Impact of one and two human papillomavirus (HPV) vaccine doses on community-level HPV prevalence in South African adolescent girls: study protocol and rationale for a pragmatic before–after design

Abstract

IntroductionVaccines against human papillomavirus (HPV) are the key to controlling cervical cancer in low/middle-income countries (LMICs) where incidence is highest, but there have been limited data from these settings on programme impact on HPV prevalence, and none in a population with endemic HIV infection. Furthermore, for many LMICs, the currently recommended two-dose schedule is difficult to deliver at scale, so there is mounting interest in a single-dose schedule.Methods and analysisThe Human Papillomavirus One and Two-Dose Population Effectiveness Study is a hybrid impact evaluation of the national South African HPV vaccination programme, which has targeted grade 4 girls aged at least 9 years in public schools with two doses of vaccine since 2014, and a single-dose vaccine ‘catch-up’ programme delivered in one district in 2019. Impacts of both schedules on the prevalence of type-specific HPV infection will be measured using repeat cross-sectional surveys in adolescent girls and young women aged 17–18 years recruited at primary healthcare clinics in the four provinces. A baseline survey in 2019 measured HPV prevalence in the cohort who were ineligible for vaccination because they were already above the target age or grade under either the national programme or the single-dose programme in the selected district. HPV prevalence surveys are repeated in 2021 in the selected district, and in 2023 in all four provinces. We will calculate prevalence ratios to compare the prevalence of HPV types 16 and 18 in the single-dose (2021) and two-dose (2023) cohorts, with the vaccine-ineligible (2019) cohort.Ethics and disseminationThe project was approved by the University of the Witwatersrand Human Research Ethics Committee (HREC #181005), and the University of New South Wales HREC (#181-005). Findings will be disseminated through peer-reviewed journals, scientific meetings, reports and community forums.

Potential benefit of extended dose schedules of human papillomavirus vaccination in the context of scarce resources and COVID-19 disruptions in low-income and middle-income countries: a mathematical modelling analysis

“…10 A pragmatic relative evaluation of the effectiveness of South Africa national vaccination programs (HOPE) that is currently ongoing will provide important additional data on the effectiveness of vaccinating young WLHIV with single and 2 HPV vaccine doses. 73 The overall impact of vaccination in South Africa could be larger than predicted by the model with a vaccine that only protect against HPV-16 and HPV-18 (without cross protection) since the bivalent vaccine currently used in South Africa national HPV vaccination program (Cervarix), provide some levels of cross protection against additional vaccine types. 57,74 Nevertheless, the impact of WHO's triple-intervention elimination strategy, and the likelihood of reaching elimination will be reduced using the bivalent vaccine.…”

Efficacy and immunogenicity of a single dose of human papillomavirus vaccine compared to multidose vaccination regimens or no vaccination: An updated systematic review of evidence from clinical trials

“…Importantly, several ongoing trials and studies evaluating the efficacy, immunogenicity and/or population-level impact of single-dose HPV vaccination will add to the evidence-base in healthy young girls and women and address some of the key evidence gaps over the next few years [9] . These include the longer-term follow-up of the DoRIS trial, the CVT and the IARC India study, and other studies from Tanzania [34] , Costa Rica [35] , [36] , [37] , Thailand [38] , South Africa [39] , the Gambia [40] , and Brazil, Haiti and Peru [41] . In addition, the National Technical Advisory Group on Immunization (NTAGI) in India met in July 2023 to discuss the Serum Institute of India’s quadrivalent HPV vaccine and proposed a cohort study of girls who receive a single dose, as well as follow-up of girls who missed a second dose, to generate data on the immunogenicity and effectiveness of one-dose HPV vaccination [42] .…”

State-of-the-Science of human papillomavirus vaccination in women with human immunodeficiency Virus: Summary of a scientific workshop

“…Beyond studying individual-level protection, vaccine impact studies that nest cross-sectional HPV prevalence surveys in PWH and immunocompetent individuals may address relevant questions. Notably, the HOPE trial in South Africa ( Machalek et al, 2022 ) has the possibility to investigate HPV protection, including the protection elicited by a single dose, in WWH and women who acquire HIV after HPV vaccination.…”