• Jean-François Laprise, Harrell W Chesson, Lauri E Markowitz, Mélanie Drolet, and Marc Brisson.
• Centre de recherche du CHU de Québec-Université Laval, Québec City, Québec, Canada (J.F.L., M.D.).
• Ann. Intern. Med. 2024 Nov 26.

BackgroundIn June 2019, the U.S. Advisory Committee on Immunization Practices recommended shared clinical decision making regarding potential human papillomavirus (HPV) vaccination of men and women aged 27 to 45 years ("mid-adults").ObjectiveTo examine the incremental cost-effectiveness ratios (ICERs) and number needed to vaccinate (NNV) to prevent 1 HPV-related cancer case of expanding HPV vaccination to subgroups of mid-adults at increased risk for HPV-related diseases in the United States.DesignIndividual-based transmission dynamic modeling of HPV transmission and associated diseases using HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation).Data SourcesPublished data.Target PopulationAll U.S. mid-adults and higher-risk subgroups within this population.Time Horizon100 years.PerspectiveHealth care sector.InterventionExpanding 9-valent HPV vaccination to mid-adults and higher-risk subgroups.Outcome MeasuresICERs and NNVs.Results Of Base Case AnalysisExpanding 9-valent HPV vaccination to all mid-adults, those with more lifetime partners, and those who have just separated was projected to cost an additional $2 005 000, $763 000, and $1 164 000 per quality-adjusted life-year (QALY) gained, respectively. The NNVs to prevent 1 additional HPV-related cancer case were 7670, 3190, and 5150, respectively, compared with 223 for vaccination of persons aged 9 to 26 years (vs. no vaccination).Results Of Sensitivity AnalysisThe mid-adult strategy with the lowest ICER and NNV was vaccinating infrequently screened mid-adult women who have just separated and have a higher number of lifetime sex partners (ICER, $86 000 per QALY gained; NNV, 470).LimitationUncertainty about rate of new sex partners and natural history of HPV among mid-adults.ConclusionVaccination of mid-adults against HPV is substantially less cost-effective and produces higher NNVs than vaccination of persons younger than 26 years under all scenarios investigated. However, cost-effectiveness and NNV are projected to improve when higher-risk mid-adult subgroups are vaccinated, such as mid-adults with more sex partners and who have recently separated, and women who are underscreened.Primary Funding SourceCenters for Disease Control and Prevention.

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