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

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

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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 our 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.

Original languageEnglish
Pages (from-to)1215-1221
Number of pages7
JournalInternational journal of cancer
Issue number4
Early online date7 Aug 2019
Publication statusPublished - 15 Aug 2020


  • DNA hypermethylation
  • biomarker
  • cervical carcinoma
  • cervical screening
  • human genome methylation
  • human papillomavirus

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