PMID- 23778529 OWN - NLM STAT- MEDLINE DCOM- 20130920 LR - 20240322 IS - 1532-1827 (Electronic) IS - 0007-0920 (Print) IS - 0007-0920 (Linking) VI - 109 IP - 1 DP - 2013 Jul 9 TI - Biological evidence for a causal role of HPV16 in a small fraction of laryngeal squamous cell carcinoma. PG - 172-83 LID - 10.1038/bjc.2013.296 [doi] AB - 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). FAU - Halec, G AU - Halec G AD - 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 FAU - Holzinger, D AU - Holzinger D FAU - Schmitt, M AU - Schmitt M FAU - Flechtenmacher, C AU - Flechtenmacher C FAU - Dyckhoff, G AU - Dyckhoff G FAU - Lloveras, B AU - Lloveras B FAU - Hofler, D AU - Hofler D FAU - Bosch, F X AU - Bosch FX FAU - Pawlita, M AU - Pawlita M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130618 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (DNA, Viral) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Squamous Cell/*virology MH - DNA, Viral/analysis/isolation & purification MH - Female MH - Genotype MH - Human papillomavirus 16/genetics/isolation & purification/*physiology MH - Humans MH - Laryngeal Neoplasms/*virology MH - Male MH - Middle Aged MH - Oropharyngeal Neoplasms/*virology MH - Papillomavirus Infections/virology MH - Viral Load PMC - PMC3708587 EDAT- 2013/06/20 06:00 MHDA- 2013/09/21 06:00 PMCR- 2014/07/09 CRDT- 2013/06/20 06:00 PHST- 2013/03/11 00:00 [received] PHST- 2013/05/16 00:00 [revised] PHST- 2013/05/21 00:00 [accepted] PHST- 2013/06/20 06:00 [entrez] PHST- 2013/06/20 06:00 [pubmed] PHST- 2013/09/21 06:00 [medline] PHST- 2014/07/09 00:00 [pmc-release] AID - bjc2013296 [pii] AID - 10.1038/bjc.2013.296 [doi] PST - ppublish SO - Br J Cancer. 2013 Jul 9;109(1):172-83. doi: 10.1038/bjc.2013.296. Epub 2013 Jun 18.