title: Impact of tumor HPV status on outcome in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: retrospective analysis of the phase III EXTREME trial.
abstract: BACKGROUND
  Tumor human papillomavirus (HPV) status is an important prognostic factor in locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). Prognostic value in recurrent and/or metastatic (R/M) disease remains to be confirmed. This retrospective analysis of the EXTREME trial, comparing chemotherapy plus cetuximab with chemotherapy first line in R/M SCCHN, investigated efficacy and prognosis according to tumor p16 and HPV status.
  
  
  METHODS
  Paired tissue samples were used: p16INK4A expression was assessed by immunohistochemistry, and HPV status determined in extracted DNA samples using oligonucleotide hybridization assays.
  
  
  RESULTS
  Altogether, 416 of 442 patients had tumor samples available for p16 and HPV: 10% of tumors were p16 positive and 5% were HPV positive. Adding cetuximab to chemotherapy improved survival, irrespective of tumor p16 or HPV status. This pattern remained in a combined analysis of p16 and HPV. p16 positivity and HPV positivity were associated with prolonged survival compared with p16 negativity and HPV negativity. Subgroup analysis of patients with oropharyngeal cancer demonstrated a similar pattern to all evaluable patients.
  
  
  CONCLUSIONS
  The results from this analysis suggest that p16 and HPV status have prognostic value in R/M SCCHN and survival benefits of chemotherapy plus cetuximab over chemotherapy alone are independent of tumor p16 and HPV status.
authors.affiliation: Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium. Electronic address: jan.b.vermorken@uza.be.
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.affiliation: Internal Medicine Propaedeutic, University of Athens Medical School, Attikon University Hospital, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Psyrri
authors.affiliation: Department of Medical Oncology, Catalan Institute of Oncology, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Mesía
authors.affiliation: Department of Onco-Hematology, Centre Régional de Lutte Contre le Cancer de Nice, Nice, France.
authors.forename: F
authors.initials: F
authors.lastname: Peyrade
authors.affiliation: Global Biostatistics, Merck KGaA, Darmstadt, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Beier
authors.affiliation: Global Clinical Development Unit, Merck KGaA, Darmstadt, Germany.
authors.forename: B
authors.initials: B
authors.lastname: de Blas
authors.affiliation: Global Clinical Development Unit, Merck KGaA, Darmstadt, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Celik
authors.affiliation: Head and Neck Medical Oncology Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Licitra
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D000068818:Cetuximab; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000302:isolation & purification*; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D011379:Prognosis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D019941:Cyclin-Dependent Kinase Inhibitor p16; D000068818:Cetuximab
keywords: cetuximab; human papillomavirus; p16; recurrent and metastatic; squamous cell carcinoma of the head and neck