Landmark HPV Vaccination Study Protects Girls Living with HIV in South Africa

South Africa's battle against cervical cancer has received a major boost from groundbreaking research highlighting the effectiveness of the national HPV vaccination programme. This landmark study, led by scientists at the University of the Witwatersrand's Reproductive Health and HIV Institute (Wits RHI), demonstrates that early vaccination delivers substantial protection against high-risk human papillomavirus (HPV) types, even among adolescent girls living with human immunodeficiency virus (HIV). In a country where cervical cancer remains one of the leading causes of cancer deaths among women, and where HIV prevalence adds an extra layer of vulnerability, these findings underscore the transformative power of proactive public health interventions.

Cervical cancer, caused primarily by persistent infection with high-risk HPV strains such as HPV-16 and HPV-18, claims thousands of lives annually in South Africa. Women living with HIV face a risk up to six times higher due to impaired immune responses that allow the virus to persist and progress to precancerous lesions and invasive cancer. With an estimated HIV prevalence of around 20% among adult women and adolescent girls in some regions like KwaZulu-Natal, the intersection of these epidemics has long posed a formidable challenge to healthcare systems.

Understanding HPV and Its Link to Cervical Cancer in High HIV Settings

Human papillomavirus refers to a group of over 200 related viruses, with at least 14 classified as high-risk for causing cancers, particularly cervical cancer. HPV-16 and HPV-18 are responsible for approximately 70% of cases worldwide. Transmission occurs primarily through skin-to-skin contact during sexual activity, but early vaccination before sexual debut can prevent initial infection effectively.

In South Africa, the disease burden is stark: cervical cancer incidence rates exceed 30 per 100,000 women in some provinces, far above global averages, with mortality rates around 15-20 per 100,000. For women living with HIV, the attributable fraction of cervical cancers linked to HIV is over 50%, driven by faster progression from infection to cancer due to weakened immunity. Despite antiretroviral therapy (ART) improving outcomes, the risk remains elevated without prevention strategies like vaccination and screening.

The introduction of HPV vaccines in the late 2000s offered hope. These vaccines, such as the bivalent vaccine targeting HPV-16 and 18 used in South Africa's programme, stimulate the production of neutralizing antibodies against the virus's L1 capsid protein, preventing cellular entry and infection.

South Africa's National HPV Vaccination Programme: A Decade of Progress

Launched in 2014, South Africa's school-based HPV vaccination initiative targets girls in Grade 4, typically aged 9 years and older, offering two doses six months apart free of charge in public schools. This delivery model leverages high school attendance rates and ensures vaccination before most girls become sexually active.

Initial coverage was impressive, reaching over 80% for the first dose in early years, with overall estimates around 75-85% for eligible girls aged 9-15. By 2024, the programme expanded to Grade 5 girls to catch up missed cohorts, and discussions around single-dose regimens—endorsed by the World Health Organization—aim to simplify logistics and boost equity. Private schools were included more recently, addressing gaps in urban affluent areas.

The programme's success stems from strong political commitment, community engagement, and integration with existing health services. However, challenges like vaccine hesitancy in some communities and disruptions from the COVID-19 pandemic temporarily affected uptake, prompting renewed campaigns.

The Landmark Wits-Led Study: Design and Methodology

Published in early March 2026 in The Lancet Global Health, the study titled "Population impact of South Africa's human papillomavirus (HPV) vaccination programme on prevalence of vaccine and non-vaccine high-risk HPV types among adolescent girls and young women with and without HIV" provides the first population-level evidence of vaccine impact in a high-HIV-prevalence setting.

Researchers from Wits RHI, in collaboration with the Kirby Institute (Australia), National Department of Health, and others, conducted a repeat cross-sectional survey. They compared HPV prevalence in 17-18-year-old girls attending 15 primary health clinics across four provinces: Free State, Gauteng, Mpumalanga, and North West.

The pre-vaccine cohort (surveyed 2019) comprised unvaccinated girls born before the programme. The post-vaccine cohort (2023) included those eligible for vaccination in 2014-15. Participants self-collected vaginal samples tested via the AnyPlex II HPV28 assay for 28 HPV types. HIV status was determined clinically, with vaccination confirmed via registers and self-report. Statistical analysis used generalized linear regression for adjusted prevalence ratios (aPR), controlling for age, province, sexual history, and more.

