Abstract
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.