BACKGROUND: Several domestically-manufactured nonavalent HPV vaccine candidates are in phase III clinical trials and their future availability may address the current dilemma of insufficient supply and high price of the overseas-manufactured nonavalent HPV vaccine in China. We compare the population-level effectiveness and cost-effectiveness of switching to nonavalent HPV vaccination in China. METHODS: We used a previously validated transmission model to project the lifetime costs and effectiveness of five same-vaccine and two mixed-vaccine strategies. Nonavalent HPV vaccines were assumed to be available and meet the production requirements for national vaccination between 2030 and 2050. All women living or projected to be born in China during 2023-2100 were considered. We adopted a societal perspective and determined optimal strategies using cost-effectiveness efficiency frontiers. FINDINGS: Under our pricing assumptions, switching to nonavalent vaccination was always cost-saving compared with maintaining the current bivalent vaccination programme, irrespective of the screening scenarios and the year when nonavalent vaccine was assumed to become available (status quo screening: net cost saving 589-5211 million
improved screening: net cost saving 852-3789 million). In the same-vaccine strategies, the optimal strategy changed from "routine nonavalent HPV vaccination with catch-up to age 18" to "switching from bivalent to nonavalent HPV vaccination" if nonavalent vaccination is available after 2035. Compared with the optimal same-vaccine strategy, adopting mixed schedules with bivalent and nonavalent vaccines would further save 336-4280 million net costs and gain 87,000-833,000 QALYs, depending on the screening scenario and the year when nonavalent vaccine becomes available. INTERPRETATION: Switching from bivalent to nonavalent HPV vaccination is likely to be cost-saving and have a significant impact on reducing the cervical cancer burden in China. FUNDING: Bill & Melinda Gates Foundation (INV-031449 and INV-003174) and CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-004).