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Prophylactic HPV Vaccines Achievements Challenges

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Prophylactic HPV Vaccines Achievements Challenges

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    1. Prophylactic HPV Vaccines Achievements & Challenges Henry C. Kitchener Lisbon December 2007

    2. Cumulative incidence of HPV infection from time of first sexual intercourse

    4. The virus is transmitted through skin to skin contact. It enters the basal keratinocyte through tiny breaches in the epithelium where the virus replicates using cellular DNA replication machinery within these basal layer cells. Expression of the E6 and E7 viral protein delays the normal differentiation which is seen as the epithelial cell moves from the basement layer and matures. The structural proteins L1 and L2 are assembled in the cell nucleus and form mature viral particles which are then released from the epithelium within the superficial epithelial cell layers.The virus is transmitted through skin to skin contact. It enters the basal keratinocyte through tiny breaches in the epithelium where the virus replicates using cellular DNA replication machinery within these basal layer cells. Expression of the E6 and E7 viral protein delays the normal differentiation which is seen as the epithelial cell moves from the basement layer and matures. The structural proteins L1 and L2 are assembled in the cell nucleus and form mature viral particles which are then released from the epithelium within the superficial epithelial cell layers.

    5. Model of HPV Carcinogenesis

    6. Human Papillomavirus

    7. Prophylactic Vaccination

    8. Cervarix (HPV 16-18) Vaccine Mean Titres & Seropositivity Rates According to HPV Type & Group

    9. Rationale for Vaccination Programme To prevent type specific infection, thus ultimately preventing type specific associated CIN3 Prevention of infection by 2 types could prevent most cancers Primary prevention of cervical cancer by vaccination could be more cost effective than secondary prevention Vaccination offers a primary prevention strategy for countries without effective screening programmes

    10. Definitions used in randomised trials of HPV vaccines “Per Protocol” Cervix HPV –ve/Sero –ve/16/18 lesions “Unrestricted Susceptible” Cervix HPV –ve/Sero –ve/ą all 3 doses/16/18 lesions “Intention to Treat” All randomised subjects (real world)? All lesions

    11. Quadrivalent vaccine against human papillomavirus to prevent high grade cervical lesions. The FUTURE II study Group NEJM (2007) 356: 1915-27

    12. Quadrivalent HPV Vaccine to prevent Cervical Lesions(15-26yrs)?

    13. Quadrivalent HPV Vaccine to prevent Cervical Lesions(16/18)

    14. Quadrivalent Vaccine Efficacy to Prevent Cervical Lesions (16/18)? Vaccine Efficacy(%)? Per Protocol 98 Unrestricted susceptible 95 ITT Population 44 ITT (Any Type) 17

    15. Prevalence rates for four of the commonest five types and HPV 45 by cytological grade

    16. Impact of Quadrivalent Vaccine on Vulval Condylomata

    17. Impact of quadrivalent vaccine (6, 11, 16 & 18) on VAIN and VIN

    18. Efficacy of a prophylactic adjuvanted bivalent L1 virus like particle vaccine against infection with HPV16 and 18 in young women:

    19. CIN2+ lesions with HPV16 or HPV18 DNA

    20. Efficacy of Cervarix in Women initially seropositive or seronegative for HPV 16/18 in a Phase II Trial

    21. Cervarix (HPV 16/18) Vaccine Vaccine Efficacy Against Incident Infection with HPV 45, HPV 31, HPV 52, HPV 33 and HPV 58 in Cervical Samples from Intention-to-Treat Analyses

    22. Key Issues (1) Who to Vaccinate Females aged 11-13 Sexually naive; good immunogenicity Catch up of older adolescents Will be less cost effective Women up to 25 years Would be less protective Should boys be vaccinated? Will the vaccine be protective? Herd immunity but male HPV-related cancer is rare

    23. Key Issues (2) Vaccine Specific Duration of protection Follow-up of current/previous studies Cross protection Other oncotypes Cost effectiveness

    24. Key Issues (3) Implementation Education Key messages for children and parents Co-existence with cervical screening Scope for de-intensifying screening How to reach women in underdeveloped countries Expense/cold chain/acceptability

    25. Chronology of Vaccination & Changes to Screening

    26. Impact of the Vaccines 50-60% of CIN2/3 will be prevented and perhaps only 20% of low grade cytological abnormalities The majority of VAIN and VIN may be prevented Prevention of genital warts (Gardasil)? Less lower genital tract disease will result in less treatment associated morbidity There should be an impact on other HPV associated cancer e.g. head and neck

    27. Impact of the Vaccines Prevention of 70% cervical cancers 450,000 cases per year, worldwide Infertility Suffering 250,000 deaths per year worldwide Uptake of vaccine in developing world will save many thousands of lives

    28. “The incidence of this disease might, in great measure, be prevented by inoculation.” “From ignorance and prejudices the parents …. instead of inoculating their children, crowd into houses …. when the disease is at its most contagious.” “Every argument is in support of inoculation, however conclusive, makes no impression upon their minds.”

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