Correlation of p16 status, hypoxic imaging using [18F]-misonidazole positron emission tomography and outcome in patients with loco-regionally advanced head and neck cancer

J Med Imaging Radiat Oncol. 2014 Feb;58(1):89-97. doi: 10.1111/1754-9485.12155.

Abstract

Introduction: 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.

Conclusion: 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.

Keywords: [18F]-misonidazole positron emission tomography; head and neck carcinoma; human papillomavirus; hypoxia; oropharyngeal; p16.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor
  • Cell Hypoxia
  • Cyclin-Dependent Kinase Inhibitor p16
  • Fluorine Radioisotopes
  • Head and Neck Neoplasms / diagnosis*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / metabolism
  • Humans
  • Male
  • Middle Aged
  • Misonidazole*
  • Neoplasm Proteins / metabolism*
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / drug therapy
  • Papillomavirus Infections / metabolism
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Statistics as Topic
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Fluorine Radioisotopes
  • Neoplasm Proteins
  • Radiopharmaceuticals
  • Misonidazole