An epidemiologic assessment of cancer risk in oral precancerous lesions in India with special reference to nodular leukoplakia

A cohort of 12,212 tobacco users was followed up annually to assess malignant potential of oral precancerous lesions in the Ernakulam district in Kerala, India. A total of 19 new oral cancers were diagnosed over a period of 8 years, and 15 (79%) of these arose from some preexisting precancerous lesion or condition. Nodular leukoplakia showed highest rate of malignant transformation (16% per year) as six of 13 nodular leukoplakia underwent malignant transformation over a mean follow-up period of 2.8 years. The relative risk (3243.2) compared with individuals with tobacco habits but without any precancerous oral lesion was also the highest for nodular leukoplakia. In addition, nodular leukoplakia was associated with submucous fibrosis in two patients, which progressed to oral cancer and was the clinical diagnosis for four lesions that turned out to be malignant on histopathologic examination. Nodular appearance was noted in two other precursor lesions as well. Thus, 14 of 19 oral cancers (74%) were either preceded by nodular leukoplakia and with lesions showing a distinct nodular appearance, or had the clinical appearance of nodular leukoplakia.     

Oral premalignant lesions: from a clinical perspective

In this review article, the clinical and histopathological characteristics of oral premalignant lesions, and primarily oral leukoplakia, are noted and the risk factors for malignant transformation of oral leukoplakia are discussed. Malignant transformation rates of oral leukoplakia range from 0.13 to 17.5%. The risk factors of malignant transformation in the buccal mucosa and labial commissure are male gender with chewing tobacco or smoking in some countries such as India, or older age and/or being a non-smoking female in other countries. Some authors have reported that leukoplakia on the tongue or the floor of the mouth showed a high risk of malignant transformation, although others have found no oral subsites at high risk. In concurrence with some authors, the authors of this review view epithelial dysplasia as an important risk factor in malignant transformation; however, there are conflicting reports in the literature. Many authors believe that nonhomogeneous leukoplakia is a high risk factor without exception, although different terms have been used to describe those conditions. The large size of lesions and widespread leukoplakia are also reported risk factors. According to some studies, surgical treatment decreased the rate of malignant transformation; however, many review articles state that no definitive treatment including surgery can decrease the malignant transformation rate of oral leukoplakia because of the lack of randomized control trials of treatment. Tobacco chewing and smoking may be causative agents for cancerization of oral leukoplakia in some groups, and evidence for a role of human papilloma virus in the malignant transformation of oral leukoplakia is inconsistent. Further research to clarify its role in malignant transformation is warranted.     

Long-term treatment outcome of oral premalignant lesions

The purpose of the present retrospective study was to learn the long-term outcome of oral premalignant lesions, leukoplakia and erythroplakia, with or without surgical intervention and to relate the outcome to factors supposed to be significant for malignant development including clinical type, demarcation, size, site, presence of epithelial dysplasia, smoking and surgery. A total of 269 lesions in 236 patients were included. Ninety-four lesions were surgically removed, 39 lesions (41%) being homogenous and 46 (49%) non-homogenous leukoplakias whereas nine (5%) were erythroplakias. Seventy-three percent of the lesions were associated with tobacco habits. The mean size of the lesions was 486 mm(2), and 71% of the lesions showed a degree of epithelial dysplasia. After excision the defects were closed primarily by transposition of mucosal flaps or they were covered by free mucosal or skin grafts. A few defects were left for secondary healing. After surgical treatment the patients were followed (mean 6.8 yrs, range 1.5-18.6 yrs), and new biopsies taken in case of recurrences. One hundred and seventy five lesions had no surgical intervention, 149 lesions (85%) being homogenous and 20 (11%) non-homogenous leukoplakias, and 6 (3%) erythroplakias. Eighty-one percent of the lesions were associated with smoking. The mean size of the lesions was 503 mm(2) and 21 of the lesions (12%) exhibited epithelial dysplasia. Sixty-five lesions were not biopsied. These patients were also followed (mean 5.5 yrs, range 1.1-20.2 yrs), and biopsies taken in case of changes indicative of malignant development. All patients were encouraged to quit smoking and candidal infections were treated. The possible role of different variables for malignant development was estimated by means of logistic regression analysis. Following surgical treatment 11 lesions (12%) developed carcinoma after a mean follow-up period of 7.5 yrs. Non-homogenous leukoplakia accounted for the highest frequency of malignant development, i.e. 20%, whereas 3% of the homogenous leukoplakias developed carcinomas. Surgically treated lesions with slight, moderate, severe and no epithelial dysplasia developed carcinoma with similar frequencies, i.e. 9-11%. Without surgical intervention 16% of the 175 lesions disappeared whereas seven lesions (4%) developed carcinoma after a mean observation period of 6.6 yrs. The highest frequency of malignant development (15%) was seen for non-homogenous leukoplakias, this figure being 3% for homogenous leukoplakias. Fourteen percent of lesions with slight epithelial dysplasia developed malignancy and 2% of lesions with no dysplasia showed malignant transformation. Logistic regression analysis showed a seven times increased risk (OR = 7.0) of non-homogenous leukoplakia for malignant development as compared with homogenous leukoplakia and a 5.4 times increased risk for malignant development for lesions with a size exceeding 200 mm(2). No other examined variables including presence of any degree of epithelial dysplasia, site, demarcation, smoking and surgical intervention were statistically significant factors for malignant development.     

Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management

In a recently held WHO workshop it has been recommended to abandon the distinction between potentially malignant lesions and potentially malignant conditions and to use the term potentially malignant disorders instead. Of these disorders, leukoplakia and erythroplakia are the most common ones. These diagnoses are still defined by exclusion of other known white or red lesions. In spite of tremendous progress in the field of molecular biology there is yet no single marker that reliably enables to predict malignant transformation in an individual patient. The general advice is to excise or laser any oral of oropharyngeal leukoplakia/erythroplakia, if feasible, irrespective of the presence or absence of dysplasia. Nevertheless, it is actually unknown whether such removal truly prevents the possible development of a squamous cell carcinoma. At present, oral lichen planus seems to be accepted in the literature as being a potentially malignant disorder, although the risk of malignant transformation is lower than in leukoplakia. There are no means to prevent such event. The efficacy of follow-up of oral lichen planus is questionable. Finally, brief attention has been paid to oral submucous fibrosis, actinic cheilitis, some inherited cancer syndromes and immunodeficiency in relation to cancer predisposition.     

Oral leukoplakia: a Clinicopathological review

Leukoplakia is the most common premalignant or potentially malignant lesion of the oral mucosa. It seems preferable to use the term leukoplakia as a clinical term only. When a biopsy is taken, the term leukoplakia should be replaced by the diagnosis obtained histologically. The annual percentage of malignant transformation varies in different parts of the world, probably as a result of differences in tobacco and dietary habits. Although epithelial dysplasia is an important predictive factor of malignant transformation, it should be realized that not all dysplastic lesions will become malignant. On the other hand non-dysplastic lesions may become malignant as well. In some parts of the world the tongue and the floor of the mouth can be considered to be high-risk sites with regard to malignant transformation of leukoplakia, while this does not have to be the case in other parts of the world. The cessation of tobacco habits, being the most common known aetiological factor of oral leukoplakia, has been shown to be an effective measure with regard to the incidence of leukoplakia and, thereby, the incidence of oral cancer as well. Screening for oral precancer may be indicated in individuals at risk.     

Impact of betel quid, tobacco and alcohol on three-stage disease natural history of oral leukoplakia and cancer: implication for prevention of oral cancer.

The natural history of the three-stage process from normal, oral leukoplakia to oral cancer in relation to betel quid chewing, smoking and drinking is rarely addressed. The aim of this study was to simultaneously quantify the effects of three risk factors on occurrence of oral leukoplakia and malignant transformation to oral cancer. A hospital-based case-control study design derived from three retrospective cohorts from 1988 to 1998 was conducted. A total of 74 oral cancer patients, 164 patients with oral leukoplakia and 187 controls were interviewed to collect information on their betel chewing, smoking and drinking habits. The effects of the three risk factors on the progression rates of the three-stage disease process were estimated using the three-state Markov model. Subjects who chewed betel quid were at greater risk of leukoplakia (adjusted odds ratio (OR) 17.7 (9.03-34.5)) but there was no significant effect on malignant transformation (OR 1.04 (0.61-1.76)). Smoking played a major role in the onset of leukoplakia (OR 4.26 (2.21-8.23)) but a minor role in malignant transformation (OR 1.36 (0.69-2.68)). Alcohol was positively associated with malignant transformation (OR 2.37 (1.47-3.82)) but unrelated to occurrence of leukoplakia (OR 0.76 (0.04-1.43)). We concluded that smoking and betel quid were two significant risk factors for the occurrence of leukoplakia, whereas alcohol was significantly responsible for malignant transformation.     

