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

Abstract

Background Introduction of human papillomavirus (HPV) vaccination has been slow in low-income and middleincome 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.Methods 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. 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.Interpretation 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.

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

“…to maximize health benefits of a limited supply of HPV vaccine doses. 8 Furthermore, assuming an inferior but lifelong single-dose HPV vaccine, a revaccination MAC campaign approach averted nearly as many cancer cases as revaccinating 100% of previously vaccinated women, which is likely due to the health benefits associated with providing a second opportunity for unvaccinated women to receive their first HPV vaccine dose (effectively increasing vaccine coverage).…”

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

“…Fig 1 provides an overview of the data sources and key steps of the modelling framework described in the following sections. We synthesised the long-term population-wide impact of HPV vaccination on cervical cancer incidence by age and time predicted by three published transmission dynamic models: (i) the Public Health England (PHE) model, a compartmental dynamic model set in the UK (32); (ii) the HPV-ADVISE model, an individual-based dynamic model set in Uganda, Nigeria, India, Vietnam (27,33), and Canada (34,35); and (iii) the Harvard model, a hybrid model that links two individual-based models, set in the US, Uganda, El Salvador, and Nicaragua (14,36). In total, we combined results from 10 model-country scenarios.…”

“…Such effects can be examined using HPV transmission dynamic models. To date, model-based analyses set in the United Kingdom (UK) (25), the United States (US), and Uganda (26,27) suggest that one-dose schedules would be cost-effective and would prevent almost as many cancers as two-dose or three-dose schedules if one dose confers at least 20 years of protection or has at least 80% efficacy against HPV 16/18 infection.…”

The Prevalence of HPV Genotypes Detected by Cobas HPV in Cervical Samples among Unvaccinated Women from Isfahan Province, Iran

“…As a low-middle income county, Iran falls in the category of countries with less than 30% coverage of HPV vaccination. Therefore, it is necessary to focus on screening programs and de ning the most valuable and effective methods based on local situations [12].…”