Cervical lymph node metastases are major prognostic determinants in head and neck squamous cell carcinoma (HNSCC), and neck dissection (ND) has long been central to regional control. As ND has evolved from radical to selective procedures, immune checkpoint inhibitors (ICIs) have emerged as a fourth treatment pillar, reframing tumor-draining lymph nodes (TDLNs) as active immune organs rather than passive conduits of metastatic spread. This narrative review synthesizes surgical, immunologic, and translational evidence on how ND and cervical irradiation interact with immunotherapy. It also examines the historical development of ND, the immunologic structure and function of cervical TDLNs, and the use of neoadjuvant, perioperative, and recurrent/metastatic immunotherapy in HNSCC. Preclinical and early clinical observations suggest that ablating or heavily irradiating non-involved nodal basins may attenuate ICI efficacy by disrupting antigen presentation, progenitor exhausted CD8+ T (Tpex) cell pools, and effector recirculation, supporting the conceptual model of an “immune desert neck.” The review critically appraises timing (pre- versus post-immunotherapy ND), response-adapted or de-escalated surgery, and imaging, tissue-based, and circulating biomarkers to guide individualized management. Current evidence does not support abandoning elective or therapeutic ND, but does highlight the need for biomarker-driven, lymphatic-sparing trials to redefine when ND is essential, modifiable, or potentially avoidable in immunotherapy-treated HNSCC.
Lorenzi et al. (Sun,) studied this question.