Diagnostic performance of CDO1 and ZSCAN12 methylation in endometrial versus cervical samples for endometrial cancer and atypical hyperplasia: a comparative study

Background This study evaluated the diagnostic performance of CDO1 and ZSCAN12 methylation in paired endometrial (Em) and exfoliated cervical (Cx) samples for detecting endometrial cancer (EC) and endometrial atypical hyperplasia (EAH).Methods We analysed 127 histologically confirmed women (43 EC, 13 EAH, 71 benign). Methylation levels were measured using bisulfite-conversion real-time PCR. Agreement, robustness, and diagnostic accuracy were assessed.Results Methylation levels increased stepwise from benign to EC across all sample types (all p < 0.001). For EC detection, CDO1m_Em and ZSCAN12m_Em achieved AUCs of 0.858 and 0.832, with ORs of 21.0 and 19.7, respectively. Bootstrap validation confirmed robustness. For the same sample source (Em or Cx), the clinical performance of CDO1m and ZSCAN12m was comparable (all p > 0.05). However, significant differences were noted between Em and Cx samples for ZSCAN12m’s negative predictive value (NPV) in EC detection (p = 0.045), and for CDO1m’s sensitivity, NPV, and negative likelihood ratio (nLR) in EAH/EC detection (p = 0.029, 0.026, and 0.031, respectively). The Em-based two-gene combination showed 97.5% sensitivity for EC (39 of 40 evaluable cases), failing to detect only 1 of 40 cases.Conclusions CDO1 and ZSCAN12 methylation demonstrated robust diagnostic performance for EC and EAH. The Em-based two-gene combination showed excellent sensitivity. Most diagnostic metrics were comparable between sample sources, with Em showing advantages specifically in NPV-related measures. Given that these differences may be assay-dependent and that most performance metrics showed no significant differences, cervical sampling remains a promising less invasive option but warrants cautious interpretation and further validation.