Burden of HPV associated diseases in Latin America MEXICO May 2008 F. Xavier Bosch Institut Catalá d’Oncología HPV: LIKELY TO BE THE NUMBER 2 HUMAN CARCINOGEN (AFTER TOBACCO) à 5% OF HUMAN CANCER à 10% OF CANCER IN WOMEN à 15% OF CANCER IN WOMEN IN DEVELOPING COUNTRIES WORLDWIDE ESTIMATES ON THE BURDEN OF HPV & RELATED GENITAL DISEASES Cervical Cancers 0.5 million 10 million Genital Warts 30 million 30 million Screen detected only High-grade Cervical Lesions Low-grade Cervical Lesions 300 million HPV infection - no abnormality The burden of HPV infections in women HPV DNA PREVALENCE IN 150.000 WOMEN WITH NORMAL CITOLOGY ADJUSTED MODEL GLOBAL 10.4% (10.2-10.7) AFRICA 22.1 % (20.9-23.4) AMERICA North Central-South 11.3 % (10.6 – 12.1) 20.4 % (19.3 – 21.4) EUROPE 8.1 % (7.8-8.4) ASIA 7.9 % (7.5-8.4) De Sanjose et al Lancet 2007 ETIOLOGICAL EVIDENCE ON THE EPIDEMIOLOGY OF HPV AND CERVICAL CANCER HPV IS A NECESSARY CAUSE § PREVALENCE: Under adequate materials and testing systems HPV DNA is always present in cervical cancer § CASE-CONTROL: The relative risk is high, consistent worldwide and includes both major histological types § COHORT STUDIES: The absolute risk of progression to cervical pre-cancer is high following persistent HPV infection. § INTERVENTION PRIMARY: HPV 16 & 18 vaccines reduced the incidence of CIN 2/3 (projected to cervical cancer) § INTERVENTION SECONDARY: HPV screening reduced the incidence of CIN 3+ (projected to cervical cancer) IARC MONOGRAPH: SCREENING FOR CERVICAL CANCER 2005 & 2007 The burden of HPV – RELATED CANCER in women HPV related cancers in women 530 000 new cases per year • Cervical • Vulvar 95-98% of the cases • Vagina 65-90 % of the cases • Anal 80 + % of the cases (both sexes) 30-35 % of the cases • Oral / Larynx 23-24% of the cases (both sexes) • Oro-pharynx 30-35-72%... (both sexes) • Other conjunctiva. ungueal bed… anecdotal HPV-attributable cancers in women Estimates 2002 SITE TOTAL cancers % HPV Attributable to HPV Attributable to HPV 16/18 % of HPV 16/18 Cervix 492,800 100 492,800 344,900 70 Vulva, Vagina 40,000 40 16,000 12,800 80 Anus 15,900 90 14,300 13,100 92 Oropharynx 9,600 11 (60 +) 1,100 1,000 91 Mouth 98,400 3 (25 +) 2,900 2,800 97 10.4 527,100 374,600 TOTAL 5.060.700 Adapted from D. M. Parkin, F. Bray, Vaccine 24 Suppl 3, S11 (2006). RANKING OF WORLD’S COUNTRIES ON INCIDENCE RATES OF CERVICAL CANCER WOMEN ALL AGES BY DEVELOPMENT LEVEL Less developed regions More developed regions N countries % N countries % 1st 58 45.7 % 0 0.0 % 2nd 46 36.2 % 4 9.1 % 3rd 7 6.0 % 4 9.1 % 4th 6 5.0 % 3 6.8 % 5th 2 1.6 % 7 15.9 % 6 or + 8 6.3 % 26 59.1 % TOTAL 127 44 GLOBOCAN 2002 RANKING RANKING OF WORLD’S COUNTRIES ON INCIDENCE RATES OF CERVICAL CANCER WOMEN AGED 15-44 BY DEVELOPMENT LEVEL Less developed regions More developed regions N countries % N countries % 1st 58 45.7 % 1 2.3 % 2nd 49 38.6 % 27 61.4 % 3rd 7 5.5 % 13 29.5 % 4th 2 1.6 % 3 6.8 % 5th 2 