Health and Economic Impact of Switching from a 4-Valent to a 9-Valent HPV Vaccination Program in the United States

J Natl Cancer Inst. 2015 Oct 4;108(1):djv282. doi: 10.1093/jnci/djv282. Print 2016 Jan.


Background: Randomized clinical trials have shown the 9-valent human papillomavirus (HPV) vaccine to be highly effective against types 31/33/45/52/58 compared with the 4-valent. Evidence on the added health and economic benefit of the 9-valent is required for policy decisions. We compare population-level effectiveness and cost-effectiveness of 9- and 4-valent HPV vaccination in the United States.

Methods: We used a multitype individual-based transmission-dynamic model of HPV infection and disease (anogenital warts and cervical, anogenital, and oropharyngeal cancers), 3% discount rate, and societal perspective. The model was calibrated to sexual behavior and epidemiologic data from the United States. In our base-case, we assumed 95% vaccine-type efficacy, lifelong protection, and a cost/dose of $145 and $158 for the 4- and 9-valent vaccine, respectively. Predictions are presented using the mean (80% uncertainty interval [UI] = 10(th)-90(th) percentiles) of simulations.

Results: Under base-case assumptions, the 4-valent gender-neutral vaccination program is estimated to cost $5500 (80% UI = 2400-9400) and $7300 (80% UI = 4300-11 000)/quality-adjusted life-year (QALY) gained with and without cross-protection, respectively. Switching to a 9-valent gender-neutral program is estimated to be cost-saving irrespective of cross-protection assumptions. Finally, the incremental cost/QALY gained of switching to a 9-valent gender-neutral program (vs 9-valent girls/4-valent boys) is estimated to be $140 200 (80% UI = 4200->1 million) and $31 100 (80% UI = 2100->1 million) with and without cross-protection, respectively. Results are robust to assumptions about HPV natural history, screening methods, duration of protection, and healthcare costs.

Conclusions: Switching to a 9-valent gender-neutral HPV vaccination program is likely to be cost-saving if the additional cost/dose of the 9-valent is less than $13. Giving females the 9-valent vaccine provides the majority of benefits of a gender-neutral strategy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Cost Savings
  • Cost-Benefit Analysis
  • Disease Transmission, Infectious / prevention & control*
  • Female
  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 / administration & dosage
  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 / economics
  • Humans
  • Male
  • Mass Vaccination / economics*
  • Models, Statistical
  • Oropharyngeal Neoplasms / economics
  • Oropharyngeal Neoplasms / prevention & control*
  • Oropharyngeal Neoplasms / virology
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / economics*
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / administration & dosage*
  • Papillomavirus Vaccines / economics*
  • Quality-Adjusted Life Years
  • Sexual Behavior
  • United States
  • Uterine Cervical Neoplasms / economics
  • Uterine Cervical Neoplasms / prevention & control*
  • Uterine Cervical Neoplasms / virology
  • Young Adult


  • Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
  • Papillomavirus Vaccines