Burden of HPV associated diseases in Latin America MEXICO May 28 F. Xavier Bosch Institut Catalá d Oncología
HPV: LIKELY TO BE THE NUMBER 2 HUMAN CARCINOGEN (AFTER TOBACCO) 5% OF HUMAN CANCER % OF CANCER IN WOMEN 5% OF CANCER IN WOMEN IN DEVELOPING COUNTRIES
WORLDWIDE ESTIMATES ON THE BURDEN OF HPV & RELATED GENITAL DISEASES Cervical Cancers.5 million million Screen detected only High-grade Cervical Lesions Genital Warts 3 million 3 million Low-grade Cervical Lesions 3 million HPV infection - no abnormality
The burden of HPV infections in women
HPV DNA PREVALENCE IN 5. WOMEN WITH NORMAL CITOLOGY ADJUSTED MODEL GLOBAL AFRICA AMERICA North Central-South EUROPE ASIA.4% (.2-.7) 22. % (2.9-23.4).3 % (.6 2.) 2.4 % (9.3 2.4) 8. % (7.8-8.4) 7.9 % (7.5-8.4) De Sanjose et al Lancet 27
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 6 & 8 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 25 & 27
The burden of HPV RELATED CANCER in women
HPV related cancers in women 53 new cases per year Cervical Vulvar Vagina Anal 95-98% of the cases 3-35 % of the cases 65-9 % of the cases 8 + % of the cases (both sexes) Oral / Larynx 23-24% of the cases (both sexes) Oro-pharynx 3-35-72%... (both sexes) Other conjunctiva. ungueal bed anecdotal
HPV-attributable cancers in women Estimates 22 SITE TOTAL cancers % HPV Attributable to HPV Attributable to HPV 6/8 % of HPV 6/8 Cervix 492,8 492,8 344,9 7 Vulva, Vagina 4, 4 6, 2,8 8 Anus 5,9 9 4,3 3, 92 Oropharynx 9,6 Mouth 98,4 (6 +) 3 (25 +),, 9 2,9 2,8 97 TOTAL 5.6.7.4 527, 374,6 Adapted from D. M. Parkin, F. Bray, Vaccine 24 Suppl 3, S (2
RANKING OF WORLD S COUNTRIES ON INCIDENCE RATES OF CERVICAL CANCER WOMEN ALL AGES BY DEVELOPMENT LEVEL Less developed regions More developed regions RANKING N countries % N countries % st 58 45.7 %. % 2 nd 46 36.2 % 4 9. % 3 rd 7 6. % 4 9. % 4 th 6 5. % 3 6.8 % 5 th 2.6 % 7 5.9 % 6 or + 8 6.3 % 26 59. % TOTAL 27 44 GLOBOCAN 22
RANKING OF WORLD S COUNTRIES ON INCIDENCE RATES OF CERVICAL CANCER WOMEN AGED 5-44 BY DEVELOPMENT LEVEL Less developed regions More developed regions RANKING N countries % N countries % st 58 45.7 % 2.3 % 2 nd 49 38.6 % 27 6.4 % 3 rd 7 5.5 % 3 29.5 % 4 th 2.6 % 3 6.8 % 5 th 2.6 %. % 6 or + 9 7.2 %. % TOTAL 27 44 GLOBOCAN 22
The Morelos HPV study Male factor studies Mexican-Us Border study IARC Prevalence Survey NCI Case Control ICO study Vaccination trials Costa Rica The Guanacaste project NCI Case Control Vaccination trials Colombia Panamá The Bogotá Cohort IARC Case Control IARC Prevalence Survey NCI Case Control ICO study Vaccination trials NCI Case Control ICO Study Vaccination trials Case control study ICO study Rivas screening project ICO study The Ludwig-McGill cohort The Latin American Screening Study (LAMS) IARC Case Control ICO study Vaccination trials IARC Case Control ICO study Guatemala Honduras Nicaragua Venezuela Paraguay Brazil The TATI Project Peru IARC Case Control ICO study Vaccination trials Chile IARC prevalence Survey ICO study IARC prevalence Survey The Latin American Screening Study (LAMS) ICO study Argentina SELECTED HPV RESEARCH PROJECTS IN AMERICA LATINA
ESTIMATED NUMBER OF CERVICAL CANCER CASES i 22 : 49. N. AMERICA 4,67 EUROPE 59,93 ASIA 265,884 C-S. AMERICA 7,862 AFRICA 78,897 < 87.3 < 32.6 < 26.2 < 6.2 < 9.3 Age-adjusted incidence rates per, women per year
