Human Papillomavirus and Related Diseases Report ISRAEL

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1 Human Papillomavirus and Related Diseases Report ISRAEL Version posted on in February 26 th, 2016

2 - ii - Rights ICO Information Centre on HPV and Cancer (HPV Information Centre) 2016 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 , PREHDICT and 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 Israel. Summary Report [Data Accessed]

3 - iii - 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 Israel 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 country. Table 1: Key Statistics on Israel Population Women at risk for cervical cancer (Female population aged >=15 yrs) 2.97 millions Burden of cervical cancer and other HPV-related cancers Annual number of cervical cancer cases 203 Annual number of cervical cancer deaths 121 Crude incidence rates per 100,000 population and year : Male Female Cervical cancer Anal cancer Vulvar cancer Vaginal cancer Penile cancer Pharynx cancer (excluding nasopharynx) Burden of cervical HPV infection Prevalence (%) of HPV 16 and/or HPV 18 among women with: Normal cytology 2.5 Low-grade cervical lesions (LSIL/CIN-1) 24.0 High-grade cervical lesions (HSIL/CIN-2/CIN-3/CIS) 84.4 Cervical cancer 89.5 Other factors contributing to cervical cancer Smoking prevalence (%), women 19.8 Total fertility rate (live births per women) 3.0 Oral contraceptive use (%) among women 13.0 HIV prevalence (%), adults (15-49 years) - Sexual behaviour Percentage of 15-year-old who have had sexual intercourse (men/women) 23 / 8 Range of median age at first sexual intercourse (men/women) - / - Cervical screening practices and recommendations Cervical cancer screening coverage, 32.0% (All women aged screened every 3y, Raz 2012) % (age and screening in- terval, reference) Screening ages (years) Screening interval (years) or 3 years frequency of screens HPV vaccine HPV vaccine introduction HPV vaccination program National program Date of HPV vaccination routine immunization programme start 2013 HPV vaccination target age for routine immunization 13 Full course HPV vaccination coverage for routine immunization: - % (calendar year) Range of crude incidence rates of the following registries: National. The data is the subregion Western Asia

4 CONTENTS - iv - Contents Executive summary iii 1 Introduction 2 2 Demographic and socioeconomic factors 4 3 Burden of HPV related cancers Cervical cancer Cervical cancer incidence in Israel Cervical cancer incidence by histology in Israel Cervical cancer incidence in Israel across Western Asia Cervical cancer mortality in Israel Cervical cancer mortality in Israel across Western Asia Cervical cancer incidence and mortality comparison, Premature deaths and disability in Israel Anogenital cancers other than the cervix Anal cancer Vulvar cancer Vaginal cancer Penile cancer Head and neck cancers Pharyngeal cancer (excluding nasopharynx) HPV related statistics HPV burden in women with normal cervical cytology, cervical precancerous lesions or invasive cervical cancer HPV prevalence in women with normal cervical cytology HPV type distribution among women with normal cervical cytology, precancerous cervical lesions and cervical cancer HPV type distribution among HIV+ women with normal cervical cytology Terminology HPV burden in anogenital cancers other than 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 56 6 Sexual and reproductive health behaviour indicators 58 7 HPV preventive strategies Cervical cancer screening practices HPV vaccination Protective factors for cervical cancer 63

5 LIST OF CONTENTS - v - 9 Indicators related to immunization practices other than HPV vaccines Immunization schedule Immunization coverage estimates

