) HPV 16 (37.1%) ( ) 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.

141 Figure 84: Ten most frequent HPV types among cases of anal cancer in Africa compared to the World Africa (a) World (b) th* th* th* 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) 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.

142 Figure 86: Ten most frequent HPV types among cases of anal cancer in Asia compared to the World Asia (a) World (b) 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) 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.

143 Figure 88: Ten most frequent HPV types among cases of anal cancer in Oceania compared to the World Oceania World (a) 1st* nd* rd* th* th* 6th* No data available th* th* th* th* 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* nd* rd* th* th* 6th* No data available th* th* th* th* 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.

144 Figure 90: Ten most frequent HPV types among cases of AIN 2/3 in Americas compared to the World Americas (a) World (b) th* th* th* th* th* th* th* 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* nd* rd* th* th* 6th* No data available th* th* th* th* 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.

145 Figure 92: Ten most frequent HPV types among cases of AIN 2/3 in Europe compared to the World Europe (a) World (b) 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* nd* rd* th* th* 6th* No data available th* th* th* th* 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.

146 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: ). 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/ ( ) HPV 16 (58.3%) HPV 18 (4.2%) HPV 45 (4.2%) HPV 52 (4.2%) ( ) HPV 16 (18.1%) HPV 18 (1.6%) HPV 44 (1.6%) HPV 45 (1.1%) HPV 52 (1.1%) ( ) ( ) HPV 16 (80.0%) HPV 33 (5.0%) HPV 35 (5.0%) HPV 52 (5.0%) HPV 54 (5.0%) ( ) HPV 16 (25.9%) HPV 33 (16.5%) ( ) ( ) ( ) - Guo 1996 (China) PCR HPV6/11, 16, ( ) - Ngan 1999 (China) L1-PCR for HPV16 and ( ) - (Continued on next page)

147 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, 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) ( ) HPV 16 (23.9%) HPV 33 (8.7%) HPV 6 (2.2%) HPV 42 (2.2%) HPV 45 (2.2%) ( ) HPV 16 (24.5%) HPV 33 (6.1%) HPV 42 (2.0%) HPV 45 (2.0%) ( ) HPV 16 (40.0%) HPV 33 (20.0%) HPV 56 (10.0%) PCR-E6/E7, TS (HPV 16) ( ) 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) ( ) HPV 16 (21.0%) HPV 18 (4.8%) HPV 33 (4.8%) ( ) HPV 16 (28.2%) HPV 33 (3.8%) ( ) HPV 16 (36.7%) HPV 33 (11.7%) HPV 73 (3.3%) HPV 6 (1.7%) HPV 51 (1.7%) ( ) HPV 16 (13.8%) HPV 33 (1.2%) HPV 18 (0.6%) HPV 31 (0.6%) HPV 44 (0.4%) ( ) HPV 16 (25.7%) HPV 18 (12.2%) HPV 33 (1.4%) ( ) HPV 16 (43.6%) HPV 33 (2.6%) ( ) HPV 16 (39.6%) HPV 33 (8.3%) HPV 31 (4.2%) HPV 18 (2.1%) ( ) HPV 16 (30.6%) HPV 33 (5.6%) HPV 6 (2.8%) HPV 11 (2.8%) HPV 18 (2.8%) ( ) HPV 16 (25.0%) ( ) HPV 16 (35.5%) HPV 18 (2.7%) HPV 33 (1.1%) HPV 6 (0.5%) HPV 11 (0.5%) (Continued on next page)

148 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) ( ) - PCR-,TS (HPV 6, 11, 16, 18) ( ) HPV 16 (36.4%) HPV 11 (9.1%) HPV 18 (9.1%) Pilotti 1995 (Italy) PCR-,TS (HPV 6, 11, 16, 18) ( ) HPV 16 (43.5%) HPV 18 (4.3%) Koyamatsu 2003 E7 ( bp) for HPV16, HPV ( ) - (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) ( ) ( ) ( ) HPV 16 (25.3%) HPV 18 (2.8%) HPV 45 (2.5%) HPV 33 (2.2%) HPV 6 (1.2%) ( ) - PCR-CPI/IIG, sequencing ( ) 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, and CP6108) Liss 1998 (Poland) PCR-MY09/11, TS(HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 52, 58) ( ) HPV 16 (10.2%) HPV 33 (5.6%) HPV 18 (1.9%) ( ) HPV 16 (15.4%) HPV 33 (5.4%) HPV 18 (2.3%) HPV 52 (1.5%) HPV 54 (1.5%) ( ) ( ) HPV 16 (27.3%) HPV 33 (3.6%) HPV 18 (2.7%) HPV 6 (1.4%) HPV 39 (1.4%) ( ) HPV 16 (20.5%) HPV 11 (11.4%) HPV 52 (4.5%) HPV 55 (4.5%) HPV 58 (4.5%) ( ) HPV 16 (11.4%) HPV 6 (2.3%) HPV 58 (2.3%) ( ) HPV 16 (16.7%) (Continued on next page)

