Relationship Between High-risk HPV Infection And Expression Of Local Defensin In Vagina

Cervical cancer is the fourth most common gynecological malignant tumor and the fourth leading cause of cancer-related deaths,with an estimated 527600 cases and 265700 deaths worldwide in 2012.However,in developing countries,it is the second most common cancer after breast cancer.It is also the third leading cause of cancer-related deaths after breast and lung cancer.A large number of studies have shown that high-risk persistent infection of human papillomavirus is the main cause of cervical cancer and precancerous lesions.In the process of carcinogenesis of cervical epithelial cells,The HPV virus integrates its E6/E7 DNA into the genome of cervical epithelial cells,enabling the cervical epithelium to obtain the oncogene E6/E7 DNA,which is activated by external carcinogenic factors and transcribed to produce E6/E7 mRNA,which produces the oncoprotein E6 / E7.After binding with tumor suppressor protein p53 and retinoblastoma protein(PRb)respectively,the latter protein was inactivated and eventually carcinogenesis.In the early stage of HPV infection,viral DNA exists in a free form and does not cause high-grade cytopathic changes.In HPV persistent infection,HPVDNA is integrated with host DNA and transcribed to produce E6/E7 mRNA,.Therefore,the detection of E6/E7 mRNA not only represents the persistent infection of HPV,but also reflects the expression of HPV E6/E7 oncoprotein and the degree of pathological activity to some extent.In this study,HPVE6/E7 mRNA was used as the grouping basis for HPV persistent infection.Defensins are active components of the innate immune system.Human beings express two defensins,?-defensins and ?-defensins,which have been proved to have antiviral activities against both envelope and non-envelope viruses.Human beings express six ? defensins and up to 31 ? defensins.According to the expression pattern and genetic structure of ? defensins,they are further divided into myeloid(HNP1-4)and intestinal [human defensin(HD)5 and 6] peptides.HD5 and HD6 are expressed in the special epithelial Paneth cells of the small intestine,as well as in the epithelial cells of the female genital tract of HD5.Human ?-defensin(Hbds)is more widely expressed on skin epithelial cells and mucous membranes exposed to environment.?-defensins,including HBD-1,HBD-2,are known to be expressed in urogenital epithelial cells.Studies have shown that HBDS is widely expressed in normal women undefineds reproductive tract and pregnancy-related tissues.In vitro,the role of HD-5 and HBD-2 in HPV infection has been confirmed.Due to the lack of complete defensin gene knockout model,the role and mechanism of defensin anti-HPV virus activity in vivo have not been solved.In this study,HPV E6/E7 mRNA was used as the grouping basis of HPV persistent infection.The purpose of this study was to explore the correlation between the two defensins and HPV persistent infection,and to provide theoretical basis for the treatment of cervical cancer.ObjectiveTo study the changes of the concentration of HD-5,HBD-2 defensins in vagina of patients with high-risk cervical human papillomavirus(HR-HPV)infection,and to explore the correlation between HD-5,HBD-2 and high-risk HPV infection in different infection conditions.To explore the anti-HPV infection mechanism of defensin in order to provide theoretical basis for early prevention and treatment of cervical cancer.Methods1.From October 2017 to March 2018,60 patients with HPV infection were selected during the precision poverty alleviation project in Henan province.At the same time,11 HPV negative women were selected.The cervical exfoliated cells of the patients were collected for HPV E6/E7 mRNA examination and vaginal lavage fluid was retained..2.Detection of HD-5,HBD-2 concentration in vaginal lavage fluid by enzyme-linked immunosorbent assay(ELISA)in three groups.Statistical analysisStatistical analysis was carried out using SPSS 21.0 software.The measurement data were expressed by(?x ± s),the analysis of variance was used for multi-group comparison,the LSD-t statistical method was used for comparison between the two groups,and the Cut-off value was determined by ROC curve(ROC),at ? = 0.05 level.The difference was statistically significant(P < 0.05).Results1.In the group of persistent HPV infection,9 cases(30%)were infected with HPV 16,6 cases(20%)were infected with),HPV 18,and 15 cases(50%)were infected with other high risk types.In the transient HPV infection group,7 cases(23.3%)were infected with HPV 16,8 cases(27.7%)were infected with HPV 18,and 15 cases(50%)were infected with other high risk types.2.The average concentration of HD-5,HBD-2 defensins in vaginal lavage fluid in HPV persistent infection group was similar to that in HPV transient infection group.There was no statistical significance(P > 0.05).The average concentration of HD-5,HBD-2 defensins in vaginal lavage fluid of HPV infection group was significantly higher than that of negative control group(P < 0 05).3.The accuracy of HD-5 and HBD-2 in detecting HPV by ROC curve analysis was(AUC=0.762 0.775),When HD-5 was used to detect HPV infection,the optimal critical value of HD-5 concentration was 37.54 PG / ml,with a sensitivity of 58.3% and a specificity of 100%.The optimal critical value of HBD-2 concentration was 458.5 PG / ml,the sensitivity was 53.3%,and the specificity was 82%.Conclusion1.Defensins HD-5 and HBD-2 play an important role in the early stage of HPV infection.2.HD-5 and HBD-2 can be used as immunological markers to distinguish whether HR-HPV is infected or not.