聂小凤 翟慧慧 冷天艳 张琴 杨丽华

摘   要：目的  探讨宫颈脱落细胞miR34a检测在HR-HPV阳性患者分流中的作用。方法  采用第二代杂交捕获技术（HC2）进行宫颈癌初筛，HPV阳性者行TCT及miRNA检查。TCT结果异常者（≥意义不明确的非典型鳞状细胞）阴道镜下活检行病理学检查。TCT阴性者行阴道镜检查，阴道镜异常者阴道镜下活检取材，比较不同级别宫颈病变中miR34a水平，探讨miR34a、Pap在宫颈病变中的诊断作用。结果  ①Pap对宫颈高度鳞状上皮内病变预测值的灵敏度为64.90%，特异度为80.70%，AUC为0.728（95%CI：0.657～0.779，P<0.001）。②miRNA34a对宫颈高度鳞状上皮内病变预测值的灵敏度为77.00%，特异度为62.30%，AUC为0.824（95%CI：0.756～0.892，P<0.001），cut off值为0.623。③miRNA34a对宫颈高度鳞状上皮内病变预测值的灵敏度高于Pap检测，特异度低于Pap。④宫颈脱落细胞miRAN34a值随着宫颈病变加重逐渐降低。结论  检测宫颈脱落细胞miR34a水平可有效分流HR-HPV阳性患者，敏感性高于Pap检查。

关键词：microRNA-34a;宫颈细胞学检查;HPV;宫颈癌;筛查

中图分类号：R737.33                                   文獻标识码：A                             DOI：10.3969/j.issn.1006-1959.2018.16.012

文章编号：1006-1959（2018）16-0043-04

Analysis of the Role of MiR34a in Cervical Exfoliated Cells in Shunt of HR-HPV Positive Patients

NIE Xiao-feng，ZHAI Hui-hui，LENG Tian-yan，ZHANG Qin，YANG Li-hua

（Department of Gynecology，Second Affiliated Hospital of Kunming Medical University，Kunming，650101，Yunnan，China）

Abstract： Objective  To investigate the role of miR34a in cervical exfoliated cells in the shunt of HR-HPV positive patients. Methods  The second generation hybridization capture technique （HC2） was used for primary screening of cervical cancer. HPV positive patients underwent TCT and miRNA examination. Pathological examination of colposcopy biopsy was performed in patients with abnormal TCT results （≥ atypical squamous cells with unclear significance）. TCT-negative patients underwent colposcopy， colposcopy biopsy was performed， and miR34a levels were compared in different grades of cervical lesions. The diagnostic role of miR34a and Pap in cervical lesions was explored. Results  ① The sensitivity of 1Pap to the predictive value of high squamous intraepithelial lesion was 64.90%， the specificity was 80.70%， and the AUC was 0.728 （95% CI： 0.657～0.779， P<0.001）.② The sensitivity of miRNA34a for predicting cervical high-grade squamous intraepithelial lesion was 77.00%， specificity was 62.30%， AUC was 0.824 （95% CI： 0.756～0.892， P<0.001）， and cut off value was 0.623. ③The sensitivity of 3miRNA34a to the predictive value of high squamous intraepithelial lesion was higher than that of Pap， and its specificity was lower than Pap. ④ The value of miRAN34a in cervical exfoliated cells gradually decreased with the increase of cervical lesions. Conclusion  Detection of miR34a levels in cervical exfoliated cells can effectively divert HR-HPV-positive patients with higher sensitivity than Pap.

Key words：MicroRNA-34a;Cervical cytology;HPV;Cervical cancer;Screening

宫颈癌（cervical cancer）是发展中国家女性常见的恶性肿瘤，发病率逐年上升[1]。高危型人类乳头状瘤病毒（highrisk human papillomavirus，HR-HPV）持续感染是宫颈癌的病因，因此，HR-HPV DNA检测成为宫颈癌筛查的方法主要之一[2]。宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN）为宫颈癌癌前病变。通过筛查发现CIN，及时治疗，是预防宫颈癌的有效措施。大量证据表明，HR-HPV测定较细胞学检测在识别高级别CIN 具有更高的敏感性，但是特异性低[3-5]。2015年1月美国阴道镜及宫颈病理学会（American society for colposcopy and cervical pathology，ASCCP）和妇科肿瘤协会（society of gynecologic oncology，SGO）更新了宫颈癌筛查指南，推荐HPV初筛可用于现代宫颈癌筛查的替代方案[6]。HPV感染是频发事件，大多数HPV感染是一过性的，90%的HPV感染在2年内可自然消除[7，8]。因此，对HPV阳性的女性必须进行相关检测以识别CIN，称之为分流。细胞学检查是首选的分流方法，但细胞学结果敏感性低，准确性依赖于读片人员，因此寻找细胞学以外的分流方法是当前研究重点。MicroRNAs（miRNAs）是重要的基因调节因子，在多种肿瘤中异常表达。……