title: Human papillomavirus in head and neck squamous cell carcinoma of unknown primary is a common event and a strong predictor of survival.
abstract: BACKGROUND
  The purpose of this study was to examine the prevalence of human papillomavirus (HPV) in patients with head and neck squamous cell carcinoma of unknown primary (CUP).
  
  
  METHODS
  All patients diagnosed with and treated for CUP between January 1, 2000, and June 1, 2011, at two Danish medical centers were included. All patients received a thorough diagnostic work-up, including FDG-PET, before being diagnosed as CUP. We determined the HPV status in all patients using a combination of HPV DNA PCR and p16 stain. In addition, clinical information on the study patients was retrieved from clinical records.
  
  
  RESULTS
  Of the identified 60 patients with CUP, 13 were shown to be positive for HPV DNA, amounting to 22% of the study population. In addition, we were able to show a clear disease-free and overall-survival benefit in the HPV-positive group, with a hazard ratio of 0.16 (95% CI: 0.038-0.67) for over-all survival. This survival benefit was also apparent when adjusted for advanced age in a multivariate Cox regression analysis.
  
  
  CONCLUSIONS
  A fairly large percentage of CUP cases are HPV-related, and because this is related to both the location and prognosis, we recommend HPV testing as part of the diagnostic work-up.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: David Hebbelstrup
authors.initials: DH
authors.lastname: Jensen
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nora
authors.initials: N
authors.lastname: Hedback
authors.affiliation: Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Specht
authors.affiliation: Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Estrid
authors.initials: E
authors.lastname: Høgdall
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Elo
authors.initials: E
authors.lastname: Andersen
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marianne Hamilton
authors.initials: MH
authors.lastname: Therkildsen
authors.affiliation: Centre for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lennart
authors.initials: L
authors.lastname: Friis-Hansen
authors.affiliation: Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bodil
authors.initials: B
authors.lastname: Norrild
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: von Buchwald
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D004279:DNA, Viral / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D004279:DNA, Viral