MOST COMMON CANCERS IN WOMEN : INCIDENCE & MORTALITY Central & South America Incidence Mortality BREAST CERVIX COLON/RECTO ESTÓMAGO PULMÓN OVARIO 4,3 29,2 3,2,4 7,6 7,3 6,4 BREAST CERVIX ESTÓMAGO PULMÓN COLON/RECTO HÍGADO CORPUS PÁNCREAS 4,2 3,9 3,6 8,7 7,4 7, 5, 2 3 4 5 6 7 2 3 4 5 6 GLOBOCAN 2
RANKING OF COUNTRIES IN LATIN AMERICA ON INCIDENCE RATES OF CERVICAL CANCER WOMEN ALL AGES RANKING st 2nd 3rd 4th 5th 6 or + N countries 4 2 % 5.% 42.9% 3.6% 3.6%.%.%
RANKING OF COUNTRIES IN LATIN AMERICA ON INCIDENCE RATES OF CERVICAL CANCER WOMEN ALL AGES RANKING st 2nd 3rd 4th 5th 6 or + N countries 4 2 % 5.% 42.9% 3.6% 3.6%.%.%
RANKING OF COUNTRIES IN LATIN AMERICA ON INCIDENCE RATES OF CERVICAL CANCER WOMEN ALL AGES RANKING st 2nd 3rd 4th 5th 6 or + N countries 4 2 * % 5.% 42.9% 3.6% 3.6%.%.% *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 Developing regions 85+ 8-84 75-79 7-74 65-69 6-64 55-59 5-54 45-49 4-44 35-39 3-34 25-29 2-24 5-9 -4 5-9 Under 5 4M 7M 23M 26M 3M 3M 39M 43M 45M 46M 44M 43M 4M 4M 4M 36M 33M 32M 9M 6M 3M 44M 58M 7M 9M 8% of cervical cancer 8M 34M 6M 86M 2M 26M 23M 254M 258M 26M 269M pulation Source: 25 estimates. United Nations, Population Division. World Population Prospects-the 24 revision. New York, 25.
Women 5 + years. Population prospects 3 Developing Regions Developed Regions Number of women (in millions) 25 2 5 5 95 955 96 965 97 975 98 985 99 995 2 25 2 25 22 225 23 235 24 245 25 Source: 25 estimates. United Nations, Population Division. World Population Prospects-the 24 revision. New York, 25.
PREDICTED NUMBER OF CASES OF CERVICAL CANCER IN 22 : THE AMERICAS BY AREA 22 22* (% CHANGE) 22* (%BURDEN) WORLD 493.243 72.746 (42%) América 86.532 22.62 (4%) % Central 7.65 29.794 (74%) 24% Sur 48.328 74.785 (55%) 6% Norte 4.67 8.2 (23%) 5% Caribe 6.369 8.685 (36%) 7% * Projections asume constant rates in the interval at the 22 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: 32 Mean age: 72. Range: 49.2-77.4 Histology SCC: 69 % Warty.basaloid: 2 % Other: % HPV DNA: 27.9 % HPV 6: 52.9 % of the HPV+ Vaginal cancer Cases: 99 Mean age: 6.9 Range: 4.4-7. Histology SCC: 98 % HPV DNA: 78.8 % HPV 6: 5.3 % of the HPV+
HPV Type 6 HPV X 45 8 6 33 52 35 39 56 58 HPV TYPE DISTRIBUTION IN VULVAR AND VAGINAL VULVA N 46 9 6 4 2 3 3 2 2 2 % 52,9,3 6,9 4,6 2,3 3,4 3.4 2.3. 2.3 2.3 VAGINA N 4 4 2 2 2 2 4 3 CANCERS % 5,3 5, 2,6 2,6,3 2.6 2.6.3 5..3 3.8 HPV Type 39/68/73 3 44 68 5 66,39 6,68 6,56 33,45,6 6,6,39/68/73 VULVA N %........... VAGINA N 2 4 6 % 2.6 5...3 7.7...3.3.3.
HPV DNA PREVALENCE & TYPE SPECIFIC RELATIVE FREQUENCY IN CANCERS OF THE PENIS AND THE ANAL CANAL HPV TYPE HPV 6 8 PENILE (n=52) 47.3 % (46-%) 68.2 % (6-%) 34. % ANAL Range of studies 8-95 % 8 % 5-8% % Smith et al 27. 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=.435) HPV 23.5 % 35.6 % 24. % 6 68.2 % 86.7 % 69.2 % 8 34. % 2.8 % 7. % ANY OTHER < % < % < % Kreimer et al 25
Non cancerous HPV related Lesions Genital warts & Recurrent Respiratory papilomatosis linked to HPV 6 and (limited information from latin ameica)
EPIDEMIOLOGY of GENITAL WARTS. Cohort study In women exposed to HPV 6 or, the cumulative incidence of GW was of 66.2% (ci 52.8-79.2) at month 36 Of 3 cases, 84% tested positive for hpv 6 or Median time to progression after infection was 2,9 months (ci 5,7 years) Median time to resolution with treatment was 5,9 months (ci 3,9-8, meses) Social and psicological problems are relevant WINER RL ET AL. J INFECT DIS. 25;9:73-738.
