Abstract 852: Smoking and HPV antibodies, a mediation analysis of HPV re-infection
Authors: Eldridge Ronald C. , Pawlita Michael , Wilson Lauren , Castle Philip E. , Waterboer Tim , Gravitt Patti E. , Schiffman Mark , Wentzensen Nicolas 
Published: August 2015

Abstract
Background: Naturally acquired antibodies against human papillomavirus (HPV) infection can protect against recurring infection. Smoking can adversely affect a person's immune response, both adaptive and innate systems; and it is also associated with increased risk of HPV-related precancers. But, it is unclear whether smoking results in higher HPV incidence because of an impaired immune response.
Objective: We investigated whether lowered HPV-16 antibody titers mediates the effect of smoking on incident HPV-16 infection.
Methods: We used a path analytic model where smoking lowers a person's antibody titer, thereby resulting in a higher risk of acquiring an incident re-infection. The model estimated the indirect effect of smoking to infection, mediated by antibodies; it also estimated the direct effect, which is not mediated. The path model includes two logistic equations with effects and confidence intervals estimated by parametric bootstrapping. Both equations were adjusted for age, age at sexual initiation, lifetime number of sexual partners, and ever diagnosis of a sexually transmitted infection other than HPV.
Study Population: A subset of women in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study provided blood samples at baseline. The samples were assessed for HPV antibodies using a multiplex Luminex assay. Smoking and sexual habits were assessed by a baseline questionnaire. During two years of follow-up, bi-annual cervical specimens were genotyped for HPV by PCR assays. The analytic population (n = 1,978) were women without a cervical intraepithelial lesion grade 2 or more severe and HPV-16 DNA negative at baseline. Among those women, 131 tested HPV-16 DNA positive during follow-up.
Results: Compared to never smokers, current smokers had an increased risk of incident HPV-16 infection by the antibody mediated pathway (OR = 1.24, 95% CI: 1.08, 1.60); the direct effect was non-significant. For former smokers, neither direct nor indirect effects were significant. The indirect effect of current smoking increased for women who smoked at least half a pack of cigarettes daily (OR = 1.47, 95% CI: 1.20, 2.02).
Conclusions: This is the first analytic model to suggest that current smoking increases the risk of incident HPV-16 infection through a reduction of HPV-16 antibody titers. The association appears dose-dependent, increasing for number of cigarettes smoked per day. Because our follow-up time was limited, we could not measure, and thus, extend these results to incident precancer outcomes.
Citation Format: Ronald C. Eldridge, Michael Pawlita, Lauren Wilson, Philip E. Castle, Tim Waterboer, Patti E. Gravitt, Mark Schiffman, Nicolas Wentzensen. Smoking and HPV antibodies, a mediation analysis of HPV re-infection. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 852. doi:10.1158/1538-7445.AM2015-852