Mark Jit

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.

Now or later: Health impacts of delaying single‐dose HPV vaccine implementation in a high‐burden setting

AbstractWe aimed to quantify the health impact of immediate introduction of a single‐dose human papillomavirus (HPV) vaccination program in a high‐burden setting, as waiting until forthcoming trials are completed to implement single‐dose HPV vaccination may result in health losses, particularly for cohorts who would age‐out of vaccination eligibility. Two mathematical models fitted to a high‐burden setting projected cervical cancer incidence rates associated with (a) immediate implementation of one‐dose HPV vaccination vs (b) waiting 5 years for evidence from randomized trials to determine if one‐ or two‐doses should be implemented. We conducted analyses assuming a single dose was either noninferior or inferior to two doses. The models projected that immediate implementation of a noninferior single‐dose vaccine led to a 7.2% to 9.6% increase in cancers averted between 2021 to 2120, compared to waiting 5 years. Health benefits remained greater with immediate implementation despite an inferior single‐dose efficacy (80%), but revaccination of one‐dose recipients became more important assuming vaccine waning. Under most circumstances, immediate vaccination avoided health losses for those aging out of vaccine eligibility, leading to greater health benefits than waiting for more information in 5 years.