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Background  The prevalence of high-risk human papillomavirus (hrHPV) is poorly described overall and in women living with HIV (WLWH) and HIV-negative women living in Botswana, a high HIV and cervical cancer-burden country. We conducted a pilot study of self-collection and high-risk HPV testing for cervical screening, from which data on HPV prevalence was available.    Methods  From five health facilities in the Kweneng East District, 1,022 women aged 30–49 years were enrolled to self-collect their cervicovaginal specimen for hrHPV testing by the Xpert HPV Test (Cepheid, Sunnyvale, CA, USA). Crude and age group-adjusted hrHPV prevalence by HIV status were calculated, and the relationship of hrHPV risk groups HPV16>HPV18/45>other hrHPV types) to the presence and severity of visible lesions.    Results  Of the 1,022 women enrolled, 1,019 (99.7%), 570 WLWH and 449 HIV-negative women, had hrHPV testing results. Crude hrHPV prevalences were 25.2% (95%CI = 21.2–29.4%) for HIV-negative women and 40.4% (95%CI = 36.3–44.5%) for WLWH. Age group-adjusted hrHPV prevalences were 23.7% (95%CI = 19.9–27.9%) for HIV-negative women and 41.3% (95%CI = 37.2–45.4%) for WLWH. Age group-adjusted prevalences of HPV16 (p<0.001), HPV18/45 (p<0.001), HPV31/33/35/52/58 (p<0.001), and HPV39/56/66/68 (p = 0.011) were greater among WLWH than HIV-negative women. Riskier hrHPV groups were more likely to have visible abnormalities (p trend  = 0.004) and visible abnormalities not eligible for cryotherapy (p trend  = 0.030).    Conclusions  hrHPV infection was common among all women in the study living in Botswana, to a greater extent in WLWH than their HIV-negative counterparts. Strategies to triage hrHPV-positive women will be needed to avoid over-treating many women with benign hrHPV infections.

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High-risk human papillomavirus prevalence in self-collected cervicovaginal specimens from human immunodeficiency virus (HIV)-negative women and women living with HIV living in Botswana