MicroRNA Detection in Cervical Exfoliated Cells as a Triage for Human Papillomavirus-Positive Women
MicroRNA Detection in Cervical Exfoliated Cells as a Triage for Human Papillomavirus-Positive Women
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宫颈脱落细胞中的 MicroRNA 检测作为人乳头瘤病毒阳性女性的分类
DOI：
10.1093/jnci/dju241
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发表时间：
2014-09-01
影响因子：
10.3
通讯作者：
Xie, Xing
中科院分区：
文献类型：
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作者：
Tian, Qifang;Li, Yang;Xie, Xing
背景巴氏（Pap）分诊法具有高度特异性，已被推荐用于原发性人乳头瘤病毒（HPV）检测，但由于敏感性差和细胞学家依赖性而存在缺陷。我们评估了微小RNA（miRNA）检测的潜在作用，在宫颈脱落细胞HPV阳性的妇女从临床population.Methods的主要HPV检测以及巴氏试验进行所有符合条件的妇女。RT-qPCR检测宫颈脱落细胞中6种miRNAs（miR-424/miR-375/miR-34 a/ miR-218/miR-92 a/miR-93）。所有HPV阳性的妇女进行阴道镜检查和进一步活检，如果有指征。使用Mann-Whitney U检验、受试者工作特征曲线、逻辑回归和Pearson卡方来评估数据。所有统计学显著性检验均为双侧检验。结果共纳入1021例符合条件的HPV阳性妇女。miR-424/miR-375/miR-34 a/miR-218在高级别宫颈上皮内瘤变（CIN）和异常细胞学中的表达分别显著低于低级别CIN和正常细胞学（均P <0.05）。与巴氏试验相比，miR-424和miR-375检测在识别CIN 2或更差（CIN 2+）时具有更高的灵敏度（76.0%和74.9% vs 63.8%，P <0.05），更高的阴性预测值（NPV）（85.7%和85.4% vs 79.3%，P <0.05）和相当的特异性。在鉴定CIN 3+时获得了类似的结果。基于miR-424、miR-375和miR-218的多标记物组进一步改善了任何单一miRNA检测或Pap test.Conclusion的性能，在宫颈脱落细胞中检测单一miR-424或miR-375以及基于miR-424/miR-375/miR-218的多标记物组显示出优于Pap分诊的上级性能，用于临床人群中的高级别CIN识别。miRNA的检测可能为HPV阳性女性提供一种新的分诊选择。
Background Papanicolaou (Pap) triage, with high specificity, has been recommended for primary Human papillomavirus (HPV) testing but is flawed by poor sensitivity and cytologist dependence. We evaluated the potential role of microRNA (miRNA) detection in cervical exfoliated cells in HPV-positive women from a clinic-based population.Methods Primary HPV testing as well as Pap test were performed on all eligible women. Six miRNAs (miR-424/miR-375/miR-34a/ miR-218/miR-92a/miR-93) were detected by RT-qPCR in cervical exfoliated cells. All HPV-positive women underwent colposcopy and further biopsy if indicated. Mann-Whitney U test, the receiver operating characteristic curve, logistic regression, and Pearson's Chi-square were used to assess data. All tests of statistical significance were two-sided.Results A total of 1021 eligible HPV-positive women were enrolled. The expression of miR-424/miR-375/miR-34a/miR-218 in high-grade cervical intraepithelial neoplasia (CIN) and abnormal cytology was statistically significantly lower than that in low-grade CIN and normal cytology, respectively (all P < .05). Compared with the Pap test, both miR-424 and miR-375 detection achieved higher sensitivity (76.0% and 74.9% vs 63.8%, P < .05), higher negative predictive value (NPV) (85.7% and 85.4% vs 79.3%, P < .05), and comparable specificity while identifying CIN2 or worse (CIN2+). Similar results were achieved while identifying CIN3+. Multi-marker panels based on miR-424, miR-375, and miR-218 further improved the performance over any single miRNA test or Pap test.Conclusion Single miR-424 or miR-375 detection and miR-424/miR-375/miR-218-based multimarker panels in cervical exfoliated cells show superior performance over Pap triage for high-grade CIN identification in a clinic-based population. Detection of miRNA may provide a new triage option for HPV-positive women.