title: Human Papillomavirus-related tumours of the oropharynx display a lower tumour hypoxia signature.
abstract: OBJECTIVE
  Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OSCC) patients have improved prognosis compared to other head and neck (HNSCC) cancers. Since poor prognosis is associated with tumour hypoxia, we studied whether the hypoxic response is different in HPV-related cells and tumours.
  
  
  METHODS
  HPV-positive and -negative cells were incubated in hypoxia and analyzed by qRTPCR, western blotting and cell proliferation assays. Tumours formed by xenografting these cells in nude mice were studied by IHC. HNSCC patient samples were analyzed by unsupervised clustering of hypoxia-related gene expression, quantitative real-time PCR (qRTPCR) and immunohistochemical (IHC) detection of neo-blood vessels.
  
  
  CONCLUSIONS
  HPV-positive and -negative cells responded differently to hypoxia, in terms of gene expression (HIF-1α, PHD-3, GLUT-1 and VEGF-A) and cell survival. Tumour xenografts formed by HPV-positive cells had fewer hypoxic areas than those formed by HPV-negative cells. HPV related tumours were less hypoxic, expressed lower levels of hypoxia-responsive genes, and had a higher density of neo-blood vessels. HPV-related OSCC display lower tumour hypoxia, which could be linked to the distinct intrinsic abilities of HPV-positive tumour cells to adapt to hypoxia and to their better prognosis.
authors.affiliation: Laboratoire de Biologie Tumorale, Centre Régional de Lutte Contre le Cancer Paul Strauss, EA3430 de l'Université de Strasbourg, F. 67065 Strasbourg, France; EA3430 de l'Université de Strasbourg, Bâtiment U113, F. 67000 Strasbourg, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Hanns
authors.affiliation: Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre le Cancer, F. 75014 Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Job
authors.affiliation: Laboratoire de Biologie Tumorale, Centre Régional de Lutte Contre le Cancer Paul Strauss, EA3430 de l'Université de Strasbourg, F. 67065 Strasbourg, France; EA3430 de l'Université de Strasbourg, Bâtiment U113, F. 67000 Strasbourg, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Coliat
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, F. 67404 Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, F. 67404 Illkirch, France; Université de Strasbourg, F. 67404 Illkirch, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Wasylyk
authors.affiliation: Laboratoire de Biologie Tumorale, Centre Régional de Lutte Contre le Cancer Paul Strauss, EA3430 de l'Université de Strasbourg, F. 67065 Strasbourg, France; EA3430 de l'Université de Strasbourg, Bâtiment U113, F. 67000 Strasbourg, France.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Ramolu
authors.affiliation: EA3430 de l'Université de Strasbourg, Bâtiment U113, F. 67000 Strasbourg, France; Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, F. 67000 Strasbourg, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Pencreach
authors.affiliation: Laboratoire de Pathologie Expérimentale, GIGA-Cancer, Université de Liège, B. 4000 Liège, Belgium.
authors.forename: Meggy
authors.initials: M
authors.lastname: Suarez-Carmona
authors.affiliation: Laboratoire de Pathologie Expérimentale, GIGA-Cancer, Université de Liège, B. 4000 Liège, Belgium.
authors.forename: Michael
authors.initials: M
authors.lastname: Herfs
authors.affiliation: Laboratoire de Biologie Tumorale, Centre Régional de Lutte Contre le Cancer Paul Strauss, EA3430 de l'Université de Strasbourg, F. 67065 Strasbourg, France; EA3430 de l'Université de Strasbourg, Bâtiment U113, F. 67000 Strasbourg, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ledrappier
authors.affiliation: Laboratoire de Biologie Tumorale, Centre Régional de Lutte Contre le Cancer Paul Strauss, EA3430 de l'Université de Strasbourg, F. 67065 Strasbourg, France; EA3430 de l'Université de Strasbourg, Bâtiment U113, F. 67000 Strasbourg, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Macabre
authors.affiliation: Laboratoire de Biologie Tumorale, Centre Régional de Lutte Contre le Cancer Paul Strauss, EA3430 de l'Université de Strasbourg, F. 67065 Strasbourg, France; EA3430 de l'Université de Strasbourg, Bâtiment U113, F. 67000 Strasbourg, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Abecassis
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, F. 67404 Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, F. 67404 Illkirch, France; Université de Strasbourg, F. 67404 Illkirch, France.
authors.forename: Bohdan
authors.initials: B
authors.lastname: Wasylyk
authors.affiliation: Laboratoire de Biologie Tumorale, Centre Régional de Lutte Contre le Cancer Paul Strauss, EA3430 de l'Université de Strasbourg, F. 67065 Strasbourg, France; EA3430 de l'Université de Strasbourg, Bâtiment U113, F. 67000 Strasbourg, France. Electronic address: AJung@strasbourg.unicancer.fr.
authors.forename: Alain C
authors.initials: AC
authors.lastname: Jung
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009959:Oropharyngeal Neoplasms / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
keywords: Gene expression; HPV; Head and neck squamous cell carcinoma; Hypoxia; Immunohistochemistry; Transcriptome