149 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) ( ) HPV 16 (14.3%) HPV 33 (2.0%) HPV 31 (1.0%) HPV 51 (1.0%) HPV 52 (1.0%) ( ) HPV 59 (10.0%) HPV 6 (3.3%) HPV 16 (3.3%) HPV 18 (3.3%) PCR-L1,TS (HPV 16, 18) ( ) 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 ( ) HPV 16 (13.0%) HPV 33 (3.3%) HPV 6 (2.2%) HPV 51 (1.1%) ( ) HPV 16 (23.8%) HPV 33 (3.8%) HPV 18 (1.5%) HPV 56 (0.8%) HPV 59 (0.8%) ( ) HPV 16 (21.3%) HPV 18 (2.7%) HPV 33 (2.7%) HPV 52 (1.3%) ( ) HPV 16 (36.0%) HPV 33 (8.0%) HPV 35 (8.0%) HPV 18 (4.0%) HPV 58 (4.0%) ( ) HPV 16 (27.3%) HPV 33 (18.2%) HPV 18 (9.1%) Gasco 2002 (UK) PCR- E6/E7,TS (HPV 16) ( ) HPV 16 (36.1%) Ogunbiyi 1994 (UK) PCR-GP5+/6+, TS (HPV 6, 11, 16, 18, 31, 33) ( ) HPV 16 (75.8%) Bloss 1991 (USA) SBH (HPV6, 11, 16, 18 and 31) and E6/E7 primers ( ) - Bodelon 2012 PCR (HPV 16/18) ( ) 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, ( ) ( ) HPV 16 (34.0%) HPV 33 (8.0%) HPV 6 (2.0%) HPV 18 (2.0%) HPV 44 (2.0%) ( ) HPV 16 (48.3%) HPV 33 (10.2%) HPV 52 (2.8%) HPV 18 (1.7%) HPV 31 (1.1%) ( ) - (Continued on next page)

150 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, ( ) - Madeleine 1997 MY09/11 (HPV6/11, 16, 18/45, ( ) - (USA) 31/33/52) or RFLP Monk 1995 (USA) MY09/11, GP5/GP6, SBH and ( ) - type-specific for HPV6, 16, 18 Nuovo 1991 (USA) SBH and probes for HPV6, 11, ( ) - 16, 18, 31, 33 and 35 Pinto 1999 (USA) PCR-RFLP MY09/ ( ) - 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, CP ( ) ( ) - Tate 1994 (USA) MY09/ ( ) - Riethdorf (World) 2004 f PCR-GP5+/6+, PCR L1-Consensus primer, TS (HPV 16) ( ) 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) ( ) HPV 16 (80.0%) HPV 6 (5.0%) HPV 18 (5.0%) HPV 33 (5.0%) HPV 35 (5.0%) ( ) HPV 16 (68.2%) HPV 26 (4.5%) HPV 33 (4.5%) HPV 52 (4.5%) HPV 82 (4.5%) HC ( ) - 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) ( ) HPV 16 (70.8%) HPV 18 (6.3%) HPV 45 (4.2%) HPV 6 (2.1%) HPV 11 (2.1%) (Continued on next page)

151 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) ( ) HPV 16 (70.0%) HPV 33 (30.0%) PCR-E6/E7, TS (HPV 16) ( ) 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) ( ) HPV 16 (78.2%) HPV 33 (10.9%) ( ) HPV 16 (69.6%) HPV 33 (11.2%) HPV 18 (2.2%) HPV 6 (1.6%) HPV 52 (1.3%) ( ) HPV 16 (79.8%) HPV 33 (10.7%) HPV 31 (4.2%) HPV 18 (3.0%) ( ) HPV 16 (79.3%) HPV 6 (13.8%) HPV 18 (3.4%) ( ) HPV 16 (64.3%) HPV 18 (7.1%) HPV 51 (7.1%) HPV 52 (7.1%) HPV 53 (7.1%) ( ) HPV 16 (36.0%) HPV 35 (8.0%) HPV 33 (4.0%) HPV 52 (4.0%) ( ) HPV 16 (57.1%) HPV 33 (8.7%) HPV 6 (4.8%) HPV 31 (4.0%) HPV 11 (1.6%) PCR-CPI/IIG, sequencing ( ) 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) ( ) HPV 16 (40.6%) HPV 6 (6.3%) HPV 31 (6.3%) HPV 33 (3.1%) ( ) HPV 16 (78.8%) HPV 33 (15.4%) HPV 18 (1.9%) ( ) 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) ( ) HPV 16 (41.7%) PCR-GP5+/6+, TS (HPV 6, 11, 16, 18, 31, 33) ( ) HPV 16 (76.9%) HPV 31 (3.8%) HPV 33 (3.8%) (Continued on next page)

152 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 ( ) 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), CP ( ) HPV 16 (67.3%) HPV 33 (16.3%) HPV 6 (10.2%) HPV 18 (2.0%) HPV 31 (2.0%) ( ) HPV 16 (73.7%) HPV 33 (5.3%) HPV 42 (5.3%) HPV 84 (5.3%) PCR-SPF10, LiPA (HPV 16) ( ) 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) ( ) HPV 16 (42.9%) ( ) HPV 16 (83.3%) HPV 18 (5.6%) HPV 33 (5.6%) ( ) HPV 16 (80.9%) HPV 33 (8.8%) HPV 59 (2.9%) HPV 18 (1.5%) IHS, RT-PCR, TS (HPV 16) ( ) 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) ( ) HPV 16 (91.2%) HPV 18 (5.9%) HPV 35 (5.9%) HPV 11 (2.9%) HPV 33 (2.9%) ( ) 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.

153 Figure 94: Ten most frequent HPV types among cases of vulvar cancer in Africa compared to the World Africa (a) World (b) th* th* th* th* th* th* 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) 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.

154 Figure 96: Ten most frequent HPV types among cases of vulvar cancer in Asia compared to the World Asia (a) World (b) 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) 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.

155 Figure 98: Ten most frequent HPV types among cases of vulvar cancer in Oceania compared to the World Oceania (a) World (b) 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* nd* rd* th* th* 6th* No data available th* th* th* th* 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.

156 Figure 100: Ten most frequent HPV types among cases of VIN 2/3 in Americas compared to the World Americas (a) World (b) 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) th* th* th* th* 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.

157 Figure 102: Ten most frequent HPV types among cases of VIN 2/3 in Europe compared to the World Europe (a) World (b) 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) 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.

