Human Papillomavirus and Related Cancers

Human Papillomavirus and Related Cancers Summary Report Update. September 15, 2010. AMERICAS

- ii - Rights c WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre) 2010 All rights reserved. Publications of the WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre) can be obtained from HPV Information Centre Secretariat, Institut Català d Oncologia, Avda. Gran Via, s/n Km 2.7 08907 L Hospitalet de Llobregat (Barcelona, Spain)(e-mail: hpvcentre@iconcologia.net). Requests for permission to reproduce or translate HPV Information Centre publications - whether for sale or for noncommercial distribution - should be addressed to HPV Information Centre Secretariat, at the above address (e-mail: hpvcentre@iconcologia.net). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of 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 by 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. Recommended citation: WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Human Papillomavirus and Related Cancers in Americas. Summary Report 2010. [Date accessed]. Available at www. who. int/ hpvcentre

- iii - Preface Preface to the third edition Since the first edition of the HPV Information Centre, GLOBOCAN, one of the landmark products of the International Agency for Research on Cancer (IARC), serves as the reference source of cancer statistics. GLOBOCAN is a resource that provides on a regular basis the most accurate assessment of global cancer burden in the world. On June 1st 2010, the new edition of GLOBOCAN, GLOBOCAN 2008, was launched and new cancer estimates for 2008 are currently available. This third edition of the HPV Information Centre incorporates the new burden estimates for all HPVrelated cancers. In addition to the publicly available GLOBOCAN 2008, IARC has kindly provided the HPV Information Centre with age-specific estimates for HPV-related cancers which are also presented in this report. Preface to the second edition The available data on the epidemiology and prevention of HPV infection and HPV-related cancers at the country-specific level has grown substantially since the first edition of the HPV Information Centre in 2007. This second edition reflects the continuous efforts to update our previous data and to expand the information to include new statistics. Thus, the user of the website (www.who.int/hpvcentre) will be able to find and manage new indicators on the burden of other HPV-related cancers (such as that of the vulva, vagina, anus, penis, oral cavity and pharynx), HPV in anogenital cancers, HPV in men, sexual and reproductive behaviour practices, HPV preventive strategies of cervical screening, HPV vaccine licensure and introduction, and male circumcision. The HPV Information Centre team hopes that this update will be a useful resource to help formulate recommendations and public health interventions towards the prevention of cervical cancer and HPVrelated diseases in each country. Preface to the first edition The main aim of this report is to summarize the information available on human papillomavirus (HPV) and cervical cancer at the country-specific level. The World Health Organization (WHO) in collaboration with the Institut Català d Oncologia (ICO) have developed the WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre) to evaluate the burden of disease in the country and to help facilitate stakeholders and relevant bodies of decision makers to formulate recommendations on cervical cancer prevention, including the implementation of the newly developed HPV vaccines. Data aggregated are derived from data and official reports produced by the World Health Organization (WHO), International Agency for Research on Cancer (IARC), United Nations, The World Bank, and published literature. Indicators include relevant statistics on cancer, epidemiological determinants of cervical cancer such as demographics, socioeconomic factors and other risk factors, estimates on the burden of HPV infection, data on immunization and cervical cancer screening. These statistics are essential when planning and implementing cervical cancer prevention strategies. Therefore, we have integrated the most important information for each country into a report and on a website (www.who.int/hpvcentre) to provide a user-friendly tool to assess the best available information in each country. The information presented here is intended as a resource for all who are working towards the prevention of cervical cancer.

- 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 and are responsible for about 70% of all cervical cancer cases worldwide. HPV vaccines that prevent against HPV and infection are now available and have the potential to reduce the incidence of cervical and other anogenital cancers. This report provides key information for Americas 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. Americas has a population of 6.43 millions women ages 15 years and older who are at risk of developing cervical cancer. Current estimates indicate that every year 80,711 women are diagnosed with cervical cancer and 36,125 die from the disease. Cervical cancer ranks as the 4th most frequent cancer among women in Americas, and the 2nd most frequent cancer among women between 15 and 44 years of age. About 14.5% of women in the general population are estimated to harbour cervical HPV infection at a given time, and 70.7% of invasive cervical cancers are attributed to HPVs or. Population Women at risk for cervical cancer (Female population aged >=15 yrs) in thousands Burden of cervical cancer Table 1: Key statistics in Americas and its regions Americas Latin America & Caribbean Caribbean Central America South America Northern America 6,432 200,008 14,8 49,968 135,207 136,424 Annual number of new cervical cancer cases 80,711 68,220 4,7 15,606 47,881 12,491 Annual number of cervical cancer deaths 36,125,712 2,2 7,6 21,836 4,413 Projected number of new cervical cancer cases in 2025* 108,132 101,092 6,5 23,693 71,043 14,590 Projected number of cervical cancer deaths in 2025* 51,139 49,825 3,255 12,660 34,002 5,515 Burden of cervical HPV infection in the general population (women with normal cytology) Prevalence (%) of HPV and/or HPV among women with: 14.5 17.6 35.4 20.6 13.2 12.5 Normal cytology 6.3 4.4 3.3 4.1 5.2 9.2 Low-grade cervical lesions (LSIL/CIN-1) 24.8 22.3 8.7.7 34.3 25.6 High-grade cervical lesions (HSIL/ CIN-2 / CIN-3 / CIS).4 46.7.6 44.3 55.3 55.2 Cervical cancer 70.7 66.4 61.1 62.9 67.7 76.5 LSIL, low-grade intraepithelial lesions; HSIL, high-grade intraepithelial lesions; CIN-2/3, cervical intraepithelial neoplasia grade 2 or 3; CIS, carcinoma in-situ. Projected burden in 2025 is estimated by applying current population forecasts for the country and assuming that current incidence/mortality rates of cervical cancer are constant over time.

