Evaluation Of PAX1 Methylation In The Diagnosis Of Cervical Lesions

ObjectiveA cross-sectional study of hospital opportunistic screening population was conducted to verify the efficacy of PAX1 gene methylation detection in the diagnosis of cervical lesions in women aged ≥ 21 years.To investigate the shunt effect of PAX1 methylation gene test on cervical cancer screening between ASC-US and non-16/18HR-HPV positive high-risk population,and to compare it with other cervical cancer screening strategies.MethodsA cross-sectional study was conducted on 465 women who met the inclusion criteria from patients admitted to our hospital from June 2016 to June 2018.Cervical exfoliated cells were collected from all groups for cervical cytology,high-risk HPV typing,and PAX1 gene methylation test.According to the positive results,colposcopy and biopsy pathology were transferred,and the data were summarized for study.The main content is divided into two parts: The first part analyzed the distribution characteristics of the study population,took TCT and HR-HPV as the reference,set pathological diagnosis as the gold standard,and statistically analyzed the sensitivity,specificity,accuracy,PPV and NPV of PAX1 methylation test in the diagnosis of cervical lesions of different levels,and compared them.The second part analysis PAX1 methylation test in cervical cancer screening shunt value,will be after a preliminary screening of ASC-US population and the non-16/18 HR-HPV positive result into the group,set the pathological diagnosis as the gold standard,using a variety of subjects working curves(ROC)analysis the sensitivity of the screening strategy,specific degree,positive predictive value,negative predictive value,AUC,P values.Results1.In this study,465 people were enrolled.Among the TCT results,243 persons were normal or inflammatory,100 persons were ASC-US,122 persons were LSIL,ASC-H,HSIL and AGC.Among the HPV results,265 persons were negative,102 personers were HPV16/18 positive and 98 persons were non-16/18 HR-HPV positive.2.Among the enrolled population,71 persons were highly methylated and 394 were low-methylated in the PAX1 methylation detection results.In the study population aged 21-30,31-40,41-50,51-60 and over 61 years old,the hypermethylation rates of PAX1 were 7.0%,9.3%,9.5%,24.7% and 37.7%.The positive rates of PAX1 in HRHPV negative,HPV16 positive,HPV18 positive,HPV16 and 18 both positive,HPV16 or 18 positive,and non-16/18 HR-HPV positive were 2.6%,7.7%,1.5%,0.9%,10.1%and 2.6%.The positive rates of PAX1 in cervical CIN2,cervical CIN3,cervical squamous cell carcinoma and cervical adenocarcinoma were 2%,13.9%,26.5% and2.6%.3.The results of PAX1 prediction of cervical lesions≥CIN2: sensitivity 50%,specificity 99.1%,PPV 87.8%,NPV 89.6%.The specificity,PPV and accuracy were all better than TCT and HR-HPV.The results of PAX1 in the prediction of cervical cancer:sensitivity 93.6%,specificity 93.5%,PPV 88.5%,and NPV 76.3%.The sensitivity,specificity,PPV,NPV and accuracy were also significantly better than TCT and HRHPV.4.In comparison of screening strategies,the results of PAX1 in the diagnosis of cervical cancer in ASC-US population: sensitivity 93.75%,specificity 96.43%,PPV83.33%,NPV 98.78%,AUC value 0.951(95%CI 0.878-1.00),and P value 0.037.Results of PAX1 test: sensitivity 39.13%,specificity 100.0%,PPV 100.0%,NPV65.85%,AUC value 0.696(95%CI 0.588-0.803),P value 0.055.5.In comparison of screening strategies,among non-16/18 HR-HPV positive people,the results of PAX1 in the diagnosis of cervical cancer: sensitivity 82.35%,specificity 97.11%,PPV 58.33%,NPV 99.12%,AUC value 0.897(95%CI 0.79-1.00),and P value < 0.001.Results of PAX1 in the diagnosis of ≥ CIN2 cervical lesions:sensitivity 30.56%,specificity 99.31%,PPV 91.67%,NPV 85.25%,AUC value 0.652(95%CI 0.569-0.730),P value < 0.001.Conclusions1.The methylation detection of PAX1 gene has high sensitivity and specificity for the diagnosis of cervical CIN2 and above lesions,especially cervical cancer.2.PAX1 methylation test has a shunt advantage for ASC-US high-risk population.3.PAX1 methylation test also had a shunt advantage for non-16/18 HR-HPV positive high-risk population.