Abstract
Human papillomavirus (HPV) causes multiple diseases in both sexes. This study evaluates the cost-effectiveness and epidemiological impact - defined as reductions in HPV-related disease cases - of a gender-neutral vaccination (GNV) strategy in China's economically developed metropolises: Beijing, Shanghai, and Guangzhou. A discrete-time Markov model simulated no vaccination, female-only vaccination (FOV), and GNV strategies among 12-year-olds. The cost matrix included vaccine procurement, administration, and treatment costs from Chinese data and literature. The case matrix translated model-estimated reductions in HPV infections into decreases in disease incidence by applying baseline incidence rates adjusted for HPV genotype attribution, relative risk reductions, and disease-specific lag times. Outcomes assessed were costs (2023 USD), quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), and cases averted. Compared to FOV, the ICERs for GNV were USD 323,134/QALY (Beijing), USD 305,816/QALY (Shanghai), and USD 251,853/QALY (Guangzhou), exceeding local willingness-to-pay thresholds, indicating cost-ineffectiveness. The GNV strategy averted 3.9%, 4.7%, and 3.9% more HPV-related cases over 30 years in Beijing, Shanghai, and Guangzhou, respectively. Sensitivity analyses showed that GNV became cost-effective when the 9vHPV uptake rate was below 20% in girls (Shanghai) or below 10% in girls (Beijing and Guangzhou), regardless of the uptake rate (≤80%) in boys. It was also cost-effective if vaccine price dropped to USD 21.4 (Shanghai), USD 18.9 (Beijing), or USD 19.1 (Guangzhou). Price thresholds rose substantially with decreasing female uptake but changed little with male uptake variation. The GNV strategy may be cost-effective when the 9vHPV uptake rate remains low in girls or the vaccine price significantly decreases.