Patients with oral cancer developing from pre‐existing oral leukoplakia: do they do better than those with de novo oral cancer?

Background:  It has been suggested that patients with squamous cell carcinomas derived from oral leukoplakia have a better prognosis than patients with carcinomas that are not associated with oral leukoplakia.
Aim:  To study the mortality rate of 19 patients with a squamous cell carcinoma derived from pre-existing oral leukoplakia.
Method:  The mortality rate of 19 patients with a proven oral squamous cell carcinoma derived from a pre-existing oral leukoplakia was compared with that of a similar size group of patients with oral carcinoma without a pre-existing oral leukoplakia, being matched for gender, age, smoking habits, use of alcohol, oral subsite and histopathologic grade. Treatment in all patients was primarily by surgical excision. The mortality rates up to 5 years have been computed according to the Kaplan–Meier method.
Result:  No significant difference of the mortality rates up to 5 years of follow-up was observed between the two groups of patients.
Conclusion:  Patients with oral cancer developing from pre-existing oral leukoplakia do not do better than those with de novo oral cancer.     

The role of cyclin‐dependent kinases in oral potentially malignant disorders and oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is a major global health problem with a relatively low‐moderate 5‐year survival rate. OSCC is often preceded by lesions and conditions known as oral potentially malignant disorders (OPMDs) that have an increased risk of malignant transformation. Despite advances in diagnostic technology and cancer research, the prognosis of OSCC remains poor as it is frequently detected a late stage. Understanding the molecular pathways involved in oral carcinogenesis provides a platform to identify biomarkers that may allow the early detection of OSCC and accurate prediction of the malignant potential of OPMDs. In addition, specific molecular inhibitors can be developed to target these important pathways and allow advanced therapeutic management to improve the prognosis of this malignancy. A common feature across a number of different cancers is the dysfunction of cell cycle moderator proteins known as cyclin‐dependent kinases. This review summarises the current literature regarding the role of cyclin‐dependent kinases in oral carcinogenesis with a particular focus on cyclin‐dependent kinases 4 (CDK4) and 6 (CDK6). This is of particular relevance as CDK4 and CDK6 inhibitors have shown some promising results in other cancer types and are interesting potential treatments for OSCC.     

Epstein–Barr virus prevalence in oral squamous cell cancer and in potentially malignant oral disorders in an eastern Hungarian population

We tested 65, 44, and 116 patients with oral squamous cell cancer (OSCC), oral leukoplakia (OL), and oral lichen planus (OLP) against 68 age-matched controls for the presence of Epstein–Barr virus (EBV). Apparently healthy mucosa was simultaneously sampled and examined in all patients. Paraffin-embedded tissue sections of all EBV-positive patients with OSCC were examined for latent membrane protein-1 (LMP-1) expression (demonstrable in most EBV-associated malignancies) using immunohistochemistry. The prevalence of EBV in the controls and in OSCC, OL, and OLP lesions was 19.1%, 73.8%, 29.5%, and 46.6%, respectively, and 66.2%, 22.7%, and 31.9% in the healthy mucosa of patients, respectively. The prevalence of EBV in OSCC patients was significantly higher than in controls or in respective samples of the other two patient groups both in the lesion and in the healthy mucosa. Comparisons including only patients with EBV-negative lesions yielded similar results. Lesions of patients with OLP, but not of patients with OL, differed significantly from controls in EBV prevalence. In OSCC, LMP-1 expression was not detected, and EBV carriage was not significantly associated with any risk factors and did not influence the outcome. Although a high prevalence of EBV was found in OSCC, comparable carriage rates on healthy mucosa of patients indicated that an aetiological role of EBV is unlikely.     

Epidemiologic studies of oral mucosal conditions – methodologic issues

The methods used in the international English-language literature of epidemiologic investigations of oral mucosal conditions were reviewed. Methods used to study leukoplakia, lichen planus, recurrent herpes labialis, recurrent aphthous ulcers, geographic tongue and candidiasis are highlighted. In addition, studies of the full range of pathologies documented in a population were reviewed. The methodologic issues raised by the epidemiologic literature as well as those to be considered for future studies of oral mucosal conditions are presented. Emphasis is placed on study population selection, diagnostic criteria development, type and training of examiners, risk factor assessment and issues related to data collection, analysis and reporting.     

Malignant transformation of oral leukoplakia in a well‐defined cohort of 144 patients

Objectives

Oral leukoplakia is a potentially malignant disorder of the oral mucosa. The aim of this retrospective study was to identify the factors that possibly predict malignant transformation in a well‐defined cohort of patients with a long‐term follow‐up. All leukoplakias were staged according to a clinicopathological classification and staging system. Furthermore, a certainty factor has been used with which the diagnosis has been established.

Material and methods

The group consisted of 144 patients. The size, presence and degree of epithelial dysplasia were incorporated into a clinicopathological classification and staging system. Initial management consisted of surgical excision, CO₂ laser vaporisation or observation only. The mean follow‐up period was 51.2 months (s.d. = 39.33, range 12–179 months).

Results

In 16 of 144 patients (11%), malignant transformation occurred between 20 and 94 months (mean 57.0 months) after the first visit, the annual malignant transformation rate being approximately 2.6%. A large size of the lesion (≥ 4 cm) showed to be the only statistically significant predictor of malignant transformation (P = 0.034).

Conclusion

A size of ≥ 4 cm showed to be the only significant predicting factor of malignant transformation in oral leukoplakia. No other epidemiological, aetiological, clinical or histopathological parameters were of statistical significance.     

