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Cervical cancer is a common preventable cancer among African women living with HIV (WLWH). Molecular diagnostics for high-risk human papillomavirus (HR-HPV) genotypes are standard components of cervical cancer screening in resource-rich countries but not in resource-limited settings. We evaluated HR-HPV genotypes among women with and without HIV in four African countries to inform cervical cancer preventive strategies.The African Cohort Study (AFRICOS) enrolled participants with and without HIV at 12 clinics in Tanzania, Kenya, Uganda and Nigeria. Cervical cytobrush specimens from women were genotyped for 14 HR-HPV types using the multiplex Seegene Anyplex real-time PCR assay. Robust Poisson regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for factors associated with HR-HPV in WLWH.From January 2015 to March 2020, 868 WLWH and 134 WLWoH were tested for HR-HPV with prevalence of 50.9% and 38.1%, respectively (p = 0.007). Among WLWH, 844 (97.4%) were ART-experienced and 772 (89.7%) virally suppressed ≦1000 copies/mL. The most frequent HR-HPV types among WLWH were HPV-16 (13.5%), HPV-52 (9.5%) and HPV-35 (9.3%). HR-HPV infection was more common among Tanzanian WLWH (adjusted RR: 1.23, 95% CI: 1.05-1.44, p = 0.012). Also, WLWH with CD4 T cells of200 cell/mm 3 had 1.51-fold increased risk of having HR-HPV (95% CI: 1.23-1.86, p 0.001).HR-HPV was common in WLWH in four African countries, particularly among women with low CD4. Scale up of HPV vaccines and development of vaccines with broader activity against less common HR-HPV types may improve cervical cancer prevention in Africa.

BackgroundThe burden of HPV-associated premalignant and malignant cervical lesions remains high in HIV+ women even under ART treatment. In order to identify possible underlying pathophysiologic mechanisms, we studied activation and HIV co-receptor expression in cervical T-cell populations in relation to HIV, HPV and cervical lesion status.MethodsCervical cytobrush (n = 468: 253 HIV- and 215 HIV+; 71% on ART) and blood (in a subset of 39 women) was collected from women in Mbeya, Tanzania. Clinical data on HIV and HPV infection, as well as ART status was collected. T cell populations were characterized using multiparametric flow cytometry-based on their expression of markers for cellular activation (HLA-DR), and memory (CD45RO), as well as HIV co-receptors (CCR5, α4β7).ResultsCervical and blood T cells differed significantly, with higher frequencies of T cells expressing CD45RO, as well as the HIV co-receptors CCR5 and α4β7 in the cervical mucosa. The skewed CD4/CD8 T cell ratio in blood of HIV+ women was mirrored in the cervical mucosa and HPV co-infection was linked to lower levels of mucosal CD4 T cells in HIV+ women (%median: 22 vs 32; p = 0.04). In addition, HIV and HPV infection, and especially HPV-associated cervical lesions were linked to significantly higher frequencies of HLA-DR+ CD4 and CD8 T cells (p-values < 0.05). Interestingly, HPV infection did not significantly alter frequencies of CCR5+ or α4β7+ CD4 T cells.ConclusionThe increased proportion of activated cervical T cells associated with HPV and HIV infection, as well as HPV-associated lesions, together with the HIV-induced depletion of cervical CD4 T cells, may increase the risk for HPV infection, associated premalignant lesions and cancer in HIV+ women. Further, high levels of activated CD4 T cells associated with HPV and HPV-associated lesions could contribute to a higher susceptibility to HIV in HPV infected women.