Cervical cancer (CC) and cervical intraepithelial neoplasia (CIN) remain major global health burdens, despite advances in HPV vaccination and screening. However, significant heterogeneity exists in disease onset, progression from CIN to invasive cancer, therapeutic response, and long-term prognosis. Current risk stratification relies heavily on HPV typing and cytology-based assessments, which incompletely capture underlying genomic, immunologic, metabolic, and microbiome determinants. The mechanisms by which host-virus interactions, immunometabolic dysregulation, and microenvironmental remodeling drive progression remain insufficiently defined.
This project aims to provide a comprehensive, systems-level characterization of cervical carcinogenesis by integrating clinical, demographic, lifestyle, molecular, and multi-omics datasets from UK Biobank. Our objectives are to:
(1) Quantify the incidence, natural history, and progression patterns of CIN and CC, characterizing risk factors, comorbidity burden, and variations across age, socioeconomic status, reproductive history, hormonal exposures, and lifestyle factors.
(2) Identify clinical, environmental, hormonal, immune, and multi-omics predictors (genomic variants, proteomics, metabolomics, inflammatory biomarkers, vaginal/gut microbiome signatures) associated with CC onset, CIN progression, treatment response, and recurrence risk.
(3) Develop integrative prognostic models for CIN progression, invasive CC, major adverse cancer-related events (MACEs), treatment complications, and long-term survival.
(4) Elucidate biological mechanisms by linking HPV persistence, host immunity, metabolic reprogramming, microbiota dysbiosis, and systemic inflammatory pathways with disease trajectories.
