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

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

Vink, Frederique J;Meijer, Chris J L M;Clifford, Gary M;Poljak, Mario;Oštrbenk, Anja;Petry, Karl Ulrich;Rothe, Beate;Bonde, Jesper;Pedersen, Helle;de Sanjosé, Silvia;Torres, Montserrat;Del Pino, Marta;Quint, Wim G V;Cuschieri, Kate;Alcañiz Boada, Elia;van Trommel, Nienke E;Lissenberg-Witte, Birgit I;Floore, Arno N;Hesselink, Albertus T;Steenbergen, Renske D M;Bleeker, Maaike C G;Heideman, Daniëlle A M;
International journal of cancer 2019
320
vink2019fam19a4mir1242international

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.

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