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

TL;DR

This study finds that extranodal extension in head and neck cancers is a strong predictor of poor survival, but it does not seem to be linked to patients' nutritional status.

Contribution

The study is the first to investigate the relationship between extranodal extension and nutritional status in head and neck squamous cell carcinoma.

Findings

Extranodal extension was present in 54.1% of patients and significantly reduced overall survival.

No significant differences in nutritional markers were found between extranodal extension-positive and -negative groups.

Extranodal extension prevalence varied significantly by tumor origin, with highest rates in hypopharyngeal cancers.

Abstract

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.

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