Dataset Information

The use of host cell DNA methylation analysis in the detection and management of women with advanced cervical intraepithelial neoplasia: a review.

ABSTRACT: This paper briefly reviews the role of hypermethylation of host cell genes in cervical carcinogenesis and discusses potential clinical applications of methylation analysis in the management of high-risk HPV (hrHPV) -positive women. We argue that methylation assays can be used: 1. for primary triage of hrHPV-positive women to detect cervical cancer and advanced cervical intraepithelial neoplasia (CIN); 2. as secondary triage for women with minor cytological abnormalities to identify those with the highest risk of CIN3 or worse; 3. as exit test for women leaving the screening programme to identify cervical cancer and advanced CIN; and 4. to support management of CIN. TWEETABLE ABSTRACT: This paper discusses potential clinical applications of DNA methylation analysis in the management of women with a high-risk HPV infection.

SUBMITTER: Kremer WW

PROVIDER: S-EPMC7818489 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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The use of host cell DNA methylation analysis in the detection and management of women with advanced cervical intraepithelial neoplasia: a review.

Kremer W W WW Steenbergen Rdm R Heideman Dam D Kenter G G GG Meijer Cjlm C

BJOG : an international journal of obstetrics and gynaecology 20200809 3

This paper briefly reviews the role of hypermethylation of host cell genes in cervical carcinogenesis and discusses potential clinical applications of methylation analysis in the management of high-risk HPV (hrHPV) -positive women. We argue that methylation assays can be used: 1. for primary triage of hrHPV-positive women to detect cervical cancer and advanced cervical intraepithelial neoplasia (CIN); 2. as secondary triage for women with minor cytological abnormalities to identify those with th ...[more]

PMID: 32619334

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Project description:BackgroundMethylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus (HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detecting high-grade cervical intra-epithelial neoplasia (CIN).MethodsWe performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women. Data were extracted in duplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effects binary regression model were applied to determine pooled effect estimates.Findings44 studies with 8819 high-risk HPV positive women were eligible. The pooled estimates for positive methylation rate in HPV16 L1 gene were higher for high-grade CIN (≥CIN2/high-grade squamous intra-epithelial lesion (HSIL) (95% confidence interval (95%CI:72·7% (47·8-92·2))) vs. low-grade CIN (≤CIN1/low-grade squamous intra-epithelial lesion (LSIL) (44·4% (95%CI:16·0-74·1))). Pooled difference in mean methylation level was significantly higher in ≥CIN2/HSIL vs. ≤CIN1/LSIL for HPV16 L1 (11·3% (95%CI:6·5-16·1)). Pooled odds ratio of HPV16 L1 methylation was 5·5 (95%CI:3·5-8·5) for ≥CIN2/HSIL vs. ≤CIN1/LSIL (p < 0·0001). HPV16 L1/L2 genes performed best in predicting CIN2 or worse (pooled sensitivity 77% (95%CI:63-87), specificity 64% (95%CI:55-71), area under the curve (0·73 (95%CI:0·69-0·77)).InterpretationHigher HPV methylation is associated with increased disease severity, whilst HPV16 L1/L2 genes demonstrated high diagnostic accuracy to detect high-grade CIN in HPV16 positive women. Direct clinical use is limited by the need for a multi-genotype and standardised assays. Next-generation multiplex HPV sequencing assays are under development and allow potential for rapid, automated and low-cost methylation testing.FundingNIHR, Genesis Research Trust, Imperial Healthcare Charity, Wellcome Trust NIHR Imperial BRC, European Union's Horizon 2020.

Dataset Information

The use of host cell DNA methylation analysis in the detection and management of women with advanced cervical intraepithelial neoplasia: a review.

Publications

The use of host cell DNA methylation analysis in the detection and management of women with advanced cervical intraepithelial neoplasia: a review.

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