Marc Brisson

Population-level impact of switching to 1-dose human papillomavirus vaccination in high-income countries: examining uncertainties using mathematical modeling

Abstract Background A concern in high-income countries is that switching to 1-dose human papillomavirus (HPV) vaccination could cause a rebound in HPV infection and cervical cancer if 1-dose efficacy or duration were inferior to 2 doses. Using mathematical modeling and up-to-date trial-based data, we projected the population-level effectiveness of switching from 2-dose to 1-dose vaccination under different vaccine efficacy and duration assumptions in high-income countries. Methods We used HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation), a transmission-dynamic model of HPV infection and cervical cancer, varying key model assumptions to identify those with the greatest impact on projections of HPV-16 and cervical cancer incidence over time: 1) 1-dose vaccine efficacy and vaccine duration, 2) mechanisms of vaccine efficacy and duration over time, 3) midadult (>30 years of age) sexual behavior, 4) progression to cervical cancer among midadults, and 5) vaccination coverage and programs. Results In high-income countries, 1-dose vaccination would cause no appreciable rebound in HPV-16 infection, except for a limited rebound under the most pessimistic assumptions of vaccine duration (average, 25 years), because 1) the switch would occur when HPV prevalence is low because of high 2-dose vaccination coverage and 2) individuals would be protected during their peak ages of sexual activity (<35 to 40 years of age). Our model projects a more limited rebound in cervical cancer because of a shift to older age at infection, resulting in fewer life-years left to potentially develop cancer. Projections were robust when varying key model assumptions. Conclusions High protection during peak ages of sexual activity in high-income countries would likely mitigate any potential rebounds in HPV infection and cervical cancer under the most pessimistic assumptions of 1-dose efficacy and duration.

Cost-Effectiveness of Extending Human Papillomavirus Vaccination to Population Subgroups Older Than 26 Years Who Are at Higher Risk for Human Papillomavirus Infection in the United States

In 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"). To 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. Individual-based transmission dynamic modeling of HPV transmission and associated diseases using HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation). Published data. All U.S. mid-adults and higher-risk subgroups within this population. 100 years. Health care sector. Expanding 9-valent HPV vaccination to mid-adults and higher-risk subgroups. ICERs and NNVs. Expanding 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). The 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). Uncertainty about rate of new sex partners and natural history of HPV among mid-adults. Vaccination 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. Centers for Disease Control and Prevention.