title: High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma.
abstract: OBJECTIVE
  Human papillomavirus (HPV) DNA tumors actively integrating the E6 and E7 oncogenes have a distinct biologic behavior resulting in a more favorable prognosis. To which extent the viral integration by itself, and/or the associated wild-type (wt) TP53 status, and/or a functional p16 contribute to prognosis is unclear.
  
  
  METHODS
  To clarify how the presence of high-risk (HR) -HPV, TP53, and p16INK4a status interact with clinical outcome, we considered a retrospective series of 90 consecutive oropharyngeal cancer patients treated primarily with surgery.
  
  
  RESULTS
  Seventeen (19%) patients showed integrated HPV 16 DNA (HPV positive), wt TP53 in all but two patients, normal p16INK4a in 15 assessable patients, and p16 expression in all 17 patients. Thirty-five patients (39%), two of whom were HPV positive, harbored TP53 mutations. p16INK4a deletion and p16 null immunophenotype occurred in 28 and 58 patients, respectively, and was similarly distributed in both patients with mutated TP53 (48% and 82%, respectively) and in patients with wt TP53 (46% and 77%, respectively). Statistical analysis showed that HPV-positive status significantly affects all investigated end points: overall survival (P = .0018), incidence of tumor relapse (P = .0371), and second tumor (P = .0152), whereas TP53 and p16INK4a status and p16 expression were not prognostic by themselves.
  
  
  CONCLUSIONS
  Our molecular and clinical results are in agreement with previous findings but provide additional information into the biologic mechanisms involved in HR-HPV oropharyngeal cancer in comparison to HPV-negative tumors. According to the reduced risk of relapse and second tumors associated with HR-HPV positivity of oropharyngeal cancer, the therapeutic strategy and follow-up procedures should be reviewed.
authors.affiliation: Head and Neck Cancer Medical Oncology Unit, Medical Statistics and Biometry, Department of Head and Neck Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. lisa.licitra@istitutotumori.mi.it
authors.forename: Lisa
authors.initials: L
authors.lastname: Licitra
authors.forename: Federica
authors.initials: F
authors.lastname: Perrone
authors.forename: Paolo
authors.initials: P
authors.lastname: Bossi
authors.forename: Simona
authors.initials: S
authors.lastname: Suardi
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Raffaella
authors.initials: R
authors.lastname: Artusi
authors.forename: Maria
authors.initials: M
authors.lastname: Oggionni
authors.forename: Chiara
authors.initials: C
authors.lastname: Rossini
authors.forename: Giulio
authors.initials: G
authors.lastname: Cantù
authors.forename: Massimo
authors.initials: M
authors.lastname: Squadrelli
authors.forename: Pasquale
authors.initials: P
authors.lastname: Quattrone
authors.forename: Laura D
authors.initials: LD
authors.lastname: Locati
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bergamini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Olmi
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000601:surgery / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D004279:DNA, Viral; D005260:Female; D005500:Follow-Up Studies; D019942:Genes, p16; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016609:Neoplasms, Second Primary; D009959:Oropharyngeal Neoplasms / Q000401:mortality* / Q000601:surgery / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral