Guo Z, Zhao D M, Zhang S K, Wu Z N, Sun X B, Jia M M, Chen Q, Guo L W, Chen P P, Zhang J G
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.
Zhonghua Zhong Liu Za Zhi. 2021 Oct 23;43(10):1094-1099. doi: 10.3760/cma.j.cn112152-20190516-00311.
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). 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 () of HPV E6/E7 mRNA, HR-HPV DNA, HPV16/18 were calculated, respectively. 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% 72.3, 100.0), 77.8% (95% 72.8, 82.1), 13.0% (95% 7.2, 22.3), 100.0% (95% 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% 64.8, 75.1), <0.05], a higher referral rate (32.1%, <0.05); while HPV 16/18 had a high specificity (93.4%, 95% 90.0, 95.7) and a low sensitivity (30.0%, 95% 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% 73.7, 83.5) versus 68.3% (95% 53.0, 80.4)], but the difference was not statistically significant (>0.05). The ASCUS woman triaging effect of HPV E6/E7 mRNA detection is better than those of HR-HPV and HPV16/18 under certain conditions. The application of HPV E6/E7 mRNA detection to triage ASCUS population can avoid unnecessary colposcopy referral and reduce the missed diagnosis of cervical lesions.
评估高危型人乳头瘤病毒（HR-HPV）E6/E7 mRNA在对意义未明的非典型鳞状细胞（ASCUS）女性进行分流中的性能。选取2017年河南省信阳市罗山县宫颈癌筛查队列中经液基细胞学检查确定为ASCUS的人群。该人群接受了阴道镜活检和病理检查，并结合HPV16或18（HPV16/18）、HR-HPV DNA和HPV E6/E7 mRNA检测。以病理结果为金标准，分别计算HPV E6/E7 mRNA、HR-HPV DNA、HPV16/18的敏感性、特异性、阳性预测值（PPV）、阴性预测值（NPV）、转诊率和95%置信区间（）。312例ASCUS女性的平均年龄为52.6±7.3岁。在290例经病理诊断为正常的女性中，64例（22.1%）HPV E6/E7 mRNA阳性，86例（29.7%）HR-HPV DNA阳性，19例（6.6%）HPV16/18阳性。所有经病理确定的宫颈上皮内瘤变（CIN）病例HPV E6/E7 mRNA和HR-HPV DNA均为阳性。HPV E6/E7 mRNA预测ASCUS女性CIN2+病变的敏感性、特异性、PPV、NPV和转诊率分别为100.0%（95% 72.3，100.0）、77.8%（95% 72.8，82.1）、13.0%（95% 7.2，22.3）、100.0%（95% 98.4，100.0）和24.7%。与HPV E6/E7 mRNA相比，HR-HPV DNA的敏感性与HPV E6/E7 mRNA相似，但特异性较低[70.2%（95% 64.8，75.1），<0.05]，转诊率较高（32.1%，<0.05）；而HPV 16/18具有较高的特异性（93.4%，95% 90.0，95.7）和较低的敏感性（30.0%，95% 10.8，60.3）。基于45岁的年龄分层，两个年龄组中HPV E6/E7 mRNA的敏感性均为100.0%。≥45岁组中HPV E6/E7 mRNA 的特异性略高于<45岁组[79.0%（95% 73.7，83.5）对68.3%（95% 53.0，80.4）]，但差异无统计学意义（>0.05）。在某些条件下，HPV E6/E7 mRNA检测对ASCUS女性的分流效果优于HR-HPV和HPV16/18。应用HPV E6/E7 mRNA检测对ASCUS人群进行分流可避免不必要的阴道镜转诊并减少宫颈病变的漏诊。
