Optimal human papillomavirus vaccination strategies to prevent cervical cancer in low-income and middle-income countries in the context of limited resources: a mathematical modelling analysis

BackgroundIntroduction of human papillomavirus (HPV) vaccination has been slow in low-income and middle-income countries (LMICs) because of resource constraints and worldwide shortage of vaccine supplies. To help inform WHO recommendations, we modelled various HPV vaccination strategies to examine the optimal use of limited vaccine supplies and best allocation of scarce resources in LMICs in the context of the WHO global call to eliminate cervical cancer as a public health problem.MethodsIn this mathematical modelling analysis, we developed HPV-ADVISE LMIC, a transmission-dynamic model of HPV infection and diseases calibrated to four LMICs: India, Vietnam, Uganda, and Nigeria. For different vaccination strategies that encompassed use of a nine-valent vaccine (or a two-valent or four-valent vaccine assuming high cross-protection), we estimated three outcomes: reduction in the age-standardised rate of cervical cancer, number of doses needed to prevent one case of cervical cancer (NNV; as a measure of efficiency), and the incremental cost-effectiveness ratio (ICER; in 2017 international $ per disability-adjusted life-year [DALY] averted). We examined different vaccination strategies by varying the ages of routine HPV vaccination and number of age cohorts vaccinated, the population targeted, and the number of doses used. In our base case, we assumed 100% lifetime protection against HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58; vaccination coverage of 80%; and a time horizon of 100 years. For the cost-effectiveness analysis, we used a 3% discount rate. Elimination of cervical cancer was defined as an age-standardised incidence of less than four cases per 100 000 woman-years.FindingsWe predicted that HPV vaccination could lead to cervical cancer elimination in Vietnam, India, and Nigeria, but not in Uganda. Compared with no vaccination, strategies that involved vaccinating girls aged 9–14 years with two doses were predicted to be the most efficient and cost-effective in all four LMICs. NNV ranged from 78 to 381 and ICER ranged from $28 per DALY averted to $1406 per DALY averted depending on the country. The most efficient and cost-effective strategies were routine vaccination of girls aged 14 years, with or without a later switch to routine vaccination of girls aged 9 years, and routine vaccination of girls aged 9 years with a 5-year extended interval between doses and a catch-up programme at age 14 years. Vaccinating boys (aged 9–14 years) or women aged 18 years or older resulted in substantially higher NNVs and ICERs.InterpretationWe identified two strategies that could maximise efforts to prevent cervical cancer in LMICs given constraints on vaccine supplies and costs and that would allow a maximum of LMICs to introduce HPV vaccination.FundingWorld Health Organization, Canadian Institute of Health Research, Fonds de recherche du Québec–Santé, Compute Canada, PATH, and The Bill & Melinda Gates Foundation.TranslationsFor the French and Spanish translations of the abstract see Supplementary Materials section. Introduction of human papillomavirus (HPV) vaccination has been slow in low-income and middle-income countries (LMICs) because of resource constraints and worldwide shortage of vaccine supplies. To help inform WHO recommendations, we modelled various HPV vaccination strategies to examine the optimal use of limited vaccine supplies and best allocation of scarce resources in LMICs in the context of the WHO global call to eliminate cervical cancer as a public health problem. In this mathematical modelling analysis, we developed HPV-ADVISE LMIC, a transmission-dynamic model of HPV infection and diseases calibrated to four LMICs: India, Vietnam, Uganda, and Nigeria. For different vaccination strategies that encompassed use of a nine-valent vaccine (or a two-valent or four-valent vaccine assuming high cross-protection), we estimated three outcomes: reduction in the age-standardised rate of cervical cancer, number of doses needed to prevent one case of cervical cancer (NNV; as a measure of efficiency), and the incremental cost-effectiveness ratio (ICER; in 2017 international $ per disability-adjusted life-year [DALY] averted). We examined different vaccination strategies by varying the ages of routine HPV vaccination and number of age cohorts vaccinated, the population targeted, and the number of doses used. In our base case, we assumed 100% lifetime protection against HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58; vaccination coverage of 80%; and a time horizon of 100 years. For the cost-effectiveness analysis, we used a 3% discount rate. Elimination of cervical cancer was defined as an age-standardised incidence of less than four cases per 100 000 woman-years. We predicted that HPV vaccination could lead to cervical cancer elimination in Vietnam, India, and Nigeria, but not in Uganda. Compared with no vaccination, strategies that involved vaccinating girls aged 9–14 years with two doses were predicted to be the most efficient and cost-effective in all four LMICs. NNV ranged from 78 to 381 and ICER ranged from $28 per DALY averted to $1406 per DALY averted depending on the country. The most efficient and cost-effective strategies were routine vaccination of girls aged 14 years, with or without a later switch to routine vaccination of girls aged 9 years, and routine vaccination of girls aged 9 years with a 5-year extended interval between doses and a catch-up programme at age 14 years. Vaccinating boys (aged 9–14 years) or women aged 18 years or older resulted in substantially higher NNVs and ICERs. We identified two strategies that could maximise efforts to prevent cervical cancer in LMICs given constraints on vaccine supplies and costs and that would allow a maximum of LMICs to introduce HPV vaccination.