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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
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%
Incidenza dei tumori per tipo di Paese
Incidenza del cancro alla cervice secondo l’età
Fasi dello sviluppo del tumore alla cervice
HPV discovery have fostered: ,[object Object],[object Object]
Albero filogenetico dei genotipi di HPV
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%
IARC Multi-centric HPV Prevalence Survey ,[object Object],[object Object],[object Object]
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
Prevalence of cervical HPV DNA in sexually active women   IARC Multi-centre HPV Prevalence Survey, 1995-2002 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],999 933 534 908 1940 685 834 1981 671 971 1340 870 918 1013 1024 3299 716 908 1007
Age-specific high risk HPV prevalence in Manchester, 1988-93 and 2001-03 (Kitchener and Peto, 2006)
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
HPV 16
VLP IARC-FIS 2002
(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
(Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008) ,[object Object],[object Object],[object Object],[object Object]
(Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008) ,[object Object],[object Object],[object Object],[object Object]
Prophylactic Vaccine Efficacy: Merck & GSK
Efficacy of quadrivalent vaccine against HPV 16/18 1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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
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
(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.
(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.
(Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008)
(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)
Global status of Merck Gardasil licensure, December 2007 3 ,[object Object],[object Object],[object Object],[object Object],7 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],18 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],11 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],39 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],15 Gardasil/Silgard Approved in 93 Markets: Most Under Accelerated Timelines   Intelligence about approvals for GSK are not as timely
Global status of GSK Cervarix® licensure, December 2007 Source: GSKbio, Belgium
Vaccine affordability and financing ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
(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
Regional Group Purchasing
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.
Ideal age group for vaccination ,[object Object],[object Object],[object Object],[object Object],[object Object]
Service delivery options ,[object Object],[object Object],[object Object],[object Object]
The Promise of Global Cervical-Cancer Prevention Schiffman and Castle, NEJM, 2005
(Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008)

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Hpv Franceschi

  • 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.
  • 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.
  • 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.
  • 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
  • 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.
  • 18.
  • 20.
  • 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.
  • 28. Global status of GSK Cervarix® licensure, December 2007 Source: GSKbio, Belgium
  • 29.
  • 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
  • 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.
  • 34.
  • 35. The Promise of Global Cervical-Cancer Prevention Schiffman and Castle, NEJM, 2005
  • 36. (Congresso Nazionale GISCI, Orvieto 3-4 aprile 2008)