Potential Role of Epstein–Barr Virus in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma: A Scoping Review

Though the oral cavity is anatomically proximate to the nasal cavity and acts as a key reservoir of EBV habitation and transmission, it is still unclear whether EBV plays a significant role in oral carcinogenesis. Many studies have detected EBV DNA in tissues and exfoliated cells from OSCC patients. However, very few studies have investigated the expression of functional EBV proteins implicated in its oncogenicity. The most studied are latent membrane protein 1 (LMP-1), a protein associated with the activation of signalling pathways; EBV determined nuclear antigen (EBNA)-1, a protein involved in the regulation of gene expression; and EBV-encoded small non-polyadenylated RNA (EBER)-2. LMP-1 is considered the major oncoprotein, and overexpression of LMP-1 observed in OSCC indicates that this molecule might play a significant role in oral carcinogenesis. Although numerous studies have detected EBV DNA and proteins from OSCC and oral potentially malignant disorders, heterogeneity in methodologies has led to discrepant results, hindering interpretation. Elucidating the exact functions of EBV and its proteins when expressed is vital in establishing the role of viruses in oral oncogenesis. This review summarises the current evidence on the potential role of EBV in oral oncogenesis and discusses the implications as well as recommendations for future research.     

Anxiety in recurrent aphthous stomatitis patients

The relationship of recurrent aphthous stomatitis (RAS) to psychological factors has been reported. The purpose of this study was to determine anxiety in RAS patients. All new patients seen during May 1988-November 1988 at the Oral Diagnosis Clinic, Department of Oral Medicine, Faculty of Dentistry, Mahidol University, completed a questionnaire regarding their history of RAS. For the measurement of anxiety, patients were given the Self-rating Anxiety Scale (SAS). Of the 3,106 patients studied, 46.7% reported a positive history of RAS. In this population, females were significantly (P less than 0.001) more anxious than males. The mean SAS score obtained from patients with RAS was significantly (P less than 0.001) higher than that of patients without RAS in each sex. It is concluded that patients with RAS are more anxious than patients without RAS.     

Alteration in the expression of cdk4 and cdk6 proteins in oral cancer and premalignant lesions

J Oral Pathol Med (2010) 39 : 793–799 Background: Cdk4 and cdk6, key players in G1 phase, have been shown to play an important role in the development of oral squamous cell carcinoma (OSCC). This study investigated the expression of these two proteins in OSCC and premalignant lesions including oral leukoplakia (OL) with and without dysplasia and determined if alterations in the expression of these two proteins could be used as markers of malignant transformation. Methods: Expressions of cdk4 and cdk6 were evaluated in 61 samples including OSCC, OL with and without dysplasia and normal oral mucosa using immunohistochemistry method. Nuclear staining of the keratinocytes was considered positive and the percentage of positive cells was calculated. Results: Expression of cdk4 was found in 11/15 (73.33%) OSCC, 13/14 (92.85%) OL with dysplasia, 13/20 (65%) OL without dysplasia and 3/12 (25%) normal mucosa. Expression of cdk6 was detected in 9/15 (60%) OSCC, 3/14 (21.43%) OL with dysplasia, 5/20 (25%) OL without dysplasia and 1/12 (8.33%) normal mucosa. In cdk4 stained specimens, the frequency of positive cases and the percentage of positive cells in normal mucosa was significantly lower than OL with dysplasia and OSCC. For cdk6 staining, the prevalence of positive cases and the percentage of positive cells in normal mucosa were significantly lower than OSCC. Conclusions: Overexpressions of cdk4 and cdk6 were observed in OSCC, indicating that these two proteins play a crucial role in OSCC. The aberrant expression of cdk4 was found in OL with dysplasia, suggesting that cdk4 may be involved in the early event of carcinogenesis.     

Expression of p16 in oral cancer and premalignant lesions

Background:  Expression of p16 has been proposed as a marker for malignant transformation. This study aimed to evaluate p16 expression in oral squamous cell carcinoma (OSCC) and premalignant lesions including oral leukoplakia (OL) with and without dysplasia.
Methods:  Expression of p16 was investigated in 56 samples including OSCC, OL with and without dysplasia, and normal oral mucosa. Expression of p16 was identified by immunohistochemistry, using the CINtecTM p16INK4a Histology Kit. Both nuclear and/or cytoplasmic staining of the keratinocytes were considered to be positive and the percentage of positive cells was calculated.
Results:  Expression of p16 was detected in 3/16 (18.75%) cases of OSCC, in 4/15 (26.7%) cases of OL without dysplasia, and in none of OL with dysplasia and normal mucosa. No significant differences in p16 expression prevalence were found among OSCC, OL with and without dysplasia and normal mucosa. The percentages of positive cells in OSCC and OL without dysplasia were 0.89 and 0.17, respectively. No significant difference in the percentage of positive keratinocytes was found.
Conclusion:  As a marker, p16 is not reliable for oral mucosal dysplasia and malignant transformation.     

