Research emphasizes the development of generalizations, principles or theories that will be helpful in the prediction of future occurrences.
We would all agree that no aspect of total patient care has been more important than the modern concepts of prevention, diagnosis, treatment and their systemic relationship.
The rate at which oral precancerous and cancerous lesions are spreading like an epidemic is alarming. The prevalence of oral precancerous lesions is much higher than that of oral cancer and these lesions provide useful clinical markers for oral cancer.
Immunological and biochemical alterations in the sera of such patients can help not only in early diagnosis, appropriate treatment but also as indicators of prognosis, as the disease progresses.
Oral cancer is an extremely deadly disease. It comprises approximately 2% of the total malignant tumors in Western Europe and North America, but in India, upto half of the cancers may be present in the mouth .
The etiology of oral squamous cell carcinomas include various carcinogens in tobacco and related products such as polynuclear aromatic hydrocarbons, and nitrosamines. Alcohol, viruses, genetic mechanisms, candida, chronic irritation and diet deficiency states rare also implicated [23, 24].
Amongst the various precancerous lesions and conditions known oral submucous fibrosis is gaining importance because of the large number of case reported in the recent years in the younger generation and because of its obscure etiology. The incidence of malignant changes in patients with oral submucous fibrosis ranges from 3 to 6%. Several factors such as chillies consumption, nutritional deficiency, areca nut chewing, genetic susceptibility, autoimmunity and collagen disorders have suggested to be involved in the pathogenesis of this condition. Currently, areca nut chewing is considered to be most important etiologic factor of oral submucous fibrosis .
The precancerous nature of the most common of chronic oral mucosal lesions, leukoplakia is much better understood now than at any time, since it was first brought to professional attention by Sir James Paget 143 years ago. Oral leukoplakia is well established as one of the very best examples of premalignancy in man. The range of the rate of malignant transformation of this lesion is 3% to 20% .
The immunological abnormalities in patients with cancer in the head and neck appear to be more profound than those associated with cancers of the bronchus, breast, cervix, colon or bladder (Litchenstein et al) . The immunoglobulin deposits may represent immune (antigen-antibody) complexes, since circulating immune complexes have been detected in 75% of patients with head and neck carcinoma (Scully et al) .
Majority of our study group consisted of males (66.67%) who had tobacco, areca nut chewing and associated habits. The mean age was higher in the patients suffering from oral carcinoma.
Gross et al  reported that ageing is associated with a decline in the cell mediated immunity which might predispose to oncogenesis. Circulating immune complexes have been implicated in autoimmune diseases, neoplastic diseases, infectious diseases caused by bacteria, viruses and parasites. Scully C, Barkas T. et al  evaluated the circulating immune complexes in patients with squamous cell carcinoma and found them significantly raised. Hoffken et al  concluded that the elevation of circulating immune complexes was attributed to change in the levels of complement fixing and non-complement fixing of tumour specific antibodies. This implied that it may be possible to monitor the malignant transformation of premalignant lesions. Also, emphasis should be laid on the detection of the antigenic component of the circulating immune complexes.
Chatterjee R. and Guha  estimated levels of circulating immune complexes using polyethylene glycol precipitation assay; which they found to be appropriate and concluded that 60% of patients with carcinoma of the buccal mucosa had markedly higher amount of immune complexes. They also noted that the amount of immune complexes present in patient's sera showed no correlation with serum level of IgG, IgA and IgM.
Balaram P et al  reported increased levels of circulating immune complexes in oral submucous fibrosis patients.
In the presence study the levels of CIC show a gradual increase in the precancer group and the cancer group is characterized by a marked increase in levels which was statistically significant. From these results it can be hypothetised that CIC represent the host's physiological and immunological defense response in eliciting specific antibodies upon exposure to most antigenic substances.
CIC deposition further leads to inflammation and tissue/cell damage. It also leads to suppression of cell mediated immunity and modulates the humoral response.
Circulating immune complexes are normally removed by the mononuclear phagocytic cells. However, circulating immune complexes formations or their defective clearance under certain circumstances becomes detrimental to the host, resulting in pathological deposition. Thus, altering the host immunological response leading to inflammation and tissue injury .
High levels of copper in areca nut, a major etiological factor in OSMF plays an initiating role in stimulation of fibrogenesis by up regulation of lysyl oxidase (Ma. R. H. et al)  and thereby causing inhibition of degradation of collagen. The rise in serum copper may be due to increased turnover of ceruloplasmin (a copper carrying globulin with essential oxidase activity) (Jaydeep et al)  in the serum of carcinoma patients. Varghese et al  concluded a significant reduction in serum copper in oral cancer, OSMF and leukoplakia patients.
Margalith et al  suggested that role of copper ions in biological damage is caused by superoxide radicals or other reducing agents such as ascorbate, which reduce the copper complex. These complexes react with hydrogen peroxide to form hydroxyl radicals that cause damage to protein, RNA and DNA that are not repairable by cellular mechanisms thus initiating the malignant process....
In this study, Serum levels of copper showed gradual increase from precancer to the cancer group as compared to normals which was statistically significant.
Serum Iron levels are considered as biochemical indicators for nutritional assessment. Utilization of iron in collagen synthesis  by the hydroxylation of proline and lysine leads to decreased serum iron levels in OSMF patients. In most cases clinical anemia may be a contributing factor. (Ramanathan et al) .
Occurrence of iron deficiency is known to present in oral cancer. Iron is known to play a key role in the development of hepatic fibrosis probably via oxidative stress and lipid peroxidation . Iron is also required for collagen synthesis by enzymes in hydroxylation of proline and lysine. This hydroxylation of proline and lysine is catalyzed by proline hydroxylase and peptidyl lysine hydroxylase respectively. Peptidyl proline hydroxylase requires as co-factory molecular oxygen, ferrous iron, alpha-ketoglutarate and ascorbic acid .
A statistically significant reduction in the serum iron level was present in the precancer group in our study. A decrease in the iron levels in the cancer group, but higher than that of pre cancer groups was found to be significant.
Recently, haematological abnormalities in oral leukoplakia was reported by Chellacombe . It was reported that poor correlation between iron indices, tumour parameters, serum iron and hemoglobin was probably due to utilization of iron by bone marrow and tumours. Ramanathan K  reported that oral submucous fibrosis may be the manifestation of chronic iron deficiency anemia.
There appears to be an association between the serum iron content and oral carcinogenesis. More detailed studies on a large data base should be instituted to elucidate the exact role of iron.
Selenium forms the integral part of the enzyme glutathione peroxidase, type I iodothyronine deiodinase, metalloprotein, fatty acid binding protein and selenoprotein P. therefore selenium is considered as an antioxidant nutrient and the diseases where low selenium is implicated range from nutritional disorders like protein energy malnutrition to degenerative diseases such as cancer .
Rajendran R  estimated the levels of cadmium, selenium, chromium, magnesium and calcium in the sera of patients with oral leukoplakia, oral submucous fibrosis, squamous cell carcinoma using atomic absorption spectrophotometry. In oral leukoplakia, significant decrease in the serum selenium level was reported. Also oral cancer patients showed reduced levels of selenium.
Krishnaswamy et al  reported decreased selenium levels in both oral/oropharyngeal cancer as compared to matched controls. Since patients in their study were at an early stage of diagnosis, they suggested low selenium level as a causative agent rather than a result of the disease.
Vijaykumar T  reported an increase in serum selenium in oral leukoplakia and oral cancer. Various epidemiological studies have implicated selenium as a cancer protective agent. Studies indicate that higher dietary intake of selenium in humans may be protective.
The serum selenium concentration was found to be decreased. The role of selenium is thus complex which can be attributed to its protective antioxidant role.
A significant positive correlation as present between the serum circulating immune complexes levels and copper in the precancer group. Both parameters showed a steady increase. There was a significant positive correlation found between age of subjects and circulating immune complexes, serum copper and iron levels in the cancer group
Linear regression estimates the coefficient of the linear equation involving one or more independent variables that best predict the value of the dependent variable. Applying linear regression analysis with type of lesions as dependent variable, we identified age, serum iron, CIC and serum levels of selenium as best predictors for the occurrence and progression of lesions in the decreasing order. However, gender and serum copper failed to show any predictive value for the type of lesion. Estimation of CIC and trace elements might help in early detection, differential diagnosis and treatment planning of oral premalignant and malignant lesions.