1.6 % 0 0.0 % 6 or + 9 7.2 % 0 0.0 % TOTAL 127 44 GLOBOCAN 2002 RANKING The Morelos HPV study ICO Study Male factor studies Vaccination trials Mexican-Us Border study Guatemala Case control study IARC Prevalence Survey Honduras ICO study NCI Case Control ICO study Rivas screening project Nicaragua ICO study Venezuela The Guanacaste project NCI Case Control The Ludwig-McGill cohort Vaccination trials The Latin American Screening Study (LAMS) NCI Case Control Colombia IARC Case Control The Bogotá Cohort ICO study IARC Case Control Vaccination trials IARC Prevalence Survey NCI Case Control ICO study IARC Case Control Vaccination trials ICO study Paraguay The TATI Project IARC Case Control Vaccination trials The Latin American Screening Study (LAMS) Chile IARC prevalence Survey IARC prevalence Survey ICO study ICO study SELECTED HPV RESEARCH PROJECTS IN AMERICA LATINA Argentina ICO study Brazil Panamá Peru Costa Rica Vaccination trials ESTIMATED NUMBER OF CERVICAL CANCER CASES in 2002 : 490.000 N. AMERICA 14,670 EUROPE 59,931 ASIA 265,884 C-S. AMERICA 71,862 < 87.3 AFRICA 78,897 < 32.6 < 26.2 < 16.2 Age-adjusted incidence rates per 100,000 women per year < 9.3 MOST COMMON CANCERS IN WOMEN : INCIDENCE & MORTALITY Central & South America Incidence Mortality 40,3 BREAST 29,2 CERVIX 13,2 COLON/RECTO 13,9 CERVIX 13,6 PULMÓN 7,4 7,0 PULMÓN 7,6 COLON/RECTO OVARIO 7,3 HÍGADO 6,4 PÁNCREAS CORPUS 0 10 20 8,7 ESTÓMAGO 11,4 ESTÓMAGO BREAST 30 40 50 60 70 0 5,1 4,2 10 20 30 40 50 60 GLOBOCAN 2002 RANKING OF COUNTRIES IN LATIN AMERICA ON INCIDENCE RATES OF CERVICAL CANCER WOMEN ALL AGES RANKING N countries % 1st 14 50.0% 2nd 12 42.9% 3rd 1 3.6% 4th 1 3.6% 5th 0 0.0% 6 or + 0 0.0% RANKING OF COUNTRIES IN LATIN AMERICA ON INCIDENCE RATES OF CERVICAL CANCER WOMEN ALL AGES RANKING N countries % 1st 14 50.0% 2nd 12 42.9% 3rd 1 3.6% 4th 1 3.6% 5th 0 0.0% 6 or + 0 0.0% RANKING OF COUNTRIES IN LATIN AMERICA ON INCIDENCE RATES OF CERVICAL CANCER WOMEN ALL AGES RANKING N countries % 1st 14 50.0% 2nd 12 42.9% 3rd 1 3.6% 4th 1* 3.6% 5th 0 0.0% 6 or + 0 0.0% *Puerto rico Time trends in target populations & predicted impact on HPV related cancers in women (all other things being equal) Worldwide Female population Developed regions 85+ 80-84 75-79 70-74 65-69 60-64 55-59 50-54 45-49 40-44 35-39 30-34 25-29 20-24 15-19 10-14 5-9 Under 5 14M 17M 23M 26M 31M 31M 39M 43M 45M 46M 44M 43M 41M 41M 40M 36M 33M 32M Developing regions 9M 16M 30M 44M 58M 70M 90M 80% of cervical cancer 118M 134M 161M 186M 200M 206M 230M 254M 258M 260M 269M Population Source: 2005 estimates. United Nations, Population Division. World Population Prospects-the 2004 revision. New York, 2005. Women 15 + years. Population prospects Number of women (in millions) 3000 Developing Regions Developed Regions 2500 2000 1500 1000 500 19 50 19 55 19 60 19 65 19 7 19 0 75 19 8 19 0 8 19 5 9 19 0 9 20 5 0 20 0 05 20 1 20 0 1 20 5 20 20 2 20 5 30 20 35 20 40 20 45 