Oral leukoplakia and malignant transformation. A follow-up study of 257 patients

Two hundred fifty-seven patients with oral leukoplakia were studied and followed for an average period of 7.2 years. All lesions were more than one cm in size and had been present and observed for a minimum of 6 months. Of the initial biopsies, 235 revealed a benign hyperkeratosis and 22 others contained some degree of epithelial dysplasia. Seventy-three percent of the patients used tobacco, with cigarette usage being the predominant form. Forty-five patients (17.5%) subsequently developed squamous carcinomas in the hyperkeratotic epithelial site in an average time of 8.1 years. Eight of these malignant transformations came from patients who originally had epithelial dysplasia. High risks for malignant transformation also included non-smoking patients, the clinical presence of erythroplasia (erythroleukoplakia), and a clinical verrucous-papillary hyperkeratotic pattern. Duration of the leukoplakia progressively increased the total number of malignant transformations, with the largest rate occurring in the second year. This study confirms that oral leukoplakia is a precancerous lesion and that certain characteristics indicate greater risks and warrant consideration of more aggressive management.     

Malignant transformation and natural history of oral leukoplakia in 57,518 industrial workers of Gujarat, India.

In Gujarat, India, 6718 industrial workers, over 35 years of age, with oral leukoplakia (confirmed clinically and microscopically), were studied. After 2 years, 4762 (71%) of the individuals were re-examined. The buccal mucosa was the most common site of occurrence; 98.3% of these individuals had oral habits, with smoking alone or smoking in combination with "pan" or "supari" chewing accounting for 74.9% of the habit forms. Six individuals (0.13%) with oral leukoplakia developed oral carcinomas within 2 years. This incidence of malignant transformation was equivalent to 63/100,000 per year, which far exceeds that of new oral cancers expected even in high-risk populations. While 57.3% the leukoplakic lesions remained unchanged during a 2-year interval, 31.6% disappeared and 11% had an altered appearance. This study confirmed the precancerous nature of oral leukoplakia.     

Smokeless tobacco and oral cancer: a cause for concern?

Until recently, the use of smokeless tobacco had been restricted to a relatively small percentage of the United States population. The increased promotion and use of both snuff and chewing tobacco raise the question: What effect will such habits have on oral disease and the incidence of oral cancer? Although information for the US is sparse, extensive epidemiologic data are available from India, where the use of tobacco is prevalent and the incidence of oral cancer very high. The Indian data suggest that oral cancer and precancerous lesions occur almost solely among those with tobacco habits, the rate of malignant transformation of precancerous lesions is not greater than in the West, the relative risk of developing oral cancer is similar in India and in the US, and this risk rises with duration of use. Thus, it seems likely that increased usage of smokeless tobacco in the US will eventually lead to an increased incidence of precancerous and cancerous oral lesions in Americans.     

Topical application of vitamin A to oral leukoplakia: A clinical case series.

BACKGROUND: Due to the possibility of malignant transformation of oral leukoplakia, these lesions must be assessed and managed closely and, if not resolved, must be reassessed on a regular basis. METHODS: This study evaluated the use of topical 0.05% vitamin A (tretinoin) acid gel for the treatment of oral leukoplakia. Tretinoin was applied topically 4 times a day for the management of nonmalignant oral white lesions in 26 patients. The clinical response was evaluated in all patients and posttreatment biopsies were performed in ten patients. RESULTS: The mean age of the patients at the time of diagnosis was 62 years. Of the 26 patients, 50% were tobacco users. Patients were followed for a mean of 23 months. Approximately 27% of the patients had a complete clinical remission. Recurrence of leukoplakia was observed in approximately 40% of patients in whom complete clinical remission occurred if topical applications were discontinued. A 50% reduction in the clinical grade of leukoplakia from a mean of 2.8 to 1.4 on a scale ranging from 0 (no leukoplakia) to 4 (speckled leukoplakia) was observed. When the pretreatment and posttreatment biopsies from 10 patients were evaluated, no change in the mean histologic grade (between mild and moderate dysplasia) was noted; however, some reduction in the histologic grade was noted in 3 of these patients (30%). CONCLUSIONS: The use of topical vitamin A acid showed a limited effect in controlling oral leukoplakia. Further studies are needed to establish the appropriate indication, efficacy, and best choice for chemoprevention agents. Close follow-up of all patients with oral leukoplakia is required.     