Key Findings: Dramatic Reductions in HPV Prevalence

The results were striking. Overall HPV-16/18 prevalence plummeted from 21.6% pre-vaccine to 3.2% post-vaccine, an 83% relative reduction (aPR 0.17, 95% CI 0.12-0.24). Among HIV-positive girls, it dropped from 29.4% (73/248) to 4.4% (13/295), a similar 82% reduction (aPR 0.18, 95% CI 0.10-0.32).

Cross-protection against HPV-31/45 saw a 59% drop overall and 41% in HIV-positive girls. No changes in non-vaccine high-risk types suggested specificity to the vaccine. Indirect herd effects were evident, with unvaccinated post-cohort girls showing 74% lower prevalence.

These outcomes held across subgroups, including ART duration and viral load, affirming vaccination's robustness pre-HIV exposure.

Photo by Markus Winkler on Unsplash

Protection for Girls Living with HIV: A Game-Changer

Prior evidence on HPV vaccines in HIV-positive individuals focused on post-infection vaccination with compromised immunity. This study uniquely shows pre-exposure school-based dosing yields excellent protection, comparable to HIV-negative peers. With HIV-positive girls comprising 19-30% of the sample, the equitable impact highlights the programme's reach despite HIV clinics not routinely vaccinating.

In South Africa, where 9% of adolescent girls aged 15-24 live with HIV, this translates to averting thousands of future cervical cancers. Early ART initiation further enhances outcomes, but vaccination provides primary prevention.

Implications for Public Health and Policy in South Africa

The findings validate the 2014 programme's design and high coverage, signaling progress toward WHO's cervical cancer elimination goals: 90% vaccination by age 15, 70% screening, 90% treatment. South Africa aims for single-dose campaigns for 10-14-year-olds to enhance equity.Full study details in The Lancet.

Challenges include integrating private sector data, monitoring type replacement, and linking vaccination to screening/treatment via electronic systems. Policymakers now have robust evidence to sustain and expand efforts.

The Pivotal Role of South African Universities in HPV Research

Wits RHI, part of the University of the Witwatersrand Faculty of Health Sciences, exemplifies SA universities' leadership in infectious disease research. With over 400 staff, it conducts epidemiological studies, clinical trials, and policy support on HIV, TB, and reproductive health. This study involved sentinel surveillance sites, showcasing inter-university collaborations with Walter Sisulu University and University of Pretoria.

SA higher education institutions drive evidence-based interventions, training next-generation researchers via PhD programmes and fellowships. Wits' contributions extend to HPV vaccine trials and impact evaluations, positioning universities as key partners in national health strategies.

Challenges, Limitations, and Future Directions

While promising, the cross-sectional design limits causality inference, and clinic-based sampling may skew toward higher-risk girls. Incomplete vaccination registers pose verification issues, though sensitivity analyses confirmed robustness.

Future steps: long-term surveillance of single-dose efficacy, HPV type shifts, and cervical outcomes. Catch-up vaccination for HIV-positive adolescents, expanded screening with HPV DNA testing, and equity for private school girls are priorities. Global lessons for sub-Saharan Africa emphasize school delivery in HIV-endemic areas.

Stakeholder Perspectives and Real-World Impact

Professor Sinead Delany-Moretlwe, Wits RHI Research Director, hailed it as "a major public health success." National Department of Health officials advocate sustained funding. Community leaders stress education to combat myths.

Early projections suggest millions of averted cases, economic savings from reduced treatment costs (R25,000-R55,000 per case), and empowered women. Actionable insights: integrate HPV services with HIV care, train community health workers, and leverage digital registers.

Photo by Sasun Bughdaryan on Unsplash

Conclusion: A Blueprint for Cervical Cancer Elimination

This Wits-led study cements South Africa's HPV programme as a model, proving vaccination protects vulnerable girls amid HIV challenges. Universities like Wits continue spearheading research, fostering hope for a cervical cancer-free future. Sustained investment promises generational health gains.