20 50 0 Source: 2005 estimates. United Nations, Population Division. World Population Prospects-the 2004 revision. New York, 2005. PREDICTED NUMBER OF CASES OF CERVICAL CANCER IN 2020 : THE AMERICAS BY AREA 2002 2020* (% CHANGE) 2020* (%BURDEN) WORLD 493.243 702.746 (42%) América 86.532 122.162 (41%) 100% Central 17.165 29.794 (74%) 24% Sur 48.328 74.785 (55%) 61% Norte 14.670 18.112 (23%) 15% Caribe 6.369 8.685 (36%) 7% * Projections asume constant rates in the interval at the 2002 estimates THE RELEVANCE OF VIRAL TYPE IN CERVICAL (and other genital) CARCINOMA : Present and future vaccine composition Understanding cross protection Management protocols in HPV based screening PRELIMINARY RESULTS • • • • • Vulvar cancer Cases: 312 Mean age: 72.1 Range: 49.2 - 77.4 Histology – SCC: 69 % – Warty.basaloid: 21 % – Other: 10 % • HPV DNA: 27.9 % • HPV 16: 52.9 % of the HPV+ • • • • • Vaginal cancer Cases: 99 Mean age: 60.9 Range: 41.4 - 70.0 Histology – SCC: 98 % • HPV DNA: 78.8 % • HPV 16: 51.3 % of the HPV+ HPV TYPE DISTRIBUTION IN VULVAR AND VAGINAL CANCERS VULVA VAGINA VULVA VAGINA HPV Type N % N % HPV Type N % N % 16 46 52,9 40 51,3 39/68/73 0 0.0 2 2.6 HPV X 9 10,3 4 5,1 31 1 1.1 4 5.1 45 6 6,9 2 2,6 44 1 1.1 0 0.0 18 4 4,6 2 2,6 68 1 1.1 1 1.3 6 2 2,3 1 1,3 51 1 1.1 6 7.7 33 3 3,4 2 2.6 66 1 1.1 0 0.0 52 3 3.4 2 2.6 11,39 1 1.1 0 0.0 35 2 2.3 1 1.3 16,68 0 0.0 1 1.3 39 1 1.1 4 5.1 16,56 0 0.0 1 1.3 56 2 2.3 1 1.3 33,45,6 0 0.0 1 1.3 58 2 2.3 3 3.8 16,6,39/68/73 1 1.1 0 0.0 HPV DNA PREVALENCE & TYPE SPECIFIC RELATIVE FREQUENCY IN CANCERS OF THE PENIS AND THE ANAL CANAL HPV TYPE PENILE (n=1152) ANAL Range of studies HPV 47.3 % (46-100%) 80-95 % 16 68.2 % (60-100%) 80 % 18 34.1 % 5-8% % Smith et al 2007. IARC monograph HPV DNA PREVALENCE & TYPE SPECIFIC RELATIVE FREQUENCY IN CANCERS OF THE HEAD & NECK HPV TYPE ORAL (N= 2.642) OROPHARYNX (N= 969) LARYNX (N= 1.435) HPV 23.5 % 35.6 % 24.0 % 16 68.2 % 86.7 % 69.2 % 18 34.1 % 2.8 % 17.0 % < 1% < 1% < 1% ANY OTHER Kreimer et al 2005 Non cancerous HPV related Lesions Genital warts & Recurrent Respiratory papilomatosis linked to HPV 6 and 11 (limited information from latin ameica) EPIDEMIOLOGY of GENITAL WARTS. Cohort study § Of 31 cases, 84% tested positive for hpv 6 or11 § Median time to progression after infection was 2,9 months (ci 0–5,7 years) § Median time to resolution with treatment was 5,9 months (ci 3,9 - 8,0 meses) § Social and psicological problems are relevant WINER RL ET AL. J INFECT DIS. 2005;191:731-738. § In women exposed to HPV 6 or 11, the cumulative incidence of GW was of 66.2% (ci 52.8-79.2) at month 36 Number of partners and % of ever GW The Copenhagen survey: Ever GW 17% 14 1% of the sexually active population? GW % 10 11,6 8,3 8 6 5,5 3,9 4 2 1 1,9 0 1-2 3-4 5-9 10-14 15-39 Number of partners 40+ MUNK C ET AL. SEX TRANSM DIS. 1997;24:567-572. 