Serum hypoxia-inducible factor-2: A candidate prognostic biomarker for laryngeal cancer

Clin Otolaryngol. 2021 Nov;46(6):1172-1183. doi: 10.1111/coa.13789. Epub 2021 Jul 22.


Objectives: To determine the serum hypoxia-inducible factor-1, -2 and -3 (HIF-1, -2 and -3) levels in patients with laryngeal neoplasm, and to investigate their role in differential diagnosis, prediction of tumour characteristic and extension, and prognosis and survival.

Study design: Prospective, cohort study at a tertiary referral centre.

Settings: The study was conducted in a tertiary medical centre.

Participants: Patients with benign, premalignant and malignant laryngeal neoplasms were included. Sixty-four patients with a laryngeal neoplasm were enrolled.

Main outcome measures: Serum HIF-1, -2 and -3 levels were measured from blood samples that were drawn before treatment, using ELISA.

Results: A statistically significant difference between benign (HIF-1, -2, -3:4046,1 pg/mL; 2581,5 pg/mL; 1321,0 pg/mL), premalignant (HIF-1, -2, -3:3630,3 pg/mL; 3229,7 pg/mL; 2549,8 pg/mL) and malignant (HIF-1, -2, -3:3576,7 pg/mL; 2595,8 pg/mL; 1106,3 pg/mL) laryngeal neoplasms was not detected when serum HIF-1, -2 and -3 levels were compared. However, high serum HIF-2 level adversely affected survival and locoregional control and had more than 7-fold increase in hazard ratio. Moreover, serum HIF-2 was an independent prognostic factor for 2-year overall, disease-free, distant metastasis-free survival and locoregional control.

Conclusion: This is the first clinical study in which the diagnostic, predictive and prognostic roles of hypoxia-related biomolecules were examined in laryngeal neoplasms. Hypoxia-inducible factor-2 is a prognostic factor in larynx cancer irrespective of treatment modality.

Keywords: biomarker; hypoxia; hypoxia inducible factor; larynx cancer; prognosis; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Basic Helix-Loop-Helix Transcription Factors / blood*
  • Biomarkers, Tumor / blood*
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Humans
  • Hypoxia
  • Laryngeal Neoplasms / blood*
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies


  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor