Study On The Performance Of High-risk Human Papillomavirus E6/E7mRNA Testing For Cervical Lesions

ObjectiveTo investigate the expression of high-risk HPV E6/E7mRNA in cervical lesions and the effect of the testing for predicting the risk of progression in cervical lesions and to provide experimental basis for its application in clinical.MethodsThe HPV DNA testing was detected by gene chip diversion hybridization technology and the high-risk HPV E6/E7mRNA was detected by branched DNA hybridization capture technology. The histopathological diagnosis was taken as the criteria, HPV DNA testing and high-risk HPV E6/E7mRNA were Compared. The relationship between the two assays and the degree of cervical diseases was explored. Consistency, sensitivity, specificity, positive predictive value and negative predictive value of the two assays were compared. HPV E6/E7mRNA expression in different high-risk HPV HPV gene types was analyzed. Sensitivity, specificity, positive predictive and negative predictive valuation of the two assays in atypical squamous cells of undetermined significance(ASCUS) was compared, and then the value of HPV E6/E7mRNA testing for triage and patient follow-up was discussed.Results1. The positive rate of HPV E6/E7mRNA in CIN was much higher than NCE. The difference had statistic significance(χ2=23.968, P＜0.001). The positive rate of HPV E6/E7mRNA in CC was little higher than CIN, but there was no significant difference (χ2=1.378, P=0.229). Meanwhile, the positive rate of HPV DNA in CIN was much higher than NCE. The difference had statistic significance(χ2=15.364, P＜0.001). The positive rate of HPV E6/E7mRNA in CC was little higher than CIN, but there was no significant difference (χ2=0.204, P=0.463). The total positive rates of HPV DNA testing and HPV E6/E7mRNA testing was66.2%and60.8%respectively. The difference had no statistic significance (χ2=0.467, P=0.304).2. The kappa-value of two assays in NCE, CIN and CC was0.46,0.58and0.84 respectively. Consistency of the two assays increased with severity of the cervical lesion. The total kappa-value of two assays was0.65. It is shown that they were in good agreement.3. In high-grade cervical lesions, the sensitivity of HPV DNA testing and HPV E6/E7mRNA testing was84.1%and90.9%respectively, but there was no statistically significant difference (x2=0.935, P＞0.05). The specificity of HPV E6/E7mRNA testing was83.3%, which was significantly higher than the number of50%by DNA testing, and the difference had statistic significance (x2=4.022, P＜0.05). The positive predictive value of HPV DNA testing and HPV E6/E7mRNA testing was75.5%and88.9%respectively, but there was no statistically significant difference (x2=2.834, P>0.05). The negative predictive value of HPV DNA testing and HPV E6/E7mRNA testing was72%and86.2%respectively, but there was no statistically significant difference (X2=1.671,P＞0.05).4. The most common genotype was HPV type16, followed by HPV-33, HPV-58, and HPV-18.We believed that E6/E7mRNA of HPV-16, HPV-33, HPV-58and HPV-18expression rate is relatively high, and in those cases E6and E7potein was actively transcribed.5. In the patients with cytological examination of ASC-US, the sensitivity of HPV DNA testing and E6/E7mRNA testing was84.6%and92.3%respectively, but there was no statistically significant difference ((x2=0.377, P＞0.05). The specificity of HPV E6/E7mRNA testing was91.7%, which was significantly higher than the number of50%by DNA testing, and the difference had statistic significance (X2=5.042, P＜0.05). The positive predictive value of HPV DNA testing and HPV E6/E7mRNA testing was64.7%and92.3%respectively, but there was no statistically significant difference (x2=3.137, P>0.05). The negative predictive value of HPV DNA testing and HPV E6/E7mRNA testing was75.0%and91.7%respectively, but there was no statistically significant difference (x2=1.046, P＞0.05).ConclusionsThe high-risk HPV E6/E7mRNA testing showed a higher specificity than the DNA testing for high-grade cervical lesions. The finding suggests that mRNA testing could be more powerful than DNA testing for predicting the risk of progression and offer a strong potential as a tool for triage and patient follow-up.