Smoking and subsequent human papillomavirus infection: A mediation analysis

Ronald C. Eldridge, Michael Pawlita, Lauren Wilson, Philip E. Castle, Tim Waterboer, Patti E. Gravitt, Philip E. Castle, Nicolas Wentzensen

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose: Smoking is an established risk factor for a human papillomavirus (HPV) infection advancing to cervical precancer and cancer, but its role earlier in the natural history is less clear. Smoking is inversely associated with possessing HPV antibodies from a past infection suggesting that smoking may influence acquiring subsequent infections. Methods: In a cohort of 1976 U.S. women, we evaluate whether reduced antibodies to HPV-16 is a mechanism for smoking's role on acquiring a subsequent HPV-16 infection, through the analytic technique of causal mediation analysis. We posit a causal model and estimate two counterfactually defined effects: a smoking impaired antibody-mediated indirect effect and a nonmediated direct effect representing all other potential mechanisms of smoking. Results: Compared to never smokers, current smokers had increased odds of HPV-16 infection by the antibody-mediated indirect effect (odds ratio [OR] = 1.29; 95% confidence interval [CI]: 1.11, 1.73); the estimated direct effect was very imprecise (OR = 0.57; 95% CI, 0.26-1.13). We observed a stronger estimated indirect effect among women who smoked at least half a pack of cigarettes daily (OR = 1.61, 95% CI, 1.27-2.15) than among women who smoked less than that threshold (OR = 1.09; 95% CI, 0.94-1.44). Conclusions: This is the first study to directly test the mechanism underlying smoking as an HPV cofactor. The results support current smoking as a risk factor earlier in the natural history of HPV and are consistent with the hypothesis that smoking increases the risk of a subsequent infection by reducing immunity.

Original languageEnglish (US)
JournalAnnals of Epidemiology
DOIs
StateAccepted/In press - 2017

Fingerprint

Papillomavirus Infections
Smoking
Human papillomavirus 16
Odds Ratio
Confidence Intervals
Antibodies
Natural History
Infection
Tobacco Products
Uterine Cervical Neoplasms
Immunity

Keywords

  • Antibodies
  • HPV
  • Human papillomavirus
  • Indirect effect
  • Mechanism
  • Mediation
  • Smoking

ASJC Scopus subject areas

  • Epidemiology

Cite this

Eldridge, R. C., Pawlita, M., Wilson, L., Castle, P. E., Waterboer, T., Gravitt, P. E., ... Wentzensen, N. (Accepted/In press). Smoking and subsequent human papillomavirus infection: A mediation analysis. Annals of Epidemiology. https://doi.org/10.1016/j.annepidem.2017.10.004

Smoking and subsequent human papillomavirus infection : A mediation analysis. / Eldridge, Ronald C.; Pawlita, Michael; Wilson, Lauren; Castle, Philip E.; Waterboer, Tim; Gravitt, Patti E.; Castle, Philip E.; Wentzensen, Nicolas.

In: Annals of Epidemiology, 2017.

Research output: Contribution to journalArticle

Eldridge, Ronald C. ; Pawlita, Michael ; Wilson, Lauren ; Castle, Philip E. ; Waterboer, Tim ; Gravitt, Patti E. ; Castle, Philip E. ; Wentzensen, Nicolas. / Smoking and subsequent human papillomavirus infection : A mediation analysis. In: Annals of Epidemiology. 2017.
@article{9f94d98c0b5f4b31b8775f9d37c706f7,
title = "Smoking and subsequent human papillomavirus infection: A mediation analysis",
abstract = "Purpose: Smoking is an established risk factor for a human papillomavirus (HPV) infection advancing to cervical precancer and cancer, but its role earlier in the natural history is less clear. Smoking is inversely associated with possessing HPV antibodies from a past infection suggesting that smoking may influence acquiring subsequent infections. Methods: In a cohort of 1976 U.S. women, we evaluate whether reduced antibodies to HPV-16 is a mechanism for smoking's role on acquiring a subsequent HPV-16 infection, through the analytic technique of causal mediation analysis. We posit a causal model and estimate two counterfactually defined effects: a smoking impaired antibody-mediated indirect effect and a nonmediated direct effect representing all other potential mechanisms of smoking. Results: Compared to never smokers, current smokers had increased odds of HPV-16 infection by the antibody-mediated indirect effect (odds ratio [OR] = 1.29; 95{\%} confidence interval [CI]: 1.11, 1.73); the estimated direct effect was very imprecise (OR = 0.57; 95{\%} CI, 0.26-1.13). We observed a stronger estimated indirect effect among women who smoked at least half a pack of cigarettes daily (OR = 1.61, 95{\%} CI, 1.27-2.15) than among women who smoked less than that threshold (OR = 1.09; 95{\%} CI, 0.94-1.44). Conclusions: This is the first study to directly test the mechanism underlying smoking as an HPV cofactor. The results support current smoking as a risk factor earlier in the natural history of HPV and are consistent with the hypothesis that smoking increases the risk of a subsequent infection by reducing immunity.",
keywords = "Antibodies, HPV, Human papillomavirus, Indirect effect, Mechanism, Mediation, Smoking",
author = "Eldridge, {Ronald C.} and Michael Pawlita and Lauren Wilson and Castle, {Philip E.} and Tim Waterboer and Gravitt, {Patti E.} and Castle, {Philip E.} and Nicolas Wentzensen",
year = "2017",
doi = "10.1016/j.annepidem.2017.10.004",
language = "English (US)",
journal = "Annals of Epidemiology",
issn = "1047-2797",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Smoking and subsequent human papillomavirus infection

