HIF-1a expression and differential effects on survival in patients with oral cavity, larynx, and oropharynx squamous cell carcinomas

Head Neck. 2021 Mar;43(3):745-756. doi: 10.1002/hed.26530. Epub 2020 Nov 5.

Abstract

Background: Hypoxia is a negative prognostic factor in head and neck squamous cell carcinomas. Under hypoxia, the hypoxia-inducible factor (HIF)-1a transcription factor is overexpressed. We investigated whether there were site differences in HIF-1a expression and its effect on patient outcomes per subsite.

Design/method: A total of 941 patients with HNSCC in the squamous cell carcinoma of the oropharynx (OPSCC, n = 302), oral cavity (OSCC, n = 391), or larynx (LSCC, n = 248) were included. Expression of HIF-1a in tissue samples was investigated using immunohistochemistry. Overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were analyzed.

Results: HIF-1a expression was higher in OSCC than in LSCC and OPSCC. High HIF-1a expression led to worse prognosis in OPSCC (OS P = .029, DFS P = .085) and LSCC (OS P = .041, DFS P = .011) and better in OSCC (OS P = .055, DFS P = .012). There was no association between HIF-1a and LRC.

Conclusions: High HIF-1a expression is related to poor outcome in OPSCC and LSCC and better outcome in OSCC.

Keywords: head and neck neoplasms; hypoxia; oropharyngeal neoplasms; survival; tumor microenvironment.

MeSH terms

  • Carcinoma, Squamous Cell*
  • Head and Neck Neoplasms*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Larynx
  • Mouth
  • Oropharynx
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck
  • Survival Rate

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit