Association Between Nutritional Status and Extranodal Extension of Lymph Node Metastases in Head and Neck Squamous...

Extranodal extension (ENE) is a well-established adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC), associated with reduced survival and the need for intensified therapy. Nutritional status-commonly assessed using the Prognostic Nutritional Index (PNI) and Body Mass Index (BMI)-also influences outcomes in HNSCC. However, whether or not ENE correlates with nutritional status has not been previously investigated.

We conducted a retrospective cohort study of 109 treatment-naïve HNSCC patients with pathologically confirmed nodal metastases who underwent primary tumor resection and neck dissection between 2014 and 2025 at a national tertiary center. ENE status was determined histologically. Nutritional status was evaluated using BMI, PNI, serum albumin, and percentage of weight loss at diagnosis. Statistical analyses included t-tests, Chi-square tests, ANOVA, Cox regression, Kaplan-Meier survival analysis, and Full Factorial General Linear Models.

ENE was present in 54.1% of patients and significantly reduced overall survival (Kaplan-Meier p = 0.006; Cox regression RR = 1.927, p = 0.008). No significant differences in BMI, PNI, weight loss, or serum albumin were observed between ENE-positive and ENE-negative groups. ENE prevalence varied significantly by tumor origin (p = 0.018), being highest in hypopharyngeal cancers (75.8%) and lowest in oral cavity tumors (25.0%). ENE status was independent of tobacco use, alcohol abuse, and all nutritional markers across TNM 8/9 subgroups.

ENE is a strong prognostic marker in HNSCC, appearing to be independent of nutritional status. The demonstrated heterogeneity of ENE prevalence among tumor subsites supports the need for individualized management approaches.