FAM19A4/miR124-2 methylation analysis as a triage test for HPV-positive women: cross-sectional and longitudinal data from a Dutch screening cohort.
Adult
Biomarkers, Tumor
/ genetics
Cross-Sectional Studies
Cytokines
/ genetics
DNA Methylation
Early Detection of Cancer
Female
Humans
Longitudinal Studies
Mass Screening
MicroRNAs
/ genetics
Middle Aged
Netherlands
/ epidemiology
Papillomaviridae
Papillomavirus Infections
/ diagnosis
Triage
/ methods
Uterine Cervical Neoplasms
/ diagnosis
Uterine Cervical Dysplasia
/ diagnosis
Biomarker
Cervical cancer screening
Cervical intraepithelial neoplasia (CIN)
DNA hypermethylation
Human genome methylation
Pre-cancer
Journal
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
ISSN: 1469-0691
Titre abrégé: Clin Microbiol Infect
Pays: England
ID NLM: 9516420
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
18
12
2019
revised:
24
02
2020
accepted:
17
03
2020
pubmed:
31
3
2020
medline:
13
8
2021
entrez:
31
3
2020
Statut:
ppublish
Résumé
The aim was to evaluate the cross-sectional and long-term triage performance of FAM19A4/miR124-2 methylation analysis in human papillomavirus (HPV)-based cervical screening. We conducted a post hoc analysis within a Dutch population-based HPV-positive study cohort of women aged 30-60 years (n = 979). Cross-sectional cervical intraepithelial neoplasia (CIN) 3+ sensitivity, specificity, positive predictive value and negative predictive value as well as cumulative CIN3+ or cervical cancer risks after 9 and 14 years were compared for three baseline triage strategies: (1) cytology, (2) FAM19A4/miR124-2 methylation analysis and (3) combined FAM19A4/miR124-2 methylation with cytology. CIN3+ sensitivity of FAM19A4/miR124-2 methylation analysis was similar to that of cytology (71.3% vs 76.0%, ratio 0.94, 95% CI 0.84 to 1.05), at a lower specificity (78.3% vs 87.0%, ratio 0.90, 95% CI 0.86 to 0.94). Combining FAM19A4/miR124-2 methylation analysis with cytology resulted in a CIN3+ sensitivity of 84.6% (95% CI 78.3 to 90.8) at a specificity of 69.6% (95% CI 66.5 to 72.7). Similar 9- and 14-year CIN3+ risks for baseline cytology-negative women and baseline FAM19A4/miR124-2 methylation-negative women were observed, with risk differences of -0.42% (95% CI -2.1 to 1.4) and -0.07% (95% CI -1.9 to 1.9), respectively. The 14-year cumulative cervical cancer incidence was significantly lower for methylation-negative women compared to cytology-negative women (risk difference 0.98%, 95% CI 0.26 to 2.0). FAM19A4/miR124-2 methylation analysis has a good triage performance on baseline screening samples, with a cross-sectional CIN3+ sensitivity and long-term triage-negative CIN3+ risk equalling cytology triage. Therefore, FAM19A4/miR124-2 methylation analysis appears to be a good and objective alternative to cytology in triage scenarios in HPV-based cervical screening.
Identifiants
pubmed: 32222459
pii: S1198-743X(20)30163-4
doi: 10.1016/j.cmi.2020.03.018
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Cytokines
0
MIRN124-2 microRNA, human
0
MicroRNAs
0
TAFA4 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
125.e1-125.e6Informations de copyright
Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.