title: A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women.
abstract: BACKGROUND
  In case-control studies, smoking, parity, and oral contraceptive use have been associated with an increased risk of cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer among women who are infected with oncogenic human papillomavirus (HPV). However, these potential risk factors have not been adequately studied in prospective studies.
  
  
  METHODS
  We studied 1812 women who were enrolled in a 10-year prospective study of cervical neoplasia at Kaiser Permanente in Portland, Oregon, and who at enrollment had tested positive for oncogenic HPV DNA and had responded to a questionnaire that included questions on smoking, oral contraceptive use, and parity. Absolute risks and crude relative risks (RRs) with 95% confidence intervals (CIs) for CIN3 or cervical cancer were computed for three time intervals (0-8, 9-68, and 69-122 months after enrollment) using the Kaplan-Meier method. Conditional logistic regression models were used to control for factors that may have influenced our risk estimates, specifically the cytologic interpretation of baseline Pap smear, number of Pap smears during follow-up, age at enrollment, age at prediagnosis visit, and age at diagnosis. All statistical tests were two-sided.
  
  
  RESULTS
  Oral contraceptive use and parity were not associated with risk of CIN3 or cervical cancer. Former smokers, women who smoked less than one pack of cigarettes per day, and women who smoked one or more packs per day had crude RRs for CIN3 or cervical cancer for the entire follow-up period of 2.1 (95% CI = 1.1 to 3.9), 2.2 (95% CI = 1.2 to 4.2), and 2.9 (95% CI = 1.5 to 5.6), respectively, compared with never smokers. In the multivariable model, former smokers, women who smoked less than one pack/day, and women who smoked one or more packs/day had RRs of 3.3 (95% CI = 1.6 to 6.7), 2.9 (95% CI = 1.4 to 6.1), and 4.3 (95% CI = 2.0 to 9.3), respectively, for CIN3 or cervical cancer compared with never smokers.
  
  
  CONCLUSIONS
  Smoking is associated with an increased risk of invasive cervical cancer in women who are infected with oncogenic HPV. Subsequent studies should examine the role of smoking in the multistage pathogenesis of cervical cancer.
authors.affiliation: National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD 20892, USA. castlep@mail.nih.gov
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Attila T
authors.initials: AT
authors.lastname: Lorincz
authors.forename: David R
authors.initials: DR
authors.lastname: Scott
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Glass
authors.forename: Brenda B
authors.initials: BB
authors.lastname: Rush
authors.forename: John E
authors.initials: JE
authors.lastname: Schussler
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004279:DNA, Viral / Q000302:isolation & purification; D018450:Disease Progression; D005260:Female; D006801:Humans; D065006:Papanicolaou Test; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications* / Q000503:physiopathology; D011247:Pregnancy; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking; D013997:Time Factors; D014412:Tumor Virus Infections / Q000150:complications* / Q000503:physiopathology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000821:virology; D014626:Vaginal Smears
chemical_list: D004279:DNA, Viral