Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.