LIST OF CONTENTS - v - Contents Executive summary iv 1 Introduction 2 2 Region profile 3 3 Burden of HPV related cancers 5 3.1 Cervical cancer........................................ 5 3.1.1 Incidence....................................... 5 3.1.2 Mortality........................................ 13 3.1.3 Comparison of incidence and mortality....................... 20 3.2 Anogenital cancers other than the cervix.......................... 21 3.2.1 Anal cancer...................................... 21 3.2.2 Vulvar cancer..................................... 21 3.2.3 Vaginal cancer.................................... 21 3.2.4 Penile cancer..................................... 21 3.3 Head and neck cancers................................... 21 4 HPV related statistics 23 4.1 HPV burden in women with normal cytology, precancerous cervical lesions or invasive cervical cancer........................................ 23 4.1.1 Terminology...................................... 24 4.1.2 HPV prevalence in women with normal cytology................. 25 4.1.3 HPV type distribution among women with normal cytology, precancerous cervical lesions and cervical cancer........................... 28 4.2 HPV burden in anogenital cancers other than cervix................... 35 4.2.1 Anal cancer...................................... 35 4.2.2 Vulvar cancer..................................... 38 4.2.3 Vaginal cancer.................................... 40 4.2.4 Penile cancer..................................... 41 4.3 HPV burden in men..................................... 44 5 Factors contributing to cervical cancer 47 6 Reproductive and sexual behaviour 51 7 HPV preventive strategies 7.1 Cervical cancer screening practices............................ 7.2 HPV vaccination....................................... 53 7.2.1 HPV vaccine licensure and introduction...................... 53 7.2.2 Male Circumcision and condom use........................ 54 8 References 56

LIST OF FIGURES - vi - List of Figures 1 Regions of Americas map............................................. 2 2 Population pyramid estimates of Americas for 2010............................... 4 3 Estimated population trends of four selected age groups in Americas..................... 4 4 Age-standardized incidence rates of cervical cancer in Americas........................ 5 5 Age-standardized incidence rates of cervical cancer in regions of Americas.................. 7 6 Ranking of cervical cancer to others cancers among all women and women ages 15-44 years, according to incidence rates in Americas............................................ 8 7 Ten most frequent cancers in women of all ages in Americas and its regions................. 9 8 Ten most frequent cancers in women ages 15-44 yrs in Americas and its regions............... 10 9 Age-specific incidence of cervical cancer in regions of Americas compared to the World........... 11 10 Annual number of new cases of cervical cancer by age group in regions of Americas............. 12 11 Age-standardized mortality rates of cervical cancer in Americas........................ 14 12 Age-standardized mortality rates of cervical cancer in regions of Americas.................. 14 13 Ranking of cervical cancer to others cancers among all women and women ages 15-44 years, according to mortality rates in Americas............................................. 15 14 Ten most frequent cancers deaths in women of all ages in Americas and its regions............. 15 Ten most frequent cancers deaths in women ages 15-44 yrs in Americas and its regions........... 17 Age-specific mortality of cervical cancer in regions of Americas compared to the World........... 17 Annual number of deaths of cervical cancer by age group in regions of Americas............... 19 Age-specific incidence and mortality rates of cervical cancer in Americas and its regions........... 20 19 Prevalence of HPV among women with normal cytology in Americas...................... 26 20 Crude age-specific HPV prevalence in women with normal cytology in Americas and its regions....... 27 21 Ten most frequent HPV types among women with and without cervical lesions in Americas and its regions 29 22 Ten most frequent HPV types among women with and without cervical lesions in Americas and its regions (continued)..................................................... 30 23 Ten most frequent HPV types among women with invasive cervical cancer by histology in Americas and its regions....................................................... 24 Ten most frequent HPV types among women with invasive cervical cancer by histology in Americas and its regions (continued)................................................. 32 25 HPV prevalence of anal cancer in Americas, by histology............................ 36 26 Ten most frequent HPV types among cases of anal cancer in Americas compared to the World....... 37 27 HPV prevalence of vulvar cancer in Americas, by histology........................... 39 28 Ten most frequent HPV types among cases of vulvar cancer in Americas compared to the World...... 39 29 Ten most frequent HPV types among vaginal cancer cases in Americas compared to the World....... 40 30 HPV prevalence of penile cancer in Americas, by histology........................... 42 Ten most frequent HPV types among cases of penile cancer in Americas compared to the World...... 43 32 Prevalence of female tobacco smoking in Americas............................... 47 Total fertility rates in Americas........................................... 48 34 Prevalence of oral contraceptive use in Americas................................ 49 35 Prevalence of HIV in Americas........................................... 50 36 Proportion of young women (15-24 years) who have had sex before the age of 15 in Americas....... 51 37 Estimated coverage of cervical cancer screening in Americas.......................... 38 Prevalence of male circumcision in Americas................................... 54 39 Prevalence of condom use in Americas...................................... 55

LIST OF TABLES - 1 - List of Tables 1 Key statistics in Americas and its regions..................................... iv 2 Population (in millions) estimates in Americas for 2010............................. 3 3 Incidence of cervical cancer in Americas by region and country......................... 6 4 Mortality of cervical cancer in Americas by region and country......................... 13 5 Prevalence of HPV among women with normal cytology in Americas by region and country......... 25 6 Prevalence of HPV / in women with normal cytology, precancerous cervical lesions and invasive cervical cancer in Americas by region and country.................................... 28 7 Type-specific HPV prevalence in women with normal cytology, precancerous cervical lesions and invasive cervical cancer in Americas............................................ 8 Type-specific HPV prevalence among invasive cervical cancer cases in Americas, by histology....... 34 9 Prevalence of HPV in anogenital cancers other than the cervix in Americas.................. 35 10 Studies on HPV prevalence among cases of anal cancer in Americas..................... 35 11 Pooled estimate of HPV prevalence among anal cancer cases in Americas, by sex.............. 37 12 Pooled estimate of HPV prevalence among men who have sex with men (MSM) and non-msm with anal cancer in Americas................................................. 37 13 Studies on HPV prevalence among cases of vulvar cancer in Americas.................... 38 14 Studies on HPV prevalence among cases of vaginal cancer in Americas.................... 40 15 Studies on HPV prevalence among cases of penile cancer in Americas.................... 41 Studies on HPV prevalence among men in Americas.............................. 44 17 Studies on high-risk HPV prevalence among men in Americas......................... HPV vaccine licensure as of March 2009..................................... 53 19 HPV vaccine schedule............................................... 53 20 References of studies included in the meta-analyses.............................. 57

