Uganda has a high burden of cervical cancer and its current coverage of screening based on visual inspection with acetic acid (VIA) is low. High-risk HPV (hrHPV) testing is recommended by the World Health Organization as part of the global elimination strategy for cervical cancer. In this context, country-specific health economic evaluations can inform national-level decisions regarding implementation. We evaluated the recommended hrHPV screen-and-treat strategy to determine the minimum required levels of coverage and treatment adherence, as well as the maximum price level per test, for the strategy to be cost-effective in Uganda.We conducted a headroom analysis to estimate potential room for spending on implementing the hrHPV screen-and-treat strategy at different levels of coverage and treatment adherence (from 10% to 100%) at each screening round, and at different price levels of the hrHPV test. We compared the strategy with the existing VIA-based screen-and-treat policy in Uganda. We calculated headroom as the product of number of life years gained by the strategy and the willingness-to-pay threshold, minus the incremental costs incurred by the strategy. Positive headroom was interpreted as an indication of cost-effectiveness.Compared with VIA-based screening with low 5% coverage, the hrHPV screen-and-treat strategy required at least 30% coverage and adherence for positive mean headroom, and compared with 30% VIA-based screening coverage, the minimum levels were 60%. At 60% coverage and adherence, the maximum acceptable price per hrHPV test was found to be between 15 and 30 international dollars.The hrHPV-based screen-and-treat strategy could be cost-effective in Uganda if the screening coverage and treatment adherence are at least 30% in each screening round, and if the price per test is set below 30 international dollars. The minimum required levels of screening coverage and adherence to treatment provide potential starting points for decision-makers in planning the rollout of hrHPV testing. The headroom estimates can guide the planning costs of screening infrastructure and campaigns to achieve the required coverage and treatment adherence in Uganda.