HR-HPV E6/E7 mRNA在宫颈细胞学ASCUS分流诊断中的意义

High- risk human papilloma virus E6/E7 mRNA test in patients with atypical squamous cells of undetermined significance of cervical cytology

目的探讨高危型人乳头瘤病毒（HR-HPV）E6/E7 m RNA在宫颈不能明确意义的非典型鳞状上皮细胞（ASCUS）分流诊断中的意义。方法选择2014年1月至2015年7月就诊且行液基薄层细胞学检测（TCT）结果为ASCUS的205例患者为研究对象,并且行阴道镜下活检、HR-HPV E6/E7 m RNA检测和HR-HPV分型DNA检测。结果根据阴道镜活检结果,将205例ASCUS患者分为慢性宫颈炎105例、低度宫颈鳞状上皮内病变（LSIL）48例、高度宫颈鳞状上皮内病变（HSIL）48例和宫颈鳞状细胞癌（SCC）4例。慢性宫颈炎、LSIL、HSIL和SCC组HR-HPV E6/E7 m RNA阳性检出率分别为56.2%、79.2%、85.4%和100.0%,差异有统计学意义（P〈0.01）;HSIL＋SCC组HR-HPV E6/E7 m RNA阳性检出率为86.5%,高于慢性宫颈炎＋LSIL组的63.4%（P〈0.01）。HR-HPV E6/E7 m RNA水平为SCC〉HSIL〉LSIL〉慢性宫颈炎症,4组差异有统计学意义（P〈0.01）。〈30岁组与≥30岁组HR-HPV E6/E7 m RNA水平分别为292.23（109.77~903.34）c op y/ml和175.26（0.00~1 032.90）c op y/ml,两组差异无统计学意义（P〉0.05）。HR-HPV E6/E7 m RNA水平与宫颈病变程度呈正相关（r=0.379,P〈0.01）。HR-HPV E6/E7 m RNA检测方法的AUC为0.702（0.617~0.786）,诊断阈值为185.74copy/ml,检测ASCUS患者HSIL＋SCC的灵敏度、特异度、阳性预测值、阴性预测值分别为76.9%、60.8%、40.0%和88.6%,而HR-HPV DNA的检测灵敏度、特异度、阳性预测值、阴性预测值分别为88.5%、31.3%、30.5%和88.9%;其中HR-HPV E6/E7 m RNA检测特异度明显高于HR-HPV DNA（P〈0.05）。结论 HR-HPV E6/E7 m RNA检测在ASCUS筛查中特异度较高,有望成为宫颈细胞学ASCUS分流的新方法。

Objective To evaluate the significance of high- risk human papilloma virus E6/E7 mRNA test in patients with atypical squamous cells of undetermined significance（ASCUS） of cervical cytology.Methods Two hundred and five gynecologicaloutpatients underwent cervical thinp re cytologicaltest（TCT） and diagnosed as ASCUS in Wenzhou People＇s Hospital from January 2014 to July 2015.High risk human papilloma virus（HR- HPV） E6/E7 mRNA test,HPVDNA test and histopathological examination were also performed in allpatients.Results Among 205 patients,there were 105 cases of chronic cervicitis,48 cases of low- grade squamous intra epithelial lesion（LSIL）,48 cased ofhigh- grade squamous intraepithelis lesion（HSIL） and 4 cases of cervical carcinoma.The positive rate of HPVE6/E7 mRNA in chronic cervicitis,LSIL,HSIL and the cervical carcinoma groups were56.2%,79.2%,85.4%and 100.0%,respectively（P〈0.01）.HPV E6/E7 mRNA positive rate in HSIL＋ carcinoma group was significantly higherthan that in LSIL＋ cervicitis group（86.5%vs 63.4%,P〈0.01）.Rank analysis demonstrated that the severity of cervical lesions was correlated the expression ofHPVE6/E7 mRNA（r=0.379,P〈0.01）.When HPVE6/E7 mRNA 185.74 copy/ml was used as criteria for screening HSIL and above lesions,the sensitivity,specificity,positive predictive value and negative predictive value of HPV E6/E7 mRNA were 76.9%,60.8%,40.0%and 88.6%,respectively in patients with ASCUS,while those parameters of HR-HPV DNA were 88.5%,31.3%,30.5%and 88.9%,respectively.The specificity of HPV E6/E7 mRNA was significantly higherthan that ofHPVE6/E7 DNA（P〈0.05）.Conclusion The specificity of HPV E6/E7 mRNA test are higherthan that of high- risk HPV DNA for diagnosis of HSIL＋ in patients with ASCUS.