DNA methylation markers as triage test for the early identification of cervical lesions in a Chinese population. Issue 7 (20th December 2020)

• Record Type: Journal Article
• Authors: Li, Na; Hu, Yuanjing; Zhang, Xinying; Liu, Yixin; He, Ya; van der Zee, Ate G. J.; Schuuring, Ed; Wisman, G. Bea A
• Is Part Of: International journal of cancer. Volume 148:Issue 7(2021)
• Page Start: 1768
• Page End: 1777
• Publication Date: 2020-12-20
• Subjects: (pre)malignant cervical cancer -- cervical cancer -- cervical scrapings -- DNA methylation markers -- quantitative methylation‐specific PCR (QMSP); Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.33430
• Languages: English
• ISSNs: 0020-7136

Abstract

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. Abstract : What's new? Cytology and high‐;risk human papillomavirus (hrHPV) testing are currently used for cervical cancer screening. However, their effective implementation and the large potential for unwanted referrals remain a challenge in China, where there is an urgent need for a proper, objective and reproducible screening strategy for cervical cancer. In this study, the authors tested three previously identified CIN2+ specific methylation marker panels, primarily validated in a Dutch cohort of women with abnormal cytology results. The promising diagnostic performance and high concordance with the previous Dutch data make these methylation panels potentially useful for triage testing in cervical cancer screening in China.