Risk factors for leukoplakia and malignant transformation to oral carcinoma: a leukoplakia cohort in Taiwan

The effects of betel nut chewing, smoking and alcohol on the occurrence of leukoplakia and its malignant transformation to oral carcinoma were quantified in a leukoplakia cohort (n = 435) from one medical centre between 1988 and 1998 in Taiwan. Sixty oral carcinomas were ascertained in this cohort. A case-control study within the leukoplakia cohort was used to study, risk factors. Using the Weibull survival model, the incidence of malignant transformation of leukoplakia was shown to increase with follow-up years. After adjustment for other relevant risk factors, betel nut chewing (adjusted odds ratio (OR) = 4.59; 95% confidence interval (CI) 1.25-16.86) remained a significant risk factor for malignant transformation. Results from the case-control study showed that the adjusted odds ratios for betel nut chewing and smoking on the occurrence of leukoplakia were 17.43 (95% CI 1.94-156.27) and 3.22 (95% CI 1.06-9.78), respectively. Similar findings were observed when daily frequency and duration were taken into account. This implies that cessation of smoking may reduce by 36% leukoplakia cases, while elimination of betel nuts may prevent 62% of leukoplakia and 26% of malignant transformation to oral carcinoma in the underlying population.     

Potency of Pfeiffer’s Crystallization to Analyze Oral Leukoplakia and Squamous Cell Carcinoma

Objective: Oral cancer usually has an early precancerous stage before its actual malignant transformation. Although there are various approaches to diagnose early stages of cancer, yet there is one less explored, cost effective and simple technique known as crystallization test. The aim of the study was to reaffirm the effectiveness of Pfeiffer’s crystallization test in screening oral leukoplakia and squamous cell carcinoma. Methods: Fifty oral leukoplakia, sixty five oral squamous cell carcinoma and sixty healthy individuals participated in crystallization test. Single blood drop was used to perform the test and obtained crystal patterns were analysed. Cross tabulation and Chi-Square test was performed to find the frequency and association between the groups. Kruskal-Wallis H test and Mann Whitney U test was applied comparing mean transverse form. Results: Sensitivity of crystallization test was 80% and 93.84% in oral leukoplakia and squamous cell carcinoma. Chi-Square analysis revealed highly significant transverse form between the study groups (p < 0.000). Conclusion: Crystallization test proves to be simple, reliable and minimal invasive diagnostic approach under strictly maintained physical conditions.     

Laser surgery as a treatment for oral leukoplakia

Various treatment procedures for oral leukoplakia have been reported. However, after some treatments, oral leukoplakia show recurrence and/or malignant transformation, even following complete resection. Furthermore, patients with oral leukoplakia may develop new lesions in other oral cavity locations. Laser surgery for oral mucosal lesions has been reported to have many advantages, and it is widely used in the treatment of oral leukoplakia. In previous studies, recurrence and malignant transformation from the lesion have occasionally been observed following laser surgery. We reviewed the records of oral leukoplakia patients treated with laser surgery to assess its clinical usefulness. It has been reported that the rate of recurrence was 7.7–38.1%, while malignant transformation was 2.6–9% for oral leukoplakia treated with laser surgery. In the present study, there was 29.3% recurrence and 1.2% malignant transformation after laser surgery. This was similar to previous findings. This suggests that non-homogeneous leukoplakia on nonkeratinized epithelia, i.e. the tongue mucosa has a high risk for malignant transformation, so lesions should be excised after detecting abnormal epithelia using vital tissue staining. The wound healing process after laser surgery was satisfactory and no significant complications were observed. Management of oral leukoplakia prevents not only recurrence and malignant transformation, but also postoperative dysfunction: laser surgery is an excellent procedure that is able to overcome these problems.     

Overexpression of p53 protein in betel- and tobacco-related human oral dysplasia and squamous-cell carcinoma in India

