Imperial College London
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DrAnitaMitra

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Lecturer
 
 
 
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a.mitra

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bowden:2019:10.1016/j.ebiom.2019.10.053,
author = {Bowden, SJ and Kalliala, I and Veroniki, AA and Arbyn, M and Mitra, A and Lathouras, K and Mirabello, L and Chadeau-Hyam, M and Paraskevaidis, E and Flanagan, JM and Kyrgiou, M},
doi = {10.1016/j.ebiom.2019.10.053},
journal = {EBioMedicine},
pages = {246--259},
title = {The use of Human Papillomavirus DNA Methylation in cervical intraepithelial neoplasia: a systematic review and meta-analysis},
url = {http://dx.doi.org/10.1016/j.ebiom.2019.10.053},
volume = {50},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 detectinghigh-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 induplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effectsbinary 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 squamousintra-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 differencein 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 islimited by the need for a multi-genotype and standardised ass
AU  - Bowden,SJ
AU  - Kalliala,I
AU  - Veroniki,AA
AU  - Arbyn,M
AU  - Mitra,A
AU  - Lathouras,K
AU  - Mirabello,L
AU  - Chadeau-Hyam,M
AU  - Paraskevaidis,E
AU  - Flanagan,JM
AU  - Kyrgiou,M
DO  - 10.1016/j.ebiom.2019.10.053
EP  - 259
PY  - 2019///
SN  - 2352-3964
SP  - 246
TI  - The use of Human Papillomavirus DNA Methylation in cervical intraepithelial neoplasia: a systematic review and meta-analysis
T2  - EBioMedicine
UR  - http://dx.doi.org/10.1016/j.ebiom.2019.10.053
UR  - http://hdl.handle.net/10044/1/74600
VL  - 50
ER  -
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