The dual role of saliva in oral carcinogenesis

Oral squamous cell carcinoma (OSCC), the most common head and neck malignancy, represents a serious public health problem. Exposure to cigarette smoke (CS)/tobacco is considered responsible for up to 90% of cases of this cancer worldwide. Free radicals, which often originate in CS and reactive nitrogen species, are frequently considered to be the reagents capable of triggering the process leading to malignant transformation. Initially dysplastic lesions of the mucosa are transformed into in situ carcinoma lesions, eventually resulting in a full-blown infiltrating and metastasizing OSCC. A synergistic, deleterious interaction between CS and saliva has been reported, which may result in the rapid destruction of biological macromolecules such as enzymes and proteins, giving it a possible pivotal role in the pathogenesis of OSCC. This lethal synergistic effect of CS and saliva is probably based on the reaction between redox-active metals in saliva and low reactive free radicals in CS. This is a novel concept recognizing that when exposed to CS, salivary behavior is reversed and saliva loses its antioxidant capacity, becoming a potent pro-oxidant milieu.