T2 - A mediation analysis

AU - Eldridge, Ronald C.

AU - Pawlita, Michael

AU - Wilson, Lauren

AU - Castle, Philip E.

AU - Waterboer, Tim

AU - Gravitt, Patti E.

AU - Castle, Philip E.

AU - Wentzensen, Nicolas

PY - 2017

Y1 - 2017

N2 - Purpose: Smoking is an established risk factor for a human papillomavirus (HPV) infection advancing to cervical precancer and cancer, but its role earlier in the natural history is less clear. Smoking is inversely associated with possessing HPV antibodies from a past infection suggesting that smoking may influence acquiring subsequent infections. Methods: In a cohort of 1976 U.S. women, we evaluate whether reduced antibodies to HPV-16 is a mechanism for smoking's role on acquiring a subsequent HPV-16 infection, through the analytic technique of causal mediation analysis. We posit a causal model and estimate two counterfactually defined effects: a smoking impaired antibody-mediated indirect effect and a nonmediated direct effect representing all other potential mechanisms of smoking. Results: Compared to never smokers, current smokers had increased odds of HPV-16 infection by the antibody-mediated indirect effect (odds ratio [OR] = 1.29; 95% confidence interval [CI]: 1.11, 1.73); the estimated direct effect was very imprecise (OR = 0.57; 95% CI, 0.26-1.13). We observed a stronger estimated indirect effect among women who smoked at least half a pack of cigarettes daily (OR = 1.61, 95% CI, 1.27-2.15) than among women who smoked less than that threshold (OR = 1.09; 95% CI, 0.94-1.44). Conclusions: This is the first study to directly test the mechanism underlying smoking as an HPV cofactor. The results support current smoking as a risk factor earlier in the natural history of HPV and are consistent with the hypothesis that smoking increases the risk of a subsequent infection by reducing immunity.

AB - Purpose: Smoking is an established risk factor for a human papillomavirus (HPV) infection advancing to cervical precancer and cancer, but its role earlier in the natural history is less clear. Smoking is inversely associated with possessing HPV antibodies from a past infection suggesting that smoking may influence acquiring subsequent infections. Methods: In a cohort of 1976 U.S. women, we evaluate whether reduced antibodies to HPV-16 is a mechanism for smoking's role on acquiring a subsequent HPV-16 infection, through the analytic technique of causal mediation analysis. We posit a causal model and estimate two counterfactually defined effects: a smoking impaired antibody-mediated indirect effect and a nonmediated direct effect representing all other potential mechanisms of smoking. Results: Compared to never smokers, current smokers had increased odds of HPV-16 infection by the antibody-mediated indirect effect (odds ratio [OR] = 1.29; 95% confidence interval [CI]: 1.11, 1.73); the estimated direct effect was very imprecise (OR = 0.57; 95% CI, 0.26-1.13). We observed a stronger estimated indirect effect among women who smoked at least half a pack of cigarettes daily (OR = 1.61, 95% CI, 1.27-2.15) than among women who smoked less than that threshold (OR = 1.09; 95% CI, 0.94-1.44). Conclusions: This is the first study to directly test the mechanism underlying smoking as an HPV cofactor. The results support current smoking as a risk factor earlier in the natural history of HPV and are consistent with the hypothesis that smoking increases the risk of a subsequent infection by reducing immunity.

KW - Antibodies

KW - HPV

KW - Human papillomavirus

KW - Indirect effect

KW - Mechanism

KW - Mediation

KW - Smoking

UR - http://www.scopus.com/inward/record.url?scp=85032259284&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032259284&partnerID=8YFLogxK

U2 - 10.1016/j.annepidem.2017.10.004

DO - 10.1016/j.annepidem.2017.10.004

M3 - Article

C2 - 29107447

AN - SCOPUS:85032259284

JO - Annals of Epidemiology

JF - Annals of Epidemiology

SN - 1047-2797

ER -