文档介绍：1 Presentation outline HPV infection and disease HPV ines Merck model Public health impact Economic impact Summary and conclusions 2 HPV infection HPV is small, non-enveloped, encapsulated, double-stranded DNA virus HPV encodes two structural proteins L1 codes for major capsid protein L2 codes for minor capsid proteins Enormous HPV diversity More than 100 HPV genotypes More than 40 types infect ano-genital tract At least 13 high-risk types cause cervical cancer Ubiquitous Lifetime Risk of HPV infection up to 70% among sexually active Major risk factor for HPV acquisition: number of sexual partners 3 Asymptomatic or common warts Neoplasm or external genital warts 4 HPV infection life cycle Few months to few years Up to 20 years Goodman A., Wilbur D. C. Case 32-2003 — A 37-Year-Old Woman with Atypical Squamous Cells on a Papanicolaou Smear. N Engl J Med 2003; 349:1555-1564 5 Conditions associated with HPV types 16, 18, 6,11 Clifford, BJ Ca 2003; Munoz Int J Cancer 2004; Brown J Clin Micro 1993; Carter Cancer Res 2001; Clifford Cancer Epi Biomarkers Prev 2005; Gissman Proc Natl Acad Science 1983; Kreimer Cancer Epidemiol Biomarkers Prev 2005 HPV 16, 18 Estimated attributable % – Cervical cancer 70 % – High grade cervical abnormalities 50 % – Low grade cervical abnormalities 30 % – Anal cancer ~70 % – Vulva / Vagina / Penile ~40 % – Head and neck cancers ~3-12 % HPV 6, 11 – Low grade cervical abnormalities 10 % – Genital warts 90 % – Recurrent respiratory papillomatosis (RRP) 90 % 6 Globocan 2002 By end of presentation, 16 women would die from cervical cancer Second mon cancer among women 274,000 deaths from cervical cancer in 2002 7 Immunologic Basis for HPV ines L1 HPV major capsid protein self-assembles into empty virus-like particles (VLPs) In animal models of papillomavirus infection using species-specific VLPs ination results in protection from infection and disease Efficacy associated with development of neutralizing antibodies Transfer of