Single-dose HPV vaccination in the United States — a multi-modeling analysis

Background: Evidence supporting the non-inferior efficacy of single-dose human papillomavirus (HPV) vaccination has prompted reconsideration of existing multi-dose HPV vaccination schedules. We evaluated the long-term health impact of adopting single-dose HPV vaccination in the United States to inform policy deliberations. Methods: We applied two validated individual-based simulation models of HPV transmission and cervical cancer to project the impact of switching from a two-dose to a single-dose HPV vaccination schedule in 2025 in the context of historical HPV vaccination uptake in the United States. Four scenarios were simulated: continuation of two-dose vaccination (or equivalent single-dose efficacy of 98%) and three alternative pessimistic single-dose strategies with lower vaccine efficacy (90%) and/or duration of protection (average of 25 years). Outcomes included age-standardized incidence rates of HPV-16 infection and cervical cancer from years 2005-2099. Additional analyses examined effects under lower vaccination coverage observed in select U.S. regions. Findings: Maintaining two doses or switching to a non-inferior single-dose HPV vaccination schedule was projected to nearly eliminate HPV-16 infections and reduce cervical cancer incidence by over 90% by the end of the century. Scenarios assuming a lower efficacy or waning protection showed increases in cervical cancer incidence of less than 2 percentage points decades after a switch to single-dose vaccination with no impact on the timeframe to cervical cancer elimination. Interpretation: Switching to a single-dose HPV vaccination schedule is projected to maintain reductions in cervical cancer, even under pessimistic efficacy and durability assumptions. Continued monitoring of single-dose HPV vaccine efficacy over time remains critical. Funding: PATH on behalf of the Single-Dose HPV Vaccine Evaluation Consortium; Bill and Melinda Gates Foundation (grant No. OPP48979), and the US National Institutes of Health/National Cancer Institute (Grant Number U01 CA253912).