Prognostic value of tissue necrosis, hypoxia-related markers and correlation with HPV status in head and neck cancer patients treated with bio- or chemo-radiotherapy

Radiother Oncol. 2018 Jan;126(1):116-124. doi: 10.1016/j.radonc.2017.10.007. Epub 2017 Nov 1.

Abstract

Background and purpose: The aim of the present study was to investigate the role of three hypoxia-related biomarkers in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiotherapy (3-weekly cisplatin) or bioradiotherapy (weekly cetuximab).

Material and methods: In tumor tissue material from 100 patients with known HPV status, we evaluated the extent of tumor necrosis, the expression level of CA-IX and the microvascular density (MVD) measured as the density of CD34+ vascular structures. The correlations between biomarker expressions and clinicopathological characteristics and treatment outcomes were analyzed.

Results: We found a significant correlation of MVD with UICC stage (p = 0.02) and T classification (p = 0.05), of CA-IX with UICC stage (p = 0.03) and N classification (p = 0.04) and a significant inverse correlation of MVD with CA-IX expression (r = -0.22, p = 0.03). Multivariate analysis showed that low MVD combined with high CA IX-expression was a significant independent prognostic factor for worse loco-regional control (HR = 2.6, 95%CI 1.1-5.0, p = 0.02) in the whole population but not in the p16+ subgroup. Patients treated with CRT had a better LRC than those with BRT independent of MVD or CA-IX expression.

Conclusions: The combination of MVD and CA-IX expression might give additional prognostic information in HNSCC patients with known HPV status.

Keywords: CA-IX; CD34; Head-and-neck squamous cell carcinoma; Human papillomavirus; Necrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Neoplasm / biosynthesis
  • Biomarkers, Tumor / biosynthesis*
  • Carbonic Anhydrase IX / biosynthesis
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Carcinoma, Squamous Cell / virology*
  • Cell Hypoxia / physiology
  • Cetuximab / administration & dosage
  • Chemoradiotherapy
  • Cisplatin / administration & dosage
  • Female
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy*
  • Head and Neck Neoplasms / virology*
  • Humans
  • Male
  • Middle Aged
  • Necrosis
  • Papillomaviridae / physiology*
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck
  • Treatment Outcome

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Cetuximab
  • Cisplatin