Association of Immunodeficiency and HIV Viremia with Cervical Precancer and Cancer Risk among Women with HIV in South Africa

Abstract Background Women with HIV (WWH) have a higher cervical cancer risk than women without HIV. The timing and extent to which HIV viremia and immunodeficiency contribute to cervical carcinogenesis remain incompletely understood. Methods We conducted a cohort study using medical claims data from a South African HIV programme (2011–2022) and calculated incidence rates of cervical precancer and cancer. Cox proportional hazards models assessed associations with CD4 cell count and HIV RNA viral load (VL). We tested summary and point-in-time CD4 and VL measures with 6–36 months lag periods. Models were adjusted for age, calendar year, and antiretroviral therapy (ART) initiation; fully adjusted models included both CD4 count and VL. Results Over 66,000 WWH contributed more than 300,000 person-years; 1,202 WWH developed moderate dysplasia (incidence rate: 394/100,000 person-years), 1,237 severe dysplasia (404/100,000 person-years), 211 carcinoma in situ (66/100,000 person-years), and 257 cervical cancer (70/100,000 person-years). Lower CD4 cell counts were strongly associated with higher rates of cervical dysplasia, carcinoma in situ, and cancer, independent of VL. Lowest CD4 count over 30-months was the most informative measure for precancer, while CD4 count lagged by 24 months was most informative for cervical cancer. Higher VL was associated with increased risk of precancer and cancer in models unadjusted for CD4 count, with associations attenuated after adjustment. Conclusions Maintaining high CD4 counts and achieving viral suppression through early ART initiation, along with using CD4 cell count for risk stratification in cervical screening, may help improve cervical cancer prevention among WWH in South Africa.