高危型人乳头状瘤病毒E6和E7基因在细胞学为意义不明的不典型鳞状细胞人群分流中的临床效果评价  

Clinical effect evaluation of high risk human papilloma virus E6/E7 mRNA in triaging women with atypical squamous cells of undetermined significance

作　　者：郭珍 赵冬梅 张韶凯 吴泽妮 孙喜斌 贾漫漫 陈琼 郭兰伟 陈佩佩 张建功 Guo Zhen;Zhao Dongmei;Zhang Shaokai;Wu Zeni;Sun Xibin;Jia Manman;Chen Qiong;Guo Lanwei;Chen Peipei;Zhang Jiangong(Central Laboratory,Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Zhengzhou 450008,China;Department of Pathology,Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Zhengzhou 450008,China;Department of Cancer Prevention and Control,Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Zhengzhou 450008,China;Department of Epidemiology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100021,China;Department of Gynecological Oncology,Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Zhengzhou 450008,China)

机构地区：[1]郑州大学附属肿瘤医院,河南省肿瘤医院中心实验室,450008 [2]郑州大学附属肿瘤医院,河南省肿瘤医院病理科,450008 [3]郑州大学附属肿瘤医院,河南省肿瘤医院癌症中心办公室,450008 [4]国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院流行病室,100021 [5]郑州大学附属肿瘤医院,河南省肿瘤医院妇瘤科,450008

出　　处：《中华肿瘤杂志》2021年第10期1094-1099,共6页Chinese Journal of Oncology

基　　金：国家自然科学基金(81502475);河南省科技攻关计划(192102310105);河南省高等学校重点科研项目计划(20A330005)。

摘　　要：目的评价高危型人乳头状瘤病毒E6和E7(HR-HPV E6/E7)mRNA对意义不明的不典型鳞状细胞(ASCUS)人群的分流效果。方法选取2017年河南省信阳市罗山县312例宫颈癌筛查队列中液基细胞学检测结果为ASCUS的人群,所有ASCUS人群均行阴道镜活检和病理学检查,行HPV16或18(HPV16/18)、HR-HPV DNA和HPV E6/E7 mRNA检测,以病理学诊断为金标准,分别计算HPV E6/E7 mRNA、HR-HPV DNA、HPV16/18检测的灵敏度、特异度、阳性预测值(PPV)、阴性预测值(NPV)、转诊率及其95%CI。结果312例ASCUS人群的年龄为(52.6±7.3)岁。病理学诊断为正常的290例人群中,HPV E6/E7 mRNA检测出阳性例数为64例(22.1%),HR-HPV DNA检测出阳性例数为86(29.7%),HPV16/18检测阳性例数为19(6.6%);病理诊断为CIN 2(3例)和CIN 3级(6例)患者中,HPV E6/E7 mRNA和HR-HPV DNA检测的阳性例数均为3和6例。以CIN2+作为疾病终点指标时,HPV E6/E7 mRNA分流ASCUS人群的灵敏度、特异度、PPV、NPV、转诊率分别为100%(95%CI:72.3~100.0)、77.8%(95%CI:72.8~82.1)、13.0%(95%CI:7.2~22.3)、100%(95%CI:98.4~100.0)、24.7%。与HPV E6/E7 mRNA相比,HR-HPV DNA分流效果的灵敏度与HPV E6/E7 mRNA一致,但特异度低[70.2%(95%CI:64.8~75.1)],转诊率较高(32.1%),差异均有统计学意义(均P<0.05)。HPV16/18检测的特异度较高(93.4%,95%CI:90.0~95.7),但灵敏度低(30.0%,95%CI:10.8~60.3)。HPV E6/E7 mRNA检测在≥45岁年龄组和<45岁年龄组中分流的灵敏度均为100%,在≥45岁年龄组中分流的特异度为79.0%(95%CI:73.7~83.5),比<45岁年龄组的特异度(68.3%,95%CI:53.0~80.4)高,差异无统计学意义(P>0.05)。结论HPV E6/E7 mRNA检测对ASCUS人群的分流效果优于HR-HPV DNA和HPV16/18,其用于ASCUS人群的分流管理可以避免不必要的阴道镜转诊,同时降低宫颈病变的漏诊。Objective To evaluate the performance of high risk human papilloma virus(HR-HPV)E6/E7 mRNA in triaging women with atypical squamous cells of undetermined signification(ASCUS).Methods The ASCUS cohort determined by liquid-based cytology test in the cervical cancer screening queue in Luoshan County,Xinyang City,Henan Province 2017 were selected.The population underwent colposcopy biopsy and pathological tests,combined with HPV16 or 18(HPV16/18),HR-HPV DNA and HPV E6/E7 mRNA test.By using the pathological result as the gold standard,the sensitivity,specificity,positive predictor(PPV),negative prediction(NPV),referral rate and 95%confident interval(CI)of HPV E6/E7 mRNA,HR-HPV DNA,HPV16/18 were calculated,respectively.Results The average age of 312 ASCUS women was 52.6±7.3 years old.Among the 290 women diagnosed as normal by pathology,64(22.1%)were HPV E6/E7 mRNA positive,86(29.7%)were HR-HPV DNA positive,and 19(6.6%)were HPV16/18 positive.All of the cervical intraepithelial neoplasia(CIN)cases determined by pathology were both HPV E6/E7 mRNA and HR-HPV DNA positive.The sensitivity,specificity,PPV,NPV and referral rate of HPV E6/E7 mRNA for predicting CIN2+lesion in women with ASCUS were 100.0%(95%CI:72.3,100.0),77.8%(95%CI:72.8,82.1),13.0%(95%CI:7.2,22.3),100.0%(95%CI:98.4,100.0)and 24.7%.Compared with HPV E6/E7 mRNA,the sensitivity of HR-HPV DNA was similar with HPV E6/E7 mRNA,but with a lower specificity[70.2%(95%CI:64.8,75.1),P<0.05],a higher referral rate(32.1%,P<0.05);while HPV 16/18 had a high specificity(93.4%,95%CI:90.0,95.7)and a low sensitivity(30.0%,95%CI:10.8,60.3).Based on the age stratification by age 45,the sensitivity of HPV E6/E7 mRNA in both age groups was 100.0%.The specificity of HPV E6/E7 mRNA in group of≥45 years was a little higher than that in group of<45 years[79.0%(95%CI:73.7,83.5)versus 68.3%(95%CI:53.0,80.4)],but the difference was not statistically significant(P>0.05).Conclusions The ASCUS woman triaging effect of HPV E6/E7 mRNA detection is better than those of HR-HPV and HPV16/18 und

关 键 词：子宫颈肿瘤 人乳头状瘤病毒 E6和E7信使RNA 意义不明的不典型鳞状细胞 分流 

分 类 号：R737.33[医药卫生—肿瘤]