1 INTRODUCTION - 2-1 Introduction Figure 1: Regions of Americas map Northern America Caribbean Central America South America United Nations Statistics Division- Standard Country and Area Codes Classifications. (http://unstats.un.org/unsd/methods/m49/m49regin.htm, accessed July 2009) The WHO/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 2009 report aims to summarize the data available to fully evaluate the burden of disease in Americas 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 summarizes the socio-demographic profile of Americas. For analytical purposes, Americas are divided into five regions: Caribbean, Central America, Latin America & Caribbean, Northern America, South America (Figure 1). Section 3 describes the current burden of invasive cervical cancer and other HPV-related cancers in Americas with estimates of prevalence, incidence and mortality rates. Section 4 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 anogential cancers (anus, vulva, vagina, and penis) are presented. Section 5 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 presents sexual and reproductive behaviour indicators that may be used as proxy measures of risk for HPV infection and anogenital cancers. Section 7 presents preventive strategies that include basic characteristics and performance of cervical cancer screening status, status of HPV vaccine licensure introduction, and recommendations in national immunization programs and the prevalence of male circumcision and condom use.

2 REGION PROFILE - 3-2 Region profile Table 2: Population (in millions) estimates in Americas for 2010 Region / Country Female Male 10-14 years 15+ years Total 10-14 years 15+ years Total Americas 38.25 362.14 476.03 39.74 3.62 464.28 Latin America & Caribbean 27.03 2.15 298.01 27.94 207.73 290.64 Caribbean 1.86 15.86 21.36 1.92 15.23 20.95 Anguilla - - - - - - Antigua & Barbuda - - - - - - Bahamas 0.01 0.13 0. 0.01 0.12 0.17 Barbados 0.01 0.11 0.13 0.01 0.10 0.12 British Virgin Islands - - - - - - Cayman Islands - - - - - - Cuba 0.34 4.65 5.59 0.36 4.62 5.62 Dominica - - - - - - Dominican Republic 0.50 3.53 5.09 0. 3. 5.13 Grenada 0.00 0.04 0.05 0.00 0.04 0.05 Guadeloupe 0.02 0.19 0.24 0.02 0.17 0.22 Haiti 0. 3.35 5. 0.60 3.17 5.03 Jamaica 0.14 1.00 1.39 0.14 0.93 1.34 Martinique 0.01 0.17 0.22 0.01 0.15 0.19 Montserrat - - - - - - Netherlands Antilles 0.01 0.08 0.11 0.01 0.07 0.09 Puerto Rico 0.14 1.69 2.08 0.15 1.51 1.92 Saint Kitts & Nevis - - - - - - Saint Lucia 0.01 0.07 0.09 0.01 0.06 0.08 Saint Vincent & The Grenadines 0.00 0.04 0.05 0.00 0.04 0.06 Trinidad & Tobago 0.04 0.55 0.69 0.05 0.51 0.65 Turks & Caicos Islands - - - - - - US Virgin Islands 0.00 0.05 0.06 0.00 0.04 0.05 Central America 7. 55.17 77.75 7.78.00 75.36 Belize 0.02 0.10 0.15 0.02 0.10 0. Costa Rica 0.20 1.71 2.28 0.21 1.75 2.36 El Salvador 0.36 2.32 3.28 0.37 1.92 2.92 Guatemala 0.89 4.43 7.37 0.91 3.98 7.01 Honduras 0.44 2.44 3.81 0.46 2.38 3.81 Mexico 5. 40.97 56. 5.30 38.76 54.47 Nicaragua 0. 1.96 2.94 0.34 1.86 2.88 Panama 0. 1.24 1.74 0.17 1.25 1.77 South America 17.59 147.13 198.90.24 140.50 194.32 Argentina 1.67 15.74 20.72 1.73 14.80 19.95 Bolivia 0.56 3.27 5.03 0. 3.17 5.00 Brazil 8.50 74.82 99.22 8.81 70.83 96.20 Chile 0.65 6.79 8.66 0.68 6.53 8.47 Colombia 2..99 23. 2.24 15.99 22.79 Ecuador 0.70 4.81 6.88 0.73 4.75 6.90 French Guiana 0.01 0.08 0.12 0.01 0.07 0.12 Guyana 0.04 0.26 0.37 0.04 0.28 0.39 Paraguay 0.34 2.14 3.20 0.36 2. 3.26 Peru 1.44 10.38 14.71 1.49 10.29 14.78 Suriname 0.02 0.19 0.26 0.03 0. 0.26 Uruguay 0.13 1.37 1.75 0.13 1.24 1.63 Venezuela 1.36 10.28 14.47 1.42 10.20 14. Northern America 11.22 143.99 178.01 11.80 137.88 173.65 Bermuda - - - - - - Canada 0.94 14.41 17.10 0.99 13.96.79 United States of America 10.28 129.54 0.85 10.80 123.88 156.79 World population prospects: the 2008 revision. New York, Population Division, Department of Economic and Social Affairs, United Nations Secretariat, 2009.

2 REGION PROFILE - 4 - Figure 2: Population pyramid estimates of Americas for 2010 Males Females 85+ 80 84 75 79 70 74 65 69 60 64 55 59 50 54 49 40 44 35 39 30 34 25 29 20 24 15 19 10 14 5 9 Under 5 3607 4651 6897 94 13046 17677 223 26127 29347 30383 32214 3 37005 38607 39776 39740 39719 39205 5102 6787 8964 11435 14722 19236 23657 275 30560 376 32846 34767 367 37900 389 38251 38113 375 Population of Americas by sex and age group Population in thousands. World population prospects: the 2008 revision. New York, Population Division, Department of Economic and Social Affairs, United Nations Secretariat, 2009. Including Bermuda, Greenland, and Saint-Pierre-et-Miquelon. Figure 3: Estimated population trends of four selected age groups in Americas Projections Projections Number of women (in millions) 80.0 60.0 40.0 20.0 Women 15 24 yrs Girls 10 14 yrs Number of women (in millions) 600.0 500.0 400.0 300.0 200.0 100.0 All Women Women 25 64 yrs 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 20 2050 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 20 2050 Female population trends in Americas Number of women by year and age group Population in thousands. World population prospects: the 2008 revision. New York, Population Division, Department of Economic and Social Affairs, United Nations Secretariat, 2009. Including Bermuda, Greenland, and Saint-Pierre-et-Miquelon.

