To explore the clinical values of human papilloma virus (HPV)-E6/E7 mRNA detection in high-risk HPV DNA-positive women(detected by Cervista HPV).

From November 30, 2015 to November 30, 2016, a total of 437 high-risk HPV DNA-positive women were enrolled as eligible women from Huzhou Maternity & Child Care Hospital. According to age of them, they were divided into ≥25-30 year-old group (n=118), ≥30-40 year-old group (n=117), ≥40-50 year-old group (n=129), ≥50-60 year-old group (n=52), and ≥60-65 year-old group (n=21). All eligible women underwent ThinPrep liquid-based cytology test (TCT), HPV-E6/E7 mRNA expressions in cervical exfoliated cells by branched DNA (bDNA), and colposcopy. Histopathological examination of biopsies was conducted on suspicious tissues, and its results were set as the " gold standard" . Consistency of results between histopathological examination of biopsies and cytopathological examination cervical exfoliated cells were compared. Expressions of HPV-E6/E7 mRNA in groups with different ages and subjects with different results of histopathological diagnosis were compared and its values in cervical lesions screening were assessed. Chi-square test or Fisher exact test was used to compare the positive expression rates of HPV-E6/E7 mRNA among groups with different ages and subjects with different results of histopathological diagnosis, and to compare the sensitivities, specificities, positive predictive values and negative predictive values between HPV-E6/E7 mRNA test and TCT in predicting cervical lesion with high-grade squamous intraepithelial lesion (HSIL)+ (HSIL or worse) by histopathological diagnosis. This study met the requirements of the World Medical Association Declaration of Helsinki revised in 2013. Clinical informed consent was obtained from each subject.

①There was no significant difference among groups with different ages in positive expression rates of HPV-E6 /E7 mRNA in subjects with high-risk HPV DNA-positive (P>0.05). ②The histopathological results of 437 women with high-risk HPV DNA-positive were as following: 149 cases of normal cervix, 60 cases of low-grade squamous intraepithelial lesion (LSIL), 215 cases of HSIL, including 73 cases of cervical intraepithelial neoplasia (CIN) 2 and 142 cases of CIN3, 9 cases of squamous cell carcinoma (SCC) and 4 cases of adenocarcinoma. ③Positive expression rate of HPV-E6/E7 mRNA in HSIL+ subjects was significantly higher than that in LSIL- (LSIL or better) subjects which were 98.2% (224/228) and 45.5% (95/209), respectively, and the difference was statistically significant (χ²=151.507, P<0.001). ④Among 437 cases of HPV DNA-positive subjects, the sensitivity and negative predictive value of HPV-E6/E7 mRNA detection in predicting histopathological examination of HSIL+ were much higher than those of TCT, which were 98.2% (224/228) vs 71.1% (162/228), and 96.6% (114/118) vs 68.7% (145/211), respectively, and both the differences were statistically significant (χ²=64.870, 35.140, P<0.001), and its specificity was remarkably lower than that of TCT, which were 54.6% (114/209) vs 69.4% (145/209), respectively, and the difference was statistically significant (χ²=8.925, P=0.003); but there was no significant difference in positive predictive values between those two methods (χ²=0.137, P=0.711). ⑤Among the high-risk HPV DNA-positive women with no intraepithelial lesion or malignant (NILM) or atypical squamous cell of undetermined significance (ASC-US), the sensitivities, specificities, positive predictive values and negative predictive values of HPV-E6/E7 mRNA detection in predicting histopathological examination of HSIL+ were 97.0% (64/66), 56.6% (82/145), 50.4% (64/127), 97.6% (82/84), and 100.0% (32/32), 62.5% (20/32), 72.7% (32/44), 100.0% (20/20), respectively.

Detection of HPV-E6/E7 mRNA by bDNA technology has certain value for cervical lesions screening of high-risk HPV DNA-positive women, and can reduce the rate of missed diagnosis and colposcopy referral for high-risk HPV DNA-positive and cytological NILM or ASC-US women.