ArticleClinical epigenetics2026
Methylation-based biomarkers from thin-prep cytology test samples for early detection of cervical cancer: application and clinical potential.
Article in Clinical epigenetics, 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
backgroundAlthough human papillomavirus (HPV) testing and Thin-Prep Cytology Test (TCT) are currently adopted as the first-line screening methods for cervical cancer, both of them have limitations. This study aimed to develop and validate new methylation-based biomarkers from formalin-fixed paraffin-embedded (FFPE) tissue and TCT samples in a Chinese population to improve early detection of cervical cancer (CC).
methodsWe performed a differential methylation analysis of cervical FFPE tissues and TCT samples through targeted methylation sequencing. Quantitative methylation-specific PCR (qMSP) was performed on cervical tissues, TCT samples and cell lines to construct a diagnostic model containing three highly methylated sites, namely JAM3, VSTM2B and EPHA7. The clinical effectiveness was evaluated on overall 279 TCT multiple group samples, comprising 33 squamous cell carcinomas (SCC), 14 adenocarcinoma(ADC), 43 high-grade squamous intraepithelial lesion (HSIL), 49 low-grade squamous intraepithelial lesion (LSIL), 78 high risk-HPV (HR-HPV)-positive/cytology-normal (NILM) cases, 32 healthy controls (NC), and 30 benign gynecological samples. The model performance was assessed using sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).
resultsIn an independent validation cohort (n = 108), the panel of three methylation-based biomarkers showed outstanding diagnostic accuracy. It achieved sensitivities of 100.0% for SCC (n = 10), 80.0% for ADC (n = 5), and 86.7% for HSIL (n = 15). Specificity was 90.6% in HR-HPV-positive women (n = 32), 100.0% in NC (n = 12), and 93.3% in other benign conditions (n = 15), with 89.5% specificity in LSIL (n = 19). Overall sensitivity and specificity were 90.0% and 92.3%, respectively. HPV subtype-stratified analysis revealed 90.9% sensitivity and 85.7% specificity for HPV16/18-positive samples, with consistent performance for non-HPV16/18 subtypes (85.7% sensitivity, 89.5% specificity).
conclusionsThe JAM3/VSTM2B/EPHA7 methylation model (JAM3
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