Smoking Is a Risk Factor for Cervical Intraepithelial Neoplasia Grade 3 among Oncogenic Human Papillomavirus DNA–Positive Women with Equivocal or Mildly Abnormal Cytology

doi:10.1158/1055-9965.EPI-04-0918

Smoking Is a Risk Factor for Cervical Intraepithelial Neoplasia Grade 3 among Oncogenic Human Papillomavirus DNA–Positive Women with Equivocal or Mildly Abnormal Cytology

¹Magee-Womens Hospital of the University of Pittsburgh Health Care System, Pittsburgh, Pennsylvania; ²Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland; and ³Departments 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

Abstract

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 (P_Trend < 0.0005) and duration (P_Trend < 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.

Footnotes

Grant support: National Cancer Institute, NIH, Department of Health and Human Services contracts CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, and CN-55105.
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Note: The ALTS Group: D. Solomon, Project Officer; M. Schiffman, Co-Project Officer; P. Castle; S. Wacholder, Statistician (National Cancer Institute, Bethesda MD). Clinical Centers: E.E. Partridge, Principal Investigator; L. Kilgore, Co-Principal Investigator; S. Hester, Study Manager (University of Alabama at Birmingham, AL). J.L. Walker, Principal Investigator; G.A. Johnson, Co-Principal Investigator; A.Yadack, Study Manager (University of Oklahoma, Oklahoma City, OK). R.S. Guido, Principal Investigator; K. McIntyre-Seltman, Co-Principal Investigator; R.P. Edwards, Investigator; J. Gruss, Study Manager (Magee-Womens Hospital of the University of Pittsburgh Medical Center Health System, Pittsburgh, PA). N.B. Kiviat, Co-Principal Investigator; L. Koutsky, Co-Principal Investigator; C. Mao, Investigator; J.M. Haug, Study Manager (University of Washington, Seattle, WA). Colposcopy Quality Control Group: D. Ferris, Principal Investigator (Medical College of Georgia, Augusta, GA); J.T. Cox, Co-Investigator (University of California at Santa Barbara, Santa Barbara, CA); L. Burke, Co-Investigator (Beth Israel Deaconess Medical Center Hospital, Boston, MA). HPV Quality Control Group: C.M. Wheeler, Principal Investigator (University of New Mexico Health Sciences Center, Albuquerque, NM); C. Peyton-Goodall, Lab Manager (University of New Mexico Health Sciences Center, Albuquerque, NM); M.M. Manos, Co-Investigator (Kaiser Permanente, Oakland, CA). Pathology Quality Control Group: R.J. Kurman, Principal Investigator (Johns Hopkins Hospital, Baltimore, MD); D.L. Rosenthal, Co-Investigator (Johns Hopkins Hospital, Baltimore, MD); M.E. Sherman, Co-Investigator (The National Cancer Institute, Rockville, MD); M.H. Stoler, Co-Investigator (University of Virginia Health Science Center, Charlottesville, VA). Westat, Coordinating Unit, Rockville, MD: J. Rosenthal, Project Director; M. Dunn, Data Management Team Leader; J. Quarantillo, Senior Systems Analyst; D. Robinson, Clinical Center Coordinator; Quality of Life Group: D.M. Harper, Digene Corp., Gaithersburg, MD: A.T. Lorincz, Senior Scientific Officer. Information Management Services, Inc., Silver Spring, MD: B. Kramer, Senior Programmer/Analyst.
- Accepted February 11, 2005.
- Received December 15, 2004.
- Revision received January 18, 2005.