The Expression Of Interferon-γ And Interleukin-10 In The Cervical Lesions Infected By High-risk Human Papillomavirus

Objective:To study the changes of IFN-y, IL-10 in the high-risk human papillomavirus infection cervical lesions. Attempts were also made to establish the relationship between local immunity of cervical lesions and high-risk human papillomavirus infection; the development of cervical squamous cell carcinoma; immune mechanism on how high-risk human papillomavirus contributed to cervical squamous cell carcinoma.Methods:Cervical tissues of 80 subjects obtained from cervical biopsy or cervical conization were included in this study group.56 cases of them were cervical intraepithelial neoplasia(15 of CIN I,19 of CINⅡ,22 of CINIII); 24 cases:cervical squamous cell carcinoma with different FIGO stages(8 of stageⅠ,12 of stageⅡ,4 of stage III) whereas the remaining 10 cases from normal subjects served as controls. All tissues went through formalin and paraffin processing. Specimens were detected for IFN-y and IL-10 expression using Two-steps Method of Immunohistochemistry later. The image analysis software of Image-Pro plus 6.0 was utilized for semi-quantitive analysis of IFN-y and IL-10 expression, in a form of integrate optic density (IOD) with mean±standard deviation. All 80 specimens from the cervical canal were gathered for HPV-DNA and the genetic type of HPV-DNA detection using Flow-through hybridization and gene chip (HybriMax).Results:The positive rate of HPV-DNA in the study group and the controls were 78.8% (63/80) and 10.0%(1/10), respectively. The infection rate of HR-HPV in CINs and cervical squamous cell carcinoma were 75.0%(42/56) and 87.5%(21/24). The difference of HR-HPV infection rate between the controls, CINs and cervical squamous cell carcinoma was significant (P<0.05).The HR-HPV infection rate detected in CINs were CINⅠ46.7%(7/15), CINⅡ78.9%(15/19), CINⅢ90.9% (20/22), respectively with a significant difference on HR-HPV infection rate between CINs subtypes (P<0.05). In the present study, HPV16 (39/80) was the predominant type, followed by HPV 58 (13/80) and HPV33 (10/80). HPV 16 infection rate among CINs:CINⅠ, CINⅡ, CINIII and cervical squamous cell carcinoma were 6.7%(1/15),42.1%(8/19),59.1%(13/22) and 70.8%(17/24), the difference was statistically important (x2=16.60, P=0.001).The IOD of IFN-y positive expression in the controls, CINⅠ,CINⅡ,CINⅢand cervical squamous cell carcinoma were 3.556±1.356,3.496±1.361,3.061±0.905,2.698±0.977, 1.617±0.754.Such differences among CINs was statistically remarkable (P<0.05). The expression of IFN-y in cervical squamous cell carcinoma was significantly lower when compared to that of the CINs (P<0.05)and the controls(P<0.01). IL-10(IOD) expression over the controls, CIN, CIN II, CINIII and cervical squamous cell carcinoma were founded to be 3.384±1.310,3.393±1.303,4.088±1.338,5.663±1.245,7.276±1.985 respectively with a p value of<0.05. This signify an important disparity among them. IL-10 expression increment was found to be associated with higher degrees of cervical lesions(F=21.586, P=0.000). The Spearman rank correlation coefficient between the positive expression of IFN-y, IL-10, IFN-y/IL-10 and the cervical lesions were-0.552, 0.703,-0.731, respectively. There was a trend spotted in present research:a decline in IFN-y expression but a raise of IL-10 IOD as the FIGO stages of cervical squamous cell carcinoma elevated, but neither these expressions between different stages was statistically significant (P>0.05). On the whole, IFN-y, IL-10, and the ratio of IFN-y/IL-10 were significantly remarkably different between HR-HPV-positive group and HR-HPV-negative group (P<0.01).Conclusion:1.The infection rate of HR-HPV increased as the cervical dysplasia deteriorated. This indicated:HR-HPV viral load was related to the progression of cervical lesion. Specific HPV 16 infection showed rank correlation with cervical dysplasia extension.2. As cervical neoplasia extended, the expression of IFN-y decreased while that of IL-10 enhanced over local cervical tissues, suggesting local immunity involvement along the pathophysiology of cervical dysplasia lesions.3. Within HR-HPV positive group, as the severity of cervical dysplasia lesions extended, the expression of IFN-y declined while that of IL-10 increased. This gave us reasons to believe:there might be a reduction of immunal role against virus and tumor locally and such alteration was correlated with the outcome of HR-HPV infection. Persistent HR-HPV infection may lead to local cervical immune impairment hence the disease progression.4. The Spearman rank correlation coefficient between the ratio of IFN-y/IL-10 and the degree of cervical lesions was better than IFN-y and IL-10. It may be used as an indicator to evaluate the local immune function of cervical lesions.