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A Cost-Effectiveness Analysis of Alternative Human papillomavirus ( HPV) Vaccination Strategies

A Cost-Effectiveness Analysis of Alternative Human papillomavirus ( HPV) Vaccination Strategies. Elamin H. Elbasha Merck Research Laboratories, USA. Presentation outline. HPV infection and disease HPV vaccines Merck model Public health impact Economic impact Summary and conclusions.

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A Cost-Effectiveness Analysis of Alternative Human papillomavirus ( HPV) Vaccination Strategies

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  1. A Cost-Effectiveness Analysis of Alternative Human papillomavirus (HPV) Vaccination Strategies Elamin H. Elbasha Merck Research Laboratories, USA

  2. Presentation outline • HPV infection and disease • HPV vaccines • Merck model • Public health impact • Economic impact • Summary and conclusions

  3. 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

  4. Neoplasm or external genital warts Asymptomatic or common warts

  5. Few months to few years Up to 20 years HPV infection life cycle 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

  6. Conditions associated with HPV types 16, 18, 6,11 • 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 % 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

  7. By end of presentation, 16 women would die from cervical cancer Second most common cancer among women 274,000 deaths from cervical cancer in 2002 Globocan 2002

  8. Immunologic Basis for HPV vaccines • L1 HPV major capsid protein self-assembles into empty virus-like particles (VLPs) • In animal models of papillomavirus infection using species-specific VLPs • Vaccination results in protection from infection and disease • Efficacy associated with development of neutralizing antibodies • Transfer of serum from vaccinated to unvaccinated animals transfers protective efficacy • Protection is prophylactic, not likely to be therapeutic • Protection is likely to be type-specific

  9. HPV vaccines • Prepared from virus-like particles (non-infectious) • Produced by recombinant technology • Do not contain any live biological product or DNA • GARDASIL® [prophylactic quadrivalent HPV (6,11,16,18) vaccine] licensed in U.S. & other countries • First vaccine to prevent cervical cancer, precancerous genital lesions, and genital warts • Series of three injections over a six-month period • Safe and highly efficacious • CERVARIX® [prophylactic bivalent HPV (16,18) vaccine] in final stages of clinical testing

  10. Research questions • What are the epidemiologic consequences of HPV vaccination? • What is the sensitivity of vaccine health impact (HPV, CIN, cervical cancer, genital warts) to: • vaccine characteristics (e.g., duration of protection)? • vaccination strategies (females and males, females-only, catch-up, etc.)? • What is the cost-effectiveness of programs using a quadrivalent HPV (6/11/16/18) vaccine?

  11. Methods • Direct and indirect ‘herd immunity’ effects of vaccination • Describe transmission of the virus and resulting disease in a population • Assess impact of vaccine on vaccinees and their contacts • An integrated disease transmission model and cost-utility analysis • Demographic model • Behavioral model • HPV infection and disease models • Economic model • US healthcare system data and perspective • Assumes existing screening practices

  12. Death Death Death Clearance 16/18 Infection 6/11 Infected, 16/18 types Immune, 16/18 types Infected, 6/11 types Infection 6/11 Death Clearance 6/11 Clearance 16/18 Infection 16/18 New Entrants Infection 6/11/16/18 Clearance 6/11/16/18 Susceptible Xklib+Sklib Coinfected Immune, all 4 types Death Waning Immunity Death Clearance 6/11 Clearance 16/18 Infection 6/11 Infection 16/18 Clearance 6/11 Infection 16/18 Infected, 6/11 types Immune, 6/11 types Infected, 16/18 types Death Death Death Transfer diagram, no vaccine compartments

  13. Infected, HR types Immune, HR types Infected, LR types Bklbkl0b Vaccinated Vklib Coinfected Immune, both types kiVklib kiVklib Infected, LR types Immune, LR types Infected, HR types Transfer diagram, vaccine compartments

  14. Infected Yh,Uh,Ph Undetected CIN1 Detected CIN1 Treated & Infected Undetected CIN3 Undetected CIN2 Detected CIN2 Treated & Infected Invasive Cancer Detected CIN3 Treated & Cured Treated & Infected Transfer diagram, CIN compartments

  15. Vaccine characteristics: data and assumptions • Vaccine take (% of vaccinees with vaccine effect) • HPV 16/18 100%, HPV 6/11 100% • Vaccine degree of protection • HPV 16/18, HPV 6/11: against infection 90% (CI:74100) • HPV 16/18, HPV 6/11: against disease 100% (CI:87100) • Vaccine duration of protection • HPV 16/18, HPV 6/11: 10 years to lifetime • Breakthrough infections • Infectiousness and clearance same as natural infections

  16. Vaccination strategies

  17. Vaccination penetration rates: assumptions • Routine 12-year olds • increase vaccine penetration linearly from 0% in Year 0 to 70% in Year 5 and after • Catch-up 1224-year olds • All cohorts (1224): increase vaccine penetration linearly from 0% in Year 0 to 50% in Year 5 • Program stops after 5 years

  18. Impact of vaccination strategies diagnosed HPV 16/18-related cervical cancer incidence, females (12+y), lifelong duration

  19. Impact of vaccination strategies diagnosed HPV 16/18-related CIN 2/3 incidence- females (12+y) lifelong duration

  20. Impact of vaccination strategies diagnosed HPV 6/11/16/18-related CIN 1 incidence - females (12+y) lifelong duration

  21. Impact of vaccination strategies diagnosed HPV 6/11-related genital warts incidence - females (12+y) lifelong duration

  22. Impact of vaccination strategies diagnosed HPV 6/11-related genital warts incidence - males (12+y) lifelong duration of protection

  23. Cumulative quality-adjusted life years

  24. Cumulative costs

  25. Cost-effectiveness analysis of HPV vaccination strategies* *Assumes cost of vaccination series is $360 and duration of protection is lifelong. **Compared with the preceding non-dominated strategy.

  26. Sensitivity analysis: Impact of vaccination strategiesdiagnosed HPV 16/18-related CIN 2/3 incidence- females (12+y) 10-years duration vs. lifetime

  27. Impact of Vaccination StrategyCervical Cancer Incidence - Females (12–85y) Lifelong duration, 50% coverage

  28. Impact of Vaccination StrategyCervical Cancer Incidence - Females (12–85y) Lifelong duration, 90% coverage

  29. Sensitivity analyses: Incremental cost-effectiveness ratio ($/QALY) vs. duration of protection & cost

  30. Sensitivity analyses: Incremental cost-effectiveness ratio ($/QALY) vs. vaccine coverage and cost

  31. Limitations & outstanding research questions • Vaccine characteristics (e.g., duration of protection) are influential • Need more and better epidemiologic and natural history of disease data to support model • Need to analyze the impact on other important HPV-related diseases such as vulvar and vaginal neoplasias and cancers, recurrent respiratory papillomatosis • Need to reflect the indirect costs of HPV-related disease • Need to model HPV types interaction/cross protection • If screening practices change, the model can reflect the shifting impact of vaccination

  32. Summary • A prophylactic quadrivalent HPV vaccine can substantially reduce the incidence of cervical cancer, CIN, and genital warts • Catch up vaccination can provide earlier and greater reductions in HPV-related disease • Vaccinating males and females before age 12 combined with a temporary 1224-year olds catch up program can be cost-effective and efficiently added to current screening programs

  33. Acknowledgement Erik J. Dasbach, PhD Ralph P. Insinga, PhD Merck Research Laboratories, USA

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