<p>Head and neck cancers (HNCs) represent a significant health burden in India, marked by regional variability in presentation and outcomes. This study aimed to evaluate the epidemiological, clinical, and prognostic characteristics of HNC patients over a five-year period at a tertiary care center in Visakhapatnam. A retrospective review was conducted on 305 histopathologically confirmed HNC cases treated between January 2018 and December 2022. Data on demographics, tumor characteristics, treatment modalities, and outcomes were extracted from institutional records. A five-year overall survival (OS) and disease-specific survival (DSS) were assessed using Kaplan–Meier estimates and log-rank tests. Independent prognostic factors were identified via multivariate Cox proportional hazards regression. The majority of patients were male (83.9%) and aged 41–60&#xa0;years (62%). The tongue was the most common site of recurrence (10.2%), and squamous cell carcinoma was the predominant histology. Moderate differentiation was noted in 47.2% of tumors. At last follow-up, 56.4% were alive, 23.0% had died, and 20.7% were lost to follow-up. Vascular and perineural invasion were significantly associated with poorer OS and DSS in univariate analysis. In multivariate analysis, only Worst Pattern of Invasion (WPOI) 2 was an independent predictor of reduced OS (HR = 2.384; 95% CI: 1.136–5.006; <i>p</i> = 0.022). Nodal involvement and recurrence also showed significant associations with survival outcomes. This study highlights the epidemiological and prognostic landscape of head and neck cancer in a regional Indian population. WPOI 2 showed a possible prognostic role, but given its rarity and wide confidence intervals, this finding is hypothesis-generating. The results emphasize the need for improved early detection, risk-adapted treatment, and follow-up, with validation in larger prospective multicentre studies.</p> Graphical Abstract <p></p>