158 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: ). 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 ( 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) ( ) HPV 16 (31.6%) HPV 45 (10.5%) HPV 18 (5.3%) HPV 31 (5.3%) HPV 33 (5.3%) ( ) HPV 16 (42.4%) HPV 31 (5.8%) HPV 18 (4.2%) HPV 33 (4.2%) HPV 52 (3.1%) ( ) HPV 16 (41.3%) HPV 33 (4.3%) HPV 68 (4.3%) HPV 18 (2.2%) HPV 26 (2.2%) ( ) HPV 16 (77.8%) HPV 33 (7.4%) HPV 18 (3.7%) HPV 39 (3.7%) HPV 45 (3.7%) ( ) HPV 16 (47.4%) HPV 18 (3.3%) HPV 73 (3.3%) HPV 33 (2.6%) HPV 56 (2.6%) ( ) ( ) HPV 16 (47.4%) HPV 33 (5.3%) HPV 18 (3.5%) HPV 31 (3.5%) HPV 52 (3.5%) ( ) HPV 16 (33.3%) HPV 31 (28.6%) HPV 40 (14.3%) HPV 6 (9.5%) HPV 18 (9.5%) (Continued on next page)

159 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, ( ) HPV 16 (56.3%) HPV 52 (6.3%) HPV 35 (3.1%) HPV 51 (3.1%) HPV 58 (3.1%) ( ) HPV 16 (37.7%) HPV 18 (2.9%) HPV 31 (2.9%) HPV 33 (2.9%) HPV 52 (2.9%) ( ) - MY09/11 for 6/11, 16, 18/45, ( ) - E6 for HPV16 and HPV ( ) - 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) ( ) HPV 16 (46.3%) HPV 18 (6.3%) HPV 52 (6.3%) HPV 73 (6.3%) HPV 6 (3.8%) ( ) HPV 16 (53.8%) HPV 52 (15.4%) HPV 59 (15.4%) HPV 45 (7.7%) HPV 73 (7.7%) ( ) HPV 16 (39.5%) HPV 58 (10.5%) HPV 33 (7.5%) HPV 39 (7.0%) HPV 52 (6.0%) ( ) HPV 16 (65.6%) HPV 33 (7.3%) HPV 18 (5.2%) HPV 52 (3.1%) HPV 73 (3.1%) ( ) HPV 16 (63.6%) (Continued on next page)

160 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) ( ) HPV 16 (64.7%) HPV 6 (11.8%) HPV 42 (11.8%) HPV 56 (11.8%) HPV 31 (5.9%) ( ) HPV 16 (20.0%) HPV 33 (20.0%) Frega 2007 (Italy) TS (HPV 16, 18) ( ) HPV 16 (86.7%) HPV 18 (13.3%) So 2009 (Korea, HC ( ) - Rep.) Rhodes 2014 HC ( ) - (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) ( ) 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) th* th* th* th* 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.

161 Figure 105: Ten most frequent HPV types among cases of vaginal cancer in Americas compared to the World Americas (a) World (b) 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) 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.

162 Figure 107: Ten most frequent HPV types among cases of vaginal cancer in Europe compared to the World Europe (a) World (b) 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) th* th* th* th* th* 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.

163 Figure 109: Ten most frequent HPV types among cases of VaIN 2/3 in Africa compared to the World Africa World (a) 1st* nd* rd* th* th* 6th* No data available th* th* th* th* 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) 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.

164 Figure 111: Ten most frequent HPV types among cases of VaIN 2/3 in Asia compared to the World Asia (a) World (b) th* th* th* th* th* 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) 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.

165 Figure 113: Ten most frequent HPV types among cases of VaIN 2/3 in Oceania compared to the World Oceania (a) World (b) th* th* th* th* th* 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.

166 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, ( ) - PCR Type specific for: 6,11, ( ) - and 18 + Primers for wide range including 16,18,31,33,35,52 PCR SPF10 + INO-LIPA ( ) - 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) ( ) ( ) HPV 16 (65.4%) HPV 18 (3.8%) HPV 31 (3.8%) ( ) HPV 16 (45.5%) HPV 33 (4.9%) HPV 18 (4.1%) HPV 45 (3.3%) HPV 6 (0.8%) ( ) HPV 16 (47.2%) HPV 59 (5.6%) HPV 6 (2.8%) HPV 11 (2.8%) HPV 33 (2.8%) ( ) 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: ( ) - 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) ( ) HPV 16 (40.4%) HPV 11 (10.6%) HPV 35 (2.1%) ( ) HPV 11 (39.0%) HPV 6 (19.5%) HPV 16 (18.3%) HPV 53 (11.0%) HPV 33 (2.4%)

167 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) ( ) ( ) 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 ( ) - PCR Type specific for HPV16/ ( ) - 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) ( ) HPV 16 (53.8%) HPV 6 (3.4%) HPV 33 (2.1%) HPV 11 (0.7%) HPV 31 (0.7%) ( ) HPV 16 (25.0%) HPV 5 (5.6%) ( ) HPV 16 (17.6%) PCR-,TS (HPV 6/11, 16, 18) ( ) 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) ( ) HPV 16 (45.5%) HPV 18 (18.2%) HPV 53 (9.1%) ( ) HPV 16 (42.6%) HPV 18 (3.3%) HPV 35 (1.6%) ( ) ( ) ( ) HPV 16 (11.5%) ( ) HPV 16 (61.8%) HPV 11 (3.9%) HPV 31 (3.9%) HPV 18 (1.3%) HPV 33 (1.3%) PCR Specific for HPV ( ) - 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) ( ) HPV 16 (28.9%) HPV 18 (3.6%) HPV 6 (2.4%) HPV 45 (2.4%) HPV 33 (1.2%) ( ) HPV 16 (22.2%) HPV 18 (1.8%) HPV 45 (1.8%) HPV 33 (1.2%) HPV 56 (0.6%) (Continued on next page)