3 BURDEN OF HPV RELATED CANCERS - 5-3 Burden of HPV related cancers 3.1 Cervical cancer Cancer of the cervix uteri is the second most common cancer among women worldwide, with an estimated 9,409 new cases and 274,883 deaths in 2008. About 86% of the cases occur in developing countries, representing 13% of female cancers. Worldwide, mortality rates of cervical cancer are substantially lower than incidence with a ratio of mortality to incidence to % (IARC, GLOBOCAN 2008). The majority of cases are squamous cell carcinoma and adenocarcinomas are less common. (Vaccine 2006, Vol. 24, Supl 3; Vaccine 2008, Vol. 26, Supl 10; IARC Monographs 2007, Vol. 90) This section describes the current burden of invasive cervical cancer in Americas with estimates of annual number of new cases, deaths, and incidence and mortality rates. 3.1.1 Incidence Figure 4: Age-standardized incidence rates of cervical cancer in Americas ASR <=6.8 <=12.9 <=20.2 <=29.8 <=.8 No data ASR, age-standardized incidence rates; Rates per 100,000 women per year. IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication. For specific estimation methodology refer to http://globocan.iarc.fr/datasource_and_methods.asp.

3 BURDEN OF HPV RELATED CANCERS - 6 - Table 3: Incidence of cervical cancer in Americas by region and country Region / Country Crude rate ASR* Cum. risk* N cases Ranking of cervical cancer All women Women 15-44 years Americas 17.3 15.3 1.6 80711 4th 2nd Latin America & Caribbean 23.4 23.5 2.4 68220 2nd 2nd Caribbean 22.5 20.8 2.1 47 2nd 1st Anguilla - - - - - - Antigua & Barbuda - - - - - - Bahamas.0 17.6 2.3 2nd 2nd Barbados 28.9 20.8 2.4 38 3rd 2nd British Virgin Islands - - - - - - Cayman Islands - - - - - - Cuba 28.7 23.1 2.2 03 4th 1st Dominica - - - - - - Dominican Republic 26.2 29.7 3.2 1299 2nd 1st Grenada - - - - - - Guadeloupe 17.0 12.3 1.2 41 3rd 2nd Haiti 11.4.0 1.6 568 2nd 2nd Jamaica.1.7 4.6 624 2nd 1st Martinique 25.2 17.4 1.9 54 3rd 2nd Montserrat - - - - - - Netherlands Antilles - - - - - - Puerto Rico 10.1 7.5 0.7 209 5th 2nd Saint Kitts & Nevis - - - - - - Saint Lucia - - - - - - Saint Vincent & The Grenadines - - - - - - Trinidad & Tobago.2 15.8 1.7 125 2nd 2nd Turks & Caicos Islands - - - - - - US Virgin Islands - - - - - - Central America 20.6 22.2 2.2 15606 2nd 1st Belize 22.1 29.6 3.2 1st 1st Costa Rica.1 17.5 1.7 403 2nd 1st El Salvador 35.4 37.2 3.6 11 1st 1st Guatemala 21.8 30.5 2.9 1530 1st 1st Honduras 27.7 37.8 3.8 1014 1st 1st Mexico.5 19.2 1.9 106 2nd 2nd Nicaragua 30.4 39.9 4.1 869 1st 1st Panama 25.3 25.3 2.4 426 2nd 1st South America 24.6 24.1 2.5 47881 2nd 2nd Argentina 19.7 17.5 1.8 3996 3rd 2nd Bolivia 29.3 36.4 3.7 1422 1st 1st Brazil 25.2 24.5 2.6 262 2nd 2nd Chile 17.4 14.4 1.5 1478 3rd 2nd Colombia 20.7 21.5 2.2 4736 2nd 1st Ecuador 24.8 27.1 3.0 66 2nd 1st French Guiana 24.5 29.1 2.9 27 2nd 1st Guyana 43.3 44.7 4.7 1 1st 1st Paraguay 28.0 35.0 3.7 864 2nd 1st Peru 30.9 34.5 3.6 4446 1st 1st Suriname 25.7 27.2 2.9 66 2nd 2nd Uruguay 20.1.5 1.7 348 3rd 2nd Venezuela 29.4.4 3.3 41 2nd 1st Northern America 7.1 5.7 0.5 12491 13th 4th Bermuda - - - - - - Canada 8.5 6.6 0.6 1419 12th 3rd United States of America 7.0 5.7 0.5 11069 13th 4th *ASR: Age-standardised rate; Cum. risk: Cumulative risk. Rates per 100,000 women per year. Standardised rates have been estimated using the direct method and the World population as the reference. Ranking of cervical cancer incidence to other cancers among all women and women ages 15-44 years according to highest incidence rates (ranking 1st). Ranking is based on crude incidence rates (actual number of cervical cancer cases) in the country/region. Ranking using ASR may differ. IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication.

3 BURDEN OF HPV RELATED CANCERS - 7 - Figure 5: Age-standardized incidence rates of cervical cancer in regions of Americas South America 24.1 Central America 22.2 Caribbean 20.8 Northern America 5.7 0 5 10 15 20 25 30 Age standardized cervical cancer incidence rates (World) per 100,000 women (all ages) per year IARC, Globocan 2008.

