诊断学理论与实践

诊断学理论与实践 ›› 2025, Vol. 24 ›› Issue (01): 65-71.doi: 10.16150/j.1671-2870.2025.01.010

• 论著 • 上一篇    下一篇

基因GYPC甲基化检测在HR-HPV阳性妇女子宫颈癌筛查中的应用

罗海军, 练亿香, 王志敢, 蒋莎莉()   

  1. 南华大学附属长沙中心医院病理科，长沙 410000
  • 收稿日期:2024-06-15 接受日期:2024-10-08 出版日期:2025-02-25 发布日期:2025-02-25
  • 通讯作者: 蒋莎莉 E‑mail：lzrjsl@163.com
  • 基金资助:
    长沙市自然科学基金(kq2208440)

Application of GYPC gene methylation detection in cervical cancer screening for HR-HPV-positive women

LUO Haijun, LIAN Yixiang, WANG Zhigan, JIANG Shali()   

  1. Department of Pathology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410000, China
  • Received:2024-06-15 Accepted:2024-10-08 Published:2025-02-25 Online:2025-02-25

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摘要：

目的 探讨子宫颈脱落细胞中GYPC（Glypican）基因甲基化（GYPC methylation, GYPCm ）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GYPCm 状态。以阴道镜引导下活检病理结果为金标准，分析GYPCm 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 GYPCm 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GYPCm 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。GYPCm 检测在子宫颈鳞状细胞癌患者中的阳性率为100%。针对CIN3+，GYPCm 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GYPCm 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+，GYPCm 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 GYPCm 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。

关键词: GYPC甲基化, 宫颈上皮内瘤变, 子宫颈癌, 高危型人乳头瘤病毒

Abstract:

Objective To investigate the diagnostic efficacy of GYPC (Glypican) gene methylation (GYPCm) 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 GYPCm status. Using the results of histopathological examination of colposcopy-guided biopsy as the gold standard, this study analyzed the diagnostic efficacy of GYPCm for detecting cervical cancer and precancerous lesions and compared it with cytological test results. Results The ΔCp value of GYPCm 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 GYPCm detection for CIN3+ was not inferior to cytological testing, the optimal cutoff value was determined to be ΔCp = 15.975. The positive rate of GYPCm detection in patients with cervical squamous cell carcinoma (SCC) was 100%. For CIN3+, the diagnostic sensitivity of GYPCm detection was comparable to that of cytological testing (86.7% vs. 84.4%, P=0.782), with no statistically significant difference. However, GYPCm 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 GYPCm were significantly higher than those of cytological testing (both P<0.001). Conclusions GYPCm 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.

Key words: GYPC methylation, Cervical intraepithelial neoplasia, Cervical cancer, High-risk human papillomavirus

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