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 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 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% CI: 2.658-299.110; OR 19.617, 95% CI: 2.135-180.253, respectively), whereas TNF-alpha, IL-6, and IL-10 were not associated with HPV-16 E6 and E7. 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 IFN-gamma may be considered to be a prognostic marker for oncogenic potential of high-risk HPV.
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 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), tumornecrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) transcripts. RESULTS: Among high-risk HPV-infectedwomen, 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% CI: 2.658-299.110; OR 19.617, 95% CI: 2.135-180.253, respectively), whereas TNF-alpha, IL-6, and IL-10 were not associated with HPV-16 E6 and E7. 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-infectedwomen, IFN-gamma is significantly associated with HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix. Thus, increased intralesional IFN-gamma may be considered to be a prognostic marker for oncogenic potential of high-risk HPV.
Authors: Kai-Erik Uleberg; Ane Cecilie Munk; Ivar Skaland; Cristina Furlan; Bianca van Diermen; Einar Gudlaugsson; Emiel A M Janssen; Anais Malpica; Weiwei Feng; Anne Hjelle; Jan P A Baak Journal: Cell Oncol (Dordr) Date: 2011-05-15 Impact factor: 6.730