| ObjectiveCervical cancer is the most common gynecological malignancy.In recent years,the incidence of cervical cancer in women in China has shown an upward trend,which continues to threaten female reproductive health.High risk-human papillomavirus(HR-HPV)infection is the main cause of its occurrence.Data show that women have a more than 80%chance of contracting human papillomavirus,especially in sexually active women,but most of these human papillomavirus(HPV)infections are benign and transient,within 1-2 years Cleared by the body’s own immune system,only a small part of the infection will cause lesions,from infection to the occurrence of cervical precancerous lesions,and then gradually develop into invasive cancer.This is a continuous and long pathological process that takes years or even decades.The long development process provides opportunities for cervical cancer screening.With the clinical application of cervical cancer vaccine,primary prevention has the potential to prevent 70%of cervical cancer caused by human papilloma virus,but cervical cancer screening as a secondary prevention is still a key strategy for early identification of cervical cancer.At present,the commonly used screening methods in clinical practice are thinprep cytologic test(TCT)and HPV DNA test.Both have limitations.TCT has high specificity,but low sensitivity,and is easily affected by the subjective judgment of pathologists.HPV DNA detection has high sensitivity but low specificity.HPV positive can only indicate infection with the virus,but the virus’s transcriptional expression And load can not be reflected,the false positive rate is high,which easily leads to overdiagnosis and treatment.In order to improve the perfection of screening methods,we are constantly looking for better methods for detecting biomarkers.With the deepening of cervical cancer research mechanism in recent years,when HPV DNA is integrated into host cells,the inhibitory effect of E2 protein on the expression of E6 and E7 oncogenes is lost,the transcription of E6 and E7 genes is subsequently up-regulated,and a large amount of E6 and E7 mRNA is transcribed Later,mRNA is translated into corresponding oncoproteins,and E6 and E7 proteins inactivate tumor suppressor genes through phosphorylation and ubiquitination pathways,leading to cervical lesions.During this process,a large number of E6/E7 mRNA translations are one of the signals that cervical cells may undergo lesions,which provides new ideas and methods for the early screening and treatment of cervical lesions caused by HR-HPV infection.However,whether the detection of HPV E6/E7 mRNA can reflect the replication and transcription of HPV,identify transient infections of HPV,and become a new tool for cervical lesion screening is still worth exploring.This study is based on clinical analysis and uses cervical histopathological results as the diagnostic gold standard to analyze and evaluate the value and role of HPV E6/E7 mRNA detection in cervical lesion screening;combined screening with TCT and HPV DNA detection to find more Efficient screening combination.MethodsPatients who underwent HPV E6/E7 mRNA testing,HPV DNA testing,TCT,and cervical biopsy at the First Affiliated Hospital of Zhengzhou University from September 2017 to April 2018 were collected.According to the inclusion and exclusion criteria,this study was finally included 320 patients.HPV E6/E7 mRNA copy number<1.0 is negative,≥1.0 is positive;HPV DNA test results are automatically interpreted as negative and positive;TCT report uses TBS classification criteria,and no intraepithelial lesions and malignant cells are defined as negative,the rest are negative Cytological abnormalities were positive;chronic cervicitis and low-grade cervical intraepithelial lesions in the cervical histopathology report were defined as negative and written as ≤LSIL;high-grade squamous intraepithelial lesions and invasive cancer were defined as positive and written as≥HSIL.Using cervical histopathology results as the gold standard,the sensitivity,specificity,Positive predictive value,negative predictive value and Yoden index of HPV E6/E7 mRNA,HPV DNA,TCT,HPV E6/E7 mRNA+TCT,HPV DNA+TCT,HPV E6/E7 mRNA+TCT+HPV DNA were compared,ROC curve