12 Selected characteristics with regard to sexual habits and genital warts in the 4 Nordic countries in Europe Characteristic Self-reported history of genital warts % (95% CI) Lifetime no. of sex partners, mean (range) Age at first diagnosis of genital warts, mean (range) Genital warts during the last 12 months, % (95% CI) Denmark Iceland 10.1 12.0 (9.7–10.5) (11.5–12.6) Norway Sweden 9.5 11.3 (9.0–9.9) (10.8–11.8) 8.4 (0–500) 8.8 (0–100) 7.4 (0–100) 8.6 (0–450) 21.9 (6–45) 21.3 (14–43) 22.7 (3–45) 21.9 (14–44) 1.3 (1.2–1.5) 1.9 (1.7–2.1) 1.1 (1.0–1.3) 1.0 (0.9–1.2) Kjaer 2007 JID Estimated cumulative incidence of selfreported clinically diagnosed genital warts Estimated cumulative incidence of self-reported clinically diagnosed genital warts, by country and birth cohort. The cumulative incidence of having had genital warts up to a certain age was estimated on the basis of information on age at first diagnosis of genital warts. Kjaer 2007 JID Laryngeal Papillomatosis Glikman (2005) New Eng J Med Laryngeal Papillomatosis Description of clinical entity • Benign growths of respiratory tract in juveniles and adults • Caused largely by HPV 6 and HPV 11 • In infants is generally attributed to exposure to genital warts in the birth canal . About 1/500 births to mothers with genital HPV ultimately develop symptomatic disease • Adult-onset disease is considered to be a rare consequence of HPV transmission during oral intercourse • Many patients require multiple surgeries, more severe prognosis for HPV 11-related, 1-3% die of the disease. • Deaths to respiratory obstruction are largely unreported Conclusions : HPV related cancers in the latin america & the caribbean region • Cervical cancer is a public health and a cancer control priority in the latin American region • HPV 16 & 18 are responsible of 70% of cervical cancer cases followed by HPV 45, 31 y 33 • These HPV types are also responsible for a significant fraction of vulvar cancer (40%), vaginal cancer (80%), penile cancer (40%), anal cancer (80%) and cancers of the oral cavity (25%) and the oropharynx (35%) • There are no significant differences in the HPV type implication in cancer across countries in the region nor over time Implications : Cancer Preventive options in the Latin America & the Caribbean region • Current HPV 16 & 18 vaccines have the potential to prevent some 70% of the cervical cancer cases, some 50% of the precursor lesions, and a significant fraction of all other cancers of the genital and oral tracts in women. • Screening should continue / expand for both vaccinated and non vaccinated women • Should male vaccination be implemented, herdprotection against female cancers is a possibility and significant reductions in penile, anal and oral/oropharyngeal cancers in man could follow LA PREVENCIÓN DEL CÁNCER CERVICAL EN TIEMPOS DEL VPH Es la segunda oportunidad sobre la tierra ICO INTERNATIONAL SURVEY PARTICIPANTS IN LATIN-AMERICA ARGENTINA BRASIL CHILE Silvio Alejandro Tatti, Susana Vighi (Hospital de