DNA methylation markers as triage test for the early identification of cervical lesions in a Chinese population

Na Li, Yuanjing Hu, Xinying Zhang, Yixin Liu, Ya He, Ate G. J. van der Zee, Ed Schuuring, G. Bea A. Wisman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Objective strategies are required in cervical cancer screening. We have identified several DNA methylation markers with high sensitivity and specificity to detect cervical intraepithelial neoplasia 2 or worse (CIN2+) in Dutch women. Our study aims to analyze the diagnostic characteristics of these markers in a Chinese cohort. A total of 246 liquid-based cytology samples were included, of which 205 women underwent colposcopy due to an abnormal cytology result (atypical squamous cells of undetermined significance [ASCUS] or worse), while 227 were tested high-risk human papillomavirus (hrHPV) positive. All six individual markers (ANKRD18CP, C13ORF18, EPB41L3, JAM3, SOX1 and ZSCAN1) showed enhanced methylation levels and frequency with increasing severity of the underlying lesion (P ≤.001). In cytological abnormal women, sensitivity to detect CIN2+ was 79%, 76% and 72% for the three panels (C13ORF18/EBP41L3/JAM3, C13ORF18/ANKRD18CP/JAM3 and ZSCAN1/SOX1, respectively), with a specificity of 57%, 65% and 68%. For the first two panels, these diagnostic characteristics were similar to the Dutch cohort, while for ZSCAN1/SOX1 the sensitivity was higher in the Chinese cohort, but with a lower specificity (both P <.05). In hrHPV-positive samples, similar sensitivity and specificity for the detection of CIN2+ were found as for the abnormal cytology cohort, which were now all similar between both cohorts and non-inferior to HPV16/18 genotyping. Our analysis reveals that the diagnostic performances are highly comparable for C13ORF18/EBP41L3/JAM3 and C13ORF18/ANKRD18CP/JAM3 methylation marker panels in both Chinese and Dutch cohorts. In conclusion, methylation panels identified in a Dutch population are also applicable for triage testing in cervical cancer screening in China.

Original languageEnglish
Pages (from-to)1768-1777
Number of pages10
JournalInternational Journal of Cancer
Early online date10-Dec-2020
DOIs
Publication statusPublished - Apr-2021

Keywords

  • (pre)malignant cervical cancer
  • cervical cancer
  • cervical scrapings
  • DNA methylation markers
  • quantitative methylation&#8208
  • specific PCR (QMSP)
  • HPV-POSITIVE WOMEN
  • DUAL-STAINED CYTOLOGY
  • CANCER
  • (PRE)CANCER
  • PERFORMANCE
  • SCRAPES
  • ATHENA
  • CADM1

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