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

Int J Cancer. 2020 Aug 15;147(4):1215-1221. doi: 10.1002/ijc.32614. Epub 2019 Sep 9.


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.

Keywords: DNA hypermethylation; biomarker; cervical carcinoma; cervical screening; human genome methylation; human papillomavirus.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Sectional Studies
  • Cytokines / genetics*
  • DNA Methylation*
  • Female
  • Genotype
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / physiology
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / physiology
  • Humans
  • Mass Screening / methods
  • MicroRNAs / genetics*
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / virology
  • Retrospective Studies
  • Uterine Cervical Dysplasia
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears / methods


  • Cytokines
  • MIRN124 microRNA, human
  • MicroRNAs
  • TAFA4 protein, human