Biological evidence for a causal role of HPV16 in a small fraction of laryngeal squamous cell carcinoma

Br J Cancer. 2013 Jul 9;109(1):172-83. doi: 10.1038/bjc.2013.296. Epub 2013 Jun 18.

Abstract

Background: Human papillomavirus (HPV) is a causal factor in virtually all cervical and a subset of oropharyngeal squamous cell carcinoma (OP-SCC), whereas its role in laryngeal squamous cell carcinoma (L-SCC) is unclear.

Methods: Formalin-fixed paraffin-embedded (N=154) and deep-frozen tissues (N=55) of 102 L-SCC patients were analysed for the presence of 51 mucosal HPV types. HPV DNA-positive (HPV DNA+) cases were analysed for E6*I mRNA transcripts of all high risk (HR)/probably/possibly (p)HR-HPV identified, and for HPV type 16 (HPV16) viral load. Expression of p16(INK4a), pRb, cyclin D1 and p53 was analysed by immunohistochemistry.

Results: Ninety-two patients were valid in DNA analysis, of which 32 (35%) had at least one HPV DNA+ sample. Among the 29 single infections, 22 (76%) were HPV16, 2 (7%) HPV56 and 1 each (4%) HPV45, HPV53, HPV70, HPV11 and HPV42. Three cases harboured HPV16 with HPV33 (twice) or HPV45. Only 32% of HPV DNA+ findings were reproducible. Among HPV16 DNA+ L-SCC, 2 out of 23 (9%) had high viral loads, 5 out of 25 (21%) expressed E6*I mRNA and 3 out of 21 (14%) showed high p16(INK4a) and low pRb expression (all three HPV16 RNA-positive), immunohistochemical marker combination not identified in any other HPV DNA+ or HPV DNA-negative (HPV DNA-) L-SCC, respectively.

Conclusion: HPV type 16 has a causative role in a small subgroup of L-SCC (<5% in this German hospital series).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / virology*
  • DNA, Viral / analysis
  • DNA, Viral / isolation & purification
  • Female
  • Genotype
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 16 / physiology*
  • Humans
  • Laryngeal Neoplasms / virology*
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / virology*
  • Papillomavirus Infections / virology
  • Viral Load

Substances

  • DNA, Viral