Survival Outcomes of Head and Neck Neuroendocrine Carcinoma: A Systematic Review.

Aïta, Morena; Galofaro, Ilario; Maniaci, Antonino; Lechien, Jerome R · Head Neck · 2026

systematic_review · Level I

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Abstract

This systematic review investigated pathological, oncological, and survival outcomes of Head and neck neuroendocrine carcinoma (HNNEC). Three independent investigators conducted a PRISMA-compliant literature search. Primary outcomes included tumor stage, overall survival (OS), disease-free survival, recurrence, metastasis, and therapeutic strategies. The most common locations were the larynx (n = 1041), sinonasal tract (n = 917), and oropharynx (n = 366), mostly cT2/cT4 and cN0/cN2. Small-cell carcinoma predominated (n = 2334). Laryngeal tumors were preferentially treated by surgery plus radiotherapy, sinonasal/nasopharyngeal tumors by chemoradiotherapy, and salivary tumors by surgery with adjuvant therapy. Surgical cohorts achieved 5-year OS of 33.0%-73.9%, and multimodal CRT-plus-surgery 57.2%-61.0%. Laryngeal and mucosal tumors had more favorable outcomes than sinonasal/salivary localizations; well/moderately-differentiated carcinoids outperformed poorly-differentiated and small-cell variants (median OS < 24 months). HNNEC survival strongly depends on histology, site, and treatment modality. Substantial therapeutic heterogeneity reflects the lack of guidelines, highlighting the need for standardized, histology- and site-specific management recommendations.