title: Synergy between cigarette smoking and human papillomavirus type 16 in cervical cancer in situ development.
abstract: BACKGROUND
  A majority of studies have implicated the involvement of cigarette smoking in cervical cancer development, although its mechanism of action remains unclear. We conducted a large population-based case-control study to address the potential interaction between smoking and human papillomavirus type 16 (HPV-16) in development of cervical cancer in situ (CIS).
  
  
  METHODS
  Information on risk factors for CIS was collected via interview, and archival cervical smears were tested for HPV-16 DNA presence in cases (n = 375) and controls (n = 363). Adjusted odds ratios (OR) for the effects of smoking, HPV-16 presence/absence, and load at first smear (taken, on average, 9 years before diagnosis) were calculated.
  
  
  RESULTS
  The risk for CIS among current smokers who were HPV-16 positive at time of first smear was >14-fold [adjusted OR, 14.4; confidence interval (95% CI), 5.6-36.8] compared with HPV-16-negative current smokers. In contrast, the risk for CIS among HPV-16-positive nonsmokers was only 6-fold (adjusted OR, 5.6; 95% CI, 2.7-11.5), compared with HPV-16-negative nonsmokers. HPV-16-positive smokers with high viral load at time of first smear exhibited a high risk for CIS (adjusted OR, 27.0; 95% CI, 6.5-114.2) compared with HPV-16-negative smokers. Within nonsmokers, however, high HPV-16 load contributed only a 6-fold increased risk compared with HPV-16-negative nonsmokers (adjusted OR, 5.9; 95% CI, 2.4-14.6). Interaction was observed (P = 0.03) between duration of smoking and HPV-16 presence in CIS development.
  
  
  CONCLUSIONS
  Results suggest a synergistic effect between smoking and both HPV-16 status and HPV-16 viral load, which may occur almost a decade before CIS detection.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, P.O. Box 281, 171 77 Stockholm, Sweden. anthony.gunnell@ki.se
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Gunnell
authors.forename: Trung N
authors.initials: TN
authors.lastname: Tran
authors.forename: Anna
authors.initials: A
authors.lastname: Torrång
authors.forename: Paul W
authors.initials: PW
authors.lastname: Dickman
authors.forename: Pär
authors.initials: P
authors.lastname: Sparén
authors.forename: Juni
authors.initials: J
authors.lastname: Palmgren
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ylitalo
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000150:complications*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000821:virology*; D019562:Viral Load