目的 探讨子宫颈脱落细胞中GYPC（Glypican）基因甲基化（GYPC methylation, GYPC^m ）在高危型人乳头瘤病毒（high-risk human papillomavirus, HR-HPV）感染女性中诊断宫颈癌及癌前病变的效能。方法 研究共纳入2022年10月至2023年7月期间，本院收治的完成阴道镜活检组织学病理检查的187例女性HR-HPV感染连续病例，中位年龄为40.0岁（17~75岁）。在阴道镜检查前先采集宫颈脱落细胞，行细胞学检查，剩余标本用于检测GYPC^m 状态。以阴道镜引导下活检病理结果为金标准，分析GYPC^m 检测诊断宫颈癌及癌前病变的效能，并与细胞学检查结果进行比较。结果 GYPC^m 的ΔCp值随子宫颈病变严重程度增加而显著降低，其临界值为15.975时，识别宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）2级及以上（CIN2+）和CIN3+病变的受试者操作特征（receiver operator characteristic, ROC）曲线下面积分别为0.800（95%CI为0.733～0.867）和0.856（95%CI为0.784～0.928）。固定GYPC^m 检测CIN3+的灵敏度不低于细胞学检查时，确定最佳临界值为ΔCp=15.975。GYPC^m 检测在子宫颈鳞状细胞癌患者中的阳性率为100%。针对CIN3+，GYPC^m 检测与细胞学检查间的诊断灵敏度（86.7%比84.4%，P=0.782）差异无统计学意义，而GYPC^m 检测的特异度（65.5%比29.6%，P<0.001）和阳性预测值（44.3%比27.5%，P<0.001）高于细胞学检查，差异有统计学意义。针对CIN2+，GYPC^m 检测的特异度和阳性预测值显著高于细胞学检查（P均<0.001）。结论 GYPC^m 检测可作为宫颈癌筛查中HR-HPV阳性分流的工具，诊断效能优于细胞学检查。

Objective To investigate the diagnostic efficacy of GYPC (Glypican) gene methylation (GYPC^m) in cervical exfoliated cells for detecting cervical cancer and precancerous lesions among women infected with high-risk human pa-pillomavirus (HR-HPV). Methods This study enrolled a total of 187 HR-HPV-positive women who underwent histopathological examination of colposcopy-guided biopsy at the hospital from October 2022 to July 2023, with a median age of 40.0 years (range: 17-75 years). Cervical exfoliated cells were collected before colposcopy for cytological testing, and the remai-ning specimens were tested for GYPC^m status. Using the results of histopathological examination of colposcopy-guided biopsy as the gold standard, this study analyzed the diagnostic efficacy of GYPC^m for detecting cervical cancer and precancerous lesions and compared it with cytological test results. Results The ΔCp value of GYPC^m decreased significantly with increa-sing severity of cervical lesions. At a cutoff value of 15.975, the areas under the receiver operating characteristic(ROC) curves for detecting cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and grade 3 or higher (CIN3+) were 0.800 (95% CI: 0.733-0.867) and 0.856 (95% CI: 0.784-0.928), respectively. To ensure that the sensitivity of GYPC^m detection for CIN3+ was not inferior to cytological testing, the optimal cutoff value was determined to be ΔCp = 15.975. The positive rate of GYPC^m detection in patients with cervical squamous cell carcinoma (SCC) was 100%. For CIN3+, the diagnostic sensitivity of GYPC^m detection was comparable to that of cytological testing (86.7% vs. 84.4%, P=0.782), with no statistically significant difference. However, GYPC^m detection demonstrated significantly higher specificity (65.5% vs. 29.6%, P<0.001) and positive predictive value (44.3% vs. 27.5%, P<0.001) compared with cytological testing. For CIN2+, the specificity and positive predictive value of GYPC^m were significantly higher than those of cytological testing (both P<0.001). Conclusions GYPC^m detection can serve as an effective triage tool for HR-HPV-positive women in cervical cancer scree-ning, offering better diagnostic efficacy compared with cytological testing.