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At least 90% of head and neck cancers are squamous cell carcinomas (SCCs). This summary discusses the integration of clinical and mechanistic studies in achieving diagnostic and therapeutic precision in the context of oral cancer. Specifically, based on recent mechanistic studies, a subsequent study reevaluated current diagnostic criteria of perineural invasion in patients with oral cavity SCC showing that overall survival could be associated with nerve-tumor distance; validation of the findings of this study from a small group of patients could lead to a personalized approach to treatment selection in patients with oral cavity SCC. 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