Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia (CIN2+): a systematic review and meta-analysis.
Adult
Aged
Aged, 80 and over
DNA Methylation
/ genetics
Female
Genome, Human
/ genetics
Human papillomavirus 16
/ genetics
Human papillomavirus 18
/ genetics
Humans
Middle Aged
Neoplasm Grading
Papillomavirus Infections
/ diagnosis
Sensitivity and Specificity
Triage
/ methods
Uterine Cervical Neoplasms
/ diagnosis
Young Adult
Uterine Cervical Dysplasia
/ diagnosis
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
20
03
2019
accepted:
10
09
2019
revised:
09
09
2019
pubmed:
17
10
2019
medline:
20
6
2020
entrez:
17
10
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
To conduct a meta-analysis of performance of DNA methylation in women with high-grade cervical intraepithelial neoplasia (CIN2+).
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Identifiants
pubmed: 31616037
doi: 10.1038/s41416-019-0593-4
pii: 10.1038/s41416-019-0593-4
pmc: PMC6889421
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
954-965Références
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