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Oral Leukoplakia: a Clinicopathological Review
Abstract
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.
... The importance of precancer lesion like oral leukoplakia, oral erythroplakia, or oral erythro leukoplakia arises from the large number of patients where a biopsy reveals dysplasia or similar "frank cancer [8][9]. There is a progressive histopathological sequence which can be graded as regular, hyperplastic as well as carcinoma in situ during the progression of premalignant lesion to the malignant lesion [10,11]. Oral pre-malignant lesions can be identified and managed with a visual inspection and are conveniently accessible for further testing including microscopy and biopsies [12,13].Early diagnosis of abnormalities reduces mortality and morbidity, but prolonged identification, particularly in places with the highest incidence rate, lowers the chance of survival, despite modern treatment procedures [14,15]. ...
... Although vitamin A, or retinoid, has been used medicinally, there is little evidence from research to substantiate its effectiveness in reducing the incidence of cancer transformation and relapse [4][5][6][7][8][9][10][11]. Among the surgical procedures that have been suggested for the management of OPMDs are LASER surgery and traditional surgery with a scalpel and blade [5][6][7][8][9][10][11][12]. ...
... Although vitamin A, or retinoid, has been used medicinally, there is little evidence from research to substantiate its effectiveness in reducing the incidence of cancer transformation and relapse [4][5][6][7][8][9][10][11]. Among the surgical procedures that have been suggested for the management of OPMDs are LASER surgery and traditional surgery with a scalpel and blade [5][6][7][8][9][10][11][12]. Conventional surgeries are limited by the disease's location and extent. ...
Four surgical treatment modalities namely cryosurgery, scalpel and blade surgery, diode LASER surgery and CO2 LASER surgery in the management of oral potentially malignant disorders (OPMDs) in terms of healing outcomes post operatively and recurrence is evaluated. The study included sixty outpatients whose biopsies revealed OPMDs (oral lichen planus, homogeneous leukoplakia, non-homogenous leukoplakia and erythroplakia). There is decrease in post-operative pain and oedema in all four treatment categories at one week follow up and two week follow up. It was observed that pain was low in cryosurgery treatment category at day of surgery as well as at one week of follow up as compared to diode LASER and CO2 LASER. Observations from the study highlights that all four surgical modalities used in this study were effective for treatment of OPMDs, and the overall summation of the results of the study showed that cryotherapy seems to offer better clinically significant results than laser therapy.
... No data similar to those reported in this study are available in the literature: there are no comparison articles available on a follow-up basis of patients presenting HPV-positive or HPV-negative lesions. However, numerous studies [30][31][32][33][34][35] and systematic reviews recommend a certain follow-up of some oral lesions, considering only the diagnosis. ...
... Another literature review that analyzed 24 studies, with a total of 12,703 cases of leukoplakia, reports that check-ups should be every 3 months [32]. Other authors recommend lifelong follow-ups, with a frequency of 6 to 12 months [35]. A recent meta-analysis in 2020 [43], which considered 24 articles for a total of 16,604 cases of leukoplakia, repeats the discrepancy between the follow-up of leukoplakia patients in the various studies, and their analysis seems to be indicative of a necessity for internationally accepted guidelines for the diagnosis and follow-up of leukoplakia cases. ...
Human papilloma virus (HPV) is known as the main cause of cervical cancer. Data also indicate its role in head–neck cancer, especially oropharyngeal cancer. The correlation between high-risk HPV and oral cancer is still controversial. HPV-related lesions of the oral cavity are frequent and, in most cases, benign. The primary aim of this study was to establish if there is a different follow-up necessity between HPV-positive compared to HPV-negative oral lesions. The secondary aim was to evaluate the recurrence of HPV-related lesions. All patients who underwent a surgical procedure of oral biopsy between 2018 and 2022, with ulterior histopathological examination and HPV typing, were examined. A total of 230 patients were included: 75 received traumatic fibroma as diagnosis, 131 HPV-related lesions, 9 proliferative verrucous leukoplakia, and 15 leukoplakia. The frequency and period of follow-up varied in relation to HPV positivity and diagnosis. This study confirms what has already been reported by other authors regarding the absence of recommendations of follow-up necessity in patients with oral mucosal lesions. However, the data demonstrate that there was a statistically significant difference in the sample analyzed regarding the follow-up of HPV-positive vs. HPV-negative patients. It also confirms the low recurrence frequency of HPV-related oral lesions.
... classification [56]. Moreover, a statistically significant correlation was observed in leucoplakia OPMDs classified following van der Waal et al., with the highest addressed to severe dysplasia [57]. ...
... In the long intervening period between initiation of carcinogenic tobacco habits and the development of invasive oral cancers, well-defined oral potentially malignant lesions may occur, of which leukoplakia is the most common. Leukoplakia is a white plaque of questionable premalignant risk, having excluded other known lesions that carry no increased risk for cancer,[12] with histological presentation ranging from mild hyperkeratosis to squamous cell carcinoma.[3] ...
Silver stainable nucleolar organizer regions (AgNORs) are replicatory markers which may have a place in objectively characterizing dysplasia.
A study of various morphometric parameters related to AgNORs was performed in basal and parabasal layers of normal human oral epithelium, nondysplastic leukoplakia, and dysplastic leukoplakia employing photomicrographs of silver stained paraffin embedded sections using image analysis, to assess the usefulness of these parameters in distinguishing dysplastic leukoplakia from nondysplastic oral leukoplakia.
Out of various mean AgNOR related parameters, AgNOR count, area, perimeter, and proportion were found to be higher in dysplastic leukoplakia as compared to nondysplastic leukoplakia. On statistical analysis, AgNOR count showed statistically significant differentiation between dysplastic and nondysplastic leukoplakia. While other parameters can distinguish normal oral epithelium from dysplastic and nondysplastic leukoplakia.
To conclude, the AgNOR count is the most appropriate marker to differentiate between dysplastic and nondysplastic leukoplakia.
... Proven factors promoting OLK carcinogenesis include sex (females have a higher cancer rate), persistent existence, nonsmoking, locations of frequent occurrence (the mouth floor or ventral tongue), heterogeneous lesions, concurrent Candida albicans infections, and abnormal tissue hyperplasia in pathology. 21,[24][25][26] Angiogenesis facilitates the provision of nutritional resources necessary for the growth and migration of tumours and plays a pivotal role in OLK carcinogenesis. Folkman et al 27 found that neovascularisation occurred when the islets of transgenic mice developed early tumours. ...
Objective
This study aimed to investigate the potential of fibroblast activation protein (FAP) as a biomarker in the progression of oral leukoplakia (OLK) carcinogenesis. This was achieved by evaluating FAP expression at different levels of the organisation, namely oral normal mucosa (NM), OLK, and oral squamous cell carcinoma (OSCC).
Materials and methods
Altogether, 88 paraffin-embedded tissue samples were examined, including 55 cases of OLK, 13 cases of OSCC, and 20 cases of NM (control group). An exhaustive investigation was performed to examine FAP expression in NM, OLK, and OSCC tissues via immunohistochemistry (IHC). The relationship between FAP expression and clinical pathologic characteristics was analysed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB) also proved the expression of FAP in NM, OLK, and OSCC cells. Aberrant FAP expression in OLK and OSCC was explored using in vitro experiments.
Results
Immunohistochemical results showed that high FAP expression was significantly correlated with histopathologic grade (P = .038) but not correlated with age, sex, or region (P = .953, .622, and .108, respectively). The expression level of FAP in NM tissues (0.15 ± 0.01) was minimal, whereas it was observed in OLK (0.28 ± 0.04) and OSCC (0.39 ± 0.02) tissues with a noticeable increase in expression levels (P < .001). The expression level of FAP in OLK with severe abnormal hyperplasia (S-OLK) tissues (0.33 ± 0.04) was significantly higher than in OLK with mild abnormal hyperplasia (MI-OLK, 0.26 ± 0.02) and OLK with moderate abnormal hyperplasia (MO-OLK, 0.28 ± 0.03) tissues (P < .001 and P = .039, respectively). The results of RT-PCR illustrated that the relative expression of FAP mRNA in OLK cells (2.63 ± 0.62) was higher than in NM cells (0.87 ± 0.14), but lower than in OSCC cells (5.63 ± 1.06; P = .027 and .012, respectively). FAP expression was minimal in NM cells (0.78 ± 0.06), modest in OLK cells (1.04 ± 0.06), and significantly elevated in OSCC cells (1.61 ± 0.09) based on the results of WB (P < .001).
Conclusions
Significant variations in FAP expression were observed in NM, OLK, and OSCC tissues and cells. These findings revealed that FAP may be a reliable biomarker for the early diagnosis and evaluation of OLK carcinogenesis.
Head and Neck (H&N) cancer represents a significant global health burden, ranking sixth among all cancer types worldwide, with a particularly high prevalence in developing countries. Oral cancer, a subset of H&N cancer, encompasses malignant growths within the oral cavity region. Oral Epithelial Dysplasia (OED) serves as a precursor lesion to oral cancer and is identifiable through histological examination by pathologists. While histological grading correlates with progression cancer risk, accurately predicting lesion advancement remains challenging due to limited research and study. Despite established grading criteria based on architectural and cytological changes in the oral cavity histological images, variability exists among pathologists in assessing OED presence and grade. The present article explores OED as a precancerous lesion, delving into various histological grading systems based on architectural and cytological changes. Additionally, it examines the role of Computer-aided Diagnostics (CAD) leveraging Artificial Intelligence (AI) in OED detection. Lastly, the paper discusses treatment modalities for oral cavity cancers.
According to epidemiological statistics, eating a diet rich in fruits and vegetables can help prevent oral cancer in a variety of ways. Lycopene is a reddish-colored carotenoid found in abundance in tomatoes and other fruits and vegetables. It is reported to be beneficial in the treatment of chronic disorders such as cancer and cardiovascular disease. Hence, the objective of this study is to summarise the lycopene's features and analyse its potential function in the development and treatment of oral precancerous lesions and mouth cancer. Lycopene has been proven to be useful in the treatment of various precancerous lesions in the oral cavity, including oral submucous fibrosis and oral leukoplakia, and could be used in concert with other medications to prevent and treat oral cancer. Lycopene's role in preventing and treating a variety of diseases is still in its infancy, and further study and large-scale clinical trials are needed to substantiate the findings. We explored the effect of Lycopene in oral illness in this review.
