Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis

Background: To eliminate cervical cancer as a public health problem, WHO currently recommends routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual debut. However, many countries have yet to implement this because of financial or logistical barriers to delivering two doses outside the infant immunisation programme. Methods: Using three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 192 countries, assuming that one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g., 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021-2120, with a one-year catch-up of 80% 11-14-year-old girls on the first year of the programme. Findings: Over the next century, one-dose vaccination at 80% coverage could avert 64 million (80%UI 62.2-64.8) and 66.6 million (80%UI 63.4-69.1) cervical cancer cases should one dose of the vaccine confer 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 68.4 million (80%UI 63.8-69.4) cervical cancer cases could be prevented. Across all country income groups, two-dose schedules conferring lifelong protection would avert only slightly more cases (2.1-8.7 million) than the one-dose scenarios explored. Around 330 to 5230 additional girls need to be vaccinated with the second dose to prevent one cervical cancer case, depending on the epidemiological profiles of the country. Interpretation: Results were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs and alleviating vaccine supply constraints. Funding: Bill & Melinda Gates Foundation