Molecular evidence of viral DNA in non-small cell lung cancer and non-neoplastic lung

Br J Cancer. 2016 Aug 9;115(4):497-504. doi: 10.1038/bjc.2016.213. Epub 2016 Jul 14.

Abstract

Background: Although ∼20% of human cancers are caused by microorganisms, only suspicion exists for a microbial cause of lung cancer. Potential infectious agents were investigated in non-small cell lung cancer (NSCLC) and non-neoplastic lung.

Methods: Seventy NSCLC tumours (33 squamous cell carcinomas, 17 adenocarcinomas, 10 adenocarcinomas with lepidic spread, and 10 oligometastases) and 10 non-neoplastic lung specimens were evaluated for molecular evidence of microorganisms. Tissues were subjected to the Lawrence Livermore Microbial Detection Array, an oncovirus panel of the International Agency for Research on Cancer, and human papillomavirus (HPV) genotyping. Associations were examined between microbial prevalence, clinical characteristics, and p16 and EGFR expression.

Results: Retroviral DNA was observed in 85% squamous cell carcinomas, 47% adenocarcinomas, and 10% adenocarcinomas with lepidic spread. Human papillomavirus DNA was found in 69% of squamous cell carcinomas with 30% containing high-risk HPV types. No significant viral DNA was detected in non-neoplastic lung. Patients with tumours containing viral DNA experienced improved long-term survival compared with patients with viral DNA-negative tumours.

Conclusions: Most squamous cell carcinomas and adenocarcinomas contained retroviral DNA and one-third of squamous cell carcinomas contained high-risk HPV DNA. Viral DNA was absent in non-neoplastic lung. Trial results encourage further study of the viral contribution to lung carcinogenesis.

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / virology*
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / complications
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / virology*
  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / virology*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA, Viral / analysis*
  • ErbB Receptors / metabolism
  • Female
  • Genotype
  • Humans
  • Lung / metabolism
  • Lung / virology*
  • Lung Neoplasms / complications
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / virology*
  • Male
  • Middle Aged
  • Oncogenic Viruses / genetics
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / virology
  • Polymerase Chain Reaction
  • Retroviridae / genetics*
  • Retroviridae Infections / complications
  • Retroviridae Infections / metabolism
  • Retroviridae Infections / virology
  • Tumor Virus Infections / complications
  • Tumor Virus Infections / metabolism
  • Tumor Virus Infections / virology

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • EGFR protein, human
  • ErbB Receptors