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Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia (CIN2+): a systematic review and meta-analysis

British journal of cancer, 2019-11, Vol.121 (11), p.954-965 [Peer Reviewed Journal]

2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;The Author(s) 2019 ;ISSN: 0007-0920 ;EISSN: 1532-1827 ;DOI: 10.1038/s41416-019-0593-4 ;PMID: 31616037

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Title:
Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia (CIN2+): a systematic review and meta-analysis
Author: Kelly, Helen ; Benavente, Yolanda ; Pavon, Miquel Angel ; De Sanjose, Silvia ; Mayaud, Philippe ; Lorincz, Attila Tibor
Subjects: Adult ; Aged ; Aged, 80 and over ; Cellular biology ; Cervical Intraepithelial Neoplasia - diagnosis ; Cervical Intraepithelial Neoplasia - genetics ; Cytology ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA Methylation - genetics ; Female ; Genome, Human - genetics ; Genotyping ; Human papillomavirus 16 - genetics ; Human papillomavirus 18 - genetics ; Humans ; Middle Aged ; Neoplasm Grading ; Papillomavirus Infections - diagnosis ; Papillomavirus Infections - genetics ; Sensitivity and Specificity ; Squamous cells ; Systematic review ; Triage - methods ; Uterine Cervical Neoplasms - diagnosis ; Uterine Cervical Neoplasms - genetics ; Young Adult
Is Part Of: British journal of cancer, 2019-11, Vol.121 (11), p.954-965
Description: To conduct a meta-analysis of performance of DNA methylation in women with high-grade cervical intraepithelial neoplasia (CIN2+). Medline and Embase databases were searched for studies of methylation markers versus histological endpoints. Pooled sensitivity, specificity and positive predictive value (PPV) for CIN2+ were derived from bivariate models. Relative sensitivity and specificity for CIN2+ compared to cytology and HPV16/18 genotyping were pooled using random-effects models. Sixteen thousand three hundred thirty-six women in 43 studies provided data on human genes (CADM1, MAL, MIR-124-2, FAM19A4, POU4F3, EPB41L3, PAX1, SOX1) and HPV16 (L1/L2). Most (81%) studies evaluated methylation assays following a high-risk (HR)-HPV-positive or abnormal cytology result. Pooled CIN2+ and CIN3+ prevalence was 36.7% and 21.5%. For a set specificity of 70%, methylation sensitivity for CIN2+ and CIN3+ were 68.6% (95% CI: 62.9-73.8) and 71.1% (95% CI: 65.7-76.0) and PPV were 53.4% (95% CI: 44.4-62.1) and 35.0% (95% CI: 28.9-41.6). Among HR-HPV+ women, the relative sensitivity of methylation for CIN2+ was 0.81 (95% CI: 0.63-1.04) and 1.22 (95% CI: 1.05-1.42) compared to cytology of atypical squamous cells of undetermined significance, or greater (ASCUS+) and HPV16/18 genotyping, respectively, while relative specificity was 1.25 (95% CI: 0.99-1.59) and 1.03 (95% CI: 0.94-1.13), respectively. DNA methylation is significantly higher in CIN2+ and CIN3+ compared to ≤CIN1. As triage test, DNA methylation has higher specificity than cytology ASCUS+ and higher sensitivity than HPV16/18 genotyping.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 0007-0920
EISSN: 1532-1827
DOI: 10.1038/s41416-019-0593-4
PMID: 31616037
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
NCBI PubMed Central（免费）
ProQuest Central

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Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia (CIN2+): a systematic review and meta-analysis

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