HPV-associated lung cancers: an international pooled analysis

Carcinogenesis. 2014 Jun;35(6):1267-75. doi: 10.1093/carcin/bgu038. Epub 2014 Feb 12.

Abstract

Human papillomavirus (HPV) is the etiologic risk factor for cervical cancer. Some studies have suggested an association with a subset of lung tumors, but the etiologic link has not been firmly established. We performed an international pooled analysis of cross-sectional studies (27 datasets, n = 3249 patients) to evaluate HPV DNA prevalence in lung cancer and to investigate viral presence according to clinical and demographic characteristics. HPV16/18 were the most commonly detected, but with substantial variation in viral prevalence between geographic regions. The highest prevalence of HPV16/18 was observed in South and Central America, followed by Asia, North America and Europe (adjusted prevalence rates = 22, 5, 4 and 3%, respectively). Higher HPV16 prevalence was noted in each geographic region compared with HPV18, except in North America. HPV16/18-positive lung cancer was less likely observed among White race (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.12-0.90), whereas no associations were observed with gender, smoking history, age, histology or stage. Comparisons between tumor and normal lung tissue show that HPV was more likely to be present in lung cancer rather than normal lung tissues (OR = 3.86, 95% CI = 2.87-5.19). Among a subset of patients with HPV16-positive tumors, integration was primarily among female patients (93%, 13/14), while the physical status in male cases (N = 14) was inconsistent. Our findings confirm that HPV DNA is present in a small fraction of lung tumors, with large geographic variations. Further comprehensive analysis is needed to assess whether this association reflects a causal relationship.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alphapapillomavirus / genetics*
  • Female
  • Genotype
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 18 / genetics
  • Humans
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / virology
  • Male
  • Middle Aged
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / epidemiology
  • Prevalence
  • Virus Integration