title: Classical risk factors, but not HPV status, predict survival after chemoradiotherapy in advanced head and neck cancer patients.
abstract: OBJECTIVE
  Despite the advent of concomitant chemoradiotherapy (CCRT), the prognosis of advanced head and neck squamous cell carcinoma (HNSCC) patients remains particularly poor. Classically, HNSCC, especially oropharyngeal carcinomas, associated with human papillomavirus (HPV) exhibits better treatment outcomes than HNSCCs in non-infected patients, eliciting a call for the de-escalation of current therapies. To improve the management of HNSCC patients, we aimed to determine the impact of active HPV infection on patient response, recurrence and survival after CCRT in a population of heavy tobacco and alcohol consumers.
  
  
  METHODS
  Paraffin-embedded samples from 218 advanced HNSCC patients, mostly smokers and/or drinkers treated by CCRT, were tested for the presence of HPV DNA by surrogate type-specific E6/E7 qPCR and p16 immunohistochemistry. Associations between the response to CCRT and patient outcomes according to HPV status and clinical data were evaluated by Kaplan-Meier analysis and both univariate and multivariate Cox regression.
  
  
  RESULTS
  Type-specific E6/E7 PCR demonstrated HPV positivity in 20 % of HNSCC. Regarding HPV status, we did not find any significant relation with response to therapy in terms of progression-free survival or overall survival. However, we observed a significantly worse prognosis for consumers of alcohol and tobacco compared to nondrinkers (p = 0.003) and non-smokers (p = 0.03). Survival analyses also revealed that the outcome is compromised in stage IV patients (p = 0.007) and, in particular, for oral cavity, hypopharynx and oropharynx carcinoma patients (p = 0.001).
  
  
  CONCLUSIONS
  The risk of death from HNSCC significantly increases when patients are exposed to tobacco and alcohol during their therapy, regardless of HPV status.
authors.affiliation: Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, University of Mons, Pentagone 2A, Avenue du Champ de Mars, 6, 7000, Mons, Belgium.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Descamps
authors.affiliation: Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, University of Mons, Pentagone 2A, Avenue du Champ de Mars, 6, 7000, Mons, Belgium.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Karaca
authors.affiliation: Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, University of Mons, Pentagone 2A, Avenue du Champ de Mars, 6, 7000, Mons, Belgium.
authors.forename: Jérôme R
authors.initials: JR
authors.lastname: Lechien
authors.affiliation: Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, University of Mons, Pentagone 2A, Avenue du Champ de Mars, 6, 7000, Mons, Belgium.
authors.forename: Nadège
authors.initials: N
authors.lastname: Kindt
authors.affiliation: Laboratories of Image, Signal Processing and Acoustics, Ecole polytechnique de Bruxelles, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Decaestecker
authors.affiliation: Department of Pathology, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Remmelink
authors.affiliation: Department of Pathology, Bordet Institute, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Denis
authors.initials: D
authors.lastname: Larsimont
authors.affiliation: Department of Head and Neck Surgery, Bordet Institute, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Andry
authors.affiliation: Department of Oto-Rhino-Laryngology, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Samantha
authors.initials: S
authors.lastname: Hassid
authors.affiliation: Department of Oto-Rhino-Laryngology, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: Department of Head and Neck Surgery, EpiCURA, Baudour, Belgium.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Khalife
authors.affiliation: Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, University of Mons, Pentagone 2A, Avenue du Champ de Mars, 6, 7000, Mons, Belgium.|Laboratory of Oncology and Experimental Surgery, Bordet Institute, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Journe
authors.affiliation: Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, University of Mons, Pentagone 2A, Avenue du Champ de Mars, 6, 7000, Mons, Belgium. sven.saussez@umons.ac.be.|Department of Oto-Rhino-Laryngology, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium. sven.saussez@umons.ac.be.|Department of Head and Neck Surgery, EpiCURA, Baudour, Belgium. sven.saussez@umons.ac.be.
authors.forename: Sven
authors.identifier: http://orcid.org/0000-0002-3655-1854
authors.initials: S
authors.lastname: Saussez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000473:pathology / Q000628:therapy* / Q000821:virology; D059248:Chemoradiotherapy; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006258:Head and Neck Neoplasms / Q000209:etiology* / Q000473:pathology / Q000628:therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D016612:Paraffin Embedding; D012907:Smoking / Q000473:pathology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D055815:Young Adult
chemical_list: D004279:DNA, Viral
keywords: Alcohol; Concomitant chemoradiotherapy; HPV; Head and neck cancers; Survival; Tobacco