this presentation gives insight into the recent controversies of HPV vaccine, in a VAST country like India mass vaccination at minimal cost may be the only way to tackle killer cancer cervix

1. Controversies of HPV Vaccine Veerendrakumar C.M. MD.,DNB Associate ProfessorDept of OBG, VIMS, Bellary. veerendrakumarcm@gmail.com 26/04/2010 1 veeru

2. Human suffering 26/04/2010 veeru 2

3. HPV has been detected in 99.7% of cervical cancers worldwide, the highest level of association identified for a specific cause of a major human cancer. Walboomers JM et al, J Pathol. 1999; 189:12-9. 26/04/2010 3 veeru

4. evidence has also been linked to cancers of the vulva, vagina, anal canal, peri-anal skin, and penis. J Natl Cancer Inst. 1997; 89:1516-23. GynecolOncol. 2002; 84:263-70. Cancer Res. 2001; 61:1934-40. Am J Med. 1997; 102:3-8. 26/04/2010 4 veeru

5. Famous Phase III trials HPV vaccines FUTURE -Females United to Unilaterally Reduce Endo/Ectocervical Disease PATRICIA - Papilloma Trial Against Cancer In Young Adults . 26/04/2010 veeru 5

6. Do we know fully about The beneficial effects of medical intervention to recommend it ?or The harmful effects before concluding that risks outweigh the benefits ? 26/04/2010 6 veeru

7. Should we err on the side of caution or hope ? Medical knowledge is always incomplete and ambiguous 26/04/2010 7 veeru

8. Confusion to clarity 26/04/2010 8 veeru

9. Screening - not even tip of iceberg… 26/04/2010 veeru 9

10. Why Ca cervix not given importance ? 26/04/2010 veeru 10

11. Universal vaccination substantial effect in reducing the morbidity and mortality of cervical cancer in developing countries, where an organized screening program may not exist for all women. Villa LL. Vaccine. 2006; 24(suppl 1):S23-8. 26/04/2010 11 veeru

12. What are the controversies ?..... appropriate age at time of vaccination parental concerns vaccination of men women age 26 years or older inadequate long-term efficacy safety data and potential for non vaccine-related strains to emerge as prominent oncogenic serotypes. 26/04/2010 12 veeru

13. AGE ? ACIP recommendations (Advisory Committee on Immunization Practices- CDC) Girls age 11 or 12 years should receive the vaccine. The vaccine is most efficacious when administered to an HPV-negative female, it is important to vaccinate patients before potential HPV exposure may occur. 26/04/2010 13 veeru

14. ACS -Guideline for HPV Vaccine administration of the quadrivalent vaccine at an early age provides an optimal opportunity to maximize protection against HPV to prevent Cervical Cancer and Its Precursors. Saslow D et al. CA Cancer J Clin. 2007; 57:7-28. 26/04/2010 14 veeru

15. Promotes Sexual promiscuity ? 26/04/2010 15 veeru

16. illusion of invulnerability An invitation to teenage sexual activity ? easy access to oral contraception, distribution of condoms in schools, and increased availability of the "morning-after pill. biennial national surveys conducted between 1991 and 2001 have demonstrated a gradual decline in sexual activity during that interval. Monk BJ, Obstet Gynecol. 2006; 108:420-4. 26/04/2010 16 veeru

17. What influence the sexual behavior? "parental monitoring,“ the influence of peers, the age of the sexual partner. religious beliefs and a fear of pregnancy as the main reasons for not having sex, not the fear of acquiring a sexually transmitted disease.Monk BJ, Obstet Gynecol. 2006; 108:420-4. 26/04/2010 17 veeru

18. Men to be vaccinated ? it seems reasonable that immunization of men may potentially prevent the transmission of the virus to both female and male partners. preventing anogenital warts in men and indirectly preventing anogenitalneoplasia and transmission of warts to sexual partners. 26/04/2010 18 veeru

19. Limitations to assess the efficacy men problems associated with the collection of cells required for detection of HPV DNA and discomfort in patients during a peniscopy with biopsy. Weaver BA, J Infect Dis. 2004; 189:677-85. 26/04/2010 19 veeru

20. FDA Approves HPV Vaccine for Men and Boys - Oct 2009 26/04/2010 20 veeru

21. Vaccination of Women Older Than 26 Years ? FDA denied request for the approval of the quadrivalent vaccine for use in women 27-45 years of age based on cost-effectiveness. (Data collected by the Harvard School of Public Health) 26/04/2010 21 veeru

22. Vaccine efficacy in older women the efficacy of the vaccine against cervical disease was reduced among women who were HPV seropositive at the time of vaccine administration N Engl J Med. 2007; 356:1915-27. 26/04/2010 22 veeru

23. Long-term Efficacy ? Of the five Phase II and III clinical trials published to date, the longest extended follow-up was 4.5-5 years. 26/04/2010 23 veeru

24. Long term surveillance and follow up required. Will prophylactic vaccination still provide benefit against the development of cervical cancer, which usually takes decades? Will a booster injection be required to maintain efficacy? 30 years required to know the efficacy ! 26/04/2010 24 veeru

25. Safety ? 26/04/2010 veeru 25

26. VAERS received 12,424 adverse reactions out of 23, 051, 336 doses distributed Vaccine Adverse Event Reporting System 26/04/2010 26 veeru

27. 54 / 1 lakh vaccines distributed 772 /12,424 were serious events including 32 deaths Only 6 % of the reactions were serious 26/04/2010 27 veeru

28. Relative risks per 1 lakh vaccine dose 8.2 syncope 7.5 local site reactions 6.8 dizziness 5 nausea 4 head ache 3.1 hypersensitivity reactions 0.2thromboembolic event 0.1 anaphylaxis and death 0.04 GB Syndrome 0.009 Motor Neuron Disease 26/04/2010 28 veeru

29. Disproportionate reporting of Syncope and thromboembolic events 26/04/2010 29 veeru

30. timesonline.co.uk Natalie Morton died after receiving a shot for cervical cancerat her school in Coventry. Sept 2009 She reportedly died from a large malignant tumor in her chest. Natalie's condition was reportedly so severe that she could have died at any point: 26/04/2010 30 veeru

31. Media accused of scaremongering on cancer jab death• "irresponsible" coverage of the death of a girl Guardian 26/04/2010 31 veeru

32. 26/04/2010 32 veeru

33. 8th April 10 Centre halts HPV vaccine project following the death of four girls, who were given this vaccine in AP. 26/04/2010 veeru 33

34. Four deaths not due to flawed cervical cancer vaccine trial 9th April 2010 26/04/2010 veeru 34

35. 2 deaths due to poisoning, 1 due to drowning and 1 due to PUO - Dr.V.M.Katoch, DG of ICMR "I decided to suspend the trials because I wanted to first prove to the public that the allegations are false. I also want the general public to know that all ethical guidelines would be followed in this trial," Katoch said. 26/04/2010 veeru 35

36. Ethical violation ? The “demonstration project” had no follow-up system in place to deal with the after-effects of the vaccination, the report said. It found that in many schools, only the verbal consent was taken from the hostel warden/ teacher-in-charge to vaccinate girls residing in the hostels and the parents had not been informed about it. 26/04/2010 veeru 36

37. Vaccine ? Screening ? Holistic approach required, Women health not to be viewed in bits Research and ethical values must be respected . If safety well established -HPV vaccine may be the immediate answer for cancer especially in India. 26/04/2010 veeru 37

38. Thank you 26/04/2010 veeru 38