title: Biological evidence for a causal role of HPV16 in a small fraction of laryngeal squamous cell carcinoma.
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.
  
  
  CONCLUSIONS
  HPV type 16 has a causative role in a small subgroup of L-SCC (<5% in this German hospital series).
authors.affiliation: Division of Genome Modifications and Carcinogenesis, Infections and Cancer Program, German Cancer Research Center, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany. g.halec@dkfz.de
authors.forename: G
authors.initials: G
authors.lastname: Halec
authors.forename: D
authors.initials: D
authors.lastname: Holzinger
authors.forename: M
authors.initials: M
authors.lastname: Schmitt
authors.forename: C
authors.initials: C
authors.lastname: Flechtenmacher
authors.forename: G
authors.initials: G
authors.lastname: Dyckhoff
authors.forename: B
authors.initials: B
authors.lastname: Lloveras
authors.forename: D
authors.initials: D
authors.lastname: Höfler
authors.forename: F X
authors.initials: FX
authors.lastname: Bosch
authors.forename: M
authors.initials: M
authors.lastname: Pawlita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000821:virology*; D030361:Papillomavirus Infections / Q000821:virology; D019562:Viral Load
chemical_list: D004279:DNA, Viral