title: Detection of human papillomavirus genotypes in bronchial cancer using sensitive multimetrix assay.
abstract: BACKGROUND
  Since first suggested in 1979, evidence on the involvement of human papillomavirus (HPV) in bronchial carcinogenesis has been accumulated through several lines of research. The causal role of HPV in lung cancer still remains controversial, however, and more data are needed particularly on genotype distribution and cofactors of HPV regarding this disease.
  
  
  METHODS
  The present series consists of 77 patients diagnosed and treated for lung cancer at the Department of Respiratory Medicine, Turku University Hospital, (Finland) during 2008-2010. All available histological samples (n=77) were subjected to HPV genotyping with the Luminex-based Multimetrix kit, detecting 24 low-risk (LR) and high-risk (HR) HPV types. Pertinent clinical data were collected and subjected to univariate and multivariate regression analysis to disclose the covariates associated with HPV detection in lung cancer.
  
  
  RESULTS
  Out of 77 histological samples analyzed, four (5.2%) (three squamous cell and one adenocarcinoma) were found to be HPV-positive, out of which three were HPV16 infections and one a double-infection with HPV6 and HPV16. All four patients were males, and all but one reported no asbestos exposure. Three of them had refrained from smoking for a period >22 years. Disease-specific survival was twice as long for individuals with HPV+ than those with HPV- tumors (25.5 vs. 12.8 months), but confounding by treatment cannot be excluded. In univariate analysis, four covariates were significantly associated with HPV detection: i) older age (p=0.003) ii) older age at smoking initiation (p=0.027), iii) fewer years of active smoking (p=0.036), and iv) fewer total pack years (p=0.002). In a multivariate regression model adjusted to all significant covariates, only absolute age was significantly associated with testing as HPV-positive (odds ratio=1.16, 95% confidence interval 1.04-1.39, p=0.008).
  
  
  CONCLUSIONS
  Given the fact that initiation of smoking at an older age, fewer pack years and long smoking abstinence were associated with HPV, it is tempting to speculate that oncogenic HPV can substitute smoking as a risk factor, leading to lung cancer in these patients despite >22 years elapsing since their smoking cessation. In the era of prophylactic HPV vaccination, there is an urgent need to provide more data on the global HPV burden and covariates of the virus associated to lung cancer.
authors.affiliation: FIAC, Department of Oncology and Radiotherapy, Turku University Hospital, Savitehtaankatu 2, FIN-20521 Turku, Finland. kari.syrjanen@tyks.fi
authors.forename: K
authors.initials: K
authors.lastname: Syrjänen
authors.forename: M
authors.initials: M
authors.lastname: Silvoniemi
authors.forename: E
authors.initials: E
authors.lastname: Salminen
authors.forename: T
authors.initials: T
authors.lastname: Vasankari
authors.forename: S
authors.initials: S
authors.lastname: Syrjänen
mesh_terms: D000230:Adenocarcinoma / Q000821:virology*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D001984:Bronchial Neoplasms / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D016022:Case-Control Studies; D015331:Cohort Studies; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000302:isolation & purification; D052163:Human papillomavirus 6 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008175:Lung Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D012044:Regression Analysis; D012907:Smoking
chemical_list: D004279:DNA, Viral