Management of zygomatic complex fractures using closed reduction, two point open reduction with internal fixation (ORIF), closed reduction with three point ORIF and two point ORIF is of interest to dentist. 150 patients with zygomatic bone fractures between the ages of 14-60 years were included in the study. At final assessment, the percentage of stable condition was greater in closed reduction + two point ORIF and closed reduction + three point ORIF when compared to two point ORIF alone and three point ORIF alone and closed reduction alone. It was observed that stable condition was lowest in closed reduction alone. It was also observed that stable condition was lower in closed reduction + two point ORIF as compared to closed reduction + three point ORIF. It was also further noticed that stable condition was lower in two point ORIF alone as compared to three point ORIF alone. The treatment approach involving closed reduction and three point ORIF had better outcomes for management of zygomatic complex fractures.
Leukoplakia has evolved as a clinico-pathologic concept over many years, with the current clinical designation being accepted worldwide. Reflective of the biology of leukoplakia is the concept of cellular atypia and epithelial dysplasia. Adding to a better understanding of leukoplakia in general has been the definition of relevant clinical subsets which, in some cases, includes etiology (snuff), while in other cases a verrucous clinical appearance will suggest a more aggressive anticipated behavior pattern. Tobacco usage, in many of its forms, remains the prime etiologic factor; however, other considerations also apply. More recently, the potential etiologic role of Candida albicans has been stressed, as well as its possible role in carcinogenesis. So-called oral hairy leukoplakia has been defined in relation to a possible Epstein-Barr viral infection, usually in the immunosuppressed patient. Other viruses, human papilloma virus in particular, have been implicated in leukoplakia, while genetic alterations involving tumor suppressor elements (p53) have also been investigated. Finally, the management of this common condition remains a variable and includes local, topical, and systemic therapies such as anti-oxidants, carotenoids, and retinoids.
Up to 6% of oral leukoplakia, a relatively common mucosal disease, can be expected to become malignant. This report describes a long-term study of 30 patients in whom a particular form of leukoplakia was identified and labeledproliferative verrucous leukoplakia (PVL), a disease of unknown origin, which exhibits a strong tendency to develop areas of carcinoma. PVL begins as a simple hyperkeratosis but tends to spread and become multifocal. PVL is slow-growing, persistent, and irreversible, and in time areas become exophytic, wartlike, and apparently resistant to all forms of therapy as recurrence is the rule. The disease was most commonly seen in elderly women and had been present for many years. Patients were followed for 1 to 20 years. Thirteen died of or with their disease, 14 were alive with PVL, and 3 were alive without PVL at last contact. PVL rarely regressed despite therapy. All patients who died had persistent or recurrent disease. PVL appears to constitute a continuum of hyperkeratotic disease, ranging from a simple hyperkeratosis at one end to invasive squamous cell carcinoma at the other. Microscopic findings are dependent upon the stage of the disease's development and the location and adequacy of the biopsy.
The efficacy of 1% toluidine blue in the identification of oral malignancies and potentially malignant oral lesions was evaluated among a group of Asian patients (n=102) with undiagnosed oral mucosal lesions and conditions (n=145). The trial, utilizing a ready-to-use kit, was controlled by histopathologic evaluation of a total of 87 dye-retained or dye-negative lesions. Eighteen oral carcinomas all retained the dye and there were no false negatives, yielding a test sensitivity of 100%. Eight of 39 oral epithelial dysplasias were toluidine blue-negative, giving a false negative rate of 20.5% and a sensitivity of 79.5% for oral epithelial dysplasias. The specificity of the technique was low (62%). Five dysplastic lesions were detected solely by the kit and this suggests that the method is valuable for surveillance of high-risk subjects in addition to its remarkable sensitivity in the detection of invasive carcinoma.
An increasing public awareness of antioxidants may prompt a patient's request to be treated without surgery if a leukoplakic lesion is discovered. However, surgical excision remains the treatment of choice for oral leukoplakia. The use of antioxidant supplements has shown some promise, but the predictability of success remains uncertain and longterm results are unavailable. Before the decision to use any antioxidant is made, it is critical to obtain a histopathologic diagnosis of the lesion. When dealing with a lesion diagnosed as hyperkeratosis, it may be appropriate to choose an antioxidant that may take some time for clinical improvement to occur. However, as the grade of epithelial dysplasia becomes more severe, consideration must be given to the possibility of malignant transformation during antioxidant treatment. We do not recommend the use of antioxidant supplements in the treatment of any carcinoma. The therapeutic use of antioxidant supplements outside of clinical trials conducted at academic medical centers should be done with considerable caution by practitioners in private practice. It should be emphasized that in these clinical trial patients were seen at frequent intervals to monitor their progress and to intervene if there was a noticeable deterioration in the clinical appearance of the lesion.