Al Roomy Moody, Chehadeh Wassim, Al Awadhi Rana
College of Graduate Studies, Kuwait University, Khaldiya, Kuwait.
Virology Unit, Department of Microbiology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
Cytopathology. 2023 May;34(3):204-210. doi: 10.1111/cyt.13213. Epub 2023 Feb 16.
This study was undertaken to evaluate the performance of FAM19A4 and hsa-mir-124-2 hypermethylation as a triage tool for women who are at risk of developing cervical cancer or high-grade cervical cancer precursor lesions by taking into consideration the cytology report, histology diagnosis, and human papillomavirus (HPV) status.
A total of 330 cervical ThinPrep samples were retrospectively collected and used for DNA isolation. HPV DNA was detected by real-time polymerase chain reaction (PCR), and HPV genotypes were identified by Sanger-based sequencing. DNA extracts were bisulphite-treated, and hypermethylation of FAM19A4 and hsa-mir-124-2 genes was detected by a quantitative methylation-specific PCR (qMSP) test using the QIAsure Methylation assay.
Hypermethylated genes were detected in 27 (9.6%) cervical samples, mostly found in women diagnosed with high-grade squamous intraepithelial legions (77.8%) or cervical intraepithelial neoplasia grade 3 (CIN3) (72.7%). The sensitivity and the specificity of the qMSP test for predicting CIN3 lesions among women with high-risk HPV was 75% and 91%, respectively.
DISCUSSION/CONCLUSION: There was a significant correlation between high-grade cervical cancer precursor lesions and detection of hypermethylated genes in samples positive for high-risk HPV. Our results suggest that the QIAsure Methylation test can be used as a triage tool to identify women at risk for cervical cancer progression.
本研究旨在通过综合考虑细胞学报告、组织学诊断和人乳头瘤病毒（HPV）状态，评估FAM19A4和hsa-mir-124-2基因高甲基化作为一种分流工具，用于筛查有患宫颈癌或高级别宫颈癌前病变风险的女性的性能。
回顾性收集330份宫颈液基薄层制片样本用于DNA提取。通过实时聚合酶链反应（PCR）检测HPV DNA，并通过基于桑格测序法鉴定HPV基因型。DNA提取物经亚硫酸氢盐处理后，使用QIAsure甲基化检测试剂盒通过定量甲基化特异性PCR（qMSP）检测FAM19A4和hsa-mir-124-2基因的高甲基化情况。
在27份（9.6%）宫颈样本中检测到高甲基化基因，这些样本大多来自被诊断为高级别鳞状上皮内病变（77.8%）或宫颈上皮内瘤变3级（CIN3）（72.7%）的女性。在高危HPV阳性的女性中，qMSP检测预测CIN3病变的敏感性和特异性分别为75%和91%。
讨论/结论：高危HPV阳性样本中高级别宫颈癌前病变与高甲基化基因检测之间存在显著相关性。我们的结果表明，QIAsure甲基化检测可作为一种分流工具，用于识别有宫颈癌进展风险的女性。