3 BURDEN OF HPV RELATED CANCERS - 8 - Figure 6: Ranking of cervical cancer to others cancers among all women and women ages 15-44 years, according to incidence rates in Americas All women Ranking incidence of cervical cancer 1st 2nd to 3rd 4th to 5th 6th and more No data Women ages 15-44 years Ranking incidence of cervical cancer 1st 2nd to 3rd 4th to 5th 6th and more No data *Highest incidence rate rank 1st. Ranking is based on crude incidence rates (actual number of cervical cancer cases) in the country/region. Ranking using ASR may differ. IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication.

3 BURDEN OF HPV RELATED CANCERS - 9 - Figure 7: Ten most frequent cancers in women of all ages in Americas and its regions Americas Latin America & Caribbean Breast 57.2 Breast 39.7 Lung 21.9 Cervix uteri 23.5 Colorectum.3 Colorectum 10.9 Cervix uteri 15.3 Stomach 8.4 Corpus uteri 10.5 Lung 8.0 Thyroid 8.8 Ovary 5.9 Non Hodgkin lymphoma 7.4 Corpus uteri 5.1 Ovary 7.2 Thyroid 4.8 Melanoma of skin 6.2 Liver 4.6 Leukaemia 6.0 Leukaemia 4.3 0 15 30 60 75 0 15 30 60 75 Caribbean Central America Breast 39.1 Breast 26.0 Cervix uteri 20.8 Cervix uteri 22.2 Colorectum 13.9 Stomach 9.3 Lung 12.1 Liver 7.0 Corpus uteri 9.0 Colorectum 6.4 Stomach 6.1 Corpus uteri 6.1 Liver 4.4 Lung 5.5 Ovary 4.3 Ovary 5.2 Pancreas 3.4 Leukaemia 5.1 Leukaemia 3.3 Gallbladder 4.9 0 15 30 60 75 0 15 30 60 75 South America Northern America Breast 44.3 Breast 76.7 Cervix uteri 24.1 Lung 35.8 Colorectum 11.9 Colorectum 25.7 Lung 8.4 Corpus uteri.4 Stomach 8.4 Thyroid 15.1 Ovary 6.2 Melanoma of skin 12.5 Thyroid 5.5 Non Hodgkin lymphoma 11.5 Corpus uteri 4.4 Ovary 8.7 Leukaemia 4.0 Kidney 8.5 Pancreas 4.0 Leukaemia 7.8 0 15 30 60 75 0 15 30 60 75 Age standardized incidence rate per 100,000 women (all ages) per year in Americas IARC, Globocan 2008.

3 BURDEN OF HPV RELATED CANCERS - 10 - Figure 8: Ten most frequent cancers in women ages 15-44 yrs in Americas and its regions Americas Latin America & Caribbean Breast 22.8 Breast.8 Cervix uteri 12.9 Cervix uteri 15.8 Thyroid 9.4 Thyroid 4.3 Melanoma of skin 4.6 Ovary 2.9 Colorectum 3.3 Leukaemia 2.4 Ovary 3.2 Colorectum 2.3 Leukaemia 2.7 Stomach 2.1 Non Hodgkin lymphoma 2.6 Non Hodgkin lymphoma 1.6 Corpus uteri 2.2 Brain, nervous system 1.6 Brain, nervous system 2.1 Lung 1.0 0 15 30 60 75 0 15 30 60 75 Caribbean Central America Cervix uteri.9 Cervix uteri 17.5 Breast.9 Breast 13.6 Thyroid 3.0 Leukaemia 3.9 Ovary 2.5 Thyroid 3.5 Colorectum 2.3 Ovary 3.1 Leukaemia 1.8 Stomach 2.4 Lung 1.7 Non Hodgkin lymphoma 1.9 Brain, nervous system 1.5 Brain, nervous system 1.8 Non Hodgkin lymphoma 1.4 Colorectum 1.7 Stomach 1.4 Hodgkin lymphoma 0.9 0 15 30 60 75 0 15 30 60 75 South America Northern America Breast.1 Breast 34.4 Cervix uteri 15.0 Thyroid 19.2 Thyroid 4.8 Melanoma of skin 12.1 Ovary 2.9 Cervix uteri 7.2 Colorectum 2.5 Colorectum 5.3 Stomach 2.1 Corpus uteri 4.6 Leukaemia 1.9 Non Hodgkin lymphoma 4.4 Non Hodgkin lymphoma 1.5 Lung 4.0 Brain, nervous system 1.5 Ovary 3.7 Lung 1.0 Hodgkin lymphoma 3.5 0 15 30 60 75 0 15 30 60 75 Age standardized incidence rate per 100,000 women (ages 15 44 years) per year in Americas IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication.

3 BURDEN OF HPV RELATED CANCERS - 11 - Figure 9: Age-specific incidence of cervical cancer in regions of Americas compared to the World Age specific rates of cervical cancer per 100,000 80 60 40 20 0 Caribbean Central America Northern America South America World 0 14yrs 15 44yrs 54yrs 55 64yrs 65+ yrs Age group IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication.

3 BURDEN OF HPV RELATED CANCERS - 12 - Figure 10: Annual number of new cases of cervical cancer by age group in regions of Americas Annual number of new cases of cervical cancer 30000 25000 20000 15000 10000 5000 43 5114 6427 13797 South America Central America 987 2860 3735 154 Northern America Caribbean 878 1971 2385 9960 1225 2544 3059 12255 0 15 44yrs 54yrs 55 64yrs 65+ yrs Age group IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication.