168 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 ( ) HPV 16 (22.8%) HPV 6 (3.0%) HPV 18 (2.0%) HPV 11 (1.5%) HPV 35 (1.5%) ( ) HPV 16 (55.0%) HPV 11 (30.0%) HPV 18 (10.0%) HPV 45 (5.0%) HPV 6 (2.5%) ( ) HPV 16 (26.9%) HPV 58 (3.8%) HPV 6 (2.6%) HPV 33 (1.3%) HPV 45 (1.3%) ( ) HPV 16 (45.8%) HPV 26 (4.2%) HPV 39 (4.2%) ( ) HPV 16 (65.3%) HPV 18 (8.2%) ( ) HPV 16 (60.3%) HPV 18 (27.2%) HPV 6 (9.3%) HPV 45 (2.0%) HPV 52 (2.0%) PCR SPF10, ISH ( ) - 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) ( ) HPV 16 (58.8%) HPV 6 (11.8%) HPV 18 (11.8%) HPV 33 (5.9%) ( ) HPV 16 (42.3%) HPV 56 (11.5%) HPV 52 (7.7%) HPV 6 (3.8%) HPV 18 (3.8%) ( ) HPV 16 (45.1%) HPV 11 (9.8%) HPV 6 (5.9%) HPV 45 (5.9%) HPV 31 (4.9%) ( ) HPV 16 (40.5%) HPV 18 (4.8%) PCR MY09/ ( ) - 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 ( ) ( ) - (Continued on next page)

169 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) ( ) 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) ( ) HPV 16 (62.8%) HPV 18 (9.3%) HPV 33 (2.3%) HPV 73 (2.3%) ( ) HPV 16 (61.5%) HPV 18 (23.1%) HPV 11 (15.4%) HPV 53 (15.4%) HPV 56 (15.4%) ( ) HPV 16 (100.0%) ( ) HPV 16 (71.0%) HPV 18 (29.0%) HPV 33 (6.5%) HPV 6 (4.8%) HPV 11 (3.2%) ( ) HPV 16 (39.3%) HPV 6 (21.4%) HPV 31 (7.1%) HPV 33 (7.1%) HPV 45 (7.1%) ( ) 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.

170 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, 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.

171 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+/ ( ) ( ) ( ) General population ( ) Husbands of control women ( ) Corona and shaft PCR-GP5+/6+ University students ( ) 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 ( ) ( ) ( ) Military conscripts ( ) Voluntary conscripts Mean ( ) 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 ( ) ( ) Mean ( ) ( ) ( ) HC2 HR, LR University students ( ) PCR-PGMY09/MY11 and HMB01 PCR-GP5+/6+ Men working in the fishing industry Men screened to participate in an RCT of male circumcision ( ) ( ) PCR-SPF10 Male students Median ( ) (Continued on next page)

172 ( 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 BPCO ( ) Military conscripts ( ) HC2 HR University students >= ( ) PCR-BGH 20 and BPCO4 PCR-PGMY09/11 and GP5/6+ PCR-PGMY09/11 Military conscripts ( ) 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 ( ) Mean ( ) ( ) HC2 HR University students >= ( ) 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 ( ) ( ) ( ) ( ) ( ) Mean ( ) ( ) Median 31 (IQR=27-38) Median 31 (IQR=27-38) ( ) ( ) (Continued on next page)

173 ( 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= ( ) ( ) Military conscripts ( ) Army conscripts with normal epithelium Men from the general population Husbands of control women ( ) Mean ( ) ( ) University students ( ) PCR-PGMY09/11 General population ( ) 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 ( ) ( ) PCR-PGMY09/11 University population Mean ( ) 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 ( ) ( ) ( ) 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 Reference publications: 1) Dunne EF, J Infect Dis 2006; 194: ) 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: 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

174 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 ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Anus PCR-DBH HIV+ >= ( ) 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= ) 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) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) (Continued on next page)

175 ( 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) ( ) China Tang 2006 Urethral meatus PCR-MY09/11 STD clinic attendees ( ) 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= ( ) HIV+ MSM >= ( ) 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= Heterosexual men Median 20 (15-24) HIV- MSM Median 22 (16-27) HIV- MSM Median 22 (16-27) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) STD clinic attendees >= ( ) 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 ( ) Mean ( ) Anal canal PCR-MY09/11 HIV+ MSM ( ) Anal canal PCR-PapilloCheck HIV+ MSM Median 45 ( ) 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 ( ) ( ) ( ) Mean ( ) ( ) ( ) Mean ( ) (Continued on next page)

176 ( 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 ( ) ( ) ( ) Anal canal PCR-MY09/11 HIV+ MSM ( ) 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 ( ) ( ) ( ) ( ) ( ) Anal canal PCR-MY09/11 HIV- MSM ( ) 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) ( ) ( ) HC2 HR, LR STD clinic attendees ( ) Anal canal PCR-PGMY09/11 HIV- MSM from organized health care systems, factories and military Urethral meatus PCR-L1 Partners of women with CIN ( ) ( ) Anus PCR-PGMY09/11 HIV+ MSM ( ) 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 ( ) ( ) ( ) ( ) ( ) ( ) (Continued on next page)

177 ( 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) ( ) ( ) Anus PCR-PGMY09/11 HIV+ MSM ( ) 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= ) Median 37.6 (IQR= ) ( ) ( ) ( ) Median 45.6 (IQR= ) ( ) ( ) ( ) STD clinic attendees Mean ( ) MSM STD clinic attendees MSW STD clinic attendees ( ) ( ) HIV- MSM ( ) HIV- MSM Median 37.6 (IQR= ) ( ) HIV+ MSM ( ) HIV+ MSM ( ) Partners of women with CIN MSM STD clinic attendees ( ) ( ) HIV- MSM ( ) Husbands of women with invasive cervical cancer ( ) Anal canal PCR-Linear Array HIV- MSM ( ) Anal canal PCR-Linear Array HIV+ MSM ( ) Slovenia Golob 2014 Penis PCR-Linear Array Men from infertile couples Mean ( ) (Continued on next page)

