| BackgroudsCervical Cancer is the most common malignant tumor in the female reproductive system.Persistent infection of high risk Human Papillonmavirus(HP-HPV)is the main cause of cervical cancer.According to research reported that the incidence of cervical cancer has increased and beome younger in our country in recent years.The development of cervical cancer is a gradual evolution that go through such a stages:HPV infection,low grade squamous intraepithelial lesions(LSIL),high grade squamous intraepithelial lesions(HSIL),it takes about average 10-15 years,and the clinical symptoms of early stage cervical cancer is not obvious,it is often overlooked.If we can early detect the cervical lesions and carcinoma and given proper interventions,it will be a very important strategy to reduce the incidence and mortality of cervical cancer.At present,the screening methods of cervical lesions mainly include cytology and HPV testing.Although the cytological detection method has high specificity,but the sensitivity is low,the misdiagnosis rate of is high.With the development and improvement of molecular biology,the HPV detection method has shown a better value in diagnosing the cervical lesions.At present,the application of HPV test has shown the tendency to beyond the cytological screening in the developed countries.The first generation test method is the HPV DNA test,which is now widely used in clinical.The second generation test method,HPV E6/E7 mRNA detection,is still in its initial exploratory stage in clinical application.From the view of pathologenesis mechanism,HPV E6/E7 mRNA molecule is an very important markers for the active stage of virus oncogenes in host cells.It can reflect the integration degree of viruse oncogenes and host genes,and intermediate links for oncogenic protein production.In theory,the molecule is better reflect to the extent of the disease progression.Therefore,our study was to investigate the diagnostic value of HPV E6/E7 mRNA,cytology,and HPV DNA genotyping in cervical lesions,and the relationship between HPV E6/E7mRNA expression and cervical lesions,providing a better screening method for cervical lesions as well as clinical evidence.ObjectiveBy comparing the three methods of HPV E6/E7 mRNA,Liquid-based thin-layer cytology and HPV DNA genotyping in diagnosis of cervical intraepithelial lesions and the ability to detect cervical lesions.To evaluate the clinical value of HPV E6/E7 mRNA in cervical lesions screening.For the purpose of providing clinical evidence for the precise screening in cervical lessions or cancer and best screening options for women.Methods1.To Collect date of liquid-based cytology and HPV DNA genotyping testing in Xijing Hospital from December 2016 to October 2017.The patient who suspected with cervical lesion or cancer will conducted colposcopy and biopsy,all collected patients have done the HPV E6/E7 mRNA testing.The test subjects were seriously selected according to the inclusion and exclusion criteria.Cervical tissue biopsy is the standard control.2.To compare the diagnostic value of HPV E6/E7 mRNA and liquid based cytology,and HPV DNA genotyping in detecting lesions?LSIL.3.To compare the diagnostic value of HPV E6/E7 mRNA and liquid-based cytology,and HPV DNA genotypingin detecting lesions?HSIL4.To compare the positive detection of HPV E6/E7 mRNA and liquid-based cytology,HPV DNA genotyping at each cervical pathology lesion.5.To assess the correlation between the expression levels of HPV E6/E7 mRNA and the cervical histopathological grade.Results1.Baseline data for the research objectAccording to the inclusion and exclusion criteria,408 cases were collected.cervicitis were 207(50.7%),LSIL were 68(14.2%),HSIL were 130(31.9%),cervical cancer were 3(7.0%);NILM were 151 cases(37.0%),ASCUS were 117 cases(28.7%),LSIL were 97cases(23.8%),HSIL were 39 cases(10.3%);HPV E6/E7 mRNA positive case were 198(48.5%);HPV E6/E7 mRNA negative case were(51.5%);HPV DNA positive case were339(83.1%);HPV DNA negative case were 339(16.9%).In the liquid-based cytology.The five most common infection types were HPV16,18,58,52,33.2.Disgnostic value of