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

ObjectivesTo 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.MethodsWe performed a prospective study of 67 patients between May 2005 and December 2005. Hybrid Capture II 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 α (TNF-α), and interferon γ (IFN-γ) transcripts.ResultsAmong high-risk HPV-infected women, intralesional TNF-α, IL-6, IL-10, and IFN-γ levels had no significant differences according to histologic grade. In multivariate logistic regression analysis, TNF-α, IL-6, IL-10, and IFN-γ were not associated with HPV-16. Increased IFN-γ was significantly associated with HPV-16 E6- and E7-positive (OR 28.197, 95% CI: 2.658–299.110; OR 19.617, 95% CI: 2.135–180.253, respectively), whereas TNF-α, IL-6, and IL-10 were not associated with HPV-16 E6 and E7. In multiple regression analysis, elevated IFN-γ was significantly associated with increased HPV viral load (P = 0.039), whereas TNF-α, IL-6, and IL-10 were not significantly associated with HPV viral load.ConclusionsAmong HPV-infected women, IFN-γ is significantly associated with HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix. Thus, increased intralesional IFN-γ may be considered to be a prognostic marker for oncogenic potential of high-risk HPV.