3 BURDEN OF HPV RELATED CANCERS - 13-3.1.2 Mortality Table 4: Mortality of cervical cancer in Americas by region and country Region / Country Crude rate ASR* Cum. risk* N deaths Ranking of cervical cancer All women Women 15-44 years Americas 7.7 6.5 0.7 36125 4th 2nd Latin America & Caribbean 10.9 10.8 1.2 712 2nd 1st Caribbean 10.7 9.4 1.0 22 4th 2nd Anguilla - - - - - - Antigua & Barbuda - - - - - - Bahamas 9.9 9.5 1.2 17 2nd 3rd Barbados.0 9.9 1.2 21 3rd 2nd British Virgin Islands - - - - - - Cayman Islands - - - - - - Cuba 12.2 8.9 0.9 684 4th 1st Dominica - - - - - - Dominican Republic 11.9 13.7 1.6 591 1st 2nd Grenada - - - - - - Guadeloupe 9.1 5.4 0.6 22 3rd 2nd Haiti 7.1 10.1 0.8 353 2nd 2nd Jamaica 21.1 20.2 2.1 292 2nd 1st Martinique 7.0 3.7 0.4 15 6th 2nd Montserrat - - - - - - Netherlands Antilles - - - - - - Puerto Rico 4.3 2.8 0.3 89 8th 2nd Saint Kitts & Nevis - - - - - - Saint Lucia - - - - - - Saint Vincent & The Grenadines - - - - - - Trinidad & Tobago 13.6 11.5 1.2 93 2nd 2nd Turks & Caicos Islands - - - - - - US Virgin Islands - - - - - - Central America 10.1 11.1 1.2 76 1st 1st Belize 11.4 15.3 1.4 17 1st 1st Costa Rica 7.1 6.7 0.7 1 4th 2nd El Salvador 17.4.2 1.9 563 1st 1st Guatemala 10.2 15.2 1.5 717 2nd 1st Honduras 13.4 19.7 2.1 490 1st 1st Mexico 9.2 9.7 1.0 5061 2nd 1st Nicaragua 14.5 20.6 2.3 414 1st 1st Panama 12.5 12.6 1.3 211 1st 1st South America 11.2 10.8 1.2 236 2nd 1st Argentina 8.9 7.4 0.8 09 5th 2nd Bolivia 13.1.7 1.7 638 1st 1st Brazil 11.4 10.9 1.2 11055 2nd 1st Chile 8.5 6.6 0.7 721 6th 1st Colombia 9.4 10.0 1.1 2154 1st 1st Ecuador 12.4 13.3 1.5 832 2nd 1st French Guiana 9.1 11.7 1.4 10 2nd 1st Guyana 19.9 20.5 2.2 74 1st 1st Paraguay 13.2.6 1.8 407 1st 1st Peru 14.6.3 1.7 2098 2nd 1st Suriname 10.5 11.1 1.2 27 2nd 1st Uruguay 9.2 6.8 0.7 159 6th 2nd Venezuela 13.2 14.4 1.5 53 1st 1st Northern America 2.5 1.7 0.2 4413 15th 3rd Bermuda - - - - - - Canada 3.2 1.9 0.2 544 14th 4th United States of America 2.4 1.7 0.2 3869 15th 3rd *ASR: Age-standardised rate; Cum. risk: Cumulative risk. Rates per 100,000 women per year. Standardised rates have been estimated using the direct method and the World population as the reference. Ranking of cervical cancer mortality to other cancers among all women and women ages 15-44 years according to highest mortality rates (ranking 1st). Ranking is based on crude mortality rates (actual number of cervical cancer deaths) in the country/region. Ranking using ASR may differ. IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication.

3 BURDEN OF HPV RELATED CANCERS - 14 - Figure 11: Age-standardized mortality rates of cervical cancer in Americas ASR <=2.5 <=5.7 <=10.3 <=17.6 <=39.1 No data ASR, age-standardized incidence rates; Rates per 100,000 women per year. IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication. For specific estimation methodology refer to http://globocan.iarc.fr/datasource_and_methods.asp. Figure 12: Age-standardized mortality rates of cervical cancer in regions of Americas Central America 11.1 South America 10.8 Caribbean 9.4 Northern America 1.7 0 5 10 15 20 Age standardized cervical cancer mortality rates (World) per 100,000 women (all ages) per year IARC, Globocan 2008.

3 BURDEN OF HPV RELATED CANCERS - 15 - Figure 13: Ranking of cervical cancer to others cancers among all women and women ages 15-44 years, according to mortality rates in Americas All women Ranking mortality of cervical cancer 1st 2nd to 3rd 4th to 5th 6th and more No data Women ages 15-44 years Ranking mortality of cervical cancer 1st 2nd to 3rd 4th to 5th 6th and more No data *Highest mortality rate rank 1st. Ranking is based on crude mortality rates (actual number of cervical cancer deaths) in the country/region. Ranking using ASR may differ. IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication.

3 BURDEN OF HPV RELATED CANCERS - - Figure 14: Ten most frequent cancers deaths in women of all ages in Americas and its regions Americas Latin America & Caribbean Lung 15.9 Breast 12.4 Breast 13.7 Cervix uteri 10.8 Colorectum 7.1 Lung 7.3 Cervix uteri 6.5 Stomach 7.0 Pancreas 4.5 Colorectum 6.1 Ovary 4.4 Liver 4.8 Stomach 4.2 Pancreas 3.8 Leukaemia 3.4 Leukaemia 3.3 Liver 3.3 Ovary 3.3 Brain, nervous system 2.5 Gallbladder 3.0 0 5 10 15 20 25 0 5 10 15 20 25 Caribbean Central America Breast 14.2 Cervix uteri 11.1 Lung 11.1 Breast 9.6 Cervix uteri 9.4 Stomach 7.9 Colorectum 8.9 Liver 7.0 Stomach 4.6 Lung 5.3 Liver 4.4 Colorectum 3.9 Corpus uteri 3.3 Leukaemia 3.8 Pancreas 3.3 Pancreas 3.8 Leukaemia 2.8 Ovary 3.4 Ovary 2.7 Gallbladder 3.1 0 5 10 15 20 25 South America 0 5 10 15 20 25 Northern America Breast 13.2 Lung 24.2 Cervix uteri 10.8 Breast 14.8 Lung 7.5 Colorectum 7.9 Stomach 6.9 Ovary 5.4 Colorectum 6.5 Pancreas 5.1 Liver 4.1 Leukaemia 3.0 Pancreas 3.9 Non Hodgkin lymphoma 2.9 Ovary 3.4 Brain, nervous system 2.4 Gallbladder 3.2 Corpus uteri 2.4 Leukaemia 3.2 Liver 1.9 0 5 10 15 20 25 0 5 10 15 20 25 Age standardized mortality rate per 100,000 women (all ages) per year in Americas IARC, Globocan 2008.