to evaluate the diagnostic accuracy of 6 methods for≥HSIL lesions;analysis of HPV E6/E7 mRNA detection in different histopathological grades;Kappa coefficient Evaluate the consistency of the two methods of HPV E6/E7 mRNA and HPV DNA in different histopathological grades and different cytopathological grades,and explore the relationship between the two methods and the degree of cervical lesions.In patients with cytopathological reports of ASCUS,The test powers of HPV E6/E7 mRNA and HPV DNA were compared to determine the significance of HPV E6/E7 mRNA detection in the shunt of ASCUS patients.Results1.HPV E6/E7 mRNA,HPV DNA,TCT,TCT+HPV DNA,TCT+HPV E6/E7 mRNA,TCT+HPV DNA+HPV E6/E7 mRNA(combination of the three)6 schemes in≥HSIL lesions Diagnostic efficacy:The largest area under the ROC curve is the combined detection of the three(0.672),followed by TCT+HPV E6/E7 mRNA,TCT+HPV DNA,TCT,HPV E6/E7 mRNA,HPV DNA(0.669,0.669,0.657,0.642,0.583),the differences were statistically significant(P<0.01).The specificity of the three combined is highest at 71.43%,and the Jordan index is highest at 0.343,which has the highest diagnostic value.It is considered that the combined screening of the three is the highest diagnostic value in≥HSIL lesions and is an effective method for early detection of cervical lesions.2.Detection rate of HPV E6/E7 mRNA in different histopathological grades:histopathology reports of 320 patients were cervicitis(115 cases),low-grade intraepithelial lesions(46 cases),and high-grade intraepithelial Lesions(119 cases),invasive carcinoma(40 cases).The positive detection rate(positive number/total number of cases)of HPV E6/E7 mRNA detection in 4 histopathological grades was 48.70%,82.61%,89.08%,and 80.00%.The results of CA trend test showed that there was a linear relationship between the detection rate of HPV E6/E7 mRNA detection and histopathology(Z=5.899,P<0.05).The binary classification logistic regression analysis showed the detection rate and tissue of HPV E6/E7 mRNA detection.There was a positive correlation between the pathological grades(β=0.8).3.Consistency analysis of HPV E6/E7 mRNA and HPV DNA:The Kappa coefficients of the two in cytopathological classification were ASCUS group 0.598,NILM group 0.496,HSIL group 0.377,and LSIL group 0.367.It has the highest consistency in cytopathology ACSUS.The Kappa coefficients of the two in the histopathological classification were 0,590 in the cancer group,0.450 in the inflammation group,0.348 in the high-grade squamous intraepithelial lesion group,and 0.246 in the low-grade intraepithelial lesion group.The overall Kappa coefficient was 0.443.HPV E6/E7 mRNA and HPV DNA detection methods have the highest consistency in the histopathological cancer group,showing moderate consistency in general,and can be used as a preliminary screening tool for cervical lesions.4.Shunt effect of HPV E6/E7 mRNA detection in patients with ASCUS in cytopathology:A total of 89 patients with cytopathological results of ASCUS,including 53 patients with histopathological reports≥HSIL lesions.In the process of identifying≥HSIL,the specificity of HPV E6/E7 mRNA detection is higher than that of HPV DNA detection(36.11%>22.22%,χ2=14.69,P<0.01),but the sensitivity is lower(84.91%<94.25%,χ2=7.59,P<0.01),the difference is statistically significant.The positive predictive value and negative predictive value of HPV E6/E7 mRNA and HPV DNA were 66.18%and 63.64%,61.9%and 66.67%,respectively,and the differences were not statistically significant.The area under the ROC curve of HPV E6/E7 mRNA and HPV DNA was 0.664>0.573,P=0.009,and the difference was statistically significant.The diagnosis of HPV E6/E7 mRNA detection and recognition of≥HSIL lesions is significantly higher than that of HPV DNA detection.Conclusions1.The combination screening of TCT,HPV DNA and HPV E6/E7 mRNA has the highest diagnostic accuracy.2.The detection rate of HPV E6/E7 mRNA increased with the increase of histopathological grade.3.HPV E6/E7 mRNA detection can be used as a preliminary screening tool for cervical lesions.4.HPV E6/E7 mRNA detection can provide a theoretical basis for the hierarchical management of ASCUS patients. |
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