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AbstractIntroductionIn settings with high HIV prevalence, cervical cancer incidence rates are up to six‐fold higher than the global average of 13.1 cases per 100,000 women‐years. To inform strategies for global cervical cancer elimination, we used a dynamic transmission model to evaluate scalable screening and treatment strategies, accounting for HIV‐associated cancer risks and weighing prevention gains against overtreatment.MethodsWe developed a dynamic model of HIV‐HPV co‐infection and disease progression, which we calibrated to KwaZulu‐Natal, South Africa. Our baseline scenario reflects the current practice of HPV vaccination with a multi‐visit screening and treatment strategy involving cytology and colposcopy triage. We evaluated 13 comparator scenarios with increased vaccination coverage and one‐time, two‐time or repeat HIV‐targeted cervical cancer screening with the following single‐visit strategies: HPV DNA testing, HPV genotyping, automated visual evaluation (AVE) and HPV DNA with AVE triage. In all scenarios, HIV antiretroviral therapy, condom use and voluntary male medical circumcision continue at baseline levels. We simulated cancer incidence under each scenario from 2020 to 2120 using the 25 best‐fitting parameter sets. We present the median and range of model output from these simulations to account for parameter uncertainty.ResultsWe estimate that cervical cancer incidence will decrease by 87% with the continuation of current cervical cancer and HIV prevention strategies, from an age‐standardized rate per 100,000 women of 80.4 (range 58.2, 112.1) in 2020 to 10.7 (4.2, 29.9) in 2120. Scenarios scaling up vaccination and single‐visit strategies resulted in near‐ and long‐term gains. With repeat HIV‐targeted screening, incidence rates were projected to be 29–34% lower in 2030 relative to the baseline scenario, and elimination (incidence <4/100,000) was achieved with HPV DNA testing in 2095 and with AVE in 2114. A strategy of HPV DNA with AVE triage optimized the tradeoff between cancer cases averted and overtreatment.ConclusionsSingle‐visit screening strategies could avert a substantial burden of cervical cancer and accelerate progress towards elimination in settings with a high burden of HIV. Increasing the screening frequency among women with HIV and reducing loss‐to‐follow‐up for treatment will be key components of a successful elimination strategy.