6 LIST OF FIGURES - vi - List of Figures 1 Israel in Western Asia Population pyramid of Israel Population trends of four selected age groups in Israel Incidence of cervical cancer compared to other cancers in women of all ages in Israel (estimations for 2012) Age-specific cervical cancer incidence compared to age-specific incidence of other cancers among women years of age in Israel (estimations for 2012) Annual number of cases and age-specific incidence rates of cervical cancer in Israel (estimations for 2012) Time trends in cervical cancer incidence in Israel (observed cases in the cancer registries) Age-standardized incidence rates of cervical cancer of Israel (estimations for 2012) Age-specific incidence rates of cervical cancer in Israel compared to its region and the world Annual number of new cases of cervical cancer by age group in Israel (estimations for 2012) Cervical cancer mortality compared to other cancers in women of all ages in Israel (estimations for 2012) Age-specific mortality rates of cervical cancer compared to other cancers among women years of age in Israel (estimations for 2012) Annual number of deaths and age-specific mortality rates of cervical cancer in Israel (estimations for 2012) Age-standardized mortality rates of cervical cancer in Israel compared to region s countries (estimations for 2012) Age-specific mortality rates of cervical cancer in Israel compared to its region and the world Annual deaths number of cervical cancer by age group in Israel (estimations for 2012) Comparison of age-specific incidence and mortality rates of cervical cancer in Israel (estimations for 2012) Number of annual premature deaths and disability from cervical cancer in Israel compared to other cancers among women (estimations for 2008) Anal cancer incidence rates by age group in Israel (observed cases in the cancer registry) Time trends in anal cancer incidence in Israel (observed cases in the selected cancer registries) Vulvar cancer incidence rates by age group in Israel Time trends in vulvar cancer incidence in Israel (observed cases in the selected cancer registries) Incidence rates of vaginal cancer by age group in Israel Time trends in vaginal cancer incidence in Israel (observed cases in the selected cancer registries) Incidence rates of penile cancer by age group in Israel Time trends in penile cancer incidence in Israel (observed cases in the selected cancer registries) Comparison of incidence and mortality rates of the pharynx (excluding nasopharynx) by age group and sex in Israel (estimations for 2012). Includes ICD-10 codes: C09-10,C Crude age-specific HPV prevalence (%) and 95% confidence interval (grey shadow) in women with normal cervical cytology in Israel Prevalence of HPV 16 among women with high-grade cervical lesions in Israel by study Prevalence of HPV 16 among women with invasive cervical cancer in Israel by study Ten most frequent HPV oncogenic types among women with and without cervical lesions in Israel Ten most frequent HPV oncogenic types among women with invasive cervical cancer by histology in Israel Ten most frequent HPV types among anal cancer cases in Asia compared to the World Ten most frequent HPV types among AIN 2/3 cases in Asia 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 VIN 2/3 cases in Asia 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 VaIN 2/3 cases in Asia compared to the World Estimated coverage of cervical cancer screening in Israel, by age and study

7 LIST OF TABLES List of Tables 1 Key Statistics on Israel iii 2 Sociodemographic indicators in Israel Cervical cancer incidence in Israel (estimations for 2012) Cervical cancer incidence by cancer registry in Israel (observed cases during the specified period) Age-standarized incidence rates of cervical cancer by histological type and cancer registry in Israel Cervical cancer mortality in Israel (estimations for 2012) Premature deaths and disability from cervical cancer in Israel, Western Asia and World (estimations for 2008) Anal cancer incidence by cancer registry and sex in Israel (observed cases during the specified period) Vulvar cancer incidence by cancer registry in Israel Vaginal cancer incidence by cancer registry in Israel Penile cancer incidence by cancer registry in Israel Incidence and mortality of cancer of the pharynx (excluding nasopharynx) by sex in Israel, Western Asia and the World (estimations for 2012). Includes ICD-10 codes: C09-10,C Incidence of oropharyngeal cancer by cancer registry and sex in Israel Prevalence of HPV16 and HPV18 by cytology in Israel Type-specific HPV prevalence in women with normal cervical cytology, precancerous cervical lesions and invasive cervical cancer in Israel Type-specific HPV prevalence among invasive cervical cancer cases in Israel by histology Studies on HPV prevalence among HIV women with normal cytology in Israel Studies on HPV prevalence among anal cancer cases in Israel Studies on HPV prevalence among cases of AIN2/3 in Israel Studies on HPV prevalence among vulvar cancer cases in Israel Studies on HPV prevalence among VIN 2/3 cases in Israel Studies on HPV prevalence among vaginal cancer cases in Israel Studies on HPV prevalence among VAIN 2/3 cases in Israel Studies on HPV prevalence among penile cancer cases in Israel Studies on HPV prevalence among PeIN 2/3 cases in Israel Studies on HPV prevalence among men in Israel Studies on HPV prevalence among men from special subgroups in Israel Studies on oral HPV prevalence among healthy in Israel Studies on HPV prevalence among cases of oral cavity cancer in Israel Studies on HPV prevalence among cases of oropharyngeal cancer in Israel Studies on HPV prevalence among cases of hypopharyngeal or laryngeal cancer in Israel Factors contributing to cervical carcinogenesis (cofactors) in Israel Percentage of 15-year-olds who have had sexual intercourse in Israel Median age at first sex in Israel Marriage patterns in Israel Average number of sexual partners in Israel Lifetime prevalence of anal intercourse in women in Israel Main characteristics of cervical cancer screening in Israel Estimated coverage of cervical cancer screening in Israel Estimated coverage of cervical cancer screening in Israel, by region HPV vaccine introduction in Israel Prevalence of male circumcision in Israel Prevalence of condom use in Israel General immunization schedule in Israel Immunization coverage estimates in Israel