3 BURDEN OF HPV RELATED CANCERS - 17 - Figure 15: Ten most frequent cancers deaths in women ages 15-44 yrs in Americas and its regions Americas Latin America & Caribbean Breast 4.0 Cervix uteri 4.7 Cervix uteri 3.6 Breast 3.7 Leukaemia 1.6 Leukaemia 1.9 Lung 1.2 Stomach 1.4 Stomach 1.1 Brain, nervous system 1.1 Brain, nervous system 1.1 Colorectum 0.9 Colorectum 1.0 Ovary 0.9 Ovary 0.9 Lung 0.9 Non Hodgkin lymphoma 0.6 Non Hodgkin lymphoma 0.7 Liver 0.5 Liver 0.7 0 5 10 15 20 25 0 5 10 15 20 25 Caribbean Central America Breast 4.4 Cervix uteri 4.8 Cervix uteri 4.4 Breast 3.6 Leukaemia 1.4 Leukaemia 2.5 Lung 1.2 Stomach 1.8 Colorectum 1.0 Ovary 1.1 Ovary 0.9 Brain, nervous system 0.9 Brain, nervous system 0.9 Liver 0.8 Stomach 0.8 Colorectum 0.8 Non Hodgkin lymphoma 0.7 Non Hodgkin lymphoma 0.8 Liver 0.6 Lung 0.7 0 5 10 15 20 25 0 5 10 15 20 25 South America Northern America Cervix uteri 4.7 Breast 4.5 Breast 3.7 Lung 1.9 Leukaemia 1.6 Cervix uteri 1.3 Stomach 1.4 Colorectum 1.1 Brain, nervous system 1.2 Leukaemia 1.0 Colorectum 1.0 Brain, nervous system 1.0 Lung 0.9 Ovary 0.9 Ovary 0.9 Non Hodgkin lymphoma 0.5 Non Hodgkin lymphoma 0.7 Melanoma of skin 0.5 Liver 0.6 Pancreas 0.4 0 5 10 15 20 25 0 5 10 15 20 25 Age standardized mortality rate per 100,000 women (15 44 years) per year in Americas IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication.

3 BURDEN OF HPV RELATED CANCERS - - Figure : Age-specific mortality of cervical cancer in regions of Americas compared to the World Age specific mortality rates of cervical cancer per 100,000 60 50 40 30 20 10 0 Caribbean Central America Northern America South America World 0 14yrs 15 44yrs 54yrs 55 64yrs 65+ yrs Age group IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication.

3 BURDEN OF HPV RELATED CANCERS - 19 - Figure 17: Annual number of deaths of cervical cancer by age group in regions of Americas Annual number of cervical cancer deaths 20000 15000 10000 5000 423 906 1764 South America Central America 4 1003 13 Northern America Caribbean 437 906 14 9 1598 2599 7844 4347 5038 4603 0 15 44yrs 54yrs 55 64yrs 65+ yrs Age group IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication.

3 BURDEN OF HPV RELATED CANCERS - 20-3.1.3 Comparison of incidence and mortality Figure : Age-specific incidence and mortality rates of cervical cancer in Americas and its regions 90 Americas 90 Latin America & Caribbean 75 Incidence Mortality 75 Incidence Mortality 60 60 30 30 15 15 0 0 0 14 yrs 15 44 yrs 54 yrs 55 64 yrs 65+ yrs 0 14 yrs 15 44 yrs 54 yrs 55 64 yrs 65+ yrs Age specific rates of cervical cancer per 100,000 90 75 60 30 15 0 0 14 yrs 90 Incidence Mortality 15 44 yrs Caribbean 54 yrs South America 55 64 yrs 65+ yrs 90 75 60 30 15 0 0 14 yrs 90 Incidence Mortality 15 44 yrs Central America 54 yrs Northern America 55 64 yrs 65+ yrs 75 Incidence Mortality 75 Incidence Mortality 60 60 30 30 15 15 0 0 0 14 yrs 15 44 yrs 54 yrs 55 64 yrs 65+ yrs 0 14 yrs 15 44 yrs 54 yrs 55 64 yrs 65+ yrs IARC, Globocan 2008. Age-specific data from GLOBOCAN 2008 were obtained from IARC, personal communication. For specific estimation methodology refer to http://globocan.iarc.fr/datasource_and_methods.asp.

3 BURDEN OF HPV RELATED CANCERS - 21-3.2 Anogenital cancers other than the cervix Data on the role of HPV 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 cancer of the cervix, their association with HPV make them potentially preventable and subject to similar preventative strategies as those for cervical cancer. (Vaccine 2006, Vol. 24, Supl 3; Vaccine 2008, Vol. 26, Supl 10; IARC Monographs 2007, Vol. 90) 3.2.1 Anal cancer Cancer of the anus is rare, with an estimated 99,000 new cases in 2002, 40% of cases in men and 60% in women. Incidence has been increasing in both men and women over the last five decades, and incidence is particularly high among populations of men who have sex with men (MSM) and those who are HIV-infected. These cancers are predominantly squamous cell carcinoma, adenocarcinomas, or basaloid and cloacogenic carcinomas. 3.2.2 Vulvar cancer Cancer of the vulva is rare among women worldwide, with an estimated 26,800 new cases in 2002, representing 3% of all gynaecologic cancers. Worldwide, about 60% of all vulvar cancer cases occur in developed countries, indicating the limited impact of cervical screening programmes to prevent vulvar and vaginal cancers. Vulvar cancer is common in older women with approximately 66% of cases diagnosed at >=70 years. The majority of vulvar cancer cases are squamous cell carcinoma (90%), followed by melanoma, Bartholin gland carcinoma, basal cell carcinoma, verrucous carcinoma, and Paget s disease. 3.2.3 Vaginal cancer Cancer of the vagina is a rare cancer, with an estimated 13,200 of new cases in 2002, representing 2% of all gynaecologic cancers. Similar to cervical cancer, the majority of vaginal cancer cases (68%) occur in developing countries. Most vaginal cancers are squamous cell carcinoma (90%), followed by clear cell adenocarcinomas and melanoma. There are few data available on vaginal cancers, which are primarily reported in developed countries, and in some settings, metastatic cervical cancer can be misclassified as cancer of the vagina. Vaginal cancer is diagnosed primarily in older women (>=65 years) with a median age at diagnosis of 69 years, and the incidence of carcinoma in situ is diagnosed between the ages of 55 and 70 years. 3.2.4 Penile cancer Cancer of the penis represents less than 0.5% of cancers in men. Incidence rates are less than 1 per 100,000 in Western countries, with higher rates found in Latin America such as Brazil, Colombia, and Peru, Uganda, and specific regions in India and Thailand. A geographical correlation between the incidence of cancer of the penis and cervix and the concordance of these two cancers in married couples suggested the common aetiology of HPV. Cancers of the penis are primarily of the squamous cell histological type. 3.3 Head and neck cancers About 400,000 new cases of the oral cavity and the pharynx (excluding nasopharynx) and 223,000 deaths occurred worldwide in 2008. Two-thirds of cases occurred in developing countries. The majority of head and neck cancers is associated with high tobacco and alcohol consumption. However, there are about 15-20% of head and neck cancer cases that are associated with HPV and there is

