The Research Of Cervical Lesions Both Induced By Expression Level Of TLR2/4 And HR-HPV Infection In Different Microbiome

Objective:To investigate the correlation between human high-risk papillomavirus(HR-HPV)and vaginal microbiome;To explore the relationship of microbiome and cervical intraepithelial neoplasias(CIN);To find out the association between microbiome,the expression level of TLR2/4 and CIN.Methods:A total of 448 outpatients and inpatients,from May 2018 to September 2019,were collected from the Fujian Provincial Maternal and Child Health Hospital.During the study,eighteen patients with missing data were excluded.Then 430 patients were matched according to HR-HPV infection rate and at a ratio of 1:2.Finally,a total of177 cases were included in the cytological and pathological research.In this study,the vaginal microecological specimens were all taken from the vaginal secretions onpsterior fornix and 1/3 of the vaginal wall.The experimental data were analyzed by Chi-square test,Fisher exact test,t-test,Mann-Whitney U test and other analytical methods.P<0.05 was significance.Results:1.The infection rate and distribution of HR-HPV in negative for intraepithelial lesion or malignancy(NILM)patients and CIN patients are different.The rate of HR-HPV infection in CIN was significantly higher than that in NILM.The difference was significance.Among patients with NILM,the most frequently HR-HPV types were HPV52,HPV58,and HPV51;among CIN I patients,the most frequently HR-HPV types were HPV52,HPV16 and HPV18;among CINⅡand CINⅡ+patients,the most frequently HR-HPV types were HPV58,HPV16 and HPV18.2.The HR-HPV infection rate was higher in bacterial vaginosis(BV)patients,and the difference was significance(36.17%vs 26.92%,χ~2=4.377,P=0.036).In patients with Gardnerella infection,the infection rate of HR-HPV was 72.73%,which was significantly higher than the HR-HPV infection rate(44.72%)in the vaginal microbiome with lactobacillus(χ~2=8.34,P=0.04).The HR-HPV infection rate was increased and the difference was significant in sialidase-positive patients(χ~2=8.508,P=0.004).However,there was no statistical significance in HPV16/18 infections.3.Among patients with Gardnerella infection,the patients with high-grade squamous intraepithelial lesion(HSIL)was significantly higher than that of patients with Lactobacillus(37.50%vs 3.23%,P=0.015).4.Compared with sialidase-negative patients,the cervical lesions in sialidase-positive patients was significantly increased(31.37%vs 17.46%,χ~2=4.168,P=0.041).However,there was no statistical difference between CIN I and CINⅡamong sialidase-positive positive patients(26.32%vs 15.79%,χ~2=0.302,P=0.583).5.The vaginal flora composition in patients with CIN and NILM is similar.But the proportion was different.In the NILM patients,Lactobacillus is the major bacterial flora.In the CIN patients,Gardnerella was the major bacterial flora.Theαdiversity in the CIN patient was significantly higher than that in the NILM,but there was no significant difference in the abundance of the two groups(Chao index and the ACE index).6.Among patients with abnormal cervical pathology,the relative expression level of TLR4 was significantly increased in patients with sialidase-positive patients(P=0.045).Conclusion:Bacterial vaginosis are associated with high-risk HPV infection.The vaginal dominant flora in patients with cervical intraepithelial neoplasia is Gardnerella.The sialidase is an important factor in cervical intraepithelial neoplasia.TLR4 relative expression is significantly increased in CIN patients with sialidase positive.Activation of the TLR4pathway may be one of the mechanisms by which the Gardnerella causes cervical intraepithelial neoplasia.