Potential Benefit of Extended Dose Schedules of Human Papillomavirus (HPV) Vaccination in the Context of Limited Resources and COVID-19 Disruptions in Low- and Middle-Income Countries: A Mathematical Modeling Analysis.

Abstract

Background: The WHO Strategic Advisory Group of Experts (SAGE) recommended that an extended interval of 3-5 years between the two doses of the HPV vaccine could be considered to alleviate vaccine supply shortages. However, concerns that girls could be infected between the two doses and reduced vaccination coverage for the 2nd dose have limited the introduction of extended schedules. Using mathematical modeling, we examined the potential impact of these concerns on the population-level effectiveness and efficiency of extended dose HPV vaccination schedules.

Methods: We used HPV-ADVISE, an individual-based, transmission-dynamic model of multi-type HPV infection/disease, calibrated to country-specific data for 4 LMIC (India, Vietnam, Uganda and Nigeria). For the extended dose scenarios, we varied the vaccination coverage of the 2nd dose among girls previously vaccinated and 1-dose vaccine efficacy and duration of protection. We also examined a strategy where 14-year-old girls were vaccinated irrespective of their previous vaccination status. We used 2-dose girls-only vaccination at 9 years old (vaccine=9valent, vaccine-type efficacy=100%, duration of protection=lifetime, coverage=80%) as our comparator. We estimated two outcomes: the relative reduction in the age-standardised cervical cancer (CC) incidence (population-level effectiveness) and the number of cervical cancers averted per 100,000 doses (efficiency).

Results: Our model predicted substantial reductions in CC incidence over 100 years with the 2-dose schedule (78%-84% depending on the country). Predictions were similar for the 5-year extended schedule assuming lower 1-dose efficacy, unless vaccination coverage of the 2nd dose is very low (70%-77% assuming 30% coverage among girls vaccinated at 9 years old). However, vaccinating 70% of 14-year-old girls irrespective of vaccination status would produce substantially greater reduction in CC incidence than the current 2-dose schedule (85%-92%). Efficiency of the extended schedule was greater than the 2-dose schedule, even with a drop in vaccination coverage.

Conclusion: The three concerns are unlikely to have a substantial impact on the population-level effectiveness of extended dose schedules. Hence, extended dose schedules will likely provide similar cervical cancer reductions as 2-dose schedules, whilst reducing the number of doses required in the short-term, providing a more efficient use of limited vaccine resources, and offering a 5-year time window to re-assess the necessity of the 2nd dose.

Note:
Funding: This study was funded by the World Health Organization, a Fonds de recherche du Québec – Santé research scholars award to MB, a foundation scheme grant from the Canadian Institutes of Health Research (FDN-143283), a grant from the Bill & Melinda Gates Foundation (grant number OPP48979), and Compute Canada. MCB acknowledge joint Centre funding from the UK Medical Research Council and Department for International Development (MR/R015600/1).

Declaration of Interests: MB, MD and MJ are members of the Single-dose HPV vaccine evaluation consortium. EB, JFL, KP and MCB declare no competing interests.