Performance of DNA methylation-based biomarkers in the cervical cancer screening program of northern Portugal: A feasibility study.
Int J Cancer
; 149(11): 1916-1925, 2021 12 01.
Article
em En
| MEDLINE
| ID: mdl-34460099
ABSTRACT
Cervical cancer remains a health concern. Effective screening programs are critical to reduce the incidence and mortality. High-risk HPV (hr-HPV) testing as primary screening tool discloses high sensitivity but suboptimal specificity. Adequate triage tests to reduce unnecessary colposcopy referrals and overdiagnosis/overtreatment are crucial. Hence, we aimed to validate a panel of DNA methylation-based markers as triage test for women hr-HPV+ in the population-based Regional Cervical Cancer Screening Program of Northern Portugal. Firstly, CADM1, MAL, FAM19A4 and hsa-miR124-2 promoter methylation levels were assessed by multiplex QMSP in a testing set of 402 FFPE tissue samples (159 normal samples and 243 cervical lesions, including 39 low-grade intraepithelial squamous lesions [LSIL], 59 high-grade intraepithelial squamous lesions [HSIL] and 145 cancerous lesions). Then, preliminary validation was performed in 125 hr-HPV+ cervical scrapes (including 59 normal samples, 30 LSIL, 34 HSIL and 2 cancerous lesions). Higher MALme , FAM19A4me and hsa-miR124-2me methylation levels were disclosed in histological HSIL or worse (HSIL+) in testing set. Individually, markers depicted over 86% specificity for HSIL+ detection. In validation set, all these genes significantly differed between histological HSIL+ and low-grade squamous intraepithelial lesions or less. In combination, these markers reached 74% specificity and 61% sensitivity for identification of histological HSIL+. We concluded that host gene methylation might constitute a useful referral triage tool of hr-HPV+ women enrolled in the Cervical Cancer Screening Program of Northern Portugal.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo do Útero
/
Metilação de DNA
/
Detecção Precoce de Câncer
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article