title: Association of serum cytokines with oral HPV clearance.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  High serum TNF-α is associated with reduced clearance of oral HPV infection.
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Jennifer O
authors.initials: JO
authors.lastname: Lam
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Bream
authors.affiliation: 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.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sugar
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Christian L
authors.initials: CL
authors.lastname: Coles
authors.affiliation: Hektoen Institute of Medicine, The CORE Center at John H. Stroger Jr. Hospital of Cook County, Chicago, IL, United States.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Weber
authors.affiliation: Departments of Pediatrics, Microbiology and Immunology, and Obstetrics, Gynecology and Women's Health, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
authors.affiliation: School of Nursing, University of California Los Angeles, Los Angeles, CA, United States.
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Wiley
authors.affiliation: School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Ross D
authors.initials: RD
authors.lastname: Cranston
authors.affiliation: Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
authors.forename: Susheel
authors.initials: S
authors.lastname: Reddy
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.affiliation: Departments of Epidemiology and Population Health, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Alicia
authors.initials: A
authors.lastname: Wentz
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Jacobson
authors.affiliation: Ohio State University Comprehensive Cancer Center, Columbus, OH, United States.
authors.forename: Yingshi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Ohio State University Comprehensive Cancer Center, Columbus, OH, United States.
authors.forename: Weihong
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Ohio State University Comprehensive Cancer Center, Columbus, OH, United States.
authors.forename: Maura L
authors.initials: ML
authors.lastname: Gillison
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. Electronic address: gdsouza2@jhu.edu.
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009059:Mouth Diseases / Q000097:blood*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000097:blood*
chemical_list: D016207:Cytokines
keywords: Infection; Natural history; Oral HPV; Persistence; TNF