8 1 INTRODUCTION Introduction Figure 1: Israel in Western Asia The ICO Information Centre on HPV and Cancer (HPV Information Centre) aims to compile and centralize updated data and statistics on human papillomavirus (HPV) and related cancers. This report aims to summarize the data available to fully evaluate the burden of disease in Israel and to facilitate stakeholders and relevant bodies of decision makers to formulate recommendations on cervical cancer prevention. Data include relevant cancer statistic estimates, epidemiological determinants of cervical cancer such as demographics, socioeconomic factors, risk factors, burden of HPV infection, screening and immunization. This report is part of the PREHDICT project (health-economic modelling of Prevention strategies for Hpv-related Diseases in European CounTries) granted by the EU Seven Franmework Programme. PREHDICT has been projected to provide objective data and supported criteria for future cancer prevention across European countries. Its overall goals are to determine prerequisites and strategies for vaccination in European countries and to predict the impact of vaccination on screening programmes. The report is structured into the following sections: The ICO Information Centre on HPV and Cancer (HPV Information Centre) participates in the PREHDICT project compiling and centralizing updated data and statistics on human papillomavirus (HPV) and HPV-related cancers of European countries. The aim is to disseminate the information to all European countries concerned to facilitate stakeholders and relevant bodies of decision makers to formulate recommendations on the prevention of cervical cancer and other HPV-related cancers. This is a Israel report based on data from the European epidemiological database specifically created for this project. Data include relevant cancer statistic estimates, epidemiological determinants of cervical cancer such as demographics, socioeconomic factors, risk factors, burden of HPV infection, screening and immunization. The report is structured into the following sections: Section 2, Demographic and socioeconomic factors. This section summarizes the socio-demographic profile of Israel, 43 European countries are covered in the PREHDICT project: EU-27 (Austria,

9 1 INTRODUCTION Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and United Kingdom), 12 Associated Countries (Albania, Bosnia and Herzegovina, Croatia, FYR Macedonia, Iceland, Israel, Liechtenstein, Montenegro, Norway, Serbia (including Kosovo), Switzerland and Turkey) and 4 countries from Eastern Europe (Russia Federation, Belarus, Republic of Moldova and Ukraine) (Figure 1). Section 3, Burden of HPV related cancers. This section describes the current burden of invasive cervical cancer and other HPV-related cancers in Israel with estimates of prevalence, incidence and mortality rates. Information in other HPV-related cancers includes other anogenital cancers (anus, vulva, vagina, and penis), head and neck cancers (oral cavity, oropharynx, and hypopharynx) genital warts and recurrent respiratory papillomatosis. Section 4, HPV related statistics. This section reports on prevalence of HPV and HPV type-specific distribution in Israel, in women with normal cytology, precancerous lesions and invasive cervical cancer. In addition, the burden of HPV in other anogenital cancers (anus, vulva, vagina, and penis), head and neck cancers (oral cavity, oropharynx, and hypopharynx) and men is presented. Section 5, Factors contributing to cervical cancer. 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, Sexual and reproductive health behaviour indicators. This section presents sexual and reproductive behaviour indicators that may be used as proxy measures of risk for HPV infection and anogenital cancers, such as age at first sexual intercourse, average number of sexual partners, and receptive anal intercourse among others. Section 7, HPV preventive strategies. This section 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. Section 8, Protective factors for cervical cancer. This section presents male circumcision and the use of condoms have shown a significant protective effect against HPV transmission.. Section 9, Indicators related to immunization practices other than HPV vaccines. This section presents data on immunization coverage and practices for selected vaccines. This information will be relevant for assessing the country s capacity to introduce and implement the new HPV vaccines.

