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T-cell priming within tumor-draining lymph nodes (TDLNs) is essential for optimal immune checkpoint inhibitor (ICI) activity. Because neck dissection (ND) removes cervical lymph nodes that may function as TDLNs in head and neck cancer (HNC), its impact on subsequent ICI efficacy remains clinically relevant. This study investigated whether prior ND influences treatment outcomes with nivolumab in recurrent or metastatic HNC.

Fifty-four patients with recurrent or metastatic HNC treated with nivolumab between 2017 and 2025 were retrospectively analyzed. Patients were stratified into locoregional disease (LRD; n=41) and distant metastasis (DM; n=13) cohorts. Within each cohort, outcomes were compared between patients with and without prior ND.

In the LRD cohort (n=41), the median progression-free survival was 2.3 vs. 4.0 months (p=0.089) and median overall survival was 9.8 vs. 18.8 months (p=0.044) for the ND and non-ND groups, respectively. In the DM cohort (n=13), outcomes were unaffected by ND. Multivariate analysis showed a non-significant trend toward worse outcomes in the ND group.

Prior ND was associated with inferior survival in LRD but not in DM-only disease, suggesting that an ND-related loss of TDLN function reduces ICI efficacy.