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

Abstract

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 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.