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

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  • 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 Steenbergen
  • Maaike 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
JournalInternational Journal of Cancer
Volume147
Issue number4
Pages (from-to)1215-1221
Number of pages7
ISSN0020-7136
DOIs
Publication statusPublished - 15 Aug 2020

Bibliographical note

© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

    Research areas

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

ID: 57728908