178 ( 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 ( ) IQR= ( ) Mean ( ) Mean ( ) Mean ( ) ( ) STD clinic attendees ( ) HIV+ MSM attending an outpatient HIV clinic HIV+ Heterosexual men attending an outpatient HIV clinic ( ) ( ) STD clinic attendees ( ) 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) ( ) ( ) ( ) ( ) ( ) ( ) (Continued on next page)

179 ( 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 ( ) IQR= ( ) >= ( ) STD clinic attendees ( ) PCR-GP5+/6+ STD clinic attendees ( ) PCR-TS 6,11,16,18,33 Army conscripts with aceto-white epithelium ( ) Anus PCR-MY09/11 HIV+ MSM ( ) PCR-MY09/11 and GP5+/6+ STD clinic attendees ( ) Anus PCR-MY09/11 HIV- MSM ( ) 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 ( ) Husbands of women with invasive cervical cancer ( ) HIV- MSM >= ( ) HIV+ MSM >= ( ) HIV+ heterosexual men HIV- heterosexual men Urethra PCR-GP5+/6+ Men infected with gonorrhea ( ) ( ) ( ) Lacey 1999 Anal canal PCR-GP5+/6+ HIV+ MSM ( ) 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 ( ) ( ) ( ) ( ) ( ) (Continued on next page)

180 ( 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 ( ) PCR-TS 6,11 STD clinic attendees ( ) 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) ( ) Mean ( ) ( ) HIV+ MSM <40 years ( ) 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 >= ( ) ( ) > ( ) PCR-PGMY09/11 STD clinic attendees ( ) PCR-MY09/11, HMB01, and HC HIV- MSM <40 years ( ) Wiley 2013 Anus PCR-PGMY09/11 HIV- MSM Mean ( ) Moscicki 2003 Anus PCR-MY09/11 and HMB01 High-risk adolescent boys in REACH cohort ( ) Berry 2009 Anal canal PCR-MY09/11 HIV- MSM ( ) 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 ( ) ( ) ( ) Wiley 2013 Anus PCR-PGMY09/11 HIV+ MSM Mean ( ) Critchlow 1998 Palefsky 1998 Anus PCR-MY09/11 HIV- homosexual men Anus PCR-MY09/11 HIV- homosexual or bisexual men Mean ( ) ( ) (Continued on next page)

181 ( 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 ( ) ( ) HIV+ MSM ( ) Berry 2009 Anal canal PCR-MY09/11 HIV+ MSM ( ) 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) ( ) Mean ( ) ( ) ( ) ( ) 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.

182 HPV burden in head and neck 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 ( ) ( ) Dental clinic visitors ( ) 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 ( ) ( ) ( ) ( ) Dental clinic visitors ( ) 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 ( ) ( ) ( ) ( )

183 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 ( ) Canada Noble-Topham 1993 TS-PCR E6/E7 for 6b/11/16/18 Amplification with TS primers (6b/ ) Canada Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) 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 ( ) Hungary Nemes 2006 MY09/MY11 (L1) Hybridization with TS probes ( ) 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 ( ) India Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) India Chaudhary 2010 MY09/MY11 (L1) Amplification with TS primers (16) Iran Saghravanian 2011 GP5+/GP6+ (L1) Amplification with TS primers HPV E6/7 ( ) Ireland Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) Italy Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Japan Shimizu 2004 TS-PCR L1 for ( ) 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 ( ) Japan Chiba 1996 TS-PCR E6/E7 for 6/11/16/18/31/33/52b/58 Restriction enzyme digestion ( b. 58) ( ) ( ) ( Table 27 continued from previous page)

184 ( 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 ( ) 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 ( ) Poland Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) Serbia Kozomara 2005 TS-PCR E6 for 16. L1 for 18. E4 for 31 and E1 for 33 Amplification with TS primers ( ) 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 ( ) Spain Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) Sudan Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) Sweden Dahlgren 2004 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers ( ) and sequencing Taiwan Chang 2003 MY09 (L1) and GP5+/GP6+ (L1) Sequencing Taiwan Chen 2002 MY09/MY11 (L1) Hybridization with TS probes ( ) United States of America Venezuela Lohavanichbutr 2009 Premoli-De-Percoco 2001 MY09/MY11 (L1) and GP5+/GP6+ (L1) Hybridization with Roche LBA ( ) TS-PCR for 6/11/16/18 Hybridization with TS probes ( ) Venezuela Miller 1994 TS-PCR E6 for 16/18 Hybridization with TS probes (16. 18) WOMEN ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( Table 27 continued from previous page)

185 ( 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 ( ) Canada Noble-Topham 1993 TS-PCR E6/E7 for 6b/11/16/18 Amplification with TS primers (6b/ ) Canada Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) 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 ( ) Hungary Nemes 2006 MY09/MY11 (L1) Hybridization with TS probes ( ) 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 ( ) India Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) India Chaudhary 2010 MY09/MY11 (L1) Amplification with TS primers (16) Iran Saghravanian 2011 GP5+/GP6+ (L1) Amplification with TS primers HPV E6/7 ( ) Ireland Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) Italy Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Japan Shimizu 2004 TS-PCR L1 for ( ) 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 ( ) Japan Chiba 1996 TS-PCR E6/E7 for 6/11/16/18/31/33/52b/58 Restriction enzyme digestion ( b. 58) Japan Bhawal 2008 TS-PCR E6 for 16 Electrophoretic analysis using SiHa DNA as positive control for HPV ( ) ( ) ( ) ( Table 27 continued from previous page)