10 2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS Demographic and socioeconomic factors Figure 2: Population pyramid of Israel 2015 Males Females Under 5 96, ,679 67,141 88,305 89, , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,047 Population of Israel by sex and age group Data accessed on 26 Aug Estimated population in a country, area or region as of 1 July of the year indicated. United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision. Available at: [Accessed: August 2015] Number of women (in thousands) 1, Figure 3: Population trends of four selected age groups in Israel Women yrs Girls yrs Projections Number of women (in thousands) 10,000 8,000 6,000 4,000 2, All Women Women yrs Projections Female population trends in Israel Number of women by year and age group Data accessed on 26 Aug Estimated population in a country, area or region as of 1 July of the year indicated. United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision. Available at: [Accessed: August 2015]

11 2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS Table 2: Sociodemographic indicators in Israel Indicator Male Female Total Population in 1,000s 1,a 3, , ,064.0 Population growth rate (%) α,± Median age of the population (years) α, Population living in urban areas (%) 2,α, Crude birth rate (births per 1,000 population) α,± Crude death rate (deaths per 1,000 population) α,± Life expectancy at birth (years) 3, Adult mortality rate (probability of dying between 15 and 60 years per 1, population) 3, Under-five mortality rate (per 1,000 live births) 3, Density of physicians (per 10,000 population) 4,b,c, Gross national income per capita (PPP int $) 5, Adult (15 years and over) literacy rate (%) 6, Youth (15-24 years) literacy rate (%) 6, Net primary school enrollment ratio 6, Net secondary school enrollment ratio 6, Data accessed between 09 Jul 2013 to 26 Aug a Estimated population in a country, area or region as of 1 July of the year indicated. b Density (per 10,000 population) and number of physicians. c Includes generalist medical practitioners and specialist medical practitioners. Year of estimation: ± ; 2010; 2013; 2012; 2014; 2011; α For methods of estimation, please refer to original source. 1 United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision. Available at: [Accessed: August 2015] 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 Health Statistics Geneva, World Health Organization, Available at: [Accessed on July 2015]. 4 WHO Global Health Workforce Statistics [online database]. Geneva, World Health Organization, Available at: on July 2015] 5 World Development Indicators Database, Washington, DC, World Bank. Available at: [Accessed on July 2015] 6 UNESCO Institute for Statistics Data Centre [online database]. Montreal, UNESCO Institute for Statistics, Available at: [Accessed on July 2015]

12 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 265,672 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 Israel and in comparison to geographic region, including estimates of the annual number of new cases, deaths, and incidence and mortality rates Cervical cancer incidence in Israel KEY STATS. About 203 new cervical cancer cases are diagnosed annually in Israel (estimations for 2012). Cervical cancer ranks as the 15 th cause of female cancer in Israel. Cervical cancer is the 6 th most common female cancer in women aged 15 to 44 years in Israel. Table 3: Cervical cancer incidence in Israel (estimations for 2012) Indicator Israel Western Asia World Annual number of new cancer cases 203 4, ,624 Crude incidence rate a Age-standardized incidence rate a Cumulative risk (%) at 75 years old b Data accessed on 15 Nov Incidence data is available from high quality national data or high quality regional (coverage greater than 50%) sources. Data is included in Cancer incidence in Five Continents (CI5) volume IX and/or X. Incidence rates were estimated projecting rates to For more detailed methods of estimation please refer to 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. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

13 3 BURDEN OF HPV RELATED CANCERS Table 4: Cervical cancer incidence by cancer registry in Israel (observed cases during the specified period) Cancer registry Period N cases a Crude rate b ASR b National National (Jews) National (Jews born in Africa or Asia) National (Jews born in America or Europe) National (Jews born in Israel) National (Non-Jews) Data accessed on 05 May ASR: Age-standardized rate, Standardized rates have been estimated using the direct method and the World population as the reference; Please refer to original source (available at a Accumulated number of cases during the period in the population covered by the corresponding registry. b Rates per 100,000 women per year. 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. 2 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. Figure 4: Incidence of cervical cancer compared to other cancers in women of all ages in Israel (estimations for 2012) Breast Colorectum (a) Lung Corpus uteri Non Hodgkin lymphoma (b) Thyroid Melanoma of skin Pancreas Leukaemia Ovary Kidney Stomach Bladder Brain, nervous system Cervix uteri Multiple myeloma Hodgkin lymphoma Lip, oral cavity Liver Gallbladder Oesophagus Kaposi sarcoma (c) Larynx Nasopharynx Other pharynx Annual crude incidence rate per 100,000 Israel: Female (All ages) Data accessed on 15 Nov a Includes anal cancer (C21). b Includes HIV disease resulting in malignant neoplasms (B21). c Includes B21.0 (HIV disease resulting in Kaposi sarcoma). Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

