HPV E6/E7 mRNA对宫颈上皮内瘤变Ⅰ级转归的预测价值

Predictive value of HPV E6/E7 mRNA for the outcome of cervical intraepithelial neoplasia grade 1

摘要:

目的 评估人乳头瘤病毒（human papilloma virus，HPV）E6/E7 mRNA预测宫颈上皮内瘤变Ⅰ级（cervical intraepithelial neoplasia grade Ⅰ，CIN Ⅰ）转归的应用价值。方法 选取2017年10月至2020年3月在重庆医科大学附属妇女儿童医院妇科门诊就诊，液基细胞学检测（thinprep cytology test，TCT）、HPV DNA检测和HPV E6/E7 mRNA检测中一项结果异常行阴道镜检查，病检结果为CIN Ⅰ的患者208例，1年后复查TCT、HPV DNA、HPV E6/E7 mRNA，检测中一项结果异常再次阴道镜下行宫颈活检，随访患者病变消退、持续存在或进展，分析HPV E6/E7 mRNA对宫颈上皮内瘤变Ⅰ级进展风险的预测价值。结果 ①208例CIN Ⅰ患者中有17例进展为CIN Ⅱ或CIN Ⅲ，进展率8.2%，进展患者中TCT阳性率为58.8%、HPV DNA阳性率为100%，HPV E6/E7 mRNA阳性率为100%；②Cox回归分析中，TCT的风险比（hazard ratio，HR）为9.184，HPV DNA的HR为158.675，HPV E6/E7 mRNA的HR为293.650，说明HPV E6/E7 mRNA对CIN Ⅰ进展的预测价值最大；③HPV DNA和HPV E6/E7 mRNA的敏感度最高，TCT的特异度最高，HPV E6/E7 mRNA特异度次之，HPV DNA的特异度较差，HPV E6/E7 mRNA既有最高的敏感度，又有较高的特异度；④TCT的受试者工作特征（receiver operating characteristic，ROC）曲线下面积（area under the curve，AUC）为0.633，HPV DNA的AUC为0.427，HPV E6/E7 mRNA 的AUC 为0.772，说明HPV E6/E7 mRNA对CIN Ⅰ进展的诊断价值最大。两两联合检测中，HPV DNA联合HPV E6/E7 mRNA的ROC曲线下AUC为0.777，HPV DNA联合TCT的ROC曲线下AUC为0.728，HPV E6/E7 mRNA联合TCT的ROC曲线下AUC为0.839，说明HPV E6/E7 mRNA联合TCT对CIN Ⅰ进展的诊断价值最大。结论 HPV E6/E7 mRNA检测对预测CIN I转归有一定意义，可用于CIN I的随访分流管理，值得在临床推广和应用。

Abstract:

Objective To evaluate the application value of human papilloma virus（HPV） E6/E7 mRNA in predicting the outcome of cervical intraepithelial neoplasia grade Ⅰ（CIN Ⅰ）.Methods From October 2017 to March 2020， a total of 208 patients admitted to the Outpatient Department of Chongqing Health Center for Women and Children with abnormalities in one of the results of thinprep cytology test（TCT）， HPV DNA and HPV E6/E7 mRNA tests and then diagnosed as CIN Ⅰby colposcopy were randomly selected. A year later， these patients were retested of TCT， HPV DNA and HPV E6/E7 mRNA tests. Cervical biopsy was performed through colposcopy again for one abnormal result. Patients were followed up for regression，persistence， or progression of the lesion. It was in this way that we tried to analyze the predictive value of HPV E6/E7 mRNA for the risk of progression of CIN Ⅰ.Results ①Among the 208 patients with CIN Ⅰ，17 patients progressed to CIN Ⅱ or CINI Ⅲ， with progression rate of 8.2%. The positive rate of TCT was 58.8%，and the positive rate of both HPV DNA and HPV E6/E7 mRNA was 100% in patients with progression. ②The hazard ratio（HR） value of TCT，HPV DNA，and HPV E6/E7 mRNA in the Cox regression analysis was 9.184， 158.675，and 293.650， respectively. The HR value of HPV E6/E7 mRNA was the highest，indicating that HPV E6/E7 mRNA had the greatest predictive value for CIN Ⅰ progression. ③HPV DNA and HPV E6/E7 mRNA had the highest sensitivity. TCT had the highest specificity，followed by the HPV E6/E7 mRNA. HPV DNA had poor specificity. Thus，HPV E6/E7 mRNA had both the highest sensitivity and high specificity. ④The area under the curve（AUC） value of TCT，HPV DNA，and HPV E6/E7 mRNA in the ROC curve was 0.633，0.427，and 0.772，respectively. The AUC value of HPV E6/E7 mRNA was the highest，indicating that HPV E6/E7 mRNA had the greatest diagnostic value for CIN Ⅰ progression. The AUC value of HPV DNA combined with HPV E6/E7 mRNA，HPV DNA combined with TCT，and HPV E6/E7 mRNA combined with TCT in the ROC curve was 0.777，0.728， and 0.839， respectively. The AUC value of HPV E6/E7 mRNA combined with TCT was the highest， indicating that HPV E6/E7 mRNA combined with TCT had the greatest diagnostic value for CIN Ⅰ progression.Conclusion The HPV E6/E7 mRNA test has certain significance in predicting the outcome of CIN Ⅰ，which can be used for the follow-up shunt management of CIN Ⅰ，and is worthy of clinical promotion and application.