Oral lichen sclerosus et atrophicus. A case report

Lichen sclerosus et atrophicus affecting only the oral mucosa is extremely rare. We report here a case of oral lichen sclerosus et atrophicus presenting as a white, flat lesion involving the right buccal and labial mucosa and vermillion border. The diagnosis was based on histopathologic features. Treatment with intralesional corticosteroid was successful in reducing the size of the lesion and the symptoms of the patient. A free gingival graft was also performed to restore the lost attached gingiva. No recurrence of the lesion was found after a 1-year follow-up period, and no skin or genital lesions developed during the 3 years of treatment.     

Efficacy of fluocinolone acetonide gel in the treatment of oral lichen planus

OBJECTIVE: The purpose of this study was to compare the efficacy of fluocinolone acetonide gel 0.1% in 2 base forms (numbers 1 and 2) with fluocinolone acetonide in an oral base 0.1%. STUDY DESIGN: Forty-eight patients with histologically confirmed oral lichen planus were enrolled in the study. Lesions were scored ranging from 0 (no lesion) to 5 (large erosion) according to the severity. Patients were randomly given fluocinolone acetonide in an oral base, fluocinolone acetonide gel no. 1 or no. 2. They were asked to apply the medication on dried lesions 4 times a day. The lesions were evaluated after 2 and 4 weeks of treatment. The severity scores were analyzed by the Kruskal-Wallis k-sample test. RESULTS: Patients who received fluocinolone acetonide in an oral base and those who received fluocinolone acetonide gel no. 1 and no. 2 improved from the average score of 3.0, 3.0, and 2.9 to 1.5, 1.5, and 1.6, respectively. There were no statistically significant differences in score changes noted in the 3 groups. The results indicate that fluocinolone acetonide gel no. 1 and no. 2 and fluocinolone acetonide in an oral base provide similar efficacy in the treatment of oral lichen planus. CONCLUSION: Fluocinolone acetonide gel 0.1% is a safe and effective alternative therapy to fluocinolone acetonide in an oral base 0.1% in the treatment of oral lichen planus.     

Detection of human papillomavirus in normal oral cavity in a group of Pakistani subjects using real-time PCR

Since there is evidence that human papillomavirus (HPV) may play some role in oral carcinogenesis, we investigated the presence of HPV in a group of Pakistani subjects with normal oral cavity using real-time PCR analysis. Two-hundred patients attending the Dental Department, Sandaman Provincial Hospital, Balochistan, Pakistan, were recruited. After interview, oral epithelial cells were collected by scraping and subjected to DNA extraction. The HPV-positive DNA samples were further analyzed using primer sets specific for HPV-16 and -18. It was found that out of 200 DNA samples, 192 were PCR-positive for the β-globin gene and these were subsequently examined for the presence of HPV DNA. Among these, 47 (24.5%) were HPV-positive with the virus copy number ranged between 0.43-32 copies per 1 μg of total DNA (9-99 copies per PCR reaction). There were 4 and 11 samples containing HPV-16 and -18, respectively. Additionally, one sample harbored both types of HPV. Among the investigated clinical parameters, smoking habit was associated with the presence of HPV (p=0.001) while others indicated no significant association. The prevalence of HPV in normal oral cavity in our Pakistani subjects appears to be comparable to other studies. However, the association between the presence of HPV and smoking warrants further investigations whether both of these factors can cooperate in inducing oral cancer in this group of patients.     

Overexpression of cdk4 and p16 in oral lichen planus supports the concept of premalignancy

J Oral Pathol Med (2011) 40 : 294–299 Background: Cell cycle arrest and increased cell proliferation have been demonstrated in oral lichen planus (OLP). This study evaluated the expression of cdk4, cdk6 and p16, important proteins in the G1 phase, in OLP and compared the expression of these proteins of OLP with those of normal mucosa. Methods: Expression of cdk4, cdk6 and p16 were investigated in 23 OLP and 10 normal mucosae using immunohistochemistry technique. Positive cells were counted and presented as a percentage of positive cells. Results: Expression of cdk4, cdk6 and p16 was observed in 3/10 (30%), 1/10 (10%) and none of normal mucosa, respectively. Expression of cdk4, cdk6 and p16 was detected in 18/23 (78.3%), 8/23 (34.8%) and 15/23 (65.2%), of OLP, respectively. The numbers of cdk4 and p16 positive cases of OLP were significantly higher than normal mucosa. In normal mucosa, the averages of the percentage of positive cells for cdk4 and cdk6 staining were 1.48 and 0.18, respectively. In OLP, the averages of the percentage of positive cells for cdk4, cdk6 and p16 staining were 2.73, 1.06 and 2.24, respectively. The percentage of cdk4‐positive cells of OLP was significantly higher than those of normal mucosa group. Conclusion: Oral lichen planus demonstrated overexpression of cdk4 and p16, but not cdk6, suggesting that epithelial cells in OLP are in the hyperproliferative state and in cell arrest. Altered expression of cdk4 and p16 provides evidence of the malignant potential in OLP.