title: Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-1.
abstract: BACKGROUND
  Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased.
  
  
  METHODS
  Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry.
  
  
  RESULTS
  No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC.
  
  
  CONCLUSIONS
  Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged ⩽40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair.
authors.affiliation: 1] Department of Medical Biosciences, Umeå University, Umeå SE-901 85, Sweden [2] Multidisciplinary Department of Medical, Surgical and Dental Specialties, Second University of Naples, Naples, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Sgaramella
authors.affiliation: Division of Medical Sciences, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Coates
authors.affiliation: Department of Medical Biosciences, Umeå University, Umeå SE-901 85, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Strindlund
authors.affiliation: Department of Medical Biosciences, Umeå University, Umeå SE-901 85, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Loljung
authors.affiliation: Multidisciplinary Department of Medical, Surgical and Dental Specialties, Second University of Naples, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Colella
authors.affiliation: Department of Clinical Sciences, ENT, Uppsala University, Uppsala SE-751 05, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Laurell
authors.affiliation: Dipartimento Universitario di Anatomia Patologica, Seconda Universita' Degli Studi di Napoli, Piazza Miraglia, Naples 80138, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rossiello
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia 71122, Italy.
authors.forename: L L
authors.initials: LL
authors.lastname: Muzio
authors.affiliation: Department of Clinical Sciences, Division of Otorhinolaryngology, Umeå University, Umeå SE-901 85, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Loizou
authors.affiliation: Multidisciplinary Department of Medical, Surgical and Dental Specialties, Second University of Naples, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tartaro
authors.affiliation: Department of Clinical Sciences, Division of Otorhinolaryngology, Umeå University, Umeå SE-901 85, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Olofsson
authors.affiliation: Department of Odontology, Umeå University, Umeå SE-90185, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Danielsson
authors.affiliation: 1] RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno 656 53, Czech Republic [2] University Paris Diderot, INSERM UMRS1162, 27 rue Juliette Dodu, Paris 75010, France.
authors.forename: R
authors.initials: R
authors.lastname: Fåhraeus
authors.affiliation: Department of Medical Biosciences, Umeå University, Umeå SE-901 85, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Nylander
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000821:virology*; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology*; D030361:Papillomavirus Infections / Q000150:complications*; D011991:Receptors, Virus / Q000502:physiology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D053668:Syndecan-1 / Q000032:analysis / Q000502:physiology*; D014062:Tongue Neoplasms / Q000401:mortality / Q000821:virology*
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D009363:Neoplasm Proteins; D011991:Receptors, Virus; D053668:Syndecan-1