Abstract Background: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer mortality in low- and middle-income countries (LMICs), with particularly high incidence in South Africa. This cancer is frequently diagnosed at advanced stages, especially among underserved populations, where access to screening and molecular diagnostics is limited. While lifestyle-related risk factors like tobacco and alcohol are well-documented, the role of oncogenic viruses (i.e., human papillomavirus (HPV) and human immunodeficiency virus (HIV)) in ESCC remains underexplored in African populations. This study explores HPV–HIV co-infection in ESCC patients from South Africa and its relevance to cancer disparities. Methods: A total of 78 ESCC patients were prospectively recruited from Steve Biko Academic Hospital between January 2022 and December 2024. HIV testing was performed, and tumor biopsies collected via endoscopy. Formalin-fixed paraffin-embedded (FFPE) tissues were processed for DNA extraction using the QIAamp DNA FFPE Tissue Kit. HPV detection and genotyping were conducted using the Sacace HPV 14 Screening and HPV 16/18/45 kits. Associations between HPV, HIV, and clinical-demographic variables were evaluated using chi-square tests and logistic regression in Stata 18 (p ≤ 0.05). Results: The cohort was predominantly African (96%), gender distribution was 55% male and 45% female, and age range was 34-86 years (median 59). HIV infection was present in 42.3% (n=33) patients, while HPV DNA was present in 56.4% (n=44) of tumors. Among HPV-positive tumors, high-risk subtypes HPV16 and HPV18 were the commonest, involving 68% and 41% cases, respectively. Co-infection with both HIV and HPV was found in 23.1% (n=18) of patients. Although no significant association was observed between overall HIV and HPV positivity (p = 0.78), a statistically significant association between HIV status and HPV18 subtype (p = 0.004) was observed, suggesting subtype-specific interactions. HIV was also significantly associated with tobacco use (p = 0.003) and alcohol consumption (p = 0.012), reinforcing the clustering of biological and behavioral risk factors in marginalized populations. Conclusion: This study shows a high burden of HIV and oncogenic HPV in South African ESCC patients, especially among Black African communities. While no direct statistical link was found between HIV and HPV co-infection, the notable prevalence of high-risk types like HPV18 in HIV-positive individuals suggests a possible biological interaction that needs further study. The findings highlight the urgent need for integrated public health strategies combining HIV care, HPV vaccination, viral screening, and risk reduction to tackle infection-related cancers in underserved populations. Future multi-center and molecular studies are essential for advancing precision oncology and equitable cancer prevention in Africa. Citation Format: Sikhumbuzo Z. Mbatha, Botle Damane, Zodwa Dlamini, Portia Nevhungoni. The interplay of HPV and HIV in esophageal squamous cell carcinoma in South Africa: Implications for viral-driven cancer disparities abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A077.
Mbatha et al. (Thu,) studied this question.
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