title: Frequency and prognostic significance of p16(INK4A) protein overexpression and transcriptionally active human papillomavirus infection in laryngeal squamous cell carcinoma.
abstract: BACKGROUND
  Human papillomavirus (HPV) infection is a powerful prognostic biomarker in a subset of head and neck squamous cell carcinomas, specifically oropharyngeal cancers. However, the role of HPV in non-oropharyngeal sites, such as the larynx, remains unconfirmed.
  
  
  METHODS
  We evaluated a cohort of 324 laryngeal squamous cell carcinoma (LSCC) patients for the expression of p16(INK4A) (p16) protein by immunohistochemistry (IHC) and for high-risk HPV E6 and E7 mRNA transcripts by RNA in situ hybridisation (ISH). p16 expression and HPV status were correlated with clinicopathological features and outcomes.
  
  
  RESULTS
  Of 307 patients assessable for p16 IHC, 20 (6.5%) were p16 positive. Females and node-positive patients were more likely to be p16 positive (P<0.05). There were no other significant clinical or demographic differences between p16-positive and -negative cases. There was no difference in overall survival (OS) between p16-positive and -negative patients with 2-year survival of 79% in each group (HR=0.83, 95% CI 0.36-1.89, P=0.65). There was no statistically significant difference in failure-free survival (FFS) with 2-year FFS of 79% and 66% for p16-positive and -negative patients, respectively (HR=0.60, 95% CI 0.26-1.36, P=0.22). Only seven cases were found to be HPV RNA ISH positive, all of which were p16 IHC positive. There was no statistically significant difference in OS between patients with HPV RNA ISH-positive tumours compared with -negative tumours with 2-year survival of 86% and 71%, respectively (HR=0.76, 95% CI 0.23-2.5, P=0.65). The 2-year FFS was 86% and 59%, respectively (HR=0.62, 95% CI 0.19-2.03, P=0.43).
  
  
  CONCLUSIONS
  p16 overexpression is infrequent in LSCC and the proportion of cases with high-risk HPV transcripts is even lower. There are no statistically significant correlations between p16 IHC or HPV RNA ISH status and OS or disease outcomes.
authors: 1] Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
authors: R J
authors: RJ
authors: Young
authors: 1] Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia [2] Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors: D
authors: D
authors: Urban
authors: 1] Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia [2] Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors: C
authors: C
authors: Angel
authors: Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors: J
authors: J
authors: Corry
authors: Department of Surgery, St Vincent's Hospital, Melbourne, Australia.
authors: B
authors: B
authors: Lyons
authors: Department of Otorhinolaryngology, Monash Medical Centre, Melbourne, Australia.
authors: N
authors: N
authors: Vallance
authors: Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors: S
authors: S
authors: Kleid
authors: Department of Surgery, Melbourne University, Royal Melbourne Hospital, Melbourne, Australia.
authors: T A
authors: TA
authors: Iseli
authors: 1] Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia [3] Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors: B
authors: B
authors: Solomon
authors: 1] Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia [2] Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors: D
authors: D
authors: Rischin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D014158:Transcription, Genetic
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral