筛查在宫颈癌二级预防中起着关键作用。高危型人乳头瘤病毒（hrHPV）检测是一种高度敏感但特异性有限的测试，已成为筛查计划的黄金标准前线。因此，强调了有效的分流策略的重要性，包括DNA甲基化标记物。尽管个别研究中报道了潜在的潜力，但在推荐临床实践之前，甲基化标记物仍需验证。本系统回顾和荟萃分析的目的是评估基于DNA甲基化标记物用于检测hrHPV阳性女性高级别上皮内病变（HSIL）的性能。因此，PubMed、Scopus和Cochrane数据库被搜索，用于筛选在宫颈刮⽭物中研究hrHPV阳性⼥性甲基化的研究⽂献。组织学确认的HSIL被⽤作终点，QUADAS-2工具评估了研究质量。采用双变量随机效应模型汇总估计的⾜度和敏感性以及阳性（PPV）和阴性（NPV）预测值。本荟萃分析包括23项研究，其中队列和转诊基于群体的研究占据了近65%。大多数分析的妇女是荷兰人，而CADM1、FAM19A4、MAL和miR124-2是研究最多的基因。对于宫颈上皮内瘤变（CIN）2+的检测，汇总敏感性和特异性分别为0.68（95% CI 0.63-0.72）和0.75（95% CI 0.71-0.80）。对于CIN3+的检测，汇总敏感性和特异性分别为0.78（95% CI 0.74-0.82）和0.74（95% CI 0.69-0.78）。对于汇总患病率，CIN2+的PPV和CIN3+的PPV分别为0.514和0.392。此外，CIN2+的NPV和CIN3+的NPV分别为0.857和0.938。本荟萃分析证实了基于DNA甲基化标记物作为hrHPV阳性女性宫颈癌筛查的分流工具的巨大潜力。然而，需要标准化和改进验证。尽管如此，这些标记物可能代表了细胞学和基因分型的优秀选择，用于对hrHPV阳性女性进行阴道镜转诊，从而实现更具成本效益的筛查计划。© 2023. 作者。

Screening plays a key role in secondary prevention of cervical cancer. High-risk human papillomavirus (hrHPV) testing, a highly sensitive test but with limited specificity, has become the gold standard frontline for screening programs. Thus, the importance of effective triage strategies, including DNA methylation markers, has been emphasized. Despite the potential reported in individual studies, methylation markers still require validation before being recommended for clinical practice. This systematic review and meta-analysis aimed to evaluate the performance of DNA methylation-based biomarkers for detecting high-grade intraepithelial lesions (HSIL) in hrHPV-positive women.Hence, PubMed, Scopus, and Cochrane databases were searched for studies that assessed methylation in hrHPV-positive women in cervical scrapes. Histologically confirmed HSIL was used as endpoint and QUADAS-2 tool enabled assessment of study quality. A bivariate random-effect model was employed to pool the estimated sensitivity and specificity as well as positive (PPV) and negative (NPV) predictive values.Twenty-three studies were included in this meta-analysis, from which cohort and referral population-based studies corresponded to nearly 65%. Most of the women analyzed were Dutch, and CADM1, FAM19A4, MAL, and miR124-2 were the most studied genes. Pooled sensitivity and specificity were 0.68 (CI 95% 0.63-0.72) and 0.75 (CI 95% 0.71-0.80) for cervical intraepithelial neoplasia (CIN) 2+ detection, respectively. For CIN3+ detection, pooled sensitivity and specificity were 0.78 (CI 95% 0.74-0.82) and 0.74 (CI 95% 0.69-0.78), respectively. For pooled prevalence, PPV for CIN2+ and CIN3+ detection were 0.514 and 0.392, respectively. Furthermore, NPV for CIN2+ and CIN3+ detection were 0.857 and 0.938, respectively.This meta-analysis confirmed the great potential of DNA methylation-based biomarkers as triage tool for hrHPV-positive women in cervical cancer screening. Standardization and improved validation are, however, required. Nevertheless, these markers might represent an excellent alternative to cytology and genotyping for colposcopy referral of hrHPV-positive women, allowing for more cost-effective screening programs.© 2023. The Author(s).