3 BURDEN OF HPV RELATED CANCERS - 22 - growing evidence that these HPV-related cases, particularly oral pharyngeal cancers, are associated with sexual behaviour including the practice of oral sex.

4 HPV RELATED STATISTICS - 23-4 HPV related statistics Human papillomavirus 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. This section presents the HPV burden at each of the anogenital tract sites. 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, Supl 3; Vaccine 2008, Vol. 26, Supl 10; 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- and, the two vaccine-preventable types. contribute to over 70% of all cervical cancer cases, between 41%-67% of high-grade cervical lesions and -32% of low-grade cervical lesions. After HPV-/, the six most common HPV types are the same in all world regions, namely,, 35,, and ; these account for an additional 20% of cervical cancers worldwide (Clifford G et al. Vaccine 2006;24(S3):26-34). HPV is also responsible for other benign genital infections such as recurrent juvenile respiratory papillomatosis and genital warts, both mainly caused by HPV types 6 and 11 (Lacey CJ et al. Vaccine 2006; 24(S3):35-41).

4 HPV RELATED STATISTICS - 24-4.1.1 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. 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) Cancerous cells are confined to the cervix and have not spread to other parts of the body. Invasive cervical cancer (ICC) / Cervical cancer If the high-grade precancerous cells invade deeper tissues of the cervix or to other tissues or organs, then the disease is called invasive cervical cancer or cervical cancer. Invasive squamous cell carcinoma Invasive carcinoma composed of cells resembling those of squamous epithelium. Adenocarcinoma Invasive tumour with glandular and squamous elements intermingled.

4 HPV RELATED STATISTICS - 25-4.1.2 HPV prevalence in women with normal cytology Table 5: Prevalence of HPV among women with normal cytology in Americas by region and country Region Number of women tested HPV prevalence % (95% CI) World 436430 11.4 (11.3-11.5) Americas 112675 14.5 (14.3-14.7) Latin America & Caribbean 42495 17.6 (17.3-.0) Caribbean 212 35.4 (29.0-42.2) Anguilla - - - Antigua & Barbuda - - - Bahamas - - - Barbados - - - British Virgin Islands - - - Cayman Islands - - - Cuba - - - Dominica - - - Dominican Republic - - - Grenada - - - Guadeloupe - - - Haiti - - - Jamaica - - - Martinique - - - Montserrat - - - Netherlands Antilles - - - Puerto Rico - - - Saint Kitts & Nevis - - - Saint Lucia - - - Saint Vincent & The Grenadines - - - Trinidad & Tobago 212 35.4 (29.0-42.2) Turks & Caicos Islands - - - US Virgin Islands - - - Central America 24783 20.6 (20.1-21.1) Belize 426 10.1 (7.4-13.4) Costa Rica 123 30.2 (29.4-.0) El Salvador - - - Guatemala 274.2 (27.7-39.1) Honduras 538 36.8 (32.7-41.0) Mexico 11229 9.4 (8.9-10.0) Nicaragua - - - Panama - - - South America 17500 13.2 (12.7-13.7) Argentina 995 20.1 (17.7-22.7) Bolivia - - - Brazil 52 14.1 (13.2-15.1) Chile 913 11.2 (9.2-13.4) Colombia 2882 15.9 (14.5-17.2) Ecuador - - - French Guiana - - - Guyana - - - Paraguay 91 19.8 (12.2-29.4) Peru 4894 7.5 (6.8-8.3) Suriname - - - Uruguay - - - Venezuela - - - Northern America 604 12.5 (12.3-12.8) Bermuda - - - Canada 048 9.9 (9.5-10.4) United States of America 430 13.3 (13.0-13.6) The samples for HPV testing come from cervical specimens (fresh / fixed biopsies or exfoliated cells). 95% CI: 95% Confidence Interval See references in Section 8.

4 HPV RELATED STATISTICS - 26 - Figure 19: Prevalence of HPV among women with normal cytology in Americas See references in Section 8. <5.0% <10.0% <20.0% <30.0% <=47.9% No data

...... 4 HPV RELATED STATISTICS - 27 - Figure 20: Crude age-specific HPV prevalence in women with normal cytology in Americas and its regions 40 Americas 40 Latin America & Caribbean 30 30 20 20 10 10 0 0 <25 25 34 35 44 54 55+ <25 25 34 35 44 54 55+ 40 Caribbean 40 Central America 30 30 20 No data available 20 10 10 0 0 <25 25 34 35 44 54 55+ <25 25 34 35 44 54 55+ 40 South America 40 Northern America 30 30 20 20 10 10 0 0 <25 25 34 35 44 54 55+ <25 25 34 35 44 54 55+ Crude age specific HPV prevalence(%) and 95% confidence interval (grey shadow) among women with normal cytology in Americas See references in Section 8.