Population impact of South Africa's human papillomavirus (HPV) vaccination programme on HPV prevalence in adolescent girls with and without HIV: a repeat cross-sectional study

Researchers: Dorothy A Machalek, PhD;  Dorothy C Nyemba, PhD; Danielle Travill;  Prof Kathy Petoumenos, PhD^; Zizipho Z A Mbulawa, PhD;  Ishana Naidoo, BTech MSc^; et al.

April 2026

What Is The Study About?

A school-based human papillomavirus (HPV) vaccination programme providing protection against types 16 and 18 of HPV was introduced in South Africa in 2014 for Grade 4 girls (aged ≥9 years), achieving 87% coverage among learners with at least one of the two recommended doses. The programme's impact on HPV prevalence among adolescent girls in a setting of high HIV prevalence, was evaluated.

Why Is This Important?

This repeat cross-sectional study provides the first direct population-level evidence of the impact of the two-dose HPV vaccination programme in South Africa, which has a large population of young women at risk of HIV and cervical cancer. This study quantified vaccine impact by comparing HPV prevalence in eligible and ineligible cohorts, assessed differences by HIV status, and measured indirect effects in unvaccinated girls, offering unique real-world insights in a setting previously under-represented in HPV vaccine post-licensure surveillance research.

What We Know…

Repeat prevalence surveys have shown that HPV vaccination programmes substantially reduce population-level HPV infection and precancerous lesions. A 2024 study also found high effectiveness against cervical cancer. However, most of the evidence comes from three-dose programmes implemented in high-income countries. To date, there is no evidence on the programmatic impact of HPV vaccination delivered in preadolescence in high HIV-burden settings, where some girls might acquire HPV and HIV after vaccination.

South Africa, the sixth most populous country in Africa, has the third highest prevalence of HIV among women of childbearing age (ie, 15–49 years), and 10 532 new cervical cancer cases and 5976 deaths were estimated (age-standardised rates of 33 and 19 per 100 000 women, respectively) in 2022. In 2014, the South African National Department of Health launched a national HPV vaccination programme aimed at Grade 4 girls in public schools (aged ≥9 years) with two doses of the bivalent HPV vaccine. The programme achieved 87% coverage among learners with at least one dose in the first year, maintaining above 80% coverage in the programme's initial years. 

What Was Discovered…

The study recorded an 83% relative reduction in the prevalence of vaccine-preventable HPV types 16 and 18 in adolescent girls and young women aged 17–18 years, who were among the first cohorts offered the HPV vaccine in South Africa's HPV school-based vaccination programme. The population impact was the same for girls living with and without HIV, as indicated by similar estimates of relative reductions in analyses stratified by HIV status. The benefits extended to reductions in the prevalence of vaccine-targeted types among unvaccinated girls (indirect effects) and reductions in circulating HPV types 31 or 45 (cross-protection). Effects were specific to these HPV types, with no reductions for other HPV types, strongly suggesting a genuine programme impact rather than changes in high-risk sexual behaviour.

The magnitude of impact we observed was consistent with that previously reported from three-dose programmes in high-income countries. A pooled analysis of 23 before-and-after studies of three-dose programmes in 13 countries showed that after 5–8 years of vaccination, the prevalence of HPV-16 or HPV-18 decreased by 83% (adjusted prevalence ratio 0·17, 95% CI 0·11–0·25) among girls aged 13–19 years. A key factor in the strong result achieved by the two-dose programme in South Africa was the very high coverage in the first years of the programme, estimated at over 80%.

The study also showed that cross-protection against non-vaccine types under a two-dose schedule was similar to that observed in three-dose programmes, with a 54% relative reduction in types 31, 33, and 45 reported in combined analyses (adjusted prevalence ratio 0·46, 95% CI 0·33–0·66). More recent data have shown that cross-protection is primarily driven by HPV-31 and HPV-45, which justifies the exclusion of HPV-33 from this cross-protection group in the analyses. Similar to the findings, combined analyses of three-dose programmes also reported modest increases in non-vaccine HPV types, possibly due to changes in sexual activity patterns or unmasking as vaccination reduces vaccine-type HPV infections, allowing previously undetectable coexisting non-vaccine HPV types to be identified during testing.

Another encouraging finding is the level of protection against HPV infection for adolescent girls living with HIV, a population at the highest future risk of cervical cancer. In the 2023 post-vaccine sample, two-thirds of the girls with HIV were diagnosed with HIV between ages 15 years and 18 years, and one-third before age 9 years; the latter probably reflecting perinatal acquisition. Most girls were on ART and had high CD4⁺ cell counts. Provided ART and long-term vaccine effectiveness can be maintained, the study suggests that the benefit of vaccination in cervical cancer prevention is equivalent to those with and without HIV infection. The findings also highlight the importance of early ART initiation and long-term surveillance in vaccinated populations living with HIV. HIV-related immune dysregulation—particularly CD4⁺ T-cell depletion—can impair vaccine response and accelerate antibody decline. Although early ART mitigates some effects, reduced HPV vaccine effectiveness might still occur over time. Effectiveness might also depend on dose number and antibody levels achieved before HIV acquisition, which are important considerations as South Africa adopts a single-dose HPV vaccination schedule. Although few participants in this survey had received a single dose, surveillance data among a one-dose catch-up cohort provide some reassurance, showing no clear differences by HIV status at 2 years post-vaccination. However, more long-term data are needed.

The Future of HPV Vaccination Programmes

The study found a substantial decline in vaccine-type HPV prevalence among South African adolescent girls, with similar reductions in those with and without HIV. Declines in vaccine-type HPV prevalence among unvaccinated girls suggest indirect protection, highlighting the success of the national school-based HPV vaccination programme. These reductions, targeting HPV types causing approximately 70% of cervical cancers, are expected to reduce cervical cancer burden over time. As South Africa transitions to a single-dose schedule, continued surveillance—especially among women with HIV—will be crucial to monitor long-term effectiveness and any emerging disparities.

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