three methods in cervical lessions?LSIL.a)The sensitivity of HPV E6/E7 mRNA,liquid-based cytology,HPV DNA genotyping in lesions?LSIL was 68.1%,73.0%,85.0%;specificity was 70.5%,46.9%,18.8%;Comparing the sensitivity of HPV E6/E7 mRNA and HPV DNA genotyping was significance difference(x~2=2.2,P(27)0.05);Comparing the specificity of HPV E6/E7 mRNA and liquid-based cytology was significance difference(x~2=23.9,P(27)0.05).b)The area under the operating characteristic curve of HPV E6/E7 mRNA in cervical lesions?LSIL was 0.710,95%CI(0.652-0.765);The area under the operating characteristic curve of liquid-based cytology in cervical lesions?LSIL was 0.600,95%CI(0.545-0.655);The area under the operating characteristic curve of HPV DNA genotyping in cervical lesions?LSIL was 0.520,95%(CI 0.464-0.576);HPV E6/E7 mRNA has a better diagnostic value than the other two.3.Disgnostic value of three methods in cervical lessiond?HSIL.a)The sensitivity of HPV E6/E7 mRNA,liquid-based cytology,HPV DNA genotyping in cervical lesions?HSIL was 87.2%,83.5%,87.2%;specificity was 70.2%,46.9%,18.9%;comparing the specificity of HPV E6/E7 mRNA and liquid-based cytology was significance difference(x~2=30.7,P(27)0.05);The sensitivity of three methods was significant difference(P(27)0.05).b)The area under the operating characteristic curve of HPV E6/E7 mRNA in cervical lesions?HSIL was 0.805,95%CI(0.759-0.850);And the area under the liquid-based cytology in cervical lesions?HSIL was 0.652,95%CI(0.597-0.706);The area under the operating characteristic curve of HPV DNA genotyping in cervical lesions?HSIL was0.531,95%CI(0.472-0.589).HPV E6/E7 mRNA has a better diagnstic value than the orthers.4.Comparison the diagnosis ability of three methods in cervical lesions?LSILUsing cervical pathology as standard.In incervicitis the detectiont rate of HPV E6/E7mRNA and HPV DNA genotyping(29.5%vs 53.1%)was significance difference(x~2=23.9,P(27)0.05),liquid-based cytology and HPV DNA genotyping(53.1%vs 81.2%)was significance difference(x~2=38.8,P(27)0.05).In LSIL,the detection rate of HPV E6/E7mRNA and liquid-based cytology(30.9%vs 52.9%)was significance difference(x~2=35.7,P(27)0.05);the the detectiont rate of liquid-based cytology and HPV DNA genotyping(52.9%vs 80.9%)was significance difference(x~2=38.8,P(27)0.05),In HSIL the detectiont rate of HPV E6/E7 mRNA,liquid-based cytology and HPV DNA genotyping was 86.9%,83.1%,86.9%,there was no significance difference(x~2=1.0,P>0.05).5.Comparison the diagnosis ability of three methods in cervical lesions?HSILThere was a positive correlation between the expression level of HPV E6/E7 mRNA and the cervical pathological grade(r=0.508).6.The co-screening value of HPV E6/E7 mRNA in cervical lesionHPV E6/E7 mRNA combined with liquid-based cytology has a higher screening value than liquid-based cytology combined with HPV DNA genotyping.Combined screening can improve disease detection efficiency than single screening.Conclution1.The overall diagnostic efficiency of HPV E6/E7 mRNA in detection cervical lesions is better than liquid-based cytology and HPV DNA genotyping.HPV E6/E7 mRNA testing combined the high sensitivity of HPV DNA genotyping ae well as the high specificity of liquid-based cytology.The advantage of HPV E6/E7 mRNA is that I can contral the missed diagnosis rate and misdiagnosis rate in a relatively small range,and easy conducted.So it has the potential for cervical lesions or cancer screening.2.With the disease progresse,the detection rate of HPV E6/E7 mRNA increases.the detection rate was lower in cervicitis and low-grade lesions.HPV E6/E7 mRNA negative may represent a well excluded relatively.3.The positive correlation between HPV E6/E7 mRNA expression level and the cervical lesions grade suggests that it has a certain significance in judgement the risk of cervical lesion progression.We predicted that HPV E6/E7 mRNA detection has a well application value in cervical lesions and cancer.4.In the co-screening,HPV E6/E7 mRNA may have a better application value than HPV DNA testing,however futher research is needed. |
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