Changing landscape of oral squamous cell carcinoma: A scoping review of the pathogenesis, clinical profiles and prognosis of young, non‑smoking patients

Oral squamous cell carcinoma (OSCC) is traditionally associated with long‑term exposure to tobacco and alcohol in older populations. However, a global epidemiological shift has revealed an increasing incidence among adults aged ≤45 years, many of whom lack canonical risk factors. The present scoping review aimed to evaluate the distinct clinicopathological, etiological and molecular landscape of young‑onset OSCC, with a focus on emerging non‑canonical drivers. For this purpose, a comprehensive synthesis of recent high‑volume meta‑analyses (encompassing >50,000 patients), genomic sequencing data and regional epidemiological reports from Central Asia and the Asia‑Pacific was performed. The interplay between traditional carcinogens and novel factors, such as chronic mechanical irritation (CMI) and occupational hazards was analyzed. The analysis revealed a ‘prognostic paradox’: While younger patients faced a higher risk of local recurrence, their 5‑year overall survival rate was superior or equivalent to that of older cohorts (hazard ratio, 0.97), likely due to greater physiological reserve and fewer comorbidities. Molecularly, young‑onset OSCC in never‑smokers and never‑drinkers represents a distinct entity characterized by CDKN2A mutations, EGFR amplifications and a robust IFN‑γ immune response, rather than human papillomavirus‑driven oncogenesis. Furthermore, CMI functions as a potent ‘effect modifier’, lowering the threshold for malignant transformation through the TGF‑β and NF‑κB pathways. On the whole, the present scoping review indicates that the ‘rejuvenation’ of OSCC profiles mandates a shift from age‑based to biology‑driven risk stratification. Addressing non‑canonical factors, such as dental trauma and occupational exposures is essential for early detection and functional preservation in this growing demographic.