BackgroundAlthough pembrolizumab is recommended as a first-line treatment for advanced recurrent/unresectable/metastatic (R/U/M) head and neck squamous carcinoma, the differences in its efficacy among different populations need to be investigated.MethodsWe reviewed 15 consecutive patients with R/U/M oral squamous cell carcinoma (OSCC) treated with pembrolizumab monotherapy at the Affiliated Hospital of Qingdao University between February 2021 and May 2022. All the 15 patients had known programmed death-ligand 1 expression and received multiple cycles of pembrolizumab monotherapy as first-line treatment. We evaluated and analyzed patients' basic characteristics, time to first remission, the clinical efficacy of pembrolizumab monotherapy, and treatment-related adverse reactions.ResultsThe objective response rate of the 15 patients was 60%. Six patients (40.0%) achieved partial response, while three patients (20.0%) achieved complete response. In our study, the objective response status of the patients was observed in two to five cycles (mean, 3.6 cycles). For patients who responded well to immunotherapy, the mean Karnofsky Performance Status (KPS) score after treatment was significantly higher than that before treatment (P< 0.001). The progression-free survival rates were 66.9% and 50.1% at 6 months and 1 year, respectively. Eight adverse events were observed, comprising four cases of rash and one case each of hypothyroidism, interstitial pneumonia, cheilitis, and cerebral thrombosis.ConclusionOur study suggests that pembrolizumab is beneficial to the most responsive patients with R/U/M OSCC in our single-center study and may shed light on the management of OSCC.