14 3 BURDEN OF HPV RELATED CANCERS Figure 5: Age-specific cervical cancer incidence compared to age-specific incidence of other cancers among women years of age in Israel (estimations for 2012) Breast Thyroid Melanoma of skin Hodgkin lymphoma Non Hodgkin lymphoma (a) Cervix uteri Colorectum (b) Brain, nervous system Leukaemia Ovary Lung Corpus uteri Kidney Stomach Pancreas Lip, oral cavity Multiple myeloma Bladder Nasopharynx Liver Larynx Oesophagus Gallbladder Other pharynx Kaposi sarcoma (c) Annual crude incidence rate per 100,000 Israel: Female (15 44 years) Data accessed on 15 Nov a Includes HIV disease resulting in malignant neoplasms (B21). b Includes anal cancer (C21). c Includes B21.0 (HIV disease resulting in Kaposi sarcoma). Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

15 3 BURDEN OF HPV RELATED CANCERS Figure 6: Annual number of cases and age-specific incidence rates of cervical cancer in Israel (estimations for 2012) Age specific rates of cervical cancer Annual number of new cases of cervical cancer * yrs: 19 cases yrs: 21 cases yrs: 22 cases yrs: 25 cases yrs: 25 cases Age group (years) 49 *15-19 yrs: 0 cases yrs: 1 cases yrs: 6 cases yrs: 14 cases yrs: 21 cases. Data accessed on 15 Nov Rates per 100,000 women per year. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

16 3 BURDEN OF HPV RELATED CANCERS Cervical cancer incidence by histology in Israel Table 5: Age-standarized incidence rates of cervical cancer by histological type and cancer registry in Israel Carcinoma Cancer registry Period Squamous Adeno Other Unspec. National National (Jews) a National (Non-Jews) a Data accessed on 24 Jul Adeno: adenocarcinoma; Other: Other carcinoma; Squamous: Squamous cell carcinoma; Unspec: Unspecified carcinoma; Standarized rates have been estimated using the direct method and the World population as the references. Rates per 100,000 women per year. Rates per 100,000 women per year. Standarized rates have been estimated using the direct method and the World population as the references. a Care should be taken in interpreting the estimates. Some limitations were present in determining the number of cases or the population at risk that could affect the ability to make direct comparisons with other registry datasets. 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.

17 3 BURDEN OF HPV RELATED CANCERS Figure 7: Time trends in cervical cancer incidence in Israel (observed cases in the cancer registries) Cervix uteri Annual crude incidence rate (per 100,000) Recent trend : 2.2 ( 4.1 to 0.2) (1, b) Overall trend : 0.6 (0.1 to 1.1) (1, a) All ages (2) yrs (2) yrs (2) Cervix uteri: Squamous cell carcinoma 20 Annual crude incidence rate (per 100,000) All ages (2) yrs (2) yrs (2) Cervix uteri: Adenocarcinoma 20 Annual crude incidence rate (per 100,000) All ages (2) yrs (2) yrs (2) * * * * * *No cases were registered for this age group. Data accessed between 22 Jul 2014 to 27 Apr a Estimated annual percentage change based on the trend variable from the net drift for the most recent two 5-year periods. b Estimated annual percentage change based on the trend variable from the net drift for 25 years, from Vaccarella S, Lortet-Tieulent J, Plummer M, Franceschi S, Bray F. Worldwide trends in cervical cancer incidence: Impact of screening against changes in disease risk factors. eur J Cancer 2013;49: Ferlay J, Bray F, Steliarova-Foucher E and Forman D. Cancer Incidence in Five Continents, CI5plus: IARC CancerBase No. 9 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from: Year

