HPV 16/18 infection and its correlation with matrix metalloproteinase-2,9 and their inhibitor-1,2 in human cervical carcinoma

Objective To investigate the infection of human papillomavirus 16/18(HPV16/18) and these expressions of matrix metalloproteinase-2,9(MMP2,9) and their inhibitor-1,2(TIMP-1,2) in human cervical carcinomas and the relationship among of them. Methods The infection of HPV16/18 DNA in 67 cases of cervical carcinoma(40 cases of squamous-cell carcinoma of the uterine cervix,20 cases of adenocarcinoma of the uterine cervix,7 cases of glandular and squamous-cell carcinoma of the uterine cervix),in 29 cases of cervical intraepithelial neoplasia(CIN) and 16 cases of normal cervices was detected by hybridization in situ.MMP-2,9 and TIMP-1,2 were detected by immunohistochemical staining(SP) in these five groups. Results The infection rates of HPV16/18 in squamous-cell carcinoma and adenocarcinoma,glandular and squamous-cell carcinoma of the uterine cervix,CIN and in normal cervical epithelium,were 67.50%(27/40),35.00%(7/20),5/7,68.97%(20/29),6.25%(1/16) respectively.There were significant differences among these cervical lesion groups and the normal cervical epithelium(P0.001).There was significant difference between the squamous-cell carcinoma group and the adenocarcinoma group(P0.001),but no significant difference was found between the squamous-cell carcinoma group and the CIN group.The positive rates of MMP-2,9 and TIMP-1,2 in normal cervical epithelium,CIN,squamous-cell carcinoma,adenocarcinoma,glandular and squamous-cell carcinoma of the uterine cervix increased gradually.There were significant differences between these cervical lesion groups and the control group.MMP-2 expression was higher in squamous cell carcinoma than that in adenocarcinoma of the uterine cervix(P0.001),but MMP-9 expression was lower in squamous cell carcinoma than that in adenocarcinoma of the uterine cervix(P=0.048).The positive rate of TIMP-1 was higher in CIN than that in squamous cell carcinoma of the uterine cervix(P=0.042),and no significant differences existed among these cervical lesion groups for TIMP-2.There were no relationships among the infection of HPV16/18 and expressions of MMP-2,9 or TIMP-1,2.The positive rates of MMP-2 and MMP-9 in lesion tissues with lymph node metastasis were obviously higher than those without lymph node metastasis(P=0.017,0.002),but the positive rate of TIMP-2 was contrary to those of MMP-2 and MMP-9.There was no significantly difference between TIMP-1 expression in lesion tissues with lymph node metastasis and that without lymph node metastasis.No significant correlation could be established between the infection of HPV16/18 and the expression of MMP-2 or 9 or TIMP-1 or 2 or the tumor diameter or clinical stage or pathologic grade or pelvic node metastasis. Conclusion The infection of HPV16/18 may play a role in the progress of carcinoma of the uterine cervix.The overexpression of MMP-2,MMP-9, TIMP-1 and TIMP-2 possibly play a key role in invasion and lymph-node metastasis of the human cervical carcinoma.