Prospects for a Prophylactic HPV Vaccine and Future Implications for Cervical Cancer Screening

1. Prospects for a Prophylactic HPV Vaccine and Future Implications for Cervical Cancer Screening Dr. Fuat Demirkıran İ.Ü Cerrahpaşa Tıp Fak. Kadın Hast. ve Doğum ABD, Jinekolojik Onkoloji Bilim Dalı Antalya ,2011

2. < 91.5 < 25.3 < 33.2 */100.000 women < 9.7 < 15.4 Prevalence of cervical cancer in the world

3. case increase 50-55% case increase 6-23% World population prospects for women >15 years.

4. Secondaryprevention Primaryprevention

5. Faz IIIEtkinlik Sonuçları • İlk doz sonrası • Kadınlar: 0. günde aşıya özgü HPV tipleri için negatif

6. American Cancer Society (ACS) Recommendations for Human Papillomavirus(HPV) Vaccine Use to Prevent Cervical Cancer and Its Precursors 2007

7. CDC

8. March 2009

9. The Countries that are made reimbursement

10. Screeningforcervicalpathologyshould be go on aftervaccination Efficacy of HPV vaccines Barriersto HPV vaccineandcovarage rate New HPV infection in advancedages Based on statistical analysis of HPV type distributions inpopulations, it appears unlikely that reducing the frequencyof specific HPV types in a population through vaccinationwould lead to an increase in the frequency of other HPVtypes

11. Worldwidedistribution of HPV types in cervicalcancer 16 16 53.5 %53.5 %70.7 %77.4 %80.3 18 18 17.2 45 45 6.7 31 31 2.9 33 33 2.6 52 52 2.3 58 58 2.2 35 35 1.4 59 59 1.3 56 56 1.2 51 51 1.0 39 39 0.7 68 68 0.6 73 73 0.5 82 82 0.3 Diğer 1.2 X X 4.4 Cancercasesassociatedwithmostfrequent HPV genotypes (%) 0 0 0 0 0 10 10 10 10 10 20 20 20 20 20 30 30 30 30 30 40 40 40 40 40 50 50 50 50 60 60 60 70 70 80 80 90 90 100 100 1. Munoz N. Againstwhichhumanpapillomavirustypesshallwevaccinateandscreen? TheinternationalperspectiveInt J Cancer 2004; 111: 278–85.

12. Efficacy Against HPV 6/11/16/18 Related CIN 2/3 or Worse and AIS (Protocols 005, 007, 013, and 015) * Total number of cases in subjects who were sero+ and/or PCR+ at baseline for the relevant HPV type which was associated with disease. Source: Table 1-1, Additional efficacy analysis requested by CBER

13. Gynecologic Oncology 115 (2009) S15–S23 Infact, in the total vaccinated cohort, efficacy against any CIN II/IIIirrespective of HPV type was 30.4% at 39 months after the firstvaccination and is expected to increase with longer follow-up.

14. Worldwide female population and a speculative anticipation on the initial introduction of HPV vaccines.

15. Covarage Rate Expanded Program of Immunization 1980–2005 DTP3 coverage by level of development

17. Prevalence of HPV infection, precancerous lesions and cervical cancer by age of women 35 % at least 5%

18. Age-specific incidence of oncogenic HPV infections in Ontario, Canada , Adapted from Sellors et al. in different regions of the world have shown that each year between approximately5% and 15% of sexually active mid-adult women acquire a newinfection with an oncogenic HPV type

19. Gynecologic Oncology 115 (2009) S15–S23 Approximately 5–15% of sexually active midadult women acquire a new infection with an oncogenic HPV type each year and in approximately 1–2% of these women, the responsibleoncogenic HPV types will be HPV-16 or -18

