Epidemiological and clinical studies over the past two decades have provided strong evidence that genetic elements interacting with environmental components can individually and collectively influence one’s susceptibility to cancer. In addition to tumorigenic properties, numerous environmental factors, such as nutrition, chemical carcinogens, and tobacco/alcohol consumption, possess pro-invasive and pro-metastatic cancer features. In contrast to traditional cancer treatment, modern therapeutics not only take into account an individual’s genetic makeup but also consider gene–environment interactions. The current review sharpens the focus by elaborating on the impact that environmental factors have on the pathogenesis and progression of head and neck cancer and the underlying molecular mechanisms involved. Recent advances, challenges, and future perspectives in this area of research are also discussed. Inhibiting key environmental drivers of tumor progression should yield survival benefits for patients at any stage of head and neck cancer.

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Our results suggest that depletion of peritumoral CD1a+ cells is a strong independent prognostic factor, predicting a higher recurrence rates and worse survival outcomes.

Funding information Brazilian Coordination of Higher EducationObjectives: Oral squamous cell carcinoma (OSCC) predominantly affects males in the fifth decade of life; nevertheless, an increased incidence in young patients has been reported worldwide, and the clinical and behavioral characteristics of tumors in this group are controversial, and the literature shows divergent results. Results: Clinicopathological features and survival rates were similar in both groups.