Number of partners and % of ever GW The Copenhagen survey: Ever GW 7% 4 GW % 2 8 6 4 2 % of the sexually active population?,9 3,9 5,5 Number of partners 8,3,6-2 3-4 5-9 -4 5-39 4+ MUNK C ET AL. SEX TRANSM DIS. 997;24:567-572.
Selected characteristics with regard to sexual habits and genital warts in the 4 Nordic countries in Europe Characteristic Denmark Iceland Norway Swede elf-reported history of genital warts % (95% CI). (9.7.5) 2. (.5 2.6) 9.5 (9. 9.9). (.8.8 Lifetime no. of sex partners, mean (range) 8.4 ( 5) 8.8 ( ) 7.4 ( ) 8. ( 45 Age at first diagnosis of genital warts, mean (range) 2.9 (6 45) 2.3 (4 43) 22.7 (3 45) 2. (4 44 Genital warts during the last 2 months, % (95% CI).3 (.2.5).9 (.7 2.). (..3). (.9.2 Kjaer 27 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 27 JID
Glikman (25) New Eng J Med Laryngeal Papillomatosis
Laryngeal Papillomatosis Description of clinical entity Benign growths of respiratory tract in juveniles and adults Caused largely by HPV 6 and HPV In infants is generally attributed to exposure to genital warts in the birth canal. About /5 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 -related, -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 6 & 8 are responsible of 7% of cervical cancer cases followed by HPV 45, 3 y 33 These HPV types are also responsible for a significant fraction of vulvar cancer (4%), vaginal cancer (8%), penile cancer (4%), anal cancer (8%) 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 6 & 8 vaccines have the potential to prevent some 7% of the cervical cancer cases, some 5% 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 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) GUATEMALA 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) HONDURAS Annabelle Ferrera (Universidad Nacional Autónoma de Honduras) PERU Carlos Santos, Eduardo Cáceres, Henry Gómez, Juvenal Sánchez, Carlos Vallejos (Instituto Especializado de Enfermedades Neoplásicas) MEXICO Patricia Alonso, Gustavo Lastra, Alma Karina Olivares Montano (Hospital General de México) PARAGUAY Elena Kasamatsu, Francisco Perrota (Instituto de Investigaciones en Ciencias de la Salud UNA) VENEZUELA 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)
GRACIAS POR SU ATENCIÓN
AGE-SPECIFIC HPV PREVALENCE AMONG WOMEN WITH NORMAL CITOLOGY djusted 4 AFRICA NORTH AMERICA CENTRAL & SOUTH AMERICA EUROPE ASIA Prevalence of HPV (%) 3 2 <25 25-34 35-44 45-54 >54 <25 25-34 35-44 45-54 >54 <25 25-34 35-44 45-54 >54 <25 25-34 35-44 45-54 >54 <25 25-34 35-44 45-54 >54 Age group
. WORLD: HPV type distribution Women with normal cytology World 6 2.5 8.9 3 58 52 33 5 56 35 42.7.6.6.6.5.4.4.4 2 3 4 e Sanjosé et al. 27 Lancet Infect Dis WHO/ICO Information Centre on HPV and Cervical Cancer www.who.int/hpvcentre
ESTIMATED ANUAL INCIDENCE: 4. CASES OF VULVAR AND VAGINAL CANCERS Developed regions Developing regions EVELOPED COUNTRIES: 5.7 Vulvar cancer 4.2 Vaginal cancer DEVELOPING COUNTRIES:. Vulvar cancer 9. Vaginal cancer
RRP by age at diagnosis 25 2 93 75 womens men 5 277 women 33 men 67 total 5 6 28 4 7 6 <= a 2 2 a 3 3 a 4 4 a 5 >= 5 Age at diagnosis JORRP 5 35 7 9 CORTESÍA DE BILL STERN, RRPF
RANKING OF LATIN AMERICA S COUNTRIES ON INCIDENCE RATES OF CERVICAL CANCER RANKING st 2nd 3rd 4th 5th 6 or + N countries 4 2 % 5.% 42.9% 3.6% 3.6%.%.%