Oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC) represents an increasing problem in the global public health. Indeed, squamous cell carcinoma is the most frequent malignancy in oral cavity and 1 of the 10 most common cancers worldwide. According to the most recent GLOBOCAN estimate in Europe between 2012 and 2015, there was an overall increasing incidence and mortality for oral cancer, mostly HPV-related in the oropharyngeal region with evidence of significant differences from the prognostic and therapeutic point of view. Areas covered: Until now, the management of the patients is based on classical histologic parameters such as TNM and tumor grading, but new molecular and cell markers have been investigated to improve patients' treatment and survival. Therefore, there is a need for new biomarkers characterizing the cancer diversity, with the consequent possibility of patient stratification for specific treatment. Expert commentary: This review aims to discuss some of the most relevant and novel genetic, epigenetic, and histological prognostic biomarkers in oral cancer, highlighting the main differences between HPV-unrelated oral squamous cell carcinoma (OSCC) and HPV-related oropharyngeal squamous cell carcinoma (OPSCC) that may aid in stratifying prognostic subgroups and rationalizing treatment decisions.
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