18 3 BURDEN OF HPV RELATED CANCERS Cervical cancer incidence in Israel across Western Asia Figure 8: Age-standardized incidence rates of cervical cancer of Israel (estimations for 2012) Georgia Armenia Azerbaijan UAE Bahrain Oman Qatar Lebanon Israel Turkey Kuwait Yemen Iraq Saudi Arabia Syria Jordan Palestine Cervical cancer: Age standardized incidence rate per 100,000 women per year World Standard. Female (All ages) Data accessed on 15 Nov Rates per 100,000 women per year. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from: Figure 9: Age-specific incidence rates of cervical cancer in Israel compared to its region and the world Age specific rates of cervical cancer Israel Western Asia World >=75 Age group (years) Data accessed on 15 Nov Rates per 100,000 women per year. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

19 3 BURDEN OF HPV RELATED CANCERS Figure 10: Annual number of new cases of cervical cancer by age group in Israel (estimations for 2012) Israel Western Asia 1000 Annual number of new cases of cervical cancer * * >=75 Age group (years) *0 cases for Israel and 2 cases for Western Asia in the age group. 1 cases for Israel and 17 cases for Western Asia in the age group. Data accessed on 15 Nov Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

20 3 BURDEN OF HPV RELATED CANCERS Cervical cancer mortality in Israel KEY STATS. About 121 cervical cancer deaths occur annually in Israel (estimations for 2012). Cervical cancer ranks as the 12 th cause of female cancer deaths in Israel. Cervical cancer is the 4 th leading cause of cancer deaths in women aged 15 to 44 years in Israel. Table 6: Cervical cancer mortality in Israel (estimations for 2012) Indicator Israel Western Asia World Annual number of deaths 121 1, ,672 Crude mortality rate a Age-standardized mortality rate a Cumulative risk (%) at 75 years old b Data accessed on 15 Nov Mortality data is available from medium quality (criteria defined in Mathers et al. 2005) complete vital registration sources. Mortality rates were estimated projecting rates to For more detailed methods of estimation please refer to 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. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

21 3 BURDEN OF HPV RELATED CANCERS Figure 11: Cervical cancer mortality compared to other cancers in women of all ages in Israel (estimations for 2012) Breast Colorectum (a) Lung Pancreas Ovary Leukaemia Non Hodgkin lymphoma (b) Stomach Brain, nervous system Liver Corpus uteri Cervix uteri Multiple myeloma Melanoma of skin Kidney Bladder Oesophagus Gallbladder Thyroid Lip, oral cavity Hodgkin lymphoma Other pharynx Larynx Kaposi sarcoma (c) Nasopharynx Annual crude mortality rate per 100,000 Israel: Female (All ages) Data accessed on 15 Nov a Includes anal cancer (C21). b Includes HIV disease resulting in malignant neoplasms (B21). c Includes B21.0 (HIV disease resulting in Kaposi sarcoma). Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

22 3 BURDEN OF HPV RELATED CANCERS Figure 12: Age-specific mortality rates of cervical cancer compared to other cancers among women years of age in Israel (estimations for 2012) Breast Leukaemia Colorectum (a) Cervix uteri Brain, nervous system Lung Stomach Ovary Non Hodgkin lymphoma (b) Melanoma of skin Hodgkin lymphoma Pancreas Thyroid Oesophagus Liver Multiple myeloma Lip, oral cavity Kidney Corpus uteri Other pharynx Nasopharynx Larynx Kaposi sarcoma (c) Gallbladder Bladder Annual crude mortality rate per 100,000 Israel: Female (15 44 years) Data accessed on 15 Nov a Includes anal cancer (C21). b Includes HIV disease resulting in malignant neoplasms (B21). c Includes B21.0 (HIV disease resulting in Kaposi sarcoma). Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

23 3 BURDEN OF HPV RELATED CANCERS Figure 13: Annual number of deaths and age-specific mortality rates of cervical cancer in Israel (estimations for 2012) Age specific rates of cervical cancer Annual number of deaths of cervical cancer * yrs: 13 cases yrs: 12 cases yrs: 10 cases yrs: 9 cases yrs: 8 cases Age group (years) 60 * yrs: 0 cases yrs: 0 cases yrs: 1 cases yrs: 2 cases yrs: 6 cases. Data accessed on 15 Nov Rates per 100,000 women per year. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

24 3 BURDEN OF HPV RELATED CANCERS Cervical cancer mortality in Israel across Western Asia Figure 14: Age-standardized mortality rates of cervical cancer in Israel compared to region s countries (estimations for 2012) Georgia Armenia UAE Azerbaijan Oman Qatar Israel Kuwait Yemen Bahrain Turkey Lebanon Iraq Syria Saudi Arabia Jordan Palestine Cervical cancer: Age standardized mortality rate per 100,000 women per year World Standard. Female (All ages) Data accessed on 15 Nov Rates per 100,000 women per year. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from: Figure 15: Age-specific mortality rates of cervical cancer in Israel compared to its region and the world Age specific rates of cervical cancer Israel Western Asia World >=75 Age group (years) Data accessed on 15 Nov Rates per 100,000 women per year. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

25 3 BURDEN OF HPV RELATED CANCERS Figure 16: Annual deaths number of cervical cancer by age group in Israel (estimations for 2012) Israel Western Asia 400 Annual number of new cases of cervical cancer * * >=75 Age group (years) *0 cases for Israel and 0 cases for Western Asia in the age group. 0 cases for Israel and 1 cases for Western Asia in the age group. 1 cases for Israel and 9 cases for Western Asia in the age group. Data accessed on 15 Nov Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from:

26 3 BURDEN OF HPV RELATED CANCERS Cervical cancer incidence and mortality comparison, Premature deaths and disability in Israel Figure 17: Comparison of age-specific incidence and mortality rates of cervical cancer in Israel (estimations for 2012) Age specific rates of cervical cancer Incidence (N) Mortality (N) >=75 Age group (years) Data accessed on 15 Nov Rates per 100,000 women per year. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from: Table 7: Premature deaths and disability from cervical cancer in Israel, Western Asia and World (estimations for 2008) Israel Western Asia World Indicator Number ASR (W) Number ASR (W) Number ASR (W) Estimated disability-adjusted life 2, , ,738, years (DALYs) Years of life lost (YLLs) 2, , ,788, Years lived with disability (YLDs) , , Data accessed on 04 Nov Soerjomataram I, Lortet-Tieulent J, Parkin DM, Ferlay J, Mathers C, Forman D, Bray F. Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. Lancet Nov 24;380(9856):

27 3 BURDEN OF HPV RELATED CANCERS Figure 18: Number of annual premature deaths and disability from cervical cancer in Israel compared to other cancers among women (estimations for 2008) Breast ca. Colorectal ca. Lung ca. Pancreatic ca. Ovarian ca. Ca. of the brain and CNS Non Hodgkin lymphoma Leukaemia Stomach ca. Cervix uteri ca. Corpus uteri ca. Liver ca. Melanoma of skin Multiple myeloma Bladder ca. Kidney ca. Thyroid ca. Oesophageal ca. Hodgkin lymphoma Ca. of the lip and oral cavity Gallbladder Laryngeal ca. Nasopharyngeal ca. Other pharynx ca. Kaposi sarcoma 6,467 5,632 5,253 4,338 4,161 3,308 2,802 2,749 1,901 1,863 1,683 1,547 1, ,147 12,783 29,327 YLLs YLDs Estimated disability adjusted life years (DALYs). Data accessed on 04 Nov CNS: Central Nervous System; YLDs: years lived with disability; YLLs: Years of life lost; Soerjomataram I, Lortet-Tieulent J, Parkin DM, Ferlay J, Mathers C, Forman D, Bray F. Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. Lancet Nov 24;380(9856):

28 3 BURDEN OF HPV RELATED CANCERS Anogenital cancers other than the cervix Data on HPV role in anogenital cancers other than cervix are limited, but there is an increasing body of evidence strongly linking HPV DNA with cancers of 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 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 8: Anal cancer incidence by cancer registry and sex in Israel (observed cases during the specified period) MALE FEMALE Cancer registry Period N cases a Crude rate b ASR b N cases a Crude rate c ASR c National National (Jews) National (Jews born in Africa or Asia) 2 National (Jews born in Europe or America) 2 National (Jews born in Israel) 2 National (Non- Jews) 1 Data accessed on 05 May ASR: Age-standardized rate, Standardized rates have been estimated using the direct method and the World population as the reference; Please refer to original source (available at 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. 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. 2 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.