BackgroundSince December 2021, Wuxi, China has offered a two-dose human papillomavirus (HPV) vaccination to 14-year-old females for free. This study evaluated the costs and benefits of this vaccination scheduled in the Expanded Program on Immunization in Wuxi from the perspective of the cities’ demographic characteristics, economic development, and policy support.MethodsThe model-based economic evaluation used TreeAge Pro software to construct a decision tree-Markov model for the vaccination strategy in which 100,000 14-year-old females received two doses of bivalent HPV vaccine or no vaccination. Costs and effects of the strategy were assessed from a societal perspective through literature research and data obtained from the Wuxi Centre for Disease Control and Prevention. Univariate, multivariate, and probabilistic sensitivity analyses assessed the stability of the findings.ResultsThe cost of the bivalent HPV vaccine in Wuxi is 711.3 CNY. The two-dose of bivalent HPV vaccine for 100,000 14-year-old females would cost an additional 658,016 CNY compared to no vaccination, but would result in 1,960 Quality Adjustment Years of Life (QALYs). Using the per capita gross domestic product of 187,415 CNY in 2021 in Wuxi as the willingness-to-pay threshold, the vaccination strategy costs 3,357.37 CNY per QALY gained, which is much lower than the threshold, suggesting that it is a very cost-effective strategy. In addition, the vaccine strategy reduced the incidence of cervical cancer by 300 cases and cervical cancer deaths by 181 cases, representing a benefit-cost ratio of 2.86 (> 1) when health output outcomes were measured in monetary terms. These results suggested that the vaccination strategy was advantageous. Sensitivity analyses showed that changes in the parameters did not affect the conclusions and that the findings were robust.ConclusionsCompared to no vaccination, the delivery of two doses of bivalent HPV vaccine for 14-year-old females was a more highly cost-effective and optimal strategy.