The Prognostic Implications of Discordance Between PD-L1 Expression and Early Lymph Node Metastasis in Hypopharyngeal Squamous Cell Carcinoma

Objectives Hypopharyngeal squamous cell carcinoma (HPSCC) has an aggressive course and poor survival despite multimodal treatment.[1–4] Programmed death-ligand 1 (PD-L1) expression and cervical lymph node metastasis at diagnosis are both linked to prognosis in head and neck squamous cell carcinoma (HNSCC), but how they act together in HPSCC is still uncertain. We asked whether agreement or disagreement between PD-L1 expression and early lymph node metastasis (ELNM) could help refine risk stratification in HPSCC. Methods We retrospectively reviewed consecutive patients with newly diagnosed, histologically confirmed primary HPSCC treated at [Institution name] between [Month Year] and [Month Year]. PD-L1 expression was assessed by immunohistochemistry on pretreatment tumour specimens using the 22C3 antibody and a semi-quantitative scoring system. PD-L1 positivity was defined using a previously validated composite score. ELNM was defined as radiologically and/or pathologically confirmed cervical lymph node metastasis present at initial diagnosis. Patients were grouped according to the combination of PD-L1 status and ELNM: double-negative (PD-L1−/ELNM−), discordant (PD-L1+/ELNM − or PD-L1−/ELNM+), and double-positive (PD-L1+/ELNM+). Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan–Meier method and compared using the log-rank test. Multivariable Cox models were used to examine the independent prognostic value of PD-L1/ELNM profiles. Results A total of 65 patients were included. The distribution of PD-L1/ELNM profiles was: double-negative (PD-L1−/ELNM−), discordant (PD-L1+/ELNM − or PD-L1−/ELNM+), and double-positive (PD-L1+/ELNM+). Patients with the double-positive profile more often had advanced T and N categories and high-grade histology but, somewhat unexpectedly, showed better OS and PFS than the double-negative and discordant groups. In contrast, patients with PD-L1−/ELNM + disease had the worst outcomes. In multivariable analyses adjusted for age, clinical stage and primary treatment, the double-positive profile remained independently associated with improved OS and PFS, whereas the discordant profile—especially PD-L1−/ELNM+—identified a high-risk group. Conclusion In this retrospective cohort of HPSCC, combining PD-L1 expression and ELNM status defined distinct prognostic subgroups. The PD-L1+/ELNM + profile was linked with better survival despite more advanced disease, while PD-L1−/ELNM + carried the highest risk of treatment failure. These findings suggest that integrating PD-L1 status with baseline nodal involvement may add prognostic information beyond standard staging in HPSCC and should be confirmed in larger, multi-centre prospective studies.