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

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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. This 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 6 individual markers (ANKRD18CP, C13ORF18, EPB41L3, JAM3, SOX1 and ZSCAN1) showed enhanced methylation levels and frequency with increasing severity of the underlying lesion (p≤0.001). In cytological abnormal women, sensitivity to detect CIN2+ was 79%, 76% and 72% for the 3 panels (C13ORF18/EBP41L3/JAM3, C13ORF18/ANKRD18CP/JAM3 and ZSCAN1/SOX1, respectively), with a specificity of 57%, 65% and 68%. For the first 2 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<0.05). 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. This article is protected by copyright. All rights reserved.

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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