Association Between Vaginal Local Immune Status And Infection Of High-risk HPV

Cervical cancer is a common malignant tumor in gynecology.The persistent infection of high risk-human papillomavirus(HR-HPV)is currently considered to be the main cause of cervical intraepithelial neoplasia and cervical cancer.Within 2 years after infection,most women could be classified as normal,and only a few number of women develop persistent HPV-infected patients.Numerous studies have shown that the integration of HPV DNA fragments into the host cervical epithelial cell genome is a prerequisite for persistent infection of high-risk HPV,whereas in transient infections,HPV DNA fragments are rarely integrated into host cervical epithelial cells.HR-HPV infects the host through slight damage.Under the stimulation of external carcinogenic factors,the integration of oncogene E6 E7 DNA into the host cervical epithelial cells leads to the deregulation of E6 E7 expression,activates E6 E7 DNA transcription to E6 E7 mRNA,and continues to produce oncoprotein E6 E7.The oncoprotein E6 E7 acts on the tumor suppressor proteins P53 and pRb,respectively,resulting in inactivation of both,ultimately leading to malignant transformation of cells.In recent years,the FDA has certified the HPV E6 / E7 mRNA fragment by the Aptima method.HPV E6 / E7 mRNA detection has become an important means of cervical cancer screening.Two methods of detection of HPV E6 / E7 mRNA and HPV DNA are compared.It is not difficult to find that HPV DNA detection focuses on HPV infection in the body.HPV E6/E7 mRNA detection,which not only reflects the persistent infection of HPV.To some extent,it can reflect the expression of HPV E6/E7 oncoprotein and the activity of cervical lesions.A positive HPV E6/E7 mRNA test indicates that HPV DNA has been integrated into the host cell and initiates transcription.Conversely,HPV DNA is not integrated into the host cell and is in a free state.There is growing evidence that the majority of women who return to normal after exposure to HPV may be due to the fact that most healthy women have cleared the virus under their own immune system surveillance and defense.The human immune system is divided into two categories,one is the innate immune response,composed of tissue barrier,innate immune cells and innate immune molecules.As the body’s first line of defense,it plays a non-specific role in the early stages of HPV infection.The other type is the adaptive immune response,which is the body’s second line of defense to prevent reinfection of the virus.Adaptive immune responses include cellular immunity in which Th1 cells are involved and humoral immunity mediated by Th2 cells,especially cellular immunity plays an important role in anti-tumor and anti-viral.The two types of immune systems interact and coordinate,playing an indispensable role in combating pathogens and preventing disease progression.Therefore,an effective immune response is a key defense measure against the invasion and elimination of the virus.Especially when the cervix is exposed to the vaginal microenvironment,the local immune status of the vagina is closely related to the infection and prognosis of HR-HPV.ObjectiveIn this study,univariate analysis of the age,smoking history,age of first sexual life and other clinical factors and HR-HPV infection correlation,and enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of tumor necrosis factor-α(TNF-α),interleukin-12(IL-12)and IL-10 in vaginal lavage fluid.By detecting the expression of these cytokines,we explored the changes of vaginal local immune status in patients with different HR-HPV infection status,and provided new ideas for the prevention and treatment of HR-HPV persistent infection in theMethods1.From October 2017 to April 2018,we received 90 patients who had undergone HPV DNA testing,HPV E6/E7 mRNA detection and liquid-based cytology in our gynecological clinic,and the patients whose cytological diagnosis was negative.According to the results of HPV detection,they were divided into three groups: HPV E6/E7 mRNA+ /DNA(+/-)group(30 cases),HPV E6/E7 mRNA-/DNA+ group(30 cases)and HPV E6/E7 mRNA-/DNA-group(30 cases).All patients were interviewed by professional face-to-face questionnaires to record in detail the age,smoking history,age of first sexual life,maternal birth,condom use,number of sexual partners,and so on.Univariate statistical analysis was performed to find out the correlation between clinical factors and HR-HPV infection.2.ELISA was used to detect and compare the expression of TNF-α,IL-12 and IL-10 in vaginal lavage fluid of each group,and then to compare the expression of cytokines in patients with different HPV types in HPV E6/E7 mRNA+/DNA(+/-)group.Statistical analysisStatistical analysis was carried out using the SPSS21.0 statistical software.The ages consistent with normal distribution were expressed as(X ±S),and the correlation between the clinical data of all subjects and HR-HPV infection was analyzed by χ 2 test.The concentration of each cytokine in vaginal lavage fluid was expressed as median(quartile).Kruskal-Wallis H test was used to analyze the difference of cytokine expression levels in different HR-HPV infection status.Bonferroni was used for comparison between groups.Test level taken bilateral α=0.05.Results1.HPV E6/E7 mRNA+ /DNA(+/-)group of 30 patients,mean age(45.00±8.95)years old,HPV E6/E7 mRNA-/DNA+ group of 30 patients,average Age(43.40±8.41)years old,HPV E6/E7 mRNA-/DNA-group of 30 patients,mean age(43.33±7.81)years old.We found that the clinal data of the three groups(age,smoking history,age of first sexual life,maternal parity,whether to use condoms,number of sexual partners)were not statistically significant(P>0.05).2.Compared with other groups,the concentration of IL-10 in HPV E6/E7 mRNA+ /DNA(+/-)group increased significantly,while the concentration of TNF-α and IL-12 decreased significantly(P < 0.0167).There was no significant difference in the concentrations of TNF-α,IL-12 and IL-10 between the HPV E6/E7 mRNA-/DNA+ group and the HPV E6/E7 mRNA-/DNA-group(P>0.0167).3.In the HPV E6/E7 mRNA+ /DNA(+/-)group,there was no significant difference in the concentrations of TNF-α,IL-12 and IL-10 between the different HPV patients(all P>0.05).Conclusion1.High-risk HPV persistent infection was associated with the change of local immune status of vagina.2.There was no correlation between HPV typing and the change of local immune status of vagina.3.Changing the local immune status of vagina may provide a new idea for the prevention and treatment of HR-HPV persistent infection in the future.