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Background <p>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 <i>(GYPC)</i> methylation (<i>GYPC</i><sup><i>m</i></sup>) in the early detection of cervical cancer.</p> Methods <p>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 <i>GYPC</i><sup><i>m</i></sup> 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.</p> Results <p>The difference of <i>GYPC</i><sup><i>m</i></sup> ΔCp values between CIN1 and CIN2 was statistically significant in the pathology results of 549 participants (<i>P</i> &lt; 0.001). The optimal threshold value of <i>GYPC</i><sup><i>m</i></sup> for detecting CIN2 + was 6.35. The <i>GYPC</i><sup><i>m</i></sup> 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 <i>GYPC</i><sup><i>m</i></sup> 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 <i>P</i> &lt; 0.001). The sensitivity and negative predictive value (NPV) of HPV16/18 combined <i>GYPC</i><sup><i>m</i></sup> for CIN3 + were not statistically different from those of HPV combined with cytology (sensitivity 95.1 vs. 97.6%, <i>P</i> = 0.317; NPV 99.4 vs. 99.0%, <i>P</i> = 0.613). The net reclassification improvement for HPV16/18 combined <i>GYPC</i><sup><i>m</i></sup> and its combined cytology to classify CIN2 + vs. &lt; CIN2 was 48.8% (95%CI: 39.7–57.9%, <i>P</i> &lt; 0.001), with a relative colposcopy referral rate of 50.1% (95%CI: 45.5–54.7%).</p> Conclusion <p><i>GYPC</i><sup><i>m</i></sup> 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.</p>

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GYPC methylation performance in detecting cervical (pre)cancer in high-risk HPV-positive women using liquid-based cervical scrapes

  • 期刊论文

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  • 发表日期：

    2025年10月9日

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  • Xing Fan,
  • Zhengjiao Tong,
  • Saiping Mao,
  • Fang Yu,
  • Rong Wang

摘要

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.