title: Oropharyngeal cancer prognosis by tumour HPV status in France: The multicentric Papillophar study.
abstract: To evaluate the impact of human papillomavirus (HPV) status, tobacco smoking and initial treatment approach on progression-free survival (PFS) and overall survival (OS) for oropharyngeal cancer (OPC) in France, a country where smoking declines started late (1990s).
  
  
  
  340 OPC patients (median age: 60years) from 14 French hospitals were followed up (median 26.7months). PCR-based positivity for both HPV DNA and E6/E7 mRNA was used to distinguish HPV-positive OPC (27.1%). Hospital-stratified hazard ratios (HR) and corresponding 95% confidence intervals (CI) were used to compare PFS and OS according to HPV and other prognostic factors in hospital-stratified unadjusted and multivariate models. The combined effect of HPV status with either smoking, stage, or initial treatment on PFS was also evaluated.
  
  
  
  PFS in multivariate analysis was better in HPV-positive patients (HR=0.42; 95% CI: 0.24-0.73) and worse in older patients (HR for 5-year age increase=1.12) and those having had firstly radiotherapy (HR=1.86; 95% CI: 1.19-2.92) or induction chemotherapy (HR=1.73; 95% CI: 1.08-2.79) instead of upfront surgery. Findings for OS were similar. Loco-regional recurrences were less frequent in HPV-positive (10.5%) than HPV-negative patients (26.0%) but distant recurrences were similarly frequent. HPV status did not modify the influence of smoking or stage on PFS but the impossibility to perform upfront surgery may be more relevant for HPV-negative patients.
  
  
  
  HPV-positive OPC patients fare better than HPV-negative OPC and may benefit from toxicity-sparing. Whether HPV-negative patients responded less well to radiation and chemotherapy because of more severe genomic damage or bulkier tumours is unclear.
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Otolaryngology-Head and Neck Surgery, Tenon Hospital, 75020 Paris, France; Pierre-et-Marie Curie University - Sorbonne Universities, University Cancerology Institute UPMC, Paris, France. Electronic address: jean.lacau@aphp.fr.
authors.forename: Jean
authors.initials: J
authors.lastname: Lacau St Guily
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Clinical Pharmacology and Clinical Research Unit of East of Paris (URC-Est), Saint Antoine Hospital, 75012 Paris, France. Electronic address: alexandra.rousseau@aphp.fr.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rousseau
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Otolaryngology-Head and Neck Surgery, Tenon Hospital, 75020 Paris, France; Pierre-et-Marie Curie University - Sorbonne Universities, University Cancerology Institute UPMC, Paris, France. Electronic address: bertrand.baujat@tnn.aphp.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Baujat
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Otolaryngology-Head and Neck Surgery, Tenon Hospital, 75020 Paris, France; Pierre-et-Marie Curie University - Sorbonne Universities, University Cancerology Institute UPMC, Paris, France. Electronic address: sophie.perie@tnn.aphp.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Périé
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Strasbourg University Hospital - Hautepierre, 67098 Strasbourg Cedex, France. Electronic address: philippe.schultz@chru-strasbourg.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Schultz
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Otolaryngology-Head and Neck Surgery, Bichat Hospital, and University-Paris 7, 75877 Paris Cedex 18, France. Electronic address: beatrix.barry@bch.aphp.fr.
authors.forename: Béatrix
authors.initials: B
authors.lastname: Barry
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Poitiers University Hospital, 86021 Poitiers Cedex, France. Electronic address: xavier.dufour@chu-poitiers.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Dufour
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nantes University Hospital - Hotel-Dieu, 44093 Nantes Cedex 1, France. Electronic address: olivier.malard@chu-nantes.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Malard
authors.affiliation: Franche-Comte University, COMUE UBFC, Besançon University Hospital - Jean Minjoz, 25030 Besançon Cedex, France; Inserm CIC 1431, 25030 Besançon Cedex, France. Electronic address: jean_luc.pretet@univ-fcomte.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pretet
authors.affiliation: INSERM UMR-S903, Reims University Hospital - Maison Blanche, 51092 Reims Cedex, France. Electronic address: cclavel@chu-reims.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Clavel
authors.affiliation: Laboratory of Biopathology, Reims University Hospital - Maison Blanche, Reims-Champagne-Ardenne University, 51092 Reims Cedex, France. Electronic address: pbirembaut@chu-reims.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembaut
authors.affiliation: International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France. Electronic address: franceschi@iarc.fr.
authors.forename: Silvia
authors.initials: S
authors.lastname: Franceschi
mesh_terms: D052685:Alphapapillomavirus / Q000302:isolation & purification*; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D009959:Oropharyngeal Neoplasms / Q000821:virology*; D011379:Prognosis
keywords: Human papillomavirus; Oropharyngeal cancer; Progression-free survival; Surgical treatment; Survival; Tobacco