The aetiological factors for oral cancer are not the same in India and in Western countries. Epidemiological studies have shown a correlation between high incidence of oral cancer and heavy consumption of betel and/or tobacco in the Indian population, while this stud/ indicates an association with a genetic change. The p53 tumour-suppressor gene is the most commonly identified mutated gene in human malignancies. Expression of p53 protein was examined in premalignant and malignant oral lesions from Indian patients who were consumers of betel, areca nut and/or tobacco, using anti-p53 monoclonal antibodies PAb 1801 and PAb 421. Cryosections from normal, premalignant or malignant oral mucosa were used for immunostaining and the observations were confirmed by immunoprecipitation. P53 protein was detected in 55% (15/27) premalignant oral lesions (leukoplakia). Strong p53-positive staining was detected in 75% (24/32) of oral squamous-cell carcinomas. Normal oral mucosa did not show positive p53 staining (0/24). The detection of p53 protein in premalignant oral lesions suggests that p53 aberrations are an early event in the development of oral cancer in India. The high incidence of p53 positivity in leukoplakia may be due to differences in aetiological factors. p53 overexpression in premalignant oral lesions is important in view of the significantly earlier onset of leukoplakia in the Indian population compared to the development of oral malignancy, and may be helpful in identifying lesions that are more likely to progress to malignancy. The frequency of p53 protein overexpression was high in premalignant and malignant oral lesions of patients who were heavy consumers of betel, areca nut and tobacco.     

Estimation of Superoxide Dismutase and Glutathione Peroxidase in Oral Submucous Fibrosis,Oral Leukoplakia and Oral Cancer - A Comparative Study

Present study was undertaken to estimate and compare erythrocyte superoxide dismutase (E-SOD) andGlutathione peroxidase (GPx) levels in oral submucous fibrosis, oral leukoplakia and oral cancer patients andage/sex matched healthy subjects, 25 in each group. Statistically significant (P<0.001) decrease in E-SOD andGPx levels were observed in OSF, oral leukoplakia and oral cancer groups as compared to the control group.Oral leukoplakia group showed lower levels in comparison with OSF (P>0.05). Oral cancer group had the lowestlevels amongst the study groups. Imbalance in antioxidant enzyme status may be considered as one of the factorsresponsible for the pathogenesis of cancer and may serve as a potential biomarker and therapeutic target toreduce the malignant transformation in oral premalignant lesions/conditions.     

Alcohol drinking, body mass index and the risk of oral leukoplakia in an Indian population

Although tobacco habits have been associated with the risk of oral leukoplakia, alcohol drinking and body mass index (BMI) as risk factors have not been well established. The purpose of this study is to evaluate the independent effects of drinking, BMI, tobacco chewing and smoking on the risk of oral leukoplakia. A case-control study was conducted, with data from an ongoing randomized oral cancer screening trial in Kerala, India. Trained health workers conducted interviews and performed oral visual inspections to identify oral premalignant lesions such as leukoplakia. The logistic regression model in SAS was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). A total of 927 leukoplakia cases and 47,773 controls were included in the analysis. Ever alcohol drinking was a significant risk factor for oral leukoplakia among nonsmokers (OR=2.1, 95%CI=1.3, 3.4) and non-chewers (OR=1.8, 95%CI=1. 3, 2.5) after adjusting for age, sex, education, BMI and tobacco habits. The association with alcohol drinking was stronger among women (OR=3.9, 95%CI=1.5, 10.4) than men (OR=1.5, 95%CI=1.3, 1.9). An inverse dose-response relationship was observed between BMI and the risk of oral leukoplakia (p for trend=0.0075). Tobacco chewing was a stronger risk factor for women (OR=37.7, 95%CI=24.2, 58.7) than for men (OR=3.4, 95%CI=2.8, 4.1). Smoking was a slightly stronger risk factor for men (OR=3.3, 95%CI=2.5, 4.3) than for women (OR=2.0, 95%CI=1.5, 2.9). In conclusion, alcohol drinking was found to be an independent risk factor while BMI might be inversely associated with the risk of oral leukoplakia in an Indian population.     

Prevalence and correlation of oral lesions among tobacco smokers, tobacco chewers, areca nut and alcohol users

Introduction: The incidence of oral premalignant and malignant lesions is on the rise due to an increasednumber of people taking in tobacco and alcohol related habits. Material and Methods: 1028 patients withtobacco, alcohol and areca nut habits attending our Department of Oral Medicine and Radiology formed thestudy sample. An interviewer based questionnaire was used to record the habit details. All the patients werethen examined clinically for the presence of lesions. Chi square and Fisher exact tests were used to assess thestatistical significance of the study parameters. Results: Males had a higher prevalence and comprised 87.9%of the sample. The commonest habit in this study sample was smoking (39.2%) followed by smokeless tobaccouse (28.1%). Out of the 1028 patients with habits 40% had no clinically detectable changes in their mucosa.Of the mucosal changes leukoplakia (14%) was the commonest. Conclusions: This study provided informationabout the habit trends in the patients visiting this institution. The study may serve as a useful tool in educatingthe patients about the deleterious effects of oral tobacco, alcohol and betel exposure.     

