Objectives Human papillomavirus (HPV) can cause cervical cancer, a leading cause of female cancer mortality in South Africa and worldwide. We assessed the burden of, and factors associated with, HPV infection using a molecular assay and cervical cytology among women living with HIV (WLHIV) in South Africa.

Methods In this cross-sectional analysis, WLHIV initiating antiretroviral therapy (ART) underwent cervical Xpert HPV testing and liquid-based cytology. The Xpert test detects 14 high-risk (hr) HPV types reported in a pooled qualitative result. We evaluated clinical and sociodemographic variables and proportions between women testing positive and negative for hr-HPV, compared cytology with hr-HPV results and assessed associations with HPV positivity.

Results We enrolled 260 WLHIV, median age 31.0 (IQR 26.0–38.0) years. Overall, 91.3% of women were never screened for cervical cancer previously and none received HPV vaccination. In total, 67.3% (175/260) of women tested positive for any hr-HPV type, of which HPV16 and HPV18/45 were detected in 17.3% (45/260) and 22.7% (59/260) of women, respectively, and 56.5% (147/260) tested positive for 11 other hr-types. Of 258 WLHIV, 33.3% (86/258) had abnormal cytology: high-grade squamous intraepithelial lesion (SIL) 7.8% (20/258), low-grade SIL 24.0% (62/258) and atypical squamous cells of undetermined significance 1.6% (4/258). Of these, 93.0% (80/86) tested positive for hr-HPV: 30.0% (24/80) for HPV16, 31.3% (25/80) for HPV18/45 and 92.5% (74/80) for other hr-HPV types. Having a CD4 count<200 cells/µL was associated with hr-HPV infection (adjusted prevalence ratio 2.24; 95% CI 1.69 to 2.99 (p<0.001)).

Conclusions hr-HPV infection and cervical abnormalities are common among WLHIV starting ART, especially those with low CD4 counts, highlighting that early HIV testing and treatment initiation must be prioritised together with cervical cancer screening. The diversity of hr-HPV types suggests a need for vaccines with expanded HPV type coverage in this setting.