Clínicas “José de San Martín”, Universidad de Buenos Aires, Sociedad Argentina de Patología) Marcus Aurelho de Lima, Sérgio Enrique de Almeida (Hospital Hélio Angotti, PATMED) Rodrigo Prado (Centro de Oncología Preventiva, Universidad de Chile); Ximena Rodríguez (Departamento de Anatomía Patológica, Hospital San José, Santiago) COLOMBIA GUATEMALA HONDURAS Luis E. Bravo, Luz Stella García, Titto Collazos (Hospital Universitario del Valle); Hector J. Posso (Liga Contra el Cáncer de Bogotá); Gustavo A. Hernández, Carlos E. Pinzón (Instituto Nacional de Cancerología, Bogotá); Gloria Inés Sánchez (Universidad de Antioquia) Edgar Kestler, Luis Lombardi, Victor Argueta, Obdulia Salic (Centro de Investigación Epidemiológica en Salud Sexual y Reproductiva – CIESAR, Hospital General San Juan de Dios - HGSJDD); Walter Guerra (Instituto Nacional del Cáncer – INCAN); Hesler Morales (Instituto Guatemalteco de Seguridad Social - IGSS, Instituto Nacional del Cáncer - INCAN); Sergio Marroquín, Victor Argueta (Hospital General San Juan de Dios – HGSJDD) Annabelle Ferrera (Universidad Nacional Autónoma de Honduras) MEXICO PARAGUAY VENEZUELA Patricia Alonso, Gustavo Lastra, Alma Karina Olivares Montano (Hospital General de México) Elena Kasamatsu, Francisco Perrota (Instituto de Investigaciones en Ciencias de la Salud – UNA) Enrique López Loyo (Sociedad Venezolana de Patología); Victoria García de Barriola, Mirian Naranjo de Gómez, Adayza Figueredo, Janira Navarro (Instituto Anatomopatológico de la Universidad Central de Venezuela) PERU Carlos Santos, Eduardo Cáceres, Henry Gómez, Juvenal Sánchez, Carlos Vallejos (Instituto Especializado de Enfermedades Neoplásicas) GRACIAS POR SU ATENCIÓN AGE -SPECIFIC HPV PREVALENCE AMONG WOMEN AGE-SPECIFIC WITH NORMAL CITOLOGY Adjusted NORTH AMERICA AFRICA CENTRAL & SOUTH AMERICA EUROPE ASIA 30 20 10 Age group <2 25 5 -3 35 4 -4 45 4 -5 4 >5 4 <2 25 5 -3 35 4 -4 45 4 -5 4 >5 4 4 >5 <2 25 5 -3 35 4 -4 45 4 -5 4 <2 25 5 -3 35 4 -4 45 4 -5 4 >5 4 >5 4 0 <2 25 5 -3 35 4 -4 45 4 -5 4 Prevalence of HPV (%) 40 WORLD: HPV type distribution Women with normal cytology World 16 2.5 18 0.9 31 0.7 58 0.6 52 0.6 33 0.6 51 0.5 56 0.4 35 0.4 42 0.4 0 1 2 3 4 . De Sanjosé et al. 2007 Lancet Infect Dis WHO/ICO Information Centre on HPV and Cervical Cancer www.who.int/hpvcentre ESTIMATED ANUAL INCIDENCE: 40.000 CASES OF VULVAR AND VAGINAL CANCERS Developed regions Developing regions DEVELOPED COUNTRIES: 15.700 Vulvar cancer 4.200 Vaginal cancer DEVELOPING COUNTRIES: § 11.100 Vulvar cancer § 9.000 Vaginal cancer RRP by age at diagnosis 250 womens 277 women 330 men 607 total 150 100 50 16 10 0 <=10 10 a 20 JORRP 28 51 40 35 17 20 a 30 30 a 40 Age at diagnosis 16 40 a 50 7 19 >= 50 CORTESÍA DE BILL STERN, RRPF 200 men 193 175 RANKING OF LATIN AMERICA’S COUNTRIES ON INCIDENCE RATES OF CERVICAL CANCER RANKING N countries % 1st 14 50.0% 2nd 12 42.9% 3rd 1 3.6% 4th 1 3.6% 5th 0 0.0% 6 or + 0 0.0%