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Int J Cancer. 2019 Aug 7. doi: 10.1002/ijc.32614. [Epub ahead of print]

FAM19A4/miR124-2 methylation in invasive cervical cancer: A retrospective cross-sectional worldwide study.

Author information

1
Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
2
International Agency for Research on Cancer, Lyon, France.
3
Institute of Microbiology and immunology, University of Ljubljana, Ljubljana, Slovenia.
4
Department of Gynecologic Oncology, Klinikum Wolfsburg, Wolfsburg, Germany.
5
Institute for clinical chemistry, laboratory and transfusion medicine, Wolfsburg, Germany.
6
Molecular Pathology Laboratory, Department of Pathology, Hvidovre Hospital, Hvidovre, Denmark.
7
PATH, Seattle, the United States of America.
8
Infections and Cancer Laboratory, Catalan Institute of Oncology (ICO), Barcelona, Spain.
9
Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine, University of Barcelona, Barcelona, Spain.
10
DDL Diagnostic Laboratory, Rijswijk, the Netherlands.
11
Scottish HPV Reference Laboratory, Royal Infirmary of Edinburgh, Edinburgh, Scotland.
12
HPV Research Group, Division of Pathology, University of Edinburgh, Edinburgh, Scotland.
13
Antoni van Leeuwenhoek / Netherlands Cancer Institute, Department of Gynaecologic Oncology, Centre of Gynaecologic Oncology Amsterdam, Amsterdam, The Netherlands.
14
Amsterdam UMC, Vrije Universiteit Amsterdam, Epidemiology and Biostatistics, De Boelelaan 1117, Amsterdam, The Netherlands.
15
Self-screen B.V, Amsterdam, the Netherlands.

Abstract

Widespread adoption of primary human papillomavirus (HPV)-based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124-2 genes has shown promise for the triage of high-risk (hr) HPV-positive women. In this study, we assessed the consistency of FAM19A4/miR124-2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation specific PCR (qMSP)-based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7 - 99.2) tested FAM19A4/miR124-2 methylation-positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124-2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV-negative carcinomas. These results indicate that a negative FAM19A4/miR124-2 methylation assay result is likely to rule out the presence of cervical cancer. This article is protected by copyright. All rights reserved.

KEYWORDS:

Biomarker; Cervical Carcinoma; Cervical Screening; DNA hypermethylation; Human Papillomavirus; Human genome methylation

PMID:
31390052
DOI:
10.1002/ijc.32614

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