Hpv Franceschi

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hpv e vaccino

hpv e vaccino

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  • 1. Vaccino contro l’HPV: la Lunga Marcia Silvia Franceschi Infections and Cancer Epidemiology Group International Agency for Research on Cancer Lyon, Franc e Ist. Mario Negri, Milano, 14 Aprile, 2008
  • 2. Tumori attribuibili a infezione nel 2002 From Parkin, 2006 Paesi sviluppati Paesi in via di sviluppo 7.7% di tutti I tumori 26.3% di tutti I tumori HPV: >4% dei tumori nelle donne HPV: >15% dei tumori nelle donne HIV/HHV-8: 0.3% EBV: 0.3% HBV & HCV: 1% HPV: 2.2% H.pylori: 3.9%
  • 3. Incidenza dei tumori per tipo di Paese
  • 4. Incidenza del cancro alla cervice secondo l’età
  • 5. Fasi dello sviluppo del tumore alla cervice
  • 6. HPV discovery have fostered:
    • Introduction of highly efficacious prophylactic HPV vaccines
    • Increase in the role of HPV testing in cervical cancer screening , i.e., in triage, treatment evaluation and as an alternative or supplement of cytology in primary screening
  • 7. Albero filogenetico dei genotipi di HPV
  • 8. 8 di più diffusi tipi di HPV in 14.097 casi di tumore invasivo della cervice divisi in regioni 70% 72% 67% 74% 76% 65%
  • 9. IARC Multi-centric HPV Prevalence Survey
    • Population-based samples of approx. 1000 women
    • 100 women per 5-year age group
    • T esting for at least 36 HPV types using GP5+/6+ PCR and antibodies against 6 HPV types.
  • 10. China Lampang Argentina IARC Multi-centre HPV Prevalence Surveys Hanoi Ho Chi Minh Korea Colombia Nigeria Spain Songkla Chile Italy Shenzhen Mexico The Netherlands India completed ongoing Mongolia Algeria Guinea Uganda Poland Shenyang Shanxi Nepal Pakistan Iran Georgia
  • 11. Prevalence of cervical HPV DNA in sexually active women IARC Multi-centre HPV Prevalence Survey, 1995-2002
    • Mongolia
    • Nigeria
    • China, Shenzhen
    • Argentina
    • India
    • China, Shenyang
    • Poland
    • Colombia
    • China, Shanxi
    • Chile
    • Mexico
    • Korea
    • Vietnam, Ho Chi Minh
    • Italy, Turin
    • Thailand, Lampang
    • Netherlands
    • Thailand, Songkla
    • Spain
    • Vietnam, Hanoi
    999 933 534 908 1940 685 834 1981 671 971 1340 870 918 1013 1024 3299 716 908 1007
  • 12. Age-specific high risk HPV prevalence in Manchester, 1988-93 and 2001-03 (Kitchener and Peto, 2006)
  • 13. HPV 16 0r 18 Other high-risk types Prevalence of cervical HPV DNA by age and HPV type IARC Multi-centre HPV Prevalence Survey Low-risk types only
  • 14. HPV 16
  • 15. VLP IARC-FIS 2002
  • 16. (Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008) GSK Cervarix ®, HPV 16,18 MSD/SPMSD Gardasil ®, HPV 6,11,16,18 L. Villa et al. Br J Cancer 95:1459-66. 2006 S. Garland et al. N Engl J Med 356:1928-1943, 2007 FUTURE Study Group ,Lancet 369: 1861-1868, 2007 FUTURE Study Group ,JID 196:1438-46, 2007 D. Harper et al. Lancet 364:1757-65, 2004 D. Harper et al. Lancet 367:1247-55, 2006 J. Paavonen et al. Lancet 369:2161-70, 2007 A.Hildesheim et al JAMA 298(7):743-753, 2007
  • 17. (Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008)
    • Seronegative and HPV-DNA negative at day 1;
    • Remained negative through 1 month after 3° dose;
    • 3 doses within 12 months;
    • No major protocol violations
  • 18. (Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008)
    • Included even if they had infection or disease to
    • HPV-16 and 18 ( 9% to HPV-16; 4% to HPV-18; 1% both genotypes)
    • Included even if protocol violations were present.
    • Included even if results on cytologic examination at day 1 were abnormal ( ASCUS and LSIL combined 12%).
  • 19. Prophylactic Vaccine Efficacy: Merck & GSK
  • 20. Efficacy of quadrivalent vaccine against HPV 16/18 1
    • Per protocol By intention to treat , against
    • HPV-negative
    • HPV 16/18 Any type
    • CIN2/3 or AIS 99% 44% 18%
    • (93 to 100) (31 to 55) (7 to 29)
    • By lesion:
    • CIN 2 100% 50% 21%
    • (93 to 100) (34 to 62) (7 to 33)
    • CIN 3 98% 39% 17%
    • (89 to 100) (21 to 53) (-0.1 to 31)
    • AIS 100% 54% 57%
    • (31 to 100) (-30 to 86) (-19 to 87)
    • 1 Future II, Lancet, 2007
  • 21. Time to CIN2/3 or AIS in intention-to-treat population HPV 16/18 Any HPV * Of randomised women, 9841 vaccine and 9904 placebo recipients received at least one dose and had at least one follow-up visit after dose 1. Future II, Lancet, 2007
  • 22. Rate of HPV-16/18 Clearance by Trial Arm Hildesheim et al ., JAMA, 2007 N = HPV16: 181(V)/232(P); HPV18: 81(V)/81(C) CVT
