Association of serum cytokines with oral HPV clearance

Jennifer O. Lam, Jay H. Bream, Elizabeth A. Sugar, Christian L. Coles, Kathleen M. Weber, Robert D. Burk, Dorothy J. Wiley, Ross D. Cranston, Susheel Reddy, Joseph B. Margolick, Howard D. Strickler, Alicia Wentz, Lisa Jacobson, Yingshi Guo, Weihong Xiao, Maura L. Gillison, Gypsyamber D'Souza

Research output: Research - peer-reviewArticle

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.

LanguageEnglish (US)
Pages85-91
Number of pages7
JournalCytokine
Volume83
DOIs
StatePublished - Jul 1 2016

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Cytokines
Serum
Hazards
Tumor Necrosis Factor-alpha
T-cells
Interleukin-2
Papillomavirus Infections
Confidence Intervals
HIV
T-Lymphocytes
Interleukin-13
Interleukin-12
Interleukin-8
Interleukin-4
Interleukin-10
Interleukin-6
Assays
DNA
CD4 Lymphocyte Count
Polymerase Chain Reaction

Keywords

  • Infection
  • Natural history
  • Oral HPV
  • Persistence
  • TNF

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

Cite this

Association of serum cytokines with oral HPV clearance. / Lam, Jennifer O.; Bream, Jay H.; Sugar, Elizabeth A.; Coles, Christian L.; Weber, Kathleen M.; Burk, Robert D.; Wiley, Dorothy J.; Cranston, Ross D.; Reddy, Susheel; Margolick, Joseph B.; Strickler, Howard D.; Wentz, Alicia; Jacobson, Lisa; Guo, Yingshi; Xiao, Weihong; Gillison, Maura L.; D'Souza, Gypsyamber.

In: Cytokine, Vol. 83, 01.07.2016, p. 85-91.

Research output: Research - peer-reviewArticle

Lam, JO, Bream, JH, Sugar, EA, Coles, CL, Weber, KM, Burk, RD, Wiley, DJ, Cranston, RD, Reddy, S, Margolick, JB, Strickler, HD, Wentz, A, Jacobson, L, Guo, Y, Xiao, W, Gillison, ML & D'Souza, G 2016, 'Association of serum cytokines with oral HPV clearance' Cytokine, vol 83, pp. 85-91. DOI: 10.1016/j.cyto.2016.04.002
Lam JO, Bream JH, Sugar EA, Coles CL, Weber KM, Burk RD et al. Association of serum cytokines with oral HPV clearance. Cytokine. 2016 Jul 1;83:85-91. Available from, DOI: 10.1016/j.cyto.2016.04.002
Lam, Jennifer O. ; Bream, Jay H. ; Sugar, Elizabeth A. ; Coles, Christian L. ; Weber, Kathleen M. ; Burk, Robert D. ; Wiley, Dorothy J. ; Cranston, Ross D. ; Reddy, Susheel ; Margolick, Joseph B. ; Strickler, Howard D. ; Wentz, Alicia ; Jacobson, Lisa ; Guo, Yingshi ; Xiao, Weihong ; Gillison, Maura L. ; D'Souza, Gypsyamber. / Association of serum cytokines with oral HPV clearance. In: Cytokine. 2016 ; Vol. 83. pp. 85-91
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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.",
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AU - Burk,Robert D.

AU - Wiley,Dorothy J.

AU - Cranston,Ross D.

AU - Reddy,Susheel

AU - Margolick,Joseph B.

AU - Strickler,Howard D.

AU - Wentz,Alicia

AU - Jacobson,Lisa

AU - Guo,Yingshi

AU - Xiao,Weihong

AU - Gillison,Maura L.

AU - D'Souza,Gypsyamber

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N2 - 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.

AB - 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.

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