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The peer-reviewed article examines the operational context and costs of the HPV vaccination program in Ethiopia, introduced in 2018 to prevent cervical cancer. Using a cross-sectional, mixed-methods study in three regions, data were collected from 60 health facilities, 17 woredas, 9 zones/sub-cities, and the national level. The study focused on the first dose given in October 2019 and the second in January 2021. Findings showed that health facilities delivered an average of 411 doses, with financial and economic costs per dose at $2.23 and $7.19, respectively, excluding vaccine and supply costs. Costs varied regionally, with financial costs ranging from $1.17 to $7.18 and economic costs from $5.80 to $18.13. These variations highlight the need to consider regional differences for effective resource planning and budgeting in HPV vaccination programs.