title: Does HPV type affect outcome in oropharyngeal cancer?
abstract: BACKGROUND
  An epidemic of human papillomavirus (HPV)-related oropharyngeal squamous cell cancer (OPSCC) has been reported worldwide largely due to oral infection with HPV type-16, which is responsible for approximately 90% of HPV-positive cases. The purpose of this study was to determine the rate of HPV-positive oropharyngeal cancer in Southwestern Ontario, Canada.
  
  
  METHODS
  A retrospective search identified ninety-five patients diagnosed with OPSCC. Pre-treatment biopsy specimens were tested for p16 expression using immunohistochemistry and for HPV-16, HPV-18 and other high-risk subtypes, including 31,33,35,39,45,51,52,56,58,59,67,68, by real-time qPCR.
  
  
  RESULTS
  Fifty-nine tumours (62%) were positive for p16 expression and fifty (53%) were positive for known high-risk HPV types. Of the latter, 45 tumors (90%) were identified as HPV-16 positive, and five tumors (10%) were positive for other high-risk HPV types (HPV-18 (2), HPV-67 (2), HPV-33 (1)). HPV status by qPCR and p16 expression were extremely tightly correlated (p < 0.001, Fishers exact test). Patients with HPV-positive tumors had improved 3-year overall (OS) and disease-free survival (DFS) compared to patients with HPV-negative tumors (90% vs 65%, p = 0.001; and 85% vs 49%, p = 0.005; respectively). HPV-16 related OPSCC presented with cervical metastases more frequently than other high-risk HPV types (p = 0.005) and poorer disease-free survival was observed, although this was not statistically significant.
  
  
  CONCLUSIONS
  HPV-16 infection is responsible for a significant proportion of OPSCC in Southwestern Ontario. Other high-risk subtypes are responsible for a smaller subset of OPSCC that present less frequently with cervical metastases and may have a different prognosis.
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, The University of Western Ontario, Room B3-431A, 800 Commissioners Road East, London, N6A 5W9, , Ontario, Canada. Anthony.Nichols@lhsc.on.ca.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Nichols
authors.forename: Sandeep S
authors.initials: SS
authors.lastname: Dhaliwal
authors.forename: David A
authors.initials: DA
authors.lastname: Palma
authors.forename: John
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authors.lastname: Basmaji
authors.forename: Corina
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authors.lastname: Chapeskie
authors.forename: Samuel
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authors.lastname: Dowthwaite
authors.forename: Jason H
authors.initials: JH
authors.lastname: Franklin
authors.forename: Kevin
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authors.lastname: Fung
authors.forename: Keith
authors.initials: K
authors.lastname: Kwan
authors.forename: Brett
authors.initials: B
authors.lastname: Wehrli
authors.forename: Chris
authors.initials: C
authors.lastname: Howlett
authors.forename: Iram
authors.initials: I
authors.lastname: Siddiqui
authors.forename: Marina I
authors.initials: MI
authors.lastname: Salvadori
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.forename: Scott
authors.initials: S
authors.lastname: Ernst
authors.forename: Sara
authors.initials: S
authors.lastname: Kuruvilla
authors.forename: Nancy
authors.initials: N
authors.lastname: Read
authors.forename: Varagur
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authors.lastname: Venkatesan
authors.forename: Biljana
authors.initials: B
authors.lastname: Todorovic
authors.forename: J Alex
authors.initials: JA
authors.lastname: Hammond
authors.forename: James
authors.initials: J
authors.lastname: Koropatnick
authors.forename: Joe S
authors.initials: JS
authors.lastname: Mymryk
authors.forename: John
authors.initials: J
authors.lastname: Yoo
authors.forename: John W
authors.initials: JW
authors.lastname: Barrett
mesh_terms: D000368:Aged; D052685:Alphapapillomavirus / Q000145:classification; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000821:virology*; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality* / Q000821:virology*; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D008297:Male; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D009959:Oropharyngeal Neoplasms / Q000401:mortality* / Q000821:virology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016036:Seroepidemiologic Studies; D000077195:Squamous Cell Carcinoma of Head and Neck