Role of Inflammation in Oral Squamous Cell Carcinoma

The most common malignant oral disease is oral squamous cell carcinoma (OSCC), and most of the time this term is used synonymously with oral cancer (1). Oral cancer is a serious and growing problem in many parts of the world. When grouped together with pharyngeal cancers, it is the sixth most common cancer globally (2). There is a wide geographic variation in the incidence of this cancer. This usually depends on the culture, life style factors and level of country development (1). In the South and Southeast Asia, parts of Western (e.g. France) and Eastern Europe, parts of Latin America and the Caribbean and in the Pacific regions, oral cancer rates are higher than the other parts of the world (3). The major risk factors of the disease are cigarette smoking (4), alcohol abuse (5), and viral infections such as HPV (6). These risk factors are primarily based on life style but do not adequately explain the increasing incidence of this cancer among the young population (7) and nonsmoking females (8). In addition, genetic susceptibility may play an important role (9, 10, 11). Epidemiological studies have shown that chronic inflammation is associated with various types of cancer (12). It is estimated that 15–20% of all deaths from cancer worldwide are linked to infections and inflammatory responses (13). In the last two decades most chronic diseases, including cancer, have been associated with dysregulated inflammatory response. The identification of transcript factors such as NF-κB, AP-1 and STAT3 and their gene products such as tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), chemokines, cyclooxygenase-2 (COX-2), 5 lipooxygenase, matrix metalloproteases (MMP) and vascular endothelial growth factor (VEGF), adhesion molecules and others has provided the molecular basis for the role of inflammation in cancer. These inflammatory pathways are activated by tobacco, stress, dietary agents, obesity, alcohol, infectious agents, irradiation, and environmental stimuli, which, combined, account for as much as 95% of all cancers (14).