Jennifer O Lam1, Jay H Bream2, Elizabeth A Sugar3, Christian L Coles1, Kathleen M Weber4, Robert D Burk5, Dorothy J Wiley6, Ross D Cranston7, Susheel Reddy8, Joseph B Margolick2, Howard D Strickler9, Alicia Wentz10, Lisa Jacobson10, Yingshi Guo11, Weihong Xiao11, Maura L Gillison11, Gypsyamber D'Souza12. 1. Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. 2. Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. 3. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. 4. Hektoen Institute of Medicine, The CORE Center at John H. Stroger Jr. Hospital of Cook County, Chicago, IL, United States. 5. Departments of Pediatrics, Microbiology and Immunology, and Obstetrics, Gynecology and Women's Health, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States. 6. School of Nursing, University of California Los Angeles, Los Angeles, CA, United States. 7. School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States. 8. Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. 9. Departments of Epidemiology and Population Health, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States. 10. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. 11. Ohio State University Comprehensive Cancer Center, Columbus, OH, United States. 12. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. Electronic address: gdsouza2@jhu.edu.
Abstract
BACKGROUND: Initial studies suggest higher serum levels of some pro-inflammatory cytokines may be associated with decreased cervical human papillomavirus (HPV) clearance. However, the relationship of cytokines with oral HPV clearance has not been explored. METHODS: From 2010 to 2014, oral rinse and serum samples were collected semi-annually from 1601 adults. Oral rinse samples were tested for HPV DNA using PCR. Based on oral HPV results, 931 serum samples were selected for cytokine evaluation to include a roughly equal number of prevalent (n=307), incident (n=313), and no oral HPV infections (n=311). Electrochemiluminescence multiplex assays were used to determine the concentrations of IL-6, IL-8, TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-10, IL-12 and IL-13. The relationship between serum cytokine concentrations (categorized into quartiles) and oral HPV clearance was evaluated with Wei-Lin-Weissfeld regression models, adjusting for HPV infection type (prevalent vs. incident), age, HIV status, and CD4 T cell count. RESULTS: Higher TNF-α concentration was associated with decreased clearance in men (highest vs. lowest quartile, adjusted hazard ratio [aHR]=0.52, 95% CI=0.34-0.79) and women (aHR=0.76, 95% confidence interval [CI]=0.55-1.04), with stronger associations in men than women (p-interaction=0.049). Higher IL-2 concentration was associated with reduced clearance in men (aHR=0.69, 95% CI=0.50-0.95), but not women (p-interaction=0.058). Results were similar within CD4 T cell strata (CD4⩾500 or CD4<500 cells/μl) among HIV-infected participants. No other cytokines were associated with clearance. CONCLUSION: High serum TNF-α is associated with reduced clearance of oral HPV infection.
BACKGROUND: Initial studies suggest higher serum levels of some pro-inflammatory cytokines may be associated with decreased cervical human papillomavirus (HPV) clearance. However, the relationship of cytokines with oral HPV clearance has not been explored. METHODS: From 2010 to 2014, oral rinse and serum samples were collected semi-annually from 1601 adults. Oral rinse samples were tested for HPV DNA using PCR. Based on oral HPV results, 931 serum samples were selected for cytokine evaluation to include a roughly equal number of prevalent (n=307), incident (n=313), and no oral HPV infections (n=311). Electrochemiluminescence multiplex assays were used to determine the concentrations of IL-6, IL-8, TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-10, IL-12 and IL-13. The relationship between serum cytokine concentrations (categorized into quartiles) and oral HPV clearance was evaluated with Wei-Lin-Weissfeld regression models, adjusting for HPV infection type (prevalent vs. incident), age, HIV status, and CD4 T cell count. RESULTS: Higher TNF-α concentration was associated with decreased clearance in men (highest vs. lowest quartile, adjusted hazard ratio [aHR]=0.52, 95% CI=0.34-0.79) and women (aHR=0.76, 95% confidence interval [CI]=0.55-1.04), with stronger associations in men than women (p-interaction=0.049). Higher IL-2 concentration was associated with reduced clearance in men (aHR=0.69, 95% CI=0.50-0.95), but not women (p-interaction=0.058). Results were similar within CD4 T cell strata (CD4⩾500 or CD4<500 cells/μl) among HIV-infectedparticipants. No other cytokines were associated with clearance. CONCLUSION: High serum TNF-α is associated with reduced clearance of oral HPV infection.
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