title: Assessment of human papillomavirus in lung tumor tissue.
abstract: BACKGROUND
  Lung cancer kills more than 1 million people worldwide each year. Whereas several human papillomavirus (HPV)-associated cancers have been identified, the role of HPV in lung carcinogenesis remains controversial.
  
  
  METHODS
  We selected 450 lung cancer patients from an Italian population-based case-control study, the Environment and Genetics in Lung Cancer Etiology. These patients were selected from those with an adequate number of unstained tissue sections and included all those who had never smoked and a random sample of the remaining patients. We used real-time polymerase chain reaction (PCR) to test specimens from these patients for HPV DNA, specifically for E6 gene sequences from HPV16 and E7 gene sequences from HPV18. We also tested a subset of 92 specimens from all never-smokers and a random selection of smokers for additional HPV types by a PCR-based test for at least 54 mucosal HPV genotypes. DNA was extracted from ethanol- or formalin-fixed paraffin-embedded tumor tissue under strict PCR clean conditions. The prevalence of HPV in tumor tissue was investigated.
  
  
  RESULTS
  Specimens from 399 of 450 patients had adequate DNA for analysis. Most patients were current (220 patients or 48.9%) smokers, and 92 patients (20.4%) were women. When HPV16 and HPV18 type-specific primers were used, two specimens were positive for HPV16 at low copy number but were negative on additional type-specific HPV16 testing. Neither these specimens nor the others examined for a broad range of HPV types were positive for any HPV type.
  
  
  CONCLUSIONS
  When DNA contamination was avoided and state-of-the-art highly sensitive HPV DNA detection assays were used, we found no evidence that HPV was associated with lung cancer in a representative Western population. Our results provide the strongest evidence to date to rule out a role for HPV in lung carcinogenesis in Western populations.
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7248, USA. koshiolj@mail.nih.gov
authors.forename: Jill
authors.initials: J
authors.lastname: Koshiol
authors.forename: Melissa
authors.initials: M
authors.lastname: Rotunno
authors.forename: Maura L
authors.initials: ML
authors.lastname: Gillison
authors.forename: Leen-Jan
authors.initials: LJ
authors.lastname: Van Doorn
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chaturvedi
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.forename: Hebin
authors.initials: H
authors.lastname: Song
authors.forename: Wim G V
authors.initials: WG
authors.lastname: Quint
authors.forename: Linda
authors.initials: L
authors.lastname: Struijk
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Pietro Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
mesh_terms: D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D014412:Tumor Virus Infections / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins