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1 Magee-Womens Hospital of the University of Pittsburgh Health Care System, Pittsburgh, Pennsylvania; 2 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland; and 3 Departments of Molecular Genetics and Microbiology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center, School of Medicine, Albuquerque, New Mexico
Requests for reprints: Philip E. Castle, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Room 7074, 6120 Executive Boulevard, EPS MSC 7234, Bethesda, MD 20892-7234. Phone: 301-435-3976; Fax: 301-402-091. E-mail: castlep{at}mail.nih.gov
Background: Smoking is a potential risk factor for cervical cancer and its immediate precursor, cervical intraepithelial neoplasia grade 3 (CIN3), but few studies have adequately taken into account the possible confounding effect of oncogenic human papillomavirus (HPV) infection.
Methods: Women (n = 5,060) with minimally abnormal Papanicolaou smears were enrolled in the ASCUS and LSIL Triage Study, a clinical trial to evaluate management strategies, and were seen every 6 months for the 2-year duration of the study. Cervical specimens were tested for HPV DNA using both Hybrid Capture 2 and PGMY09/11 L1 consensus primer PCR with reverse line blot hybridization for genotyping. Multivariate logistics regression models were used to assess associations [odds ratio (OR) with 95% confidence intervals (95% CI)] between smoking behaviors and rigorously reviewed cases of cervical intraepithelial neoplasia grade 3 or cancer (
CIN3) identified throughout the study (n = 506) in women with oncogenic HPV (n = 3,133).
Results: Current smoking was only weakly associated with increased HPV infection. Among infected women, current smokers (OR, 1.7; 95% CI, 1.4-2.1) and past smokers (OR, 1.7; 95% CI, 1.2-2.4) were more likely to be diagnosed with
CIN3 than nonsmokers. Greater smoking intensity (PTrend < 0.0005) and duration (PTrend < 0.0005) increased the strength of the association, with smoking
2 packs/d (OR, 3.3; 95% CI, 1.5-7.5) and smoking for
11 years (OR, 2.1; 95% CI, 1.5-2.9) most strongly associated with
CIN3 as compared to non-smokers. The effects of intensity and duration seemed additive.
Conclusions: Women with oncogenic HPV and minimally abnormal Papanicolaou smears who smoke were up to three times more likely to be diagnosed with
CIN3 than nonsmokers. Smoking cessation trials targeting this population might be warranted.
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