title: Human papillomavirus DNA and p16(INK4a) expression in hypopharyngeal cancer and in relation to clinical outcome, in Stockholm, Sweden.
abstract: OBJECTIVE
  Hypopharyngeal cancer is a subset of head neck squamous cell carcinoma (HNSCC) with particularly poor prognosis. Human papillomavirus (HPV) is a risk factor for some HNSCC, and its presence is of prognostic value for certain subsites. However, its influence on survival in hypopharyngeal cancer has not been thoroughly investigated. Here we examine HPV DNA and p16(INK4a) (p16) overexpression in relation to clinical outcome.
  
  
  METHODS
  Hypopharyngeal tumour biopsies from 82 patients diagnosed 2008-2013 were examined for presence of HPV DNA by a bead-based multiplex assay and for p16 expression by immunohistochemistry, and the obtained data compared to that acquired previously from 109 patients diagnosed 2000-2007 at the same clinic. A survival analysis was then performed on 142 patients (from both studies) treated with curative intent and a 3-year follow-up time.
  
  
  RESULTS
  Of the tumour biopsies 3/82 (3.7%) were HPV16 DNA and p16 positive, while 12/82 (14.6%) were p16 positive, equivalent to that in the previous study. Overall 3-year survival was significantly more favourable for patients with HPV16 DNA and p16 positive tumours as compared to survival of the other patients (86% vs. 31%, p=0.0185). A similar but not statistically significant trend was found for disease specific survival.
  
  
  CONCLUSIONS
  HPV DNA and p16 positive hypopharyngeal cancer was rare and had not increased, but had a better clinical outcome as compared to other HPV-unrelated hypopharyngeal cancer. In addition, p16 overexpression was not a suitable surrogate marker for presence of HPV or for prediction of survival in this type of cancer.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Electronic address: Tina.Dalianis@ki.se.
authors.forename: Tina
authors.initials: T
authors.lastname: Dalianis
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grün
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jana
authors.initials: J
authors.lastname: Koch
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Oto-Rhino-Laryngology, Head and Neck Surgery, CLINTEC, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vlastos
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tertipis
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nordfors
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Näsman
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, CLINTEC, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Wendt
authors.affiliation: Department of Audiology and Neurotology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Mircea
authors.initials: M
authors.lastname: Romanitan
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bersani
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, CLINTEC, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Munck-Wikland
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Ramqvist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism*; D005260:Female; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000378:metabolism / Q000401:mortality*; D011379:Prognosis; D016019:Survival Analysis; D013548:Sweden / Q000453:epidemiology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral
keywords: Disease specific survival; HPV; Hypopharyngeal cancer; Overall survival; P16