Clinical Application Value Of HPVE6/E7mRNA In Postmenopausal Women With High-grade Cervical Intraepithelial Neoplasia And Cervical Cancer

Objective:1.To analyze the expression difference of HPVE6/E7mRNA in different grades of cervical histology and pathology;2.To study the application value and clinical efficacy of HPVE6/E7mRNA in menopausal women for high-level cervical intraepithelial neoplasia(HSIL)and cervical cancer;3.Superiority study of cervical thin-layer liquid-based cytology(TCT)combined with HPVE6/E7mRNA detection in menopausal women compared with separate detection in high-level intraepithelial neoplasia and cervical cancer;4.Correlation between vaginal microecological factors and persistent HPV infection in menopausal women.Methods:429 menopausal women who were admitted to Dalian Maternal and Child Health Hospital and Dalian Maternity Hospital affiliated to Dalian Medical University from February 2017 to August 2018 for cervical lesions,underwent TCT and HPVE6/E7mRNA examination and had the final cervical histopathological results(the highest pathological grade after cervical biopsy or conization was the final cervical histopathological results)were retrospectively analyzed and studied.The positive rate of HPVE6/E7mRNA and viral copy in different pathological grades were compared between groups and Spearman rank correlation analysis was carried out respectively.Logist regression analysis was conducted on the correlation trend of HPVE6/E7mRNA in low-grade and high-grade cervical intraepithelial neoplasia and cervical cancer.ROC curve was used to evaluate the clinical efficacy of HPVE6/E7mRNA.HPVE6/E7mRNA,TCT,sensitivity,specificity,positive predictive value and negative predictive value of combined detection were calculated,and the inter-group comparison and clinical consistency analysis of various detection methods were carried out through single factor variance and Kappa Coefficient.The vaginal inflammation of menopausal women with positive HPVE6/E7mRNA was collected and the correlation coefficient(R)was used to analyze whether the vaginal microecological environment was related to HPV persistent infection.Statistical methods SPSS 19.0 software was used for data analysis and statistics,and X2 was used for comparison between counting units.The measurement data of non-normal distribution are expressed by M(Q1,Q2).The inter-group comparison is tested by Kruskal-Wallis H,and the correlation between the two groups of variables is Spearman rank correlation.ROC curve was used to express the effectiveness of detection methods.One-way ANOVA was used for comparison between normal distribution groups.Kappa Coefficient was used for clinical diagnosis consistency.P<0.05 is statistically significant.Results:In 429 menopausal women,the positive rate of HPVE6/E7mRNA in normal cervical tissue pathology was 28.68%.The positive rate of HPVE6/E7mRNA in LSIL was 82.00%.The positive rate of HSIL was 93.29%.The positive rate of HPVE6/E7mRNA in cervical invasive carcinoma was 98.04%.The higher the pathological grade of cervical tissue,the higher the positive rate of HPVE6/E7mRNA(X2=173.06,P<0.05.the difference is statistically significant).In the analysis of copy expression of HPVE6/E7mRNA positive patients,the expression of patients with normal pathological grade was 9.7(3.9,11);The expression of LSIL was 10.9(9.7,13);HSIL expression was 21.2(19.6,24);The expression of invasive cervical carcinoma was 28.9(23.5,31.3).In different pathological grades,the copy expression of HPVE6/E7mRNA was significantly different and positively correlated(Kruskal Wallis statistic 236.55,Kruskal Wallis P<0.0001,the difference was statistically significant;Rank correlation spearman correlation 0.86,spearman p<0.0001).Logist regression analysis was carried out for pathological lesions with HPVE6/E7mRNA below HSIL and HSIL and above.OR estimation value(EXP(B))=2.522.For every unit of increase in HPVE6/E7mRNA expression data,the corresponding pathological change value was 2.522 times,indicating that the larger the copy quantity,the more pathological changes will develop towards HSIL and above lesions.ROC curve analysis of HPVE6/E7mRNA showed that AUC=0.993,close to 1.Taking cervical histopathological results as gold standard,the sensitivity,specificity,positive predictive value and negative predictive value of TCT were calculated to be 90.50%,34.50%,54.68%and 80.61%,respectively(x=35.721;P<0.05);The sensitivity,specificity,positive predictive value and negative predictive value of HPVE6/E7mRNA detection were 94.50%,48.03%,61.36%and 90.91%respectively(X=94.770;P<0.05);The sensitivity,specificity,positive predictive value and negative predictive value of combined detection were 86%,57.60%,63.94%and 82.50%.respectively(x=68.817;P<0.05)?Through one-way ANOVA,there was no significant difference in sensitivity,positive predictive value and negative predictive value among the three detection methods(F=3.281;2.252;2.214,P>0.05)?The specificity of the three detection methods was significantly different between groups(F=10.039,P<0.05),while the specificity of combined screening was higher than TCT and HPVE6/E7mRNA detected separately.Through Kappa Coefficient,HPVE6/E7mRNA 0.41(0.34-0.49),TCT 0.24(0.17-0.31)and joint detection 0.43(0.35-0.51),the joint detection is superior to the other two separate detection in the consistency with the final pathological results.The incidence of vaginal inflammation when HPV E6/E7 mRN A is positive(12.4%)is higher than that when HPV E6/E7 mRNA is negative(4.9%),the difference is statistically significant(X2=8.206,P<0.05).the correlation coefficient(r)between the two is 0.1 19,P<0.05,and the two are weakly correlated.Conclusion:1.Among menopausal women,HPVE6/E7mRNA expression is more significant in high-level cervical intraepithelial neoplasia and cervical cancer.2.HPVE6/E7mRNA in menopausal women has high clinical application efficiency in detecting high-level cervical intraepithelial neoplasia and cervical cancer.3.In menopausal women,the consistency of combined detection is higher than that of HPVE6/E7mRNA and TCT alone in comparison with pathological diagnostic gold standard.Combined screening can improve the specificity of separate detection of HPVE6/E7mRNA and TCT,improve the accuracy of disease detection,reduce misdiagnosis and over-diagnosis,and can be used as the preferred detection method for high-level cervical intraepithelial neoplasia and cervical cancer in menopausal women.4.Persistent infection of cervical HPV in menopausal women may be related to vaginal inflammation.