  • 23. (Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008) SEROCONVERSION IMMUNOGENICITY (GMT neutralizing IgG) ANAMNESTIC IMMUNE-RESPONSE MEMORY (Sven-Eric Olsson, Vaccine 2007) immunity following vaccination exceeds 5 years and appears to be sustained.
  • 24. (Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008) SEROCONVERSION IMMUNOGENICITY (GMT neutralizing IgG) ANAMNESTIC IMMUNE-RESPONSE MEMORY (Sven-Eric Olsson, Vaccine 2007) It is possible that re-infection will provide a means of naturally sustaining immunity in the absence of vaccine boosting.
  • 25. (Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008)
  • 26. (Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008) Presented at the 24 th Int. Papillomavirus Conference and Clinical Workshop, Beijing, 3-9 November, 2007 HPV Types Objective QuadrivalentVaccine Placebo Efficacy 95% CI n cases n cases 31,45 CIN2-3 AIS 4616 8 4675 21 62% (10, 85) 31,33,4552,58 CIN2-3 AIS 4616 27 4675 48 43% (7,66) 31,33,3539,45,5152,56,58 59 CIN2-3 AIS 4616 38 4675 62 38% (6, 60)
  • 27. Global status of Merck Gardasil licensure, December 2007 3
    • North America :
      • USA
      • Canada
      • Mexico
    7
    • South America:
      • Brazil
      • Argentina
      • Peru
      • Colombia
      • Chile
      • Ecuador
      • Uruguay
    18
    • Middle East & Africa:
    • Israel
      • Morocco
      • UAE
      • Egypt
      • ---------
      • 14 others
    11
    • Asia Pacific:
    • Australia
    • Indonesia
      • Korea
      • Taiwan
      • Hong Kong
      • Singapore
      • --------------
      • 5 others
    39
    • Europe:
    • Germany
      • France
      • UK
      • Spain
      • Italy
      • ---------
      • 34 others
    • Caribbean & Central America:
      • Costa Rica
      • Puerto Rico
      • Guatemala
      • Bermuda
      • --------------
      • 11 others
    15 Gardasil/Silgard Approved in 93 Markets: Most Under Accelerated Timelines Intelligence about approvals for GSK are not as timely
  • 28. Global status of GSK Cervarix® licensure, December 2007 Source: GSKbio, Belgium
  • 29. Vaccine affordability and financing
    • High-income (industrialized) countries — can afford to introduce HPV vaccine in the public sector, and several countries launched vaccine introduction in 2007.
    • Poorest (GAVI-eligible) countries — will most likely have access to heavily subsidized vaccine from GAVI Alliance.
    • Greatest difficulty now facing middle-income countries, that cannot afford current high prices and are not eligible for subsidized vaccine. Options under discussion:
      • Local private philanthropic financing schemes.
      • Tiered pricing for available vaccines, in accordance with capacity to pay, promised by current manufacturers.
      • Eventual price decline as developing-country manufacturers enter the market (starting 2015).
  • 30. (Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008) 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 Germania Francia Italia Svizzera Austria Norvegia Belgio Lussemb. Svezia Danimarca Spagna Grecia UK Portogallo
  • 31. Regional Group Purchasing
  • 32. HPV vaccine theoretical/optimal global timeline for GAVI-eligible countries Late 2008: WHO pre-qualifies HPV vaccine for UN procurement. WHO Strategic Advisory Group of Experts (SAGE) recommends global HPV vaccine use. GAVI/UNICEF/PAHO negotiate with manufacturers for HPV vaccine supply. Early 2009: WHO issues position paper on HPV vaccine. GAVI incorporates HPV vaccine in portfolio of subsidized vaccines. GAVI invites eligible countries to apply for vaccine. Mid 2010 : Vaccine delivered to first countries.
  • 33. Ideal age group for vaccination
    • Girls aged 10–13 years
    • Before sexual debut and exposure to the virus that causes cervical cancer—for highest impact.
    • Age when girls are easier to reach efficiently.
    • First priority given to single cohort in low-resource settings.
    • Vaccinating older adolescents and young women (“catch-up”) less cost-effective and logistically more difficult; gives earlier result but with much lower “net” benefit.
  • 34. Service delivery options
    • School-based programs (all four countries).
    • Comparing performance during and outside Child Health Days (Uganda).
    • Comparing performance with and without community outreach for out-of-school girls (Peru, India).
    • Comparing performance in school-based and health facility-based settings (Vietnam).
  • 35. The Promise of Global Cervical-Cancer Prevention Schiffman and Castle, NEJM, 2005
  • 36. (Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008)