Résumé
Objective To compare the synchronous changes of high risk human papillomavirus load(HPV-DNA)and CD4+CD25+Foxp3+regulatory T cells(Treg)in local microenvironment of cervix,and investigate the ef-fects of HPV virus replication and progression of cervical lesions on Treg cells. Methods 304 cases of HR-HPV infection with cervical lesions were divided into 5 groups,cervical intraepithelial neoplasia(CIN)I,CINII,CINIII, cervical cancer and chronic cervicitis.The HPV-DNA of cervical secretion was detected by PCR fluorescence,and the relative Treg cells numbers from cervical brush samples were determined by flow cytometry with CD4+CD25+Foxp3+gating,and the data were statistically analyzed. Results(1)There was significant difference of cervical Treg cells in different degrees of cervical lesion and different copy numbers by variance comparison(F = 24.93, 109.86,P < 0.05),and a further pairwise comparison showed that there was no significant difference of Treg cell between chronic cervicitis and CINI and low load(HPV DNA 104~105copies/mL)and medium load(HPV DNA 105~106copies/mL)(P>0.05).There was a significant difference between the other groups(P<0.05);(2)Treg cells as variable,interaction effect of cervical lesions and viral load factors were significant different(F=3.39,P<0.05). The effect of different cervical lesions and HR-HPV viral load on the expression of Treg cells was differen-tial. An overall showing with the degree of cervical lesions increased,HR-HPV virus copy number increased, Treg cells expression increased gradually;(3)CD4+CD25+Foxp3+Treg cells were highly expressed in cervical cancer patients,but the expression level fluctuated widely and the numerical distribution was the most dispersedly. Conclusion The immune suppression function of local CD4+CD25+Foxp3+Treg cells with different cervical lesions and different HR-HPV DNA may bilaterally regulate the prognosis of cervical lesions,as a whole,between Treg cells and HR-HPV load and cervical lesions were the consistent progress trend.
Résumé
Objective The aims of this study were to compare the different expression between high-risk human papilloma-virus load(HR-HPV DNA)and Th1/Th2 type cytokines in local different microenvironments of cervix,and to explore the possibility and significance of predicting cervical cancer. Methods A total of 339 patients with persistent HR-HPV infection were divided into cervical intraepithelial neoplasia(CIN)and cervical cancer. Forty patients with HPV-negative and cytological examination of normal cervix were used as controls. PCR fluorescence assay and double antibody sandwich were used. ELISA assay were used to detect HPV-DNA and Th1 type cytokines including IL-2,IFN-γ,TNF-ɑ and Th2 type cytokines including IL-4,IL-6 and IL-10 from cervical secretion. The ratio of TNF-ɑ/IL-10 was used as an index to measure the immune balance of Th1/Th2. Univariate and multivariate logistic regression were performed to analyze the data and then to screen the predicting indicators of cervical cancer. Results Univariate analysis showed that HR-HPV DNA,IL-2,IL-4,IL-6,IL-10,IFN-γ,TNF-ɑ and TNF-ɑ/IL-10 were significantly different between CIN and cervical cancer groups(P<0. 05),which could be used as a risk factor for predicting cervical cancer. Multivariate logistic regression analysis showed that IL-10,IFN-γ,TNF-ɑ,TNF-ɑ/IL-10 were the influencing factors of cervical cancer. The regression model fitted goodness test was Nagelkerke(R2= 0. 982),the pre-judgment rate for CIN was 99. 5% ,the pre-judgment rate of cervical cancer was 100% ,and the total positive rate was 99. 7% ,suggesting good fitting effect was good and the prediction accuracy was high. Conclusion CINⅠand CINⅡhave abnormal expression of Th cytokine,but they do not affect Th1/Th2 balance. Th1/Th2 imbalance in CINⅢ stage and Th2 dominant expression promote the occurrence of cervical cancer. Based on the regression model for predicting cervical carcinogenesis,cervical immunity caused inhibitory microenvironment by local immune imbalance is the key link in HR-HPV persistent infection and cervical cancer,and has nothing to do with HR-HPV DNA.