20. ≥ CIN3 HPV16+ HPV18+ HC2+ Cumulative incidence of cervical intraepithelial neoplasia grade 3 and cancer ( ≥ CIN3) over a 10-year period in 12 976 women 30 years old and older with negative cytology at enrollment, according to oncogenic human papillomavirus (HPV) status at enrollment. HPV status is defi ned hierarchically as: positive for HPV 16 ( closed circles ), else positive for HPV18 ( open circles ), else positive for the non-HPV16/18 oncogenic types in Hybrid Capture 2 (HC2) ( closed triangles ), else oncogenic HPV negative ( open triangles ). HC2- Cumulative incidence of cervical intraepithelial neoplasia grade 3 and cancer ( ≥ CIN3) over a 10-year period in 20 514 women according to oncogenic human papillomavirus (HPV) status at enrollment. HPV status is defi ned hierarchically as: positive for HPV 16 ( closed circles ), else positive for HPV18 ( open circles ), else positive for the non-HPV16/18 oncogenic types in Hybrid Capture 2 ( closed triangles ), else oncogenic HPV negative ( open triangles

21. It is unclear whether new acquisition or reactivation of alatent infection is responsible for the higher detection rates observedin older women. It has been proposed that what we call incidentinfections at higher ages may be due to new infections as well as reactivation of latent persistent infections it is unclear whether a prophylactic vaccine can be efficacious in preventing reactivation of latent infection.

22. Anysuggestedscreening program….

23. Implementation of a prophylactic HPV vaccination program would have important implications for cervical cancer screening. During the initial period following the introduction of a vaccine program, the population will include both vaccinated women at low risk for cervical neoplasia and women who have not been vaccinated who will be at greater risk.

24. TEN MOST FREQUENT HPV TYPES AMONG HIGH GRADE CERVICAL LESIONS WORLDWIDE WORLD DEVELOPING REGIONS DEVELOPED REGIONS Data source: IARC Infection and Cancer Epidemiology Group. Clifford et al Br J Cancer 2003, Smith et al Int J Cancer 2007 Available at: HPV Information Centre. Human Papillomavirus and Related Cancers in World. Summary Report 2009. [Accessed: 27 May 2010]. Available at www. who. int/ hpvcentre

25. TEN MOST FREQUENT HPV TYPES AMONG LOW GRADE CERVICAL LESIONS WORLDWIDE WORLD DEVELOPING REGIONS DEVELOPED REGIONS Data source: IARC Infection and Cancer Epidemiology Group. Clifford et al CEBP 2005 Available at: HPV Information Centre. Human Papillomavirus and Related Cancers in World. Summary Report 2009. [Accessed: 27 May 2010]. Available at www. who. int/ hpvcentre

26. Vaccination of adolescents reduction in rates of HPV infection low-grade SIL High-grade SIL- Cancer

27. With Vaccinationprogram, over time The SILs remaining in the population would berelated increasingly to HPV types that are less likely topersist and to progress to cancer. Consequently, there wouldbe fewer SILs in the population, and the SILs remaining would be more likely to spontaneously regress withouttreatment.

28. In general population, the lifetime risk for developingcarcinoma in women with low-grade SIL….….1%. Invaccinatedpopulation, this risk………….1/500-1000 Would LSILrequiretreatment ? focus on the detection of high-grade SIL. After post-vaccination program

29. Increaseincidence of low risk lesions following vaccination Manyproblemsrelatedtoscreening program afterBroad-SpectrumVaccination Decreasethe alertness of the cytology screeners, decreasethepositive predictive value of cytological screening.

31. Long term impact of vaccination As timegoes on, more women will receive the HPV vaccine before the onsetof sexual activity. This will result in a fall in positive predictivevalue of the Pap test. Modifications to the screening Program. a change inthe age of commencement of screening, a change to the screeninginterval, the addition of HPV DNA tests.

32. Cost-efective cancer prevention in HPV-vaccinated population…. probably require targeted screeningwith HPV testing a fewtimesduringentirelifetime secondaryscreeningwithcytology

33. . Combining vaccination with screening stillwill be the most effective wayto reduce the lifetime risk of cervical cancer in nextyears.

34. Forward looking views on cervical cancer prevention strategies

35. Widespread implementation of an HPV vaccine programis unlikely to occur until the next century,and its impact would not be fully appreciated for decades. Dramaticchanges in screening program of cervicalcancer has not beenseenreasonable fornextfewdecades.

36. Modifications to the screeningprogram will benecessary in the long term. A clearmessage is that the vaccine is not a substitute for screening tests