DNA methylation as a triage marker for colposcopy referral in HPV-based cervical cancer screening: a systematic review and meta-analysis.

IF 5.7 2区 医学 Q1 Medicine
Sofia Salta, João Lobo, Bruno Magalhães, Rui Henrique, Carmen Jerónimo
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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

DNA 甲基化作为基于 HPV 的宫颈癌筛查中阴道镜检查转诊的分流标记:系统综述与荟萃分析。
背景:筛查在宫颈癌二级预防中起着关键作用。高危人乳头瘤病毒(hrHPV)检测是一种灵敏度很高但特异性有限的检测方法,已成为筛查项目的前沿金标准。因此,包括 DNA 甲基化标记在内的有效分流策略的重要性得到了强调。尽管个别研究报告了甲基化标记物的潜力,但在推荐用于临床实践之前仍需要验证。本系统综述和荟萃分析旨在评估基于DNA甲基化的生物标记检测hrHPV阳性女性高级别上皮内病变(HSIL)的性能。以组织学确诊的HSIL为终点,采用QUADAS-2工具对研究质量进行评估。采用双变量随机效应模型对估计的敏感性、特异性以及阳性(PPV)和阴性(NPV)预测值进行汇总:本次荟萃分析共纳入 23 项研究,其中队列研究和转诊人群研究占近 65%。大多数被分析的女性是荷兰人,CADM1、FAM19A4、MAL 和 miR124-2 是研究最多的基因。宫颈上皮内瘤变(CIN)2+检测的汇总灵敏度和特异性分别为0.68(CI 95% 0.63-0.72)和0.75(CI 95% 0.71-0.80)。对于 CIN3+ 的检测,汇总灵敏度和特异性分别为 0.78(CI 95% 0.74-0.82)和 0.74(CI 95% 0.69-0.78)。就汇总患病率而言,CIN2+和CIN3+检测的PPV分别为0.514和0.392。此外,CIN2+和CIN3+检测的NPV分别为0.857和0.938:这项荟萃分析证实了基于 DNA 甲基化的生物标记物作为宫颈癌筛查中 hrHPV 阳性妇女的分诊工具的巨大潜力。不过,还需要进行标准化和改进验证。不过,这些标记物可能是细胞学和基因分型检查的绝佳替代品,可用于hrHPV阳性妇女的阴道镜检查转诊,使筛查项目更具成本效益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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