Background: China has recently incorporated HPV vaccination into their National Immunization Programs. Assessing vaccine effectiveness (VE) under real-world conditions is critical for evaluating program impact and guiding policy adjustments. This study, aligned with the WHO-IARC CHRONOS global framework, aims to implement an adapted and sustainable monitoring system in China, generating locally relevant evidence while strengthening national research capacity.

Objectives: This study aims to: (1) assess the real-world effectiveness of HPV vaccination among young women in China; (2) establish a standardized, context-adapted monitoring framework that integrates capacity building, procedural harmonization, and quality assurance; and (3) provide transferable methodologies and evidence to support other countries in monitoring HPV vaccine impact following national introduction.

Methods: CHRONOS-CN comprises two non-interventional, multicenter cross-sectional surveys: baseline (2026–2027) and repeat (2031–2032). Each survey will include 5,560 sexually active women aged 18–24 years. Participants will provide first-void urine samples and complete questionnaires on sociodemographics, sexual/reproductive history, and vaccination status. HPV genotyping will be performed using the validated Allplex HPV28 assay. To ensure quality and sustainability, the study incorporates local research capacity building through standardized training of field staff and laboratory personnel, and establishment of a comprehensive documentation system including study protocols, standard operating procedures (SOPs), and data management guidelines aligned with international standards while tailored to local contexts.

Anticipated Results: The study will follow a structured implementation timeline, beginning with the finalization of standardized protocols and training of local teams in 2026, followed by participant recruitment during 2026–2027. We anticipate a measurable decline in vaccine-targeted HPV prevalence post-vaccination, enabling estimation of overall, indirect, and total VE through comparison of type-specific infection rates between baseline and follow-up surveys, adjusted for confounders. In addition to epidemiological outcomes, the study will yield key capacity-building outputs, including trained personnel, validated workflows, and a sustained quality-control system, to support long-term monitoring of the national HPV vaccination program in China.

Implications: By aligning with the globally harmonized CHRONOS protocol while deliberately contextualizing its implementation, CHRONOS-CN contributes not only country-specific VE estimates but also a replicable model for localized impact evaluation in China. The integration of capacity building, procedural standardization, and phased implementation represents a significant methodological contribution, ensuring both cross-country comparability and local ownership. Findings will directly inform national cervical cancer prevention strategies and provide real-world evidence on the current HPV vaccination schedules, with broader relevance for global efforts toward cervical cancer elimination.
Funding: Bill & Melinda Gates Foundation (INV-091242)