Smoking and subsequent human papillomavirus infection: a mediation analysis

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

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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)
Pages (from-to)724-730.e1
JournalAnnals of Epidemiology
Issue number11
StatePublished - Nov 2017


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

ASJC Scopus subject areas

  • Epidemiology


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