Immunostaining of p53 Is Associated With Efficacy of Anti-PD-1 Immune Checkpoint Inhibitors in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

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Current evidence demonstrates the efficacy of anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in patients with recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC), but only a limited number of patients can benefit. TP53 alteration is one of the most frequent genetic events in HNSCC and may be reflected by aberrant p53 protein expression in tumor cells. Nevertheless, the association between p53 immunohistochemical expression and clinical outcomes in RMHNSCC patients receiving anti-PD-1 therapy remains unclear. We retrospectively analyzed 141 patients with recurrent or metastatic HNSCC who received anti-PD-1 ICIs between January 2017 and December 2023. Immunohistochemical staining in the pretreatment tumor was used to evaluate the expression of p53 and was correlated with the treatment outcome of anti-PD-1 ICIs. Positive p53 expression and tumor proportion score (TPS) <50% were significantly correlated with a poor response to anti-PD-1 ICIs. The overall response rates were 31% and 11% in patients with negative and positive p53 expressions, respectively (P=0.008). Univariate survival analysis showed that positive p53 expression (P=0.012) and TPS <50% (P=0.035) were significantly associated with worse progression-free survival (PFS), and positive p53 expression (P<0.001) was significantly correlated with inferior overall survival (OS). Multivariate analysis revealed that positive p53 expression was an independent poor prognosticator for worse PFS and inferior OS. The 2-year PFS and OS rates were 16% and 32% in patients with negative p53 expression and 8% and 10% in patients with positive p53 expression, respectively. In conclusion, p53 expression in pretreatment tumor specimens was associated with response and survival outcomes in patients with RMHNSCC receiving anti-PD-1 ICIs. Positive p53 expression may serve as a potential prognostic marker for inferior clinical outcomes in this population. Further prospective studies incorporating TP53 sequencing and immune microenvironmental profiling are warranted to validate its clinical utility.