| Background and ObjectiveCervical cancer(CC)has long been one of the malignancies threatening women’s health worldwide.Especially in developing countries,cervical cancer has the second highest morbidity and mortality among women’s cancers,second only to breast cancer.Cervical cancer screening,as a secondary prevention,is of great clinical significance in reducing the incidence and mortality of cervical cancer.Persistent human papillomavirus(HPV)infection is a definite cause of cervical cancer,which is closely related to the occurrence,development,follow-up and prognosis of cervical cancer.But it takes more than a decade to progress from an HPV infection to cervical squamous intraepithelial lesions(SIL)to invasive cervical cancer.Therefore,the early screening of cervical cancer is very important for the early diagnosis,treatment and prognosis of cervical cancer.Pap smear is the earliest method used in cervical cancer screening,but its sensitivity is low and its subjective effect is strong.With the development of diagnosis and treatment technology,the production of liquid based cytologic test(TCT)has a greater improvement in cervical cancer screening compared with Pap smear.Currently,HPV-DNA test and TCT test have been widely used in cervical cancer screening in China.The 2019 ASCCP Guidelines for Cervical Cancer Screening specify the use of HPV or combined cervical cytology for primary screening of cervical cancer.In the vast majority of women,HPV infection is transient and does not actually cause cervical lesions or cervical cancer.Therefore,HPV testing may cause excessive panic and overtreatment in the population.With the further study of cervical cancer genomics,it was found that E6 and E7 proteins encoded by E6/E7 oncogenes in the HPV genome acted on P53 and Rb genes,respectively,causing the infinite proliferation of cells,thus leading to the occurrence and development of tumors.HPV E6/E7 mRNA detection can determine whether HPV infection is in active phase,can predict the progression and prognosis of cervical lesions,and has important clinical significance for stratified management of cervical lesions.With the further study of molecular biology and the improvement of diagnostic techniques,studies have confirmed that the abnormal expression of oncogenes and tumor suppressor genes affects the occurrence and development of tumors,especially the abnormal methylation of tumor suppressor genes inhibits the expression and regulation of tumor suppressor genes.Recent research results indicate that the methylation suppressor gene in cervical cancer tissue is closely related to the development and prognosis of cervical cancer,especially paired box family gene 1(pair box family genes 1,PAX1)the promoter regions of high abnormal methylation and cervical cancer linked to cervical cancer,and can be detected in cervical exfoliated cells.Therefore,PAX1 gene methylation can be used as an important molecular biomarker for cervical cancer and precancerous lesions screening.The aim of this study was to evaluate the clinical application value of HPV E6/E7 mRNA and PAXl gene methylation in the diagnosis of cervical lesions by analyzing the exfoliated cells of cervical lesions.Materials and MethodsA total of 1201 patients with cervical lesions who were admitted to the gynecological outpatient department of the First Affiliated Hospital of Zhengzhou University from March 2018 to January 2020 were selected as the research subjects.All patients underwent tissue biopsy under electronic colposcopy,and the pathological results of biopsy or postoperative routine pathology were taken as the gold diagnostic standard.All patients were divided into four groups:the cervicitis group,the low grade squamous intraepithelial lesions(LSIL)group,the high grade squamous intraepithelial lesions(HSIL)group,and the cervical cancer group.PAX1 methylation was detected by methylation specific PCR amplification technology and in accordance with the product instructions of PAX1 gene methylation detection kit(Hunan Hongya Genome).The mRNA expression of high-risk HPVE6/E7 was detected by B-DNA technique,including 14 types of HPVE6/E7,including 16,18,31,33,35,39,45,51,52,56,58,59,66 and 68.The sensitivity,specificity,negative predictive value,positive predictive value,diagnostic coincidence rate and other indicators of PAX1 gene methylation test,HPV E6/E7mRNA test and their combined test were compared.SPSS22.0 statistical software was used for statistical analysis,and P<0.05 was statistically significant.Results1 General situation of patientsA total of 1201 patients with cervical lesions were included in this study,including 530 cases in cervicitis group,155 cases in LSIL group,345 cases in HSIL group,and 171 cases in cervical cancer group.The mean age of all patients was 41.89±11.10 years,the minimum age was 17 years,and the maximum age was 79 years.The mean age of the cervicitis group was 41.57±11.24 years,the LSIL group was 40.43±10.44 years,the HSIL group was 40.00±10.57 years,and the cervical cancer group was 48.02±10.09 years.There was no statistical significance in age difference between the four groups(P>0.05).2 Detection of HPVE6/E7mRNA and its diagnostic efficacy in patients with cervical lesionsCervicitis groups,low grade squamous intraepithelial lesions(LSIL)group,the high-grade squamous intraepithelial lesion(HSIL),cervical cancer HPV E6/E7mRNA test positive rate were 49.33%,60.71%,77.39%,84.16%,and increased with the increase of disease severity,and the overall comparison between four groups was statistically difference(P<0.05),two comparison between the four groups:except for HSIL there was no statistically significant difference between the group and cervical cancer group(P=0.168),the other two differences between the two had statistical significance(P<0.05).The sensitivity,specificity,positive predictive value,negative predictive value,diagnostic coincidence rate and Youden index were 79.67%,48.04%,48.68%,79.25%,60.13%and 0.2771 respectively.3 Detection of PAXl methylation and its diagnostic efficacy in patients with cervical lesionsCervicitis groups,low grade squamous intraepithelial lesions(LSIL)group,the high-grade squamous intraepithelial lesion(HSIL)and cervical cancer group PAX1 gene hypermethylation rate were 5.27%,10.74%,41.36%,79.01%,and increased with the increase of disease severity,and the overall comparison has significant statistical difference(P<0.05),two comparison between the four groups are statistically difference(P<0.05).The sensitivity,specificity,positive predictive value,negative predictive value,diagnostic coincidence rate and Youden index were 53.91%,93.49%,85.90%,73.40%,76.72%and 0.4740 respectively.4 Efficacy of PAX1 methylation combined with HPVE6/E7mRNA in the diagnosis of cervical lesionsThe sensitivity,specificity,positive predictive value,negative predictive value,diagnostic coincidence rate and Youden index were 76.34%,91.02%,85.59%,83.52%,84.69%and 0.6736 respectively.The diagnostic efficiency of the combined detection is obviously better than that of the single detection.Conclusion1.The positive rate of HPVE6/E7mRNA increased with the progression of cervical lesions,and it has good clinical application value for the diagnosis of cervical lesions.2.The hypermethylation rate of PAX1 gene increased with the progression of cervical lesions,and it has good clinical application value for the diagnosis of cervical lesions.3.The efficacy of PAXI methylation combined with HPVE6/E7mRNA detection in the diagnosis of cervical lesions is better than that of HPVE6/E7mRNA detection alone,and it has a higher clinical application value in the diagnosis of cervical lesions. |
PDF Full Text Request