The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia : A systematic review and meta-analysis

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dc.contributor.author Bowden, Sarah J.
dc.contributor.author Kalliala, Ilkka
dc.contributor.author Veroniki, Areti A.
dc.contributor.author Arbyn, Marc
dc.contributor.author Mitra, Anita
dc.contributor.author Lathouras, Kostas
dc.contributor.author Mirabello, Lisa
dc.contributor.author Chadeau-Hyam, Marc
dc.contributor.author Paraskevaidis, Evangelos
dc.contributor.author Flanagan, James M.
dc.contributor.author Kyrgiou, Maria
dc.date.accessioned 2020-01-17T11:08:01Z
dc.date.available 2020-01-17T11:08:01Z
dc.date.issued 2019-12
dc.identifier.citation Bowden , S J , Kalliala , I , Veroniki , A A , Arbyn , M , Mitra , A , Lathouras , K , Mirabello , L , Chadeau-Hyam , M , Paraskevaidis , E , Flanagan , J M & Kyrgiou , M 2019 , ' The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia : A systematic review and meta-analysis ' , EBioMedicine , vol. 50 , pp. 246-259 . https://doi.org/10.1016/j.ebiom.2019.10.053
dc.identifier.other PURE: 130216726
dc.identifier.other PURE UUID: fc047c36-bccc-40ea-8449-d06f52d86f1b
dc.identifier.other WOS: 000503226300029
dc.identifier.other ORCID: /0000-0002-7664-0587/work/68614630
dc.identifier.uri http://hdl.handle.net/10138/309753
dc.description.abstract Background: Methylation 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). Methods: We 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. Findings: 44 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 (= CIN2/HSIL vs. = CIN2/HSIL vs. Interpretation: Higher 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. (C) 2019 The Authors. Published by Elsevier B.V. en
dc.format.extent 14
dc.language.iso eng
dc.relation.ispartof EBioMedicine
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Human papillomavirus
dc.subject DNA methylation
dc.subject Cervical intraepithelial neoplasia
dc.subject Cervical screening
dc.subject Meta-analysis
dc.subject E2 BINDING-SITES
dc.subject RESOLUTION MELTING ANALYSIS
dc.subject HPV 16 METHYLATION
dc.subject L1 GENE
dc.subject QUANTITATIVE MEASUREMENT
dc.subject POTENTIAL BIOMARKER
dc.subject CPG METHYLATION
dc.subject MESSENGER-RNA
dc.subject TYPE-16 DNA
dc.subject E6 GENE
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.subject 3123 Gynaecology and paediatrics
dc.title The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia : A systematic review and meta-analysis en
dc.type Review Article
dc.contributor.organization Clinicum
dc.contributor.organization Department of Obstetrics and Gynecology
dc.contributor.organization HUS Gynecology and Obstetrics
dc.contributor.organization University of Helsinki
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1016/j.ebiom.2019.10.053
dc.relation.issn 2352-3964
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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