ReviewCancer management and research2026
A Holistic Framework for Cervical Cancer Screening and Risk Stratification: Integrating Etiology, Morphology, Epigenetics, and Microecology.
Review in Cancer management and research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Authors and funding
5 authors.
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Abstract
Cervical cancer (CC) remains a major global health burden despite being highly preventable through early detection. Current screening strategies, predominantly high-risk human papillomavirus (HR-HPV) testing and liquid-based cytology (LBC), have limited specificity, leading to unnecessary colposcopic referrals and overtreatment. This narrative review proposes a conceptual holistic screening framework-termed HADm-that integrates four complementary pillars into a unified risk stratification system: (1) Etiology (HR-HPV genotyping), (2) Morphology (artificial intelligence-assisted LBC, Ai-LBC), (3) Epigenetics (DNA methylation [DNAm] biomarkers, with PAX1 methylation as an example), and (4) Microecology (genital pathogens and vaginal microbiota). Persistent HR-HPV infection is the primary etiological factor, while disease progression is modulated by host epigenetic alterations and the local microenvironment. DNAm markers may serve as molecular indicators of malignant transformation and have shown high specificity for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) among human papillomavirus (HPV)-positive women in some studies. Ai-LBC may improve both sensitivity and standardization of morphological interpretation, whereas genital pathogen and microbiota may help explain persistent HPV infection and chronic inflammation. However, evidence for the combined HADm framework remains limited, and prospective multicenter validation is lacking. This framework represents a shift from single-analyte testing toward integrated risk assessment, but its incremental clinical value, cost-effectiveness, and feasibility in low- and middle-income countries require rigorous evaluation. If validated, HADm may support precise risk stratification, individualized follow-up, and more efficient resource allocation, aligning with the World Health Organization (WHO) global goal of accelerating CC elimination by 2030.
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