Differences in PD-L1, PD-L2, and EGFR Expression Between Naive and Recurrent Tumors in Patients With Head and Neck Squamous Cell Carcinoma: A Retrospective Study

Head Neck. 2025 Aug;47(8):2260-2269. doi: 10.1002/hed.28151. Epub 2025 Mar 28.

Abstract

Background: The efficacy of anti-PD-1 and EGFR therapies for head and neck squamous cell carcinoma (HNSCC) can be predicted using various markers; however, the stability of these markers remains unclear.

Methods: In this retrospective study, laboratory findings and tissue expression of PD-L1, PD-L2, and EGFR were analyzed in 79 paired naive and recurrent HNSCC tumors. Laboratory findings were also analyzed in nonrecurrent patients using a propensity score-matched analysis. PD-L1 and PD-L2 expression levels were assessed using tumor proportion score (TPS) and combined positive score (CPS), whereas EGFR was evaluated using the H-score.

Results: White blood cell, neutrophil, lymphocyte, and monocyte counts and lymphocyte-monocyte ratios were significantly lower in the patients after the first-line treatment regardless of recurrence. PD-L1, PD-L2, and EGFR expression changed in 30%-40% of tumor pairs. Immune but not tumoral PD-L1 positivity rates were significantly higher in the patients with early recurrence.

Conclusions: The expression of immune checkpoints including PD-L1 in naive tumors does not reflect those in recurrent tumors. Increasing PD-L1 expression in immune cells may cause early recurrence of HNSCC.

Keywords: EGFR; PD‐L1; PD‐L2; head and neck cancer; immunohistochemistry.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen* / metabolism
  • Biomarkers, Tumor / metabolism
  • ErbB Receptors* / metabolism
  • Female
  • Head and Neck Neoplasms* / metabolism
  • Head and Neck Neoplasms* / pathology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local* / metabolism
  • Neoplasm Recurrence, Local* / pathology
  • Programmed Cell Death 1 Ligand 2 Protein* / metabolism
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / mortality
  • Squamous Cell Carcinoma of Head and Neck* / pathology

Substances

  • B7-H1 Antigen
  • ErbB Receptors
  • CD274 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • PDCD1LG2 protein, human
  • EGFR protein, human
  • Biomarkers, Tumor