Oral squamous cell carcinoma: epidemiology, etiology, and treatment

Oral squamous cell carcinoma is one of the most important forms of oral cancers with unfortunately very poor prognosis rate. Surgery, radiation and chemotherapy constitute the mainstay treatment so far. With our progressing knowledge in molecular biology and the increasing understanding of the various signaling pathways there is no question of doubt that in the near future the prognosis for OSCC would be considerably improved. As with any other disease, prevention is better than cure. Avoiding the well-known risk factors, a well-balanced nutritional plan and regular dental health checkups are the most effective means of preventing Oral cancers.

Oral cancer continues to be one of the most dangerous forms of cancer worldover. While the fatality rate of cancer in general has declined over the last several years the survival rates for oral cancer has not shown a similar decline. In the United States alone more than 30000 people are diagnosed with oral cancer every year with an annual death rate of around 7500 people. [1] Squamous cell carcinoma is the single most important oral malignancy accounting for almost 90% of the oral cancers. [2] Oral cancer includes malignancy of the lip, tongue, salivary glands, gum, mouth, pharynx, oropharynx and the hypopharynx. [3] The poor prognosis of oral cancer is largely due to the very late stage diagnosis often identified only when the cancer has already metastasized into other regions of the body such as the neck and the upper digestive tract. Early diagnosis of oral cancer is important, as poor oral hygiene and periodontal disease have been implicated as high risk factors for developing neck, head and esophageal cancers. A brief overview of the epidemiology, etiology, and the treatment interventions would provide better insight into this important health issue.

Epidemiology of Oral Squamous cell Carcinoma

Oral cancers are among the top ten cancers in humans constituting around 3% of all cancers and oral Squamous Cell Carcinoma (OSCC) represents around 90 to 95% of all oral cancers. OSCC is more common among men compared to women with a ratio of 3:2. Though, known to have a very high incidence rate among those in the fifties and sixties recent data indicate a growing prevalence of OSCC among people under 40 years of age. Race wise, Caucasians and African-Americans have higher prevalence rates compared to Hispanics and Asians. While 46% of Caucasians presented with regional disease the comparable rate was higher in African-Americans at 57%. The survival rates also vary significantly between the races at 50% for whites and 31% for African-Americans for the regional form of OSCC. Clinical statistics also indicate that around 10 to 35% of the people with oral SCC develop secondary tumors in the aerodigestive tract. [4, pg 345]

Clinical Features and Histopathology

Usually oral lesions tend to be unnoticed and asypmtomatic during the initial stages. This is the main reason why the survival rates are poor for oral cancers, as most patients are not diagnosed until they are in advanced stages of the disease. Routine dental screening would help in early diagnosis and intervention. Symptoms of Oral squamous cell carcinoma include abnormal lip or mouth sores that do not heal. A red (erythroplakia) or white patch (leukoplakia) on the inner cheek lining, lips or the mouth floor, swelling of the jaw, unusual bleeding, chronic sore throat with pain during swallowing, [8] Keratinization occurs in areas of physical or chemical trauma. Histopathology of the Oral lesions reveal large irregular granular mass protrusions of anaplastic squamous cells that destroy the normal anatomy. For example, study of the tongue affected by tumor would reveal abnormal surface growth with degenerated tongue skeletal muscles. Keratin pearl formation would be distinctly visible under microscopic examination. Unusually enlarged hyperchromatic nuclei with intercellular bridges can also be clearly observed. The different degrees of keratinization are used in the morphological classification of squamous cell carcinoma. [9]

A recent study by Rao et. al (2008) studied the expression pattern of cytokeratin 1, 5, 8,18 and Vimentin in 48 patients with diagnosed condition of oral squamous cell carcinoma. Immunohistochemical study was performed using monoclonal antibodies for CK 1, 5, 8, 18 and vimentin. The results from the study clearly attested abnormal expression of the CK1 30%, CK8 in 54%, CK18 in 44% and vimentin in 85% of the tumors. The researchers also observed that in 88% (7/8) of the subjects who had recurrence within 6 months there was a marked expression of CK 8 or 18 and vimentin clearly suggesting them as effective biomarkers for OSCC. [10] Another recent study by gang et.al (2008) focused on the expression of ?-Catenin in seventy six patients identified with oral sqamous cell carcinoma and 16 metastatic lymph node cases. Healthy oral epithelium has strong expression of ?-Catenin along the cell membranes but almost no expression at the cytoplasmic or nuclear sites. However, the researchers found reduced expression of ?-Catenin at the cell membrane in almost 71% of the cases (54 patients), cytoplasmic expression in 17 patients (22.4%) and three cases with nuclear ?-Catenin expression. In the patients with lymph node metastasis, cell membrane level expression was severely reduced in 13 of the 16 patients and very weak expression was noticed in the remaining three patients. These results indicate that ?-Catenin expression at the cell membrane maybe inversely associated with OSCC [11]

Treatment of OSCC

Treatment for OSCC involves a variety of methodologies including radiation, chemotherapy, surgery and the new genetic therapy. Surgery is usually limited to cancers that are diagnosed early and limited to a very small region. For well advanced oral cancers where the cancer has metastasized to the lymph nodes surgery along with radiation and chemotherapy maybe required. If the tongue is totally affected then the surgeon would have to perform a glossectomy. (Removal of the tongue) Therapeutic interventions target the tyrosine-kinase inhibitors. In particular, most drugs target the epidermal growth factor-receptor (EGFR) and cyclin dependent kinase (CDK) inhibitors.[5] Alternative therapies are also gaining increasing focus in the recent years. One particular study by King et.al (2007) focused on the efficacy of proanthocyanidin (PAC), a plant derived compound in controlling the progress of oral squamous cell cancer. Using in vitro cell assays the researchers studied the effects of PAC on cell proliferation. The researchers also studied the effects of PAC on HPV transfected OSCC. The results from the study indicated that PAC administration had a significant suppressive effect on OSCC proliferation. The researchers also observed that the use of PAC controlled the increase in cell proliferation observed after transfection with HPV clearly suggesting a positive treatment potential for PAC. Though the exact molecular pathway of action of PAC still stands to be understood ((mitogen activated protein kinase), ODC (ornithine decarboxylase), EGFR (epidermal growth factor receptor)

) the researchers concluded that PAC excels as a non-toxic and powerful anti-cancer agent that could be used in the management of OSCC. [1]

Conclusion

Oral squamous cell carcinoma is one of the most important forms of oral cancers with an unfortunately very poor prognosis rate. The asymtomatic nature of oral cancers make early diagnosis literally impossible. Routine oral screening and the development of new biomarkers would enable us to detect OSCC much earlier and intervene most effectively. The development of genetic therapy and the use of adjuvant alternative therapies would significantly improve the disease prognosis for OSCC. With our progressing knowledge in molecular biology and the increasing understanding of the various signaling pathways there is no question of doubt that in the near future the prognosis for OSCC would be considerably improved. As with any other disease, prevention is better than cure. Avoiding the well-known risk factors, a well-balanced nutritional plan and regular dental health checkups are the most effective means of preventing Oral cancers.