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

Summary 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 Research in context Evidence before this study Primary prevention of cervical cancer is now available with human papillomavirus (HPV) vaccination. Initially administered as a three-dose regimen, the HPV vaccine schedule recommended by WHO has now switched to two doses for individuals below the age of 15 years. Although WHO recommends all countries to routinely immunise adolescent girls with two doses, many low- and middle-income countries, with high disease burden, have yet to implement national HPV vaccination programmes because of the challenges of delivering two vaccine doses to adolescent females. Recently, HPV vaccine implementation in many countries has been further delayed due to constraints in vaccine supply and difficulties in access during COVID-19 epidemics. These financial, logistical, and supply constraints have motivated research into one-dose vaccination schedules. Evidence emerging from trials and observational studies suggests that one dose may also provide a high level of protection against incident and persistent HPV infections. If proven effective, the one-dose HPV vaccination schedule would simplify vaccine delivery and lower costs of national vaccination programmes, potentially enabling more countries to implement one and as a result, facilitating global cervical cancer prevention. We searched PubMed for trials, cohort and modelling studies published in 2018 and 2020, with the terms “(health impact OR impact OR modelling OR cost-effectiveness OR CEA OR durability OR effectiveness) AND (HPV OR human papillomavirus OR cervical cancer)” and identified 151 results. Ten published articles—four trials, three cohort studies, two modelling analyses, one systematic review of trials—evaluated the population impact of one dose of the vaccine on cervical cancer disease outcome among females and all studies showed one dose of the vaccine might be as effective as two doses in preventing HPV infection. However as the trials and cohorts were single-country studies in select populations, the global impact remains unknown. Both published modelling analyses only used one model to estimate the impact of one-dose vaccination, and only examined a few countries. To our knowledge, no published article has modelled the global impact of routine one-dose vaccination on cervical cancer prevention by synthesising the results from more than one model. Added value of this study This study presents the first evidence on the potential global impact of a routine one-dose regimen, from a comparative modelling analysis that synthesises results from three published dynamic models calibrated to countries with varying epidemiological and demographic profiles. We found consistent results across all models suggesting that routine one-dose vaccination provides the majority of health benefits to the two-dose programme should a single dose of the vaccine confer more than 20 years of protection at full potential efficacy or 80% efficacy with lifelong protection. Implications of all the available evidence Findings suggest that routine one-dose vaccinations could avert almost as many cervical cancer cases as a two-dose programme. The one-dose regimen would be cheaper and easier to implement for most countries while alleviating vaccine supply constraints. To cope with the COVID-19 pandemic, many governments have had to implement stringent physical distancing measures, which has led to the suspension of routine immunisation programmes. Public health authorities grapple with the logistic challenges of delivering immunisation services while minimising the risk of SARS-CoV-2 transmission. Compared to the two-dose vaccination schedule, a one-dose vaccination schedule would reduce interactions between vaccinees and health workers, simplifying vaccine delivery while also decreasing SARS-CoV-2 exposure.