VIRUS VACCINES & CANCER a story with two chapters

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1 VIRUS VACCINES & CANCER a story with two chapters F X BOSCH Institut Catala d Oncologia Sant Pau 2017

2 Potential conflict of interest Research and educational institutional grants: GSK, SPMSD, Merck, Qiagen Personal / speaking / travel grants: GSK, SPMSD, Merck, Qiagen, RMS This presentation is the sole responsibility of the author

3 Vaccines are often victims of its success Small pox in an infant Cervical cancer incidence in Finland

4 ESTIMATED NUMBER OF CASES OF VACCINE PREVENTABLE DISEASES IN THE US. BEFORE AND AFTER GENERALIZED VACCINATION CONDITION PRE-VACCINE YEAR 1999** CHANGE (%) Diphtheria ,99 Measles ,99 mumps ,76 Pertussis ,63 Polio ,00 Varicella ,58 Cong. Varicella ,58 Tetanus ,88 Hemophilus >5y ,83 TOTAL

5 Incidence of some of the most common cancers in The Gambia: 1987 al 2002 Edat Edat Viviani S, et al. Cancer Epidemiol Biomarkers Prev Nov;17(11):

6 Hepatitis B persistent infection and liver cancer

7 16 equips de vacunacio territorials The Gambia Hepatitis Intervention trial 124,000 newborns in ; 65,000 HB vaccinated ; 35 years follow up CONTROLS (EPI) HBV + EPI July 86 1ªdose February 90 Registration completed National Cancer Registry

8 The human papilloma virus and genital cancers

9 110 years of research in hpv & cancer Human papillomavirus discovered 1907 Cotton rabbit papillomavirus (CRPV) discovered 1933 Bovine papillomavirus (BPV) causes warts and GI cancer in cows 1959 Link between HPV and cervical cancer HPV/Cervical cancer Vaccines developed FDA approves HPV vaccines to prevent cervical cancer G9 license Epidemiological studies Induction of carcinomas in domestic rabbits by CRPV first DNA tumor virus 1935 HPV-6, -11, -16, -18 characterized Wart induction with cell-free extracts of epidermodysplasia verruciformis (EV) patients 1972 FDA approves first HPV DNA test for screening countries adopted HPV vaccination and HPV tests are proposed as the primary option for screening 2008 H Z Hausen

10 35 years of research in hpv & (cervical) cancer Epidemiological & Clinical studies Etiology and natural history Biology and carcinogenesis Intervention studies Case control studies Prevalence surveys Correlation studies Follow up cohorts International surveys Type attribution Other cancer sites Viral characterization Viral variants Phylogenetic studies Animal models Biomarker research Therapeutic Vaccines HPV treatments Screening studies Vaccination trials Vaccination programs Strategic modeling Anti Vax options Viral & Disease elimination Videla MA Pavon Bloem / de Sanjose

11 HPV prevalence among 1M. women with normal cytology Adjusted HPV prevalence (%) Caribbean Eastern Africa Eastern Europe Western Africa Southern Africa South America South- Eastern Asia Central America WORLD Eastern Asia Northern Europe Northern Africa Western Europe Southern Europe Southern Asia Northern America Western Asia Meta-analysis of 1,016,719 women. Adjusted HPV prevalence standardized by the regional geographical structure Bruni L et al J Infect Dis

12 European Union (30 countries) HPV-Related Disease Burden: Annual estimations of 52,000 Cancers and close to 6M precancerous lesions Male Female 1,680 3,386 Penile cancer 2 Vulva & Vagina Cancer 1 2,390 3,996 Anal Cancer 1 1,042 4,505 22,974 34,708 1,166 Ref. Oropharyngeal Cancer 2 AIN2/3 + VaIN2/3 + VIN2/3 1 Cervical Cancer 1 388,980 x11 CIN , ,165 Genital Warts 1 5,570,988 x159 ASCUS+ * 198,714, ,332,641 Pop 20y 3 (Austria, Belgium, Bulgaria, Croatia, Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxemburg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovenia, Slovakia, Spain, Sweden, UK) + Switzerland. * Estimations assuming 3.5% of ASCUS+ among women aged years. 1. Hartwig et al. submitted; 2. Forman et al.2012 Vaccine; 3. World Population Prospects 2012 Revision

13 ICO survey Relative contribution (%) of 9 vaccine types and non-vaccine types to cervical cancer etiology by region World (n=8,977) 71% 19% 10% Africa (n=544) Asia (n=2,641) Eastern Asia (n=1,805) Western/Central Asia (n=836) North America (n=160) Latin America (n=3,404) Central America (n=775) South America (n=2,629) Europe (n=2,058) Oceania (n=170) 16/18 31/33/45/52/58/(6-11) Other HPV types 13% 9% 9% 8% 5% 12% 15% 11% 11% 11%

14 Options to control cervical cancer SCREENING (PAP) 1 3 SCREENING (HPV) HPV 16/18 VACCINATION 3 6 Target Cervical cancer / pre- cancer Cervical cancer / pre-cancer & Interrupt Transmission Impact Participant Participant + Herd effect Number of interventions Follow-up tests lifetime 5+ tests lifetime Local diagnostic & treatments network 3 / 2 doses no booster dose to date Phase IV studies in selected countries Side effects Mild / Obstetrics /over-diagnostics Local/short-lived Impact on other cancers Limited / none Significant in all HPV-related cancers 1. Kesic V, et al. Cancer Epidemiol Biomarkers Prev 2012; 21: ; 2. Anttila A, et al. Eur J Cancer 2009; 45: ; 3. Cuzick J, et al. Vaccine 2008; 26S:K29 K41; 4. EMA. Cervarix, European Summary of Product Characteristics, 2013; 5. GSK. Clinical Study Register. 2013; 6. Downs LS Jr, et al. Gynecol Oncol 2010; 117:

15 HPV type-specific contribution to cervical cancer and potential for prevention of existing vaccines Type specific Vaccine efficacy VIRAL TYPES RC % Gardasil Cervarix Gardasil % Parcial % Parcial Parcial? 95+% 95+% 95+% 95+% % na 90 % Relative Contribution RC (%) 95% Confidence Interval de Sanjosé S et al. Lancet Oncol, 2010 Serrano B et al. Infect Ag Cancer, 2012 Schiller J et al Vaccine 30 S Lehtinen M et al. Nat Rev Clin Oncol

16 Accuracy of HPV screening vs. cytology, Summary of controlled trials (N) Screening test N of trials Sensitivity (95% CI) Specificity (95% CI) Detection of CIN3+ Cytology (ASC-US+) % ( %) 91.8% ( %) HC % ( %) 89.0% ( %) Co-testing* % ( %) 82.9% ( %) *Cytology (ASC-US+) and HC2 Updated meta-analysis data from Arbyn et al. 21,22 In Bosch FX et al. Nature reviews Clinical oncology % 3%

17 Reasonable objectives for the next generation Disease Control Disease elimination Infection elimination Eradication Extinction Reduction to acceptable limits. Requires continuous intervention Reduction to zero in a given population. Requires continuous intervention Reduction to zero in a given population. Requires continuous intervention Permanent reduction to zero worldwide. Terminate intervention Infectious agent does not exist, naturally or in labs. Cervical cancer in Increase the some developed number countries of populations Cervical Cancer in neonatal some developed Tetanus populations Polio, measles Small pox None

18 Gracies i sort