BackgroundHuman papillomavirus (HPV) is a common sexually transmitted infection and the leading cause of cervical cancer. The HPV vaccine is a safe and effective way to prevent HPV infection. In Zambia, the vaccine is given during Child Health to girls aged 14 years who are in and out of school in two doses over two years. The focus of this evaluation was to establish the cost to administer a single dose of the vaccine well as for full immunisation of two doses.MethodsFor HPV costing, both top-down and micro-costing approaches were used, depending on the cost data source, and economic costs were gathered from Expanded Programme for Immunisation Costing and Financing Project (EPIC). Data was collected from eight districts in four provinces, mainly using a structured questionnaire, document reviews and key informant interviews with staff at national, district and provincial levels.ResultsFindings show that schools made up 53.3% of vaccination sites, community outreach sites 30.9% and finally health facilities 15.8%. In terms of coverage for 2020, for the eight districts sampled, schools had the highest coverage at 96.0%. Community outreach sites were at 6.0% of the coverage and health facilities accounted for only 1.0% of the coverage. School based delivery had the lowest cost economic cost at USD13.2 per dose and USD 26.4 per fully immunised child (FIC). Overall financial costs were US$6.0 per dose and US$11.9 per fully immunised child. Overall economic costs taking all delivery models into account were US$23.0 per dose and US$46.0 per FIC. The main cost drivers were human resources, building overhead and vehicles, microplanning, supplies and service delivery/outreach. were the top cost drivers. Nurses, environmental health technicians and community-based volunteers were the most involved in HPV vaccination.ConclusionsFuture planning in Zambia and other African countries conducting HPV vaccination needs to prioritise these cost drivers as well as possibly find strategies to minimise some costs. Although not a challenge now due to Gavi support, vaccine costs are a major threat to sustainability in the long run. Countries like Zambia must find strategies to mitigate against this.