Leukoplakia--an epidemiologic study of 1504 cases observed at the Tata Memorial Hospital, Bombay, India

An epidemiological study of 1504 cases of leukoplakia seen at the Tata Memorial Hospital, Bombay, indicates that the oral cavity was the site of the disease in 95% of the cases. The buccal mucosa was the commonest site affected in all religious communities of Western India except among Parsis. Parsis, a majority of whom are non-smokers and non-chewers of tobacco, had leukoplakia more often on the anterior 2/3rd tongue than on the buccal mucosa and this pattern persisted in the distribution of cancer also, whereas people from Gujarat more often smoke; in these the buccal mucosa was commonly affected with leukoplakia, but cancer was not so frequent in this site. Statistical computation of the risk of malignant transformation indicates that males have a 4·8 times higher risk of developing cancer when they have leukoplakia than the normal population, and the females have 7 times higher risk of developing cancer in the presence of leukoplakia. It was felt that leukoplakia not associated with smoking habits had a greater chance of malignant transformation.     

Oral erythroplakia--a review

Oral erythroplakia (OE) is considered a rare potentially malignant lesion of the oral mucosa. Reports entirely devoted to OE are very few, and only two reviews none of which are of recent date have been published. Only the true, velvety, red homogeneous OE has been clearly defined while the terminology for mixed red and white lesions is complex, ill-defined and confusing. A recent case control study of OE from India reported a prevalence of 0.2%. A range of prevalences between 0.02% and 0.83% from different geographical areas has been documented. OE is predominantly seen in the middle aged and elderly. One study from India showed a female:male ratio of 1:1.04. The soft palate, the floor of the mouth and the buccal mucosa is commonly affected. A specific type of OE occurs in chutta smokers in India. Lesions of OE are typically less than 1.5 cm in diameter. The etiology of OE reveals a strong association with tobacco consumption and the use of alcohol. Histopathologically, it has been documented that in OE of the homogenous type, 51% showed invasive carcinoma, 40% carcinoma in situ and 9% mild or moderate dysplasia. Recently, genomic aberrations with DNA aneuploidy has been demonstrated. p53 mutations with different degrees of dysplasia may play a role in some cases of OE. Transformation rates are considered to be the highest among all precancerous oral lesions and conditions. Surgical excision is the treatment of choice. Data on laser excision are not available. Recurrence rates seem to be high, reliable data are, however, missing. More studies on OE are strongly needed to evaluate a number of so far unanswered questions. The natural history of OE is unknown. Do OEs develop de novo or are they developing from oral leukoplakia through several intermediate stages of white/red lesions? The possible role of fungal infection (Candida micro-organisms) is not clear as is the possible role of HPV co-infection in the development of OE. More data on incidence and prevalence, biological behaviour and adequate treatment are urgently needed.     

Comparison of Salivary and Serum Alkaline Phosphates Level and Lactate Dehydrogenase Levels in Patients with Tobacco Related Oral Lesions with Healthy Subjects - A Step Towards Early Diagnosis

Aim: To evaluate and compare salivary and serum levels of Alkaline Phosphates and Lactate Dehydrogenase in patients without the habit of tobacco, in patients with the habit of tobacco, in patients with benign oral lesions and in patients with oral premalignant lesions and oral malignant lesions. Material and Methodology: This study was comprised of 500 subjects, Group I: 100 healthy individuals without the habit of tobacco usage formed the control group. Group II: 100 patients with the habit of tobacco/ smoking consumption without any oral lesion. Group III: 100 patients with benign oral lesions. Group IV: 100 patients having the history of tobacco consumption and having apparent precancerous lesions like leukoplakia, erythroplakia. Group V:100  patients having frank oral cancer. The grade of dysplasia in these patients was statically correlated with the levels of serum and salivary ALP and LDH. Results: This study revealed that there was high expression of both serum and salivary ALP and LDH  in group IV and Group V as compared with the other groups and mean difference showed a statistically significant p value of less than 0.01. This study revealed that the in group V, the highest level of serum and salivary ALP was found in those patients who were reported with poorly differentiated oral cancer. Conclusion: Both Alkaline phosphates and Lactate dehydrogenase could be considered a sensitive markers for the detection of dysplasia with already existing precancancerous and cancerous lesions.