DNA甲基化在宫颈病变中的应用进展

doi:10.12280/gjfckx.20251049

摘要/Abstract

摘要：

宫颈癌是严重威胁女性健康的妇科常见恶性肿瘤，其发生发展与高危型人乳头瘤病毒（high risk human papilloma virus，HR-HPV）持续感染密切相关。目前宫颈癌筛查主要依赖细胞学检查和HR-HPV DNA检测，但前者主观性强、敏感度有限，后者特异度不足，易导致过度诊疗。DNA甲基化作为重要的表观遗传学修饰，参与基因转录调控。近年研究表明，HR-HPV感染可诱导宿主细胞特定基因位点发生异常甲基化，该改变与宫颈上皮内瘤变的进展及宫颈癌的发生发展密切相关。检测这些特定基因的甲基化状态，在宫颈癌筛查分流、预后评估及治疗效果监测方面展现出巨大潜力。综述DNA甲基化在宫颈病变中的应用价值，以期为宫颈癌的精准防治提供新思路。

关键词: DNA甲基化, 宫颈肿瘤, 癌, 宫颈上皮内瘤样病变, 乳头状瘤病毒感染, 早期诊断, 治疗, 预后

Abstract:

Cervical cancer is a common gynecological malignancy that seriously threatens women's health, and its occurrence and development is closely related to persistent infection with high risk human papilloma virus (HR-HPV). Current cervical cancer screening primarily relies on cytological examination and HR-HPV DNA testing. However, the former is subjective and has limited sensitivity, while the latter lacks specificity and may lead to overdiagnosis and overtreatment. DNA methylation, as a crucial epigenetic modification, is involved in the regulation of gene transcription. Recent studies have shown that HR-HPV infection can induce abnormal methylation at specific gene loci in host cells, and these alterations are closely associated with the progression of cervical intraepithelial neoplasia and the occurrence and development of cervical cancer. Detecting the methylation status of these specific genes demonstrates significant potential in triaging cervical cancer screening, prognostic evaluation, and monitoring therapeutic efficacy. This article reviews the application value of DNA methylation in cervical lesions, aiming to provide new insights for the precise prevention and treatment of cervical cancer.

Key words: DNA methylation, Uterine cervical neoplasms, Carcinoma, Cervical intraepithelial neoplasia, Papillomavirus infections, Early diagnosis, Therapy, Prognosis

张燕, 宋淑芳. DNA甲基化在宫颈病变中的应用进展[J]. 国际妇产科学杂志, 2026, 53(2): 206-210.

ZHANG Yan, SONG Shu-fang. Advances in the Application of DNA Methylation in Cervical Lesions[J]. Journal of International Obstetrics and Gynecology, 2026, 53(2): 206-210.

图/表 2

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标志物	主要临床用途	敏感度	特异度	优势	局限性
PAX1^[20]	HPV阳性分流，预测ECC必要性	中	高	特异度高，尤其在HPV16/18阳性人群中预测价值高	敏感度相对较低；可能存在人群差异
ZNF582^[21]	HPV阳性分流	中-高	高	在亚洲人群中性能稳定	在其他人群中的普适性需进一步验证
FAM19A4/miR124-2^{[4,22 -23]}	HPV阳性分流；预后预测（病变消退）	中-高	中-高	大型前瞻性研究支持；高阴性预测值；具有预后预测价值	对宫颈腺癌的检测效能待评估
CADM1/EPB41L3^[18]	HPV阳性分流，常组合使用	中-高	中-高	组合使用可提升整体性能	单一标志物性能可能有限
多基因Panel（如S5）^[24]	长期风险预测	高	中	评估甲基化负荷，预测远期进展风险	检测成本与分析复杂性相对较高

标志物	主要临床用途	敏感度	特异度	优势	局限性
PAX1^[20]	HPV阳性分流，预测ECC必要性	中	高	特异度高，尤其在HPV16/18阳性人群中预测价值高	敏感度相对较低；可能存在人群差异
ZNF582^[21]	HPV阳性分流	中-高	高	在亚洲人群中性能稳定	在其他人群中的普适性需进一步验证
FAM19A4/miR124-2^{[4,22 -23]}	HPV阳性分流；预后预测（病变消退）	中-高	中-高	大型前瞻性研究支持；高阴性预测值；具有预后预测价值	对宫颈腺癌的检测效能待评估
CADM1/EPB41L3^[18]	HPV阳性分流，常组合使用	中-高	中-高	组合使用可提升整体性能	单一标志物性能可能有限
多基因Panel（如S5）^[24]	长期风险预测	高	中	评估甲基化负荷，预测远期进展风险	检测成本与分析复杂性相对较高