Infect Agent Cancer. 2025 Oct 9;20(1):69. doi: 10.1186/s13027-025-00699-3.
ABSTRACT
BACKGROUND: Methylation of host genes is promising for the triage of women with high-risk human papillomavirus (HR-HPV) infections. This study aimed to validate the potential value of Glycophorin C (GYPC) methylation (GYPCm) in the early detection of cervical cancer.
METHODS: We recruited HR-HPV-positive women at the hospital outpatient clinic between August and December 2023, using cytology triage. The remaining exfoliated cervical cells were subjected to GYPCm testing. A total of 549 cases were finally included for analysis: 156 cervicitis, 303 cervical intraepithelial neoplasia (CIN)1, 49 CIN2, 37 CIN3, and 4 CC.
RESULTS: The difference of GYPCm ΔCp values between CIN1 and CIN2 was statistically significant in the pathology results of 549 participants (P < 0.001). The optimal threshold value of GYPCm for detecting CIN2 + was 6.35. The GYPCm adjusted ORs for CIN2 + and CIN3 + were 31.23 (95%CI: 16.53-58.99) and 34.68 (95%CI: 11.90-101.11), respectively. In all individuals, the sensitivity of GYPCm for CIN2 + and CIN3 + was consistent with that of cytology (CIN2 + 83.3%; CIN3 + 90.2%), with higher specificity than that of cytology (CIN2 + 85.8 vs. 29.4%; CIN3 + 79.7 vs. 28.7%, all P < 0.001). The sensitivity and negative predictive value (NPV) of HPV16/18 combined GYPCm for CIN3 + were not statistically different from those of HPV combined with cytology (sensitivity 95.1 vs. 97.6%, P = 0.317; NPV 99.4 vs. 99.0%, P = 0.613). The net reclassification improvement for HPV16/18 combined GYPCm and its combined cytology to classify CIN2 + vs. < CIN2 was 48.8% (95%CI: 39.7-57.9%, P < 0.001), with a relative colposcopy referral rate of 50.1% (95%CI: 45.5-54.7%).
CONCLUSION: GYPCm has a higher CIN2 + OR and higher specificity and positive predictive value than cytology in HR-HPV-positive women and is a potential molecular biomarker for triaging HR-HPV (+) to detect cervical (pre)cancer.
PMID:41068755 | DOI:10.1186/s13027-025-00699-3