186 ( 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 ( ) 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 ( ) Poland Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) Serbia Kozomara 2005 TS-PCR E6 for 16. L1 for 18. E4 for 31 and E1 for 33 Amplification with TS primers ( ) 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 ( ) Spain Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) Sudan Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) Sweden Dahlgren 2004 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers ( ) and sequencing Taiwan Chang 2003 MY09 (L1) and GP5+/GP6+ (L1) Sequencing Taiwan Chen 2002 MY09/MY11 (L1) Hybridization with TS probes ( ) United States of America Venezuela Lohavanichbutr 2009 Premoli-De-Percoco 2001 MY09/MY11 (L1) and GP5+/GP6+ (L1) Hybridization with Roche LBA ( ) TS-PCR for 6/11/16/18 Hybridization with TS probes ( ) 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) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( Table 27 continued from previous page)

187 ( 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) ( ) China Wen 1997 TS-PCR E6 for 16/18 Hybridization with TS probes (HPV16.18 E6) ( ) ( ) ( ) China Tang 2003 TS-PCR E6 for 16/18/33 Sequencing ( ) 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 ( ) ( ) ( ) ( ) Finland Koskinen 2003 SPF10 (L1) LiPA ( ) 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/ ) 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 ( ) 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 ( ) 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 ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Japan Kojima 2002 TS-PCR L1 and E6 for 38 Sequencing ( ) Japan Shima 2000 TS-PCR E6/E7 for 6/11/16/18/31/33/52b/58 RFLP (16. 18) ( ) ( Table 27 continued from previous page)

188 ( 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 ( ) Japan Tang 2003 TS-PCR E6 for 16/18/33 Sequencing ( ) 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 ( /MM /IS39. 71/CP /CP ) Norway Matzow 1998 GP5+/GP6+ (L1). CPI/CPIIG (E1) and TS-PCR for 6/16/18/31/33 Amplification with TS primers ( ) Norway Mork 2001 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers ( ) 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 ( and 68 - the technique only differentiates 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 ( ) Sweden Mork 2001 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers ( ) Sweden Sand 2000 MY09/MY11 (L1) Amplification with TS primers (6b/ ) Taiwan Yang 2004 MY09/MY11 (L1) Amplification with TS primers ( ) 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 ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( Table 27 continued from previous page)

189 ( 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 ( ) 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 ( ) MY09/MY11 (L1) and GP5+GP6+ (L1) Sequencing L1 consensus primers Hybridization with TS probes ( ) 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 ) MY09/MY11 (L1) and TS-PCR E6 for 6/11/16/18 Hybridization with TS probes ( /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) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 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 ( ) Czech Republic Rotnáglová 2011 GP5+/GP6+ (L1) RBLH ( ) ( ) ( ) ( ) ( Table 28 continued from previous page)

190 ( 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 ( ) 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 ( ) ( ) ( ) ( ) ( ) Norway Hannisdal 2010 GP5+/GP6+ (L1) Sequencing ( ) Spain Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) Sweden Dahlgren 2004 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers ( ) 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 ( ) ( ) ( ) ( ) ( ) Switzerland Lindel 2001 SPF10 (L1) Sequencing ( ) Taiwan Kuo 2008 MY09 (L1) and GP5+/GP6+ (L1) Hybridization with HPV gene chip ( ( ) CP8061.CP8304.L1AE5MM4.MM7.MM8) Taiwan Al-Swiahb 2010 MY09/MY11 (L1) and GP5/GP6 (L1) In situ hybridization with TS probes ( ) 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 ( ) 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) ( ) ( ) ( ) ( ) ( ) ( ) ( Table 28 continued from previous page)

191 ( 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 ( ) 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 ( ) Czech Republic Rotnáglová 2011 GP5+/GP6+ (L1) RBLH ( ) France Charfi 2008 GP5+/GP6+ (L1) and TS-PCR for 6/11/16/18/33 Amplification with TS primers ( ) 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 ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Norway Hannisdal 2010 GP5+/GP6+ (L1) Sequencing ( ) Spain Herrero 2003 GP5+/GP6+ (L1) Hybridization with EIA oligonucleotide probes ( ) Sweden Dahlgren 2004 GP5+/GP6+ (L1) and CPI/CPII (L1) Amplification with TS primers ( ) 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 ( ) ( ) ( ) ( ) ( ) Switzerland Lindel 2001 SPF10 (L1) Sequencing ( ) ( Table 28 continued from previous page)

192 ( 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 ( ( ) CP8061.CP8304.L1AE5MM4.MM7.MM8) Taiwan Al-Swiahb 2010 MY09/MY11 (L1) and GP5/GP6 (L1) In situ hybridization with TS probes ( ) 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 ( ) 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 ( ) Argentina Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Australia Hong 2010 E6-based MT-PCR Amplification with MT-PCR kit ( ) Brazil Cortezzi 2004 GP5+/GP6+ (L1) DBH ( ) 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 ( ) France Fouret 1997 TS-PCR E6 for 16/18/31/33/45 Hybridization with TS probes ( ) Germany Andl 1998 TS-PCR for 6/11/16/18 Hybridization with TS probes ( ) and cycle sequencing system of BRL ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( Table 28 continued from previous page)

193 ( 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 ( ) 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 ( ) RT-PCR E2/E6 for 16 Hybridization with HPV genotyping DNA chip arrayed by multiple oligonucleotide probes ( ) Netherlands Braakhuis 2004 GP5+/GP6+ (L1) and TS-PCR RLBH ( /MM /IS39. 71/CP /CP ) 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 ( and 68 - the technique only differentiates 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) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( Table 28 continued from previous page)

194 ( 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 ( ) United Kingdom Thavaraj 2011 GP5+/GP6+ (L1) Luminex 200 IS ( ) 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 ( ) 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 ( ) GP5+/GP6+ (L1) and TS-PCR Sequencing MY09/MY11 (L1) and HMB01 (L1) DBH (40 HPV types including ) TS-PCR L1 for 16 Amplification with TS primers (16) Kingma 2010 PGMY09/11 (L1) Inno-LiPA ( ) 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 ( /33/35) MY09/MY11 (L1) and HMB01 (L1) Sequencing ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 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)

