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  • Title: Multiple High-Risk HPV Types Contribute to Cervical Dysplasia in Ugandan Women Living With HIV on Antiretroviral Therapy.
    Author: Nakisige C, Adams SV, Namirembe C, Okoche L, Ferrenberg J, Towlerton A, Larsen A, Orem J, Casper C, Frenkel L, Uldrick TS.
    Journal: J Acquir Immune Defic Syndr; 2022 Jul 01; 90(3):333-342. PubMed ID: 35195571.
    Abstract:
    BACKGROUND: Cervical cancer mortality remains high in sub-Saharan Africa, especially among women living with HIV (WLWH). Characterization of prevalent high-risk human papillomavirus (hrHPV) types and immune function in WLWH with cervical abnormalities despite antiretroviral therapy (ART) can inform prevention strategies. SETTING: Kampala, Uganda. METHODS: From 2017 to 2020, we enrolled Ugandan women with cervical dysplasia detected with visual inspection with acetic acid (VIA). WLWH were required to be on ART >3 months with plasma HIV RNA <1000 copies/mL. Biopsies from VIA-positive lesions underwent histopathologic grading and cervical swab specimens were tested for hrHPV. Clinical correlations were evaluated with Poisson regression to estimate adjusted prevalence ratios (aPR). RESULTS: One hundred eighty-eight WLWH and 116 HIV-seronegative women participated. Among WLWH, median ART duration was 6 years and median CD4 667 cells/µL. Cervical intraepithelial neoplasia (CIN) grade 2/3 was found in 29% of WLWH versus 9% of HIV-seronegative women. In women with CIN1 or without histopathology-confirmed dysplasia, hrHPV (aPR [95% confidence interval]: 2.17 [1.43 to 3.29]) and multiple hrHPV (aPR 3.73 [1.07 to 13.1]) were more common in WLWH, as were vaccine-targeted and vaccine-untargeted hrHPVtypes. Differences in hrHPV prevalence by HIV serostatus were not observed in women with CIN2/3 (interaction P < 0.01). Among WLWH, low CD4/8 ratio was associated with hrHPV while detectable plasma HIV RNA (20-1000 copies/mL) was associated with CIN2/3 or invasive cancer. CONCLUSION: Despite ART, WLWH with cervical VIA abnormalities remain at elevated risk for multiple hrHPV and high-grade dysplasia. Cervical cancer prevention and research tailored for WLWH are warranted in the ART era.
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