Smoking is a risk factor for cervical intraepithelial neoplasia grade 3 among oncogenic human papillomavirus DNA-positive women with equivocal or mildly abnormal cytology.
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 (> or =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 > or =CIN3 than nonsmokers. Greater smoking intensity (P(Trend) < 0.0005) and duration (P(Trend) < 0.0005) increased the strength of the association, with smoking > or =2 packs/d (OR, 3.3; 95% CI, 1.5-7.5) and smoking for > or =11 years (OR, 2.1; 95% CI, 1.5-2.9) most strongly associated with > or =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 > or =CIN3 than nonsmokers. Smoking cessation trials targeting this population might be warranted.
McIntyre-Seltman
Kathleen
K
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Room 7074, 6120 Executive Boulevard, EPS MSC 7234, Bethesda, MD 20892-7234, USA.
Castle
Philip E
PE
Guido
Richard
R
Schiffman
Mark
M
Wheeler
Cosette M
CM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009367:Neoplasm Staging; D009538:Nicotine / Q000633:toxicity; D009857:Oncogenes; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology*; D014218:Triage; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000821:virology*; D014626:Vaginal Smears / Q000379:methods; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000821:virology*
D004279:DNA, Viral; D009538:Nicotine