195 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/ ) ( ) Chile Torrente 2005 MY09/MY11 (L1) RFLP ( ) 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 ( ) 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 ( ) Italy Cattani 1998 MY09/MY11 (L1) and TS-PCR for 33 Hybridization with TS probes ( ) 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 ( ) ( ) ( ) ( ) ( ) Italy Azzimonti 2004 GP5+/GP6+ (L1) Sequencing ( ) Japan Anwar 1993 TS-PCR for 16/18/33 Hybridization with TS probes ( ) Japan Shidara 1994 L1C1/L1C2 RFLP ( ) Norway Lie 1996 CP (E1). MY09/MY11 (L1) and GP5+/GP6+ (L1) Amplification with TS primers ( ) ( ) ( ) ( ) Poland Morshed 2008 SPF10 (L1) LiPA ( ) 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 ( ) WOMEN Canada Fliss 1994 TS-PCR E6/E7 for 6b/11/16/18 Amplification with TS primers (6b/ ) ( ) ( ) ( ) Chile Torrente 2005 MY09/MY11 (L1) RFLP ( ) China Liu 2010 GP5+/GP6+ (L1) and TS-PCR E6/E7 for 16 and E6 for 18 Amplification with TS primers (16. 18) ( ) ( Table 29 continued from previous page)

196 ( 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 ( ) 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 ( ) Italy Cattani 1998 MY09/MY11 (L1) and TS-PCR for 33 Hybridization with TS probes ( ) 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 ( ) ( ) ( ) ( ) Italy Azzimonti 2004 GP5+/GP6+ (L1) Sequencing ( ) Japan Anwar 1993 TS-PCR for 16/18/33 Hybridization with TS probes ( ) Japan Shidara 1994 L1C1/L1C2 RFLP ( ) Norway Lie 1996 CP (E1). MY09/MY11 (L1) and GP5+/GP6+ (L1) Amplification with TS primers ( ) ( ) ( ) ( ) Poland Morshed 2008 SPF10 (L1) LiPA ( ) 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 ( ) UNSPECIFIED Argentina Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Belgium Duray 2011 GP5+/GP6+ (L1) and RT-PCR E6/E7 for L1. 68 TS real-time and consensus PCR E6/E7 ( L1. 68) Brazil Ribeiro 2011 PGMY09/11 (L1) Amplification with TS primers (16) Brazil Miranda 2009 GP5+/GP6+ (L1) Amplification with TS primers ( ) and sequencing China Ma 1998 TS-PCR E6/E7 for 6/11/16/18/31/33/52b/58 SBH ( b. 58) ( ) ( ) ( ) ( ) ( ) ( ) ( Table 29 continued from previous page)

197 ( 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 ( ) 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 ( ) 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 ( ) ( ) ( ) ( ) ( ) ( ) ( ) Finland Koskinen 2003 SPF10 (L1) LiPA ( ) France Fouret 1997 TS-PCR E6 for 16/18/31/33/45 Hybridization with TS probes ( ) ( ) Germany Fischer 2003 L1-CP65F. 66F. 69F. 70F Sequencing ( ) 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 ( ) Greece Gorgoulis 1999 MY09/MY11 (L1) and GP5/GP6 (L1) Amplification with TS primers ( ) and confirmation by DBH with TS probes ( ). 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 ( ) India Jacob 2002 TS-PCR E1 for 6/11/18 and L1 for 16 SBH with TS probes ( ) Italy Badaracco 2000 MY09/MY11 (L1) Amplification with TS primers (6.16) and hybridization with TS probes ( ) 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) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( Table 29 continued from previous page)

198 ( 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 ( ) 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 ( ) 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 ( ) Spain Alvarez Alvarez 1997 TS-PCR E6 and L1 for 6b/16/18 Amplification with TS primers (6b ) 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 ( ) Switzerland Adams 1999 MY09/MY11 (L1) RFLP ( ) Turkey Gungor 2007 SP10296 (L1) Amplification with mpcr kit ( ) United Kingdom Salam 1995 MY09/MY11 (L1) RFLP ( ) United Kingdom Snijders 1996 GP5+/GP6+ (L1) Amplification with TS primers and SBH with TS probes ( ) United Kingdom Anderson 2007 GP5+/GP6+ (L1) Hybridization with Roche LBA ( ) United States of America United States of America Brandwein 1993 Furniss 2007 Perkin Census L1 consensus primers Hybridization with TS probes ( ) TS-PCR L1 for 16 Amplification with TS primers (16) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( Table 29 continued from previous page)

199 ( 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 ) 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 ( ) ( ) ( ) ( ) ( ) 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.

200 5 FACTORS CONTRIBUTING TO CERVICAL CANCER (LAST UPDATE 08 AUG 2013) 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 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, <BR> Available at

201 5 FACTORS CONTRIBUTING TO CERVICAL CANCER (LAST UPDATE 08 AUG 2013) 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 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; <BR> Available at: [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 (POP/DB/Fert/Rev2008).<BR> Available at: [Accessed on July 2013]

202 5 FACTORS CONTRIBUTING TO CERVICAL CANCER (LAST UPDATE 08 AUG 2013) 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> (

203 5 FACTORS CONTRIBUTING TO CERVICAL CANCER (LAST UPDATE 08 AUG 2013) 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 ( 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 Available at:

204 6 REPRODUCTIVE AND SEXUAL BEHAVIOUR (LAST UPDATE 08 AUG 2013) 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

205 7 HPV PREVENTIVE STRATEGIES 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)

206 7 HPV PREVENTIVE STRATEGIES 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 >= 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)

