title: Correlation of p16 status, hypoxic imaging using [18F]-misonidazole positron emission tomography and outcome in patients with loco-regionally advanced head and neck cancer.
abstract: BACKGROUND
  We investigated the relationship between hypoxia, human papillomavirus (HPV) status and outcome in head and neck squamous cell carcinoma.
  
  
  METHODS
  Patients with stage III and IV head and neck squamous cell carcinoma treated on phase I and II chemoradiation trials with 70-Gy radiation combined with tirapazamine/cisplatin or cisplatin/fluorouracil (5FU), hypoxic imaging using [18F]-misonidazole positron emission tomography and known HPV status (by p16 immunohistochemistry) were included in this sub-study. Separate analyses were conducted to consider the impact of tirapazamine on HPV-negative tumours in the phase II trial.
  
  
  RESULTS
  Both p16-positive oropharyngeal tumours and p16-negative head and neck squamous cell carcinoma tumours had a high prevalence of tumour hypoxia; 14/19 (74%) and 35/44 (80%), respectively. The distribution of hypoxia (primary, nodal) was similar. On phase II, trial patients with p16-negative hypoxic tumours had worse loco-regional control with cisplatin and 5FU compared with tirapazamine and cisplatin (P < 0.001) and worse failure-free survival (hazard ratio = 5.18; 95% confidence interval, 1.98-13.55; P = 0.001). Only 1 out of 14 p16-positive patients on the phase II trial experienced loco-regional failure.
  
  
  CONCLUSIONS
  Hypoxia, as assessed by [18F]-misonidazole positron emission tomography, is frequently present in both p16-positive and negative head and neck cancer. Further research is required to determine whether hypoxic imaging can be used to predict benefit from hypoxia-targeting therapies in patients with p16-negative tumours.
authors: Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors: Mateya E
authors: ME
authors: Trinkaus
authors: Rodney J
authors: RJ
authors: Hicks
authors: Richard J
authors: RJ
authors: Young
authors: Lester J
authors: LJ
authors: Peters
authors: Ben
authors: B
authors: Solomon
authors: Mathias
authors: M
authors: Bressel
authors: June
authors: J
authors: Corry
authors: Richard
authors: R
authors: Fisher
authors: David
authors: D
authors: Binns
authors: Grant A
authors: GA
authors: McArthur
authors: Danny
authors: D
authors: Rischin
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D015687:Cell Hypoxia; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005462:Fluorine Radioisotopes; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008920:Misonidazole; D009363:Neoplasm Proteins / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005462:Fluorine Radioisotopes; D009363:Neoplasm Proteins; D019275:Radiopharmaceuticals; D008920:Misonidazole
keywords: [18F]-misonidazole positron emission tomography; head and neck carcinoma; human papillomavirus; hypoxia; oropharyngeal; p16