Association Between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma

Cancer Res Treat. 2016 Apr;48(2):527-36. doi: 10.4143/crt.2015.249. Epub 2015 Sep 15.

Abstract

Purpose: Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the PD-1:PD-L1 pathway. We investigated the expression of programmed cell death-ligand 1 (PD-L1) in HPV-negative and HPV-positive OSCC to determine its prevalence and prognostic relevance.

Materials and methods: Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ≥20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed.

Results: Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(-) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (≥65) (p=0.017) and T3-4 stage (p<0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis.

Conclusion: PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OCSS are warranted regardless of HPV status.

Keywords: Human papillomavirus (HPV); Immune checkpoint inhibitor; Immune therapy; Oropharyngeal Neoplasms; Programmed death ligand-1 (PD-L1).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / analysis*
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / complications*
  • Carcinoma, Squamous Cell / diagnosis*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / complications*
  • Oropharyngeal Neoplasms / diagnosis*
  • Papillomavirus Infections / complications*
  • Prognosis

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human