A comparison of the management of potentially malignant oral mucosal lesions by oral medicine practitioners and oral & maxillofacial surgeons in the UK

This study describes the results of a survey undertaken to assess the management of potentially malignant oral mucosal lesions by oral medicine practitioners and compares their approach with that of oral & maxillofacial surgeons that we have previously described. Significant differences were noted between the two groups in the use of photography to document the lesions and in the use of certain special investigations, which included measurement of serum iron, serum ferritin, serum Vit B12, red cell folate and candidal isolation. The groups also varied in the perceived importance of the age of the patient and anatomical site of the lesion when deciding on the need for further biopsy. There was also significant variation in the use of certain treatment modalities, including excising non-dysplastic and severely dysplastic/carcinoma in-situ lesions and eliminating trauma when treating mild/moderately dysplastic and severely dysplastic/carcinoma in-situ lesions. Significant differences in the frequency and duration of follow-up were noted for non-dysplastic lesions. Finally, the two groups differed significantly when asked to rank the perceived importance of certain factors (the histopathology of the most recent biopsy and the anatomical site of the lesion) when deciding the need to follow-up. Possible reasons for the variation are discussed.     

E‐cadherin downregulation and Twist overexpression since early stages of oral carcinogenesis

There is some evidence of Twist participation in oral carcinogenesis; however, little is known about its interaction with E‐cadherin in oral squamous cell carcinoma (OSCC) development. This experimental study included an immunohistochemical analysis of Twist and E‐cadherin proteins in paraffin‐embedded specimens of oral leukoplakia (OL), OSCC, and normal oral mucosa. In addition, it was also performed a Western blot and double‐immunofluorescence analysis of Twist and E‐cadherin expression in OSCC cell lines. Significant differences in Twist and E‐cadherin immunoexpression were observed between normal oral mucosa and OL, with an inverse relation since the earliest stages of oral dysplasia (r = ?0,512; P < 0.001). Western blot and double‐immunofluorescence analysis showed differences in Twist and E‐cadherin expression among human oral keratinocytes and OSCC cell lines suggesting that downregulation of E‐cadherin occurs in a dependent manner of Twist in OSCC. Our results showed a possible value of Twist and E‐cadherin in the prediction of risk of oral epithelium malignant transformation.     

Morphometric computer‐assisted image analysis of oral epithelial cells in normal epithelium and leukoplakia

J Oral Pathol Med (2010) 39 149–154 Background: There are very few studies documenting morphometric parameters of normal oral mucosa and leukoplakia. The present study was undertaken to establish the morphometric parameters of the parabasal and spinous cells of normal oral epithelium. Analysis of changes occurring in these cells in leukoplakia was also done. Methods: This study was conducted on tissue sections of clinically normal oral mucosa and leukoplakia. Morphometric analysis was done for parabasal and spinous cells. Statistical analysis was done using one way ANOVA and Mann–Whitney test. Results: Morphometric parameters were greater in the spinous cells than in parabasal cells in normal oral mucosa. Leukoplakia showed greater cellular and nuclear parameters than normal mucosa. Conclusion: Normal oral epithelium showed site‐wise difference in cell and nuclear measurements. Nuclear parameters showed a statistically significant change than cellular parameters in dysplasia. These changes were expressed in the earliest stage of transformation to dysplasia.     

The efficacy of oral lumenoscopy™ (ViziLite®) in visualizing oral mucosal lesions

Early diagnosis of oral mucosal lesions has been advocated as a means of improving outcomes of cancer therapy. Improved visualization of mucosal lesion* may aid in diagnosis by guiding tinue sampling or referral. This multi‐center study reports the effect of chemiluminescent light (ViziLite) upon visualization of mucosal lesions. The cftemiluminescent light did not appear to improve visualization of red lesions, but white lesions and lesions that were both red and white showed enhanced brightness and sharpness.     

Pathogenesis of oral lichen planus – a review

J Oral Pathol Med (2010) 39 : 729–734 Oral lichen planus (OLP) is a T‐cell‐mediated chronic inflammatory oral mucosal disease of unknown etiology. OLP presents as white striations, white papules, white plaques, erythema, erosions, or blisters affecting predominantly the buccal mucosa, tongue and gingiva. Both antigen‐specific and non‐specific mechanisms are hypothesized to be involved in the pathogenesis of oral lichen planus (OLP). Antigen‐specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen‐specific keratinocyte killing by CD8⁺ cytotoxic T cells. Non‐specific mechanisms include mast cell degranulation and matrix metalloproteinase activation in OLP lesions. These mechanisms may combine to cause T cell accumulation in the superficial lamina propria, basement membrane disruption, intra‐epithelial T cell migration and keratinocyte apoptosis in OLP. The various hypotheses proposed for pathogenesis of oral lichen planus are discussed in this review.     

Human papillomavirus and oral disease – emerging evidence: a review

Human papillomavirus (HPV) infections have received considerable attention in recent years. Of the 120 or so known types of the virus, some cause a variety of benign wart‐like lesions of the skin and genital and oral mucosae, whilst others are aetiologically associated with cervical and anogenital cancers. Recent epidemiologic evidence suggests that HPV may also be an independent risk factor for oropharyngeal cancer. In this context it has been suggested that HPV virus may modulate the process of carcinogenesis in some tobacco and alcohol induced oropharyngeal cancers and act as the primary oncogenic agent for inducing carcinogenesis among non‐smokers. Dental practitioners have a major role in detecting all lesions of the oral mucosa caused, or possibly caused, by HPV. This paper briefly reviews the current state of knowledge of molecular and clinical aspects of HPV infections of the oral mucosa.