ArticleBMC cancer2026
A combined PAX1/JAM3 methylation and HPV viral load model for exploratory risk stratification of ≥CIN2 among women with positive cervical screening results.
Article in BMC cancer, 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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Abstract
backgroundHigh-risk human papillomavirus (Hr-HPV) testing is highly sensitive for cervical cancer screening but lacks specificity, leading to unnecessary colposcopy referrals. Host-gene methylation and HPV viral load capture different aspects of disease risk and may support triage.
methodsIn this prospective real-world triage cohort, 126 women with Hr-HPV positivity and/or abnormal cervical cytology identified through opportunistic cervical screening and clinical referral were enrolled. All participants underwent cytology, HPV genotyping with viral load quantification, and PAX1/JAM3 methylation testing. Histopathology served as the reference standard. A logistic regression model integrating methylation status and viral load was constructed to evaluate its performance for detecting ≥CIN2, with subgroup analysis in ASCUS.
resultsMethylation levels, expressed as ΔCt values, decreased with increasing lesion severity and were associated with HPV viral load. In the overall screening-positive cohort, the logistic regression model discriminated ≥CIN2 better than either marker alone. In the ASCUS subgroup, the biomarker-only logistic regression model showed the highest observed AUC among the three evaluated approaches, although this subgroup finding remained exploratory. Scenario-specific strategies showed different trade-offs: the OR rule provided higher sensitivity, whereas the AND rule improved specificity but had lower sensitivity and should be interpreted as a confirmatory triage approach rather than a stand-alone screening rule.
conclusionCombining PAX1/JAM3 methylation with HPV viral load may refine ≥CIN2 risk stratification among women with positive cervical screening results, particularly among women with ASCUS. However, given the referral-enriched nature, limited sample size, and single-center design, the clinical applicability of this approach requires validation in larger, more representative cohorts.
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