Associations among pretreatment tumor necrosis and the expression of HIF-1α and PD-L1 in advanced oral squamous cell carcinoma and the prognostic impact thereof

• Our classical treatment for advanced OSCC with necrotic changes are not effective.
• Association between HIF-1α and PD-L1 is strong in OSCC surrounding necrosis.
• Metastatic lymph node with both necrosis and positive PD-L1 had the worst outcomes.
• PD-L1 immune escape may be one of the underlying sources of treatment resistance.
• Anti-PD-L1 immunotherapy may be choice for advanced OSCC patients with necrosis.

SummaryObjectiveThe treatment strategies for advanced oral squamous cell carcinoma (OSCC), especially with necrotic changes, are not effective. The programmed death ligand 1 (PD-L1) immune escape may be one of the underlying sources of resistance. Furthermore, anti-PD-L1 directed immunotherapy may be another choice for adjuvant therapy. Therefore, the expression of PD-L1 in advanced OSCC with necrotic changes is very important.Materials and methodsA total of 218 eligible patients with advanced stage (stage III/IV) OSCC and neck metastasis were enrolled. The presence of necrosis was reviewed by pretreatment magnetic resonance imaging. Paired paraffin-embedded primary tumor and metastatic lymph nodes (LN) sections were stained with antibodies against hypoxia-inducible factor-1α (HIF-1α) and PD-L1. Moderate-to strong HIF-1α nuclear staining in >10% and cell surface PD-L1 expression in >5% of OSCC cells were recorded as a positive result.ResultsFor advanced OSCC with necrotic changes, there was substantial agreement in primary tumor (kappa value 0.54) and almost perfect agreement in metastatic LN (kappa value 0.86) between HIF-1α and PD-L1 expression. The patients with both necrosis and positive PD-L1 expression in OSCC surrounding necrosis had worse disease control and survival outcomes. After multivariate analysis, metastatic LN necrosis and positive PD-L1 expression were found to be significant independent adverse factors.ConclusionAdvanced OSCC patients with both necrosis and positive PD-L1 expression in OSCC surrounding necrosis had worse outcome. The aggressive behavior of advanced OSCC could be partially related to PD-L1 immune escape. These patients may be good candidates for anti-PD-L1 immunotherapy.