Smoking and subsequent human papillomavirus infection: a mediation analysis

• Published in: Annals of epidemiology 2017-11, Vol.27 (11), p.724-730.e1
• Main Authors: Eldridge, Ronald C., Pawlita, Michael, Wilson, Lauren, Castle, Philip E., Waterboer, Tim, Gravitt, Patti E., Schiffman, Mark, Wentzensen, Nicolas
• Format: Article
• Language: English
• Subjects: Adult; Antibodies; Case-Control Studies; Female; HPV; Human papillomavirus; Human papillomavirus 16; Humans; Indirect effect; Mechanism; Mediation; Middle Aged; Papillomavirus Infections - complications; Papillomavirus Infections - diagnosis; Papillomavirus Infections - epidemiology; Risk Factors; Smoking; Smoking - adverse effects; Smoking - epidemiology; Uterine Cervical Neoplasms - epidemiology; Uterine Cervical Neoplasms - etiology
• ISSN: 1047-2797; 1873-2585
• DOI: 10.1016/j.annepidem.2017.10.004

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. 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. 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). 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.