The relationship between cytokines and HPV-16, HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix

Objectives. To investigate intralesional cytokine levels in precancerous lesions of the uterine cervix and their relationship with human papillomavirus (HPV) type 16, HPV type 16 E6/E7, and high-risk HPV viral load. Methods. We performed a prospective study of 67 patients between May 2005 and December 2005. Hybrid Capture 11 testing was used to identify patients as high-risk HPV DNA-positive or -negative. HPV DNA Chip test was performed for HPV genotyping in all cases found to be HPV DNA-positive. Real-time PCR was used to quantify HPV-16 E6, E7, interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) transcripts. Results. Among high-risk HPV-infected women, intralesional TNF-alpha, IL-6, IL-10, and IFN-gamma levels had no significant differences according to histologic grade. In multivariate logistic regression analysis, TNF-alpha, IL-6, IL-10, and IFN-gamma were not associated with HPV-16. Increased IFN-gamma was significantly associated with HPV-16 E6- and E7-positive (OR 28.197, 95% Cl: 2.658-299.110; OR 19.617, 95% Cl: 2.135-180.253, respectively), whereas TNF-alpha, IL-6, and IL-10 were not associated with HPV- 16 E6 and ET In multiple regression analysis, elevated IFN-gamma was significantly associated with increased HPV viral load (P=0.039), whereas TNF-alpha, IL-6, and IL-10 were not significantly associated with HPV viral load. Conclusions. Among HPV-infected women, IFN-gamma is significantly associated with HPV- 16 E6, E7, and high-risk HPV viral load in the uterine cervix. Thus, increased intralesional TFN-gamma may be considered to be a prognostic marker for oncogenic potential of high-risk HPV (c) 2006 Elsevier Inc. All rights reserved.