207 7 HPV PREVENTIVE STRATEGIES 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 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 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 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 No visual inspection program 1 Pilot program National program 1 Pilot program No visual inspection program 1 No HPV DNA National program 4 No HPV DNA Dominica No visual inspection program 1 Dominican Republic Ecuador El Salvador (months) 3 No visual inspection program 1 No HPV DNA No HPV DNA Pilot program No visual inspection program National program 1 Pilot program 1 Haiti Honduras Non-populationbased Non-populationbased Non-populationbased Grenada Pilot program 1 No HPV DNA Guatemala Non-populationbased National program 1 No HPV DNA Guyana National program 1 No HPV DNA Non-populationbased Non-populationbased - - Pilot program 1 No HPV DNA Pilot program 1 No HPV DNA (Continued)

208 7 HPV PREVENTIVE STRATEGIES 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) Every 3 years after 3 consecutive annual negative smears ( ) 3 No visual inspection program 1 DNA test No HPV DNA National program 1 National program 1 Pilot program 1 >= National program 1 No HPV DNA Every 3 years National program 1 Pilot program 1 after 3 consecutive annual negative smears ( ) 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 Every 3 years after 2 consecutive annual negative smears (1-1-3) 3 No visual inspection program No visual inspection program 1 No HPV DNA National program 1 > No visual inspection Pilot program 4 program 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 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) No visual inspection program 1 Pilot program 1 (Continued)

209 7 HPV PREVENTIVE STRATEGIES Table 30 Continued Screening Screening Screening HPV Iran No visual inspection program 1 Iraq No visual inspection program 1 Israel No visual inspection program 1 Japan Population-based >= 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 Pilot program 1 Pilot program 1 Indonesia National program 1 No HPV DNA Non-populationbased (call-recall system in few regions on unregular basis) No visual inspection program 1 Korea, DPR No visual inspection program 1 Korea, Republic of National Health insurance Corp. (NHIC) >= 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 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 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 No visual inspection program 1 No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA No HPV DNA National program 1 No HPV DNA (Continued)

210 7 HPV PREVENTIVE STRATEGIES 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 Pilot program 1 Pilot program 9 Turkmenistan Non-populationbased No visual inspection program 1 No HPV DNA Non-populationbased (organized in some pilot regions) 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 No visual inspection program No visual inspection program 1 20 to no limit 2 Every 3 years after 3 consecutive annual negative smears ( ) 2 No visual inspection program 1 Finland Population-based (some counties 25-65) 10 France Germany Non-populationbased Non-populationbased Non-populationbased Non-populationbased Non-populationbased Bulgaria Non-populationbased No visual inspection program 1 Croatia Non-populationbased No visual inspection program 1 Cyprus Non-populationbased - - No visual inspection program 1 Czech Republic Population-based No visual inspection program 1 Denmark Population-based age: 3, No visual inspection age: 5 2 program 1 Estonia Population-based No visual inspection program 1 Non-populationbased (organized in some regions) Non-populationbased Non-populationbased Regional variation: From (20) 25 to not specified No visual inspection program 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 No visual inspection Greece 20 to not specified 2 program 1 Hungary Population-based No visual inspection program 1 Iceland Population-based age: 2, 40-65(69) age: 4 2 Ireland Population-based (regional but nationwide planned) No visual inspection program in age No visual inspection (5 for 45+ age) 2 program 1 (Continued) No HPV DNA No HPV DNA No HPV DNA No HPV DNA

211 7 HPV PREVENTIVE STRATEGIES Table 30 Continued Screening Screening Screening HPV Country name type ages (years) interval VIA DNA test (years) Italy Population-based No visual inspection program 1 Pilot program 1 Portugal Republic of Moldova Romania Russian Federation Russian Federation Latvia Population-based No visual inspection program 1 Lithuania Population-based No visual inspection program 1 Luxembourg Non-populationbased 15 to not 1 2 No visual inspection specified 2 program 1 Macedonia, TFYR Non-populationbased No visual inspection program 1 Malta Non-populationbased - - No visual inspection program 1 Monaco No visual inspection program 1 Montenegro Non-populationbased No visual inspection program 1 Netherlands Population-based No visual inspection program 1 Norway Population-based No visual inspection program 1 Poland Population-based 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) No visual inspection program 1 20 to no limit No visual inspection program No visual inspection program No visual inspection program 1 18 to no limit No visual inspection program 1 San Marino No visual inspection program 1 Serbia Non-populationbased (organized in process of implementation) Non-populationbased (69) No visual inspection program 1 Slovakia No visual inspection program 1 Slovenia Population-based 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 age: 3, No visual inspection Pilot program age: 5 10 program 1 Switzerland Ukraine Non-populationbased Non-populationbased United Kingdom Population-based Regional variation: From (20) 25 to (60) to no limit No visual inspection program No visual inspection program No visual inspection program 1 No HPV DNA No HPV DNA No HPV DNA Oceania Australia Population-based (under review) 6 No visual inspection program 1 Fiji No visual inspection program 1 (Continued) No HPV DNA No HPV DNA

212 7 HPV PREVENTIVE STRATEGIES 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 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 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 Sep;21(9): 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:L 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): 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), 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 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 Oct;45(15): IARC Handbooks of Cancer Prevention Vol. 10: Cervix Cancer Screening. IARC Press. Lyon, 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 Nov 20;30 Suppl 5:F Sander BB, Rebolj M, Valentiner-Branth P, Lynge E. Introduction of human papillomavirus vaccination in Nordic countries (2012) Vaccine, 30 (8): Abdullah F, Su TT. Enhancement of the cervical cancer screening program in Malaysia: a qualitative study. Asian Pac J Cancer Prev. 2010;11(5): 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.

213 7 HPV PREVENTIVE STRATEGIES HPV vaccination 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), 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 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 Available at