title: Effect of radiation on cell proliferation and tumor hypoxia in HPV-positive head and neck cancer in vivo models.
abstract: OBJECTIVE
  Human papilloma virus-associated head and neck squamous cell carcinomas (HNSCC) represent a distinct subgroup of HNSCC characterized by a favorable prognosis and a distinct molecular biology. There is a range of unresolved questions regarding the different biology and clinical outcome of HPV-positive HNSCC. The purpose of the present project was to obtain insight into the biology of treatment responsiveness of HPV-related HNSCC.
  
  
  METHODS
  Tumor xenografts were established from HPV-negative (FaDuDD,) and HPV-positive (UD2 and UMSCC47) HNSCC cell lines. Tumors were treated with 10 Gy or 20 Gy and the effect on the tumor microenvironment was studied at different time points after treatment. Cryosections were imaged for cell proliferation, hypoxia, vessel density and vessel perfusion.
  
  
  RESULTS
  In the HPV-positive tumor models the levels of cell proliferation decreased significantly following irradiation. This was not seen in the HPV-negative model (FaDuDD). Furthermore, it was found that the tumor hypoxic fraction decreased over time after treatment in irradiated HPV-positive tumors and not in the HPV-negative tumors.
  
  
  CONCLUSIONS
  The radiosensitivity previously observed in vitro could be applied in vivo in respect to a radiation-induced decrease in proliferating cells. A decreasing hypoxic fraction following irradiation in the HPV-positive tumors could explain the lack of benefit from hypoxic modifiers observed in patients.
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark bsin@oncology.dk.
authors.forename: Brita Singers
authors.initials: BS
authors.lastname: Sørensen
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Busk
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Horsman
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Alsner
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
authors.affiliation: BC Cancer Research Centre, Radiation Biology Unit, Vancouver, Canada.
authors.forename: Alastair H
authors.initials: AH
authors.lastname: Kyle
authors.affiliation: BC Cancer Research Centre, Radiation Biology Unit, Vancouver, Canada.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Minchinton
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy* / Q000821:virology; D015687:Cell Hypoxia / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects*; D005720:Gamma Rays; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000821:virology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000473:pathology / Q000532:radiotherapy* / Q000821:virology; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
keywords: HPV; head and neck cancer; hypoxia; radiosensitivity