title: Human papillomavirus and gene mutations in head and neck squamous carcinomas.
abstract: BACKGROUND
  Human papillomavirus (HPV) infection is implicated as an aetiological factor in head and neck squamous carcinomas (HNSCC), especially in the tonsils of the oropharyngeal region. This study investigates the frequency of HPV infection, p16 and p53 tumour profile and mutations in epidermal growth factor receptor (EGFR), Kirsten RNA Associated Rat Sarcoma 2 Virus (KRAS) and B-Raf proto-oncogene serine/threonine protein kinase (BRAF) genes in tonsillar and non-tonsillar HNSCCs and correlates with clinical outcome and histopathological parameters in previously unstudied cohort of patients.
  
  
  METHODS
  A retrospective clinical study was performed utilising the demographic data and pathological specimens from 60 out of 726 head and neck cancer patients. Smoking and alcohol history, tumour staging, treatment and outcomes were recorded. Histopathology and immunochemistry for p16 and p53 was performed and HPV DNA was detected with polymerase chain reaction. Genomic DNA from all cancers were analysed for somatic mutations of EGFR, BRAF and KRAS genes.
  
  
  RESULTS
  20 (33%) of 60 cases were tonsillar squamous carcinomas and 38 (66%) were non-tonsillar. 19 (95%) of the 20 tonsillar cancers and three (8%) of 38 non-tonsillar patients were patients who were HPV 16-positive. Nine (47%) of the 19 HPV 16-positive tonsillar cases were p16 positive. Gene mutations were rare. There was a statistically significant (P < 0.05) improved survival of patients with HPV positive tonsillar tumours, younger age and non-smokers.
  
  
  CONCLUSIONS
  Although limited in numbers, this study reinforces the role of HPV infection in HNSCC and its association with a more favourable clinical course in younger non-smokers worldwide. Gene mutation frequencies were low in all cancers tested and routine testing not recommended.
authors.affiliation: School of Surgery, The University of Western Australia, Perth, Western Australia, Australia. peter.friedland@uwa.edu.au
authors.forename: Peter
authors.initials: P
authors.lastname: Friedland
authors.forename: Anitha
authors.initials: A
authors.lastname: Thomas
authors.forename: Anupam
authors.initials: A
authors.lastname: Naran
authors.forename: Benhur
authors.initials: B
authors.lastname: Amanuel
authors.forename: Fabienne
authors.initials: F
authors.lastname: Grieu-Iacopetta
authors.forename: Amerigo
authors.initials: A
authors.lastname: Carrello
authors.forename: Gerald
authors.initials: G
authors.lastname: Harnett
authors.forename: Christine
authors.initials: C
authors.lastname: Meyer
authors.forename: Michael
authors.initials: M
authors.lastname: Phillips
mesh_terms: D052685:Alphapapillomavirus; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D004279:DNA, Viral; D066246:ErbB Receptors / Q000235:genetics; D019942:Genes, p16; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000821:virology; D006801:Humans; D009154:Mutation; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics* / Q000821:virology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D014904:Western Australia; D018631:ras Proteins / Q000235:genetics
chemical_list: D004279:DNA, Viral; C117307:KRAS protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins