Oral Potentially Malignant Disorders and Oral Cancer in Saudi Arabia: An Epidemiological Review of the Literature.

Background: Oral potentially malignant disorders (OPMDs) are a group of chronic oral mucosal diseases associated with an increased risk of malignant transformation. Multiple studies have investigated the prevalence of these conditions in multiple regions; however, there are limited data about the prevalence of OPMDs in the Kingdom of Saudi Arabia (KSA). This paper aims to review the prevalence of OPMDs in the KSA, to ensure better understanding of the population risk and propose a more standardised approach to the diagnosis and management of this group across the KSA. In addition, this review will discuss the prevalence of oral cancer in the KSA, considering independent risk factors for oral cancer development. Methods: Electronic databases including PubMed, Medline, Medscape, ScienceDirect, StatPearls, BMC Oral Health and the Cochrane Library were searched with the keywords "Oral Potentially Malignant Disorders"; "Saudi Arabia"; and "Oral Cancer". Identified articles were reviewed independently by 2 reviewers against defined inclusion and exclusion criteria. Results: 16 studies were included in this review. The prevalence of OPMDs in KSA varies significantly depending on age, gender, social habits, background disease and dental status. Conclusions: This review highlights the need for up-to-date data on the prevalence, distribution, and characteristics of OPMDs in KSA. The diverse prevalence rates and distinct characteristics of various OPMDs emphasise the necessity for targeted preventive measures. As the data on OPMDs in KSA remains limited, future research efforts should prioritise the establishment of comprehensive epidemiological studies to inform effective public health interventions in this region.

Oral lichenoid lesions in two snuff users with contact allergy to carvone.

BACKGROUND: Contact allergy to the mint-tasting flavour carvone has been observed in patients with oral lichenoid lesions (OLL). Mint-flavoured products such as toothpaste frequently contain carvone. Snuff is a smokeless tobacco product that is chewed or placed in the mouth rather than smoked. In Sweden, the use of snuff and its flavoured versions is extremely common. OBJECTIVES: To investigate whether the consumption of mint-flavoured snuff is associated with contact allergy to carvone and subsequently plays a role in the aetiology of OLL. METHODS: Regarding the two patients, patch testing with snuff pouches was performed. High-performance liquid chromatography and gas chromatography-mass spectrometry analysis were used for identification of carvone in different snuff samples. RESULTS: Two patients with OLL were contacted allergic to carvone when patch tested. Both were using mint-flavoured snuffs several hours a day for many years. One patient was contacted allergic to the snuff pouch tested as is. Carvone was detected in the snuff samples of both patients. CONCLUSIONS: The patients were recommended to avoid the use of mint-flavoured snuffs, toothpaste and foodstuffs. At follow-up 3 months later, the patients had a dramatic clinical improvement of the OLL and oral symptoms. Exposure to mint-flavoured snuffs can be overlooked as a possible aggravating/provoking factor in OLL.

A Rare Case of Hair Dye Induced Oral Lichenoid Reaction.

Oral lichenoid lesions or reactions (OLLs/OLRs), which are clinical and histological contemporaries of the traditional oral lichen planus (OLP), had already garnered a great deal of attention in the literature. In contrast to idiopathic OLP, OLLs frequently have a definite, recognizable initiating component. Although a cursory clinical and histological evaluation of lesions frequently demonstrates numerous similarities with OLP, relatively new data has demonstrated that distinct features exist and serve as the foundation for the majority of categories. Although many systemic pharmaceuticals can lead to end oral lichenoid reactions, medications for diabetes, hypertension, nonsteroidal anti-inflammatory, antimalarial, and antifungal treatments are frequently blamed. Oral drugs, metallic dental restorations, acrylates, composite resins, glass ionomer cement, cinnamates, flavorings, and other chemical substances have all been associated when in direct contact. The objective of the case report is to elaborate the correlation between the oral lichenoid reaction and the use of hair dye. The incident under consideration is significant because the majority of past reports of allergic reactions to hair dye involved the face and scalp rather than the oral cavity. This report recommends that oral physicians inquire about the patient's use of cosmetics during history-taking whenever dealing with abrupt inflammatory responses in the orofacial area in order to diagnose and treat lesions more efficiently.

Lichen planus after COVID-19 infection and vaccination.

Lichen planus (LP) is an inflammatory disorder believed to result from CD8 + cytotoxic T-cell (CTL)-mediated autoimmune reactions against basal keratinocytes. We present a review of LP following COVID-19 infection and vaccination. Literature searches were conducted on PubMed and Google Scholar from 2019 to 7/2022. 36 articles were selected based on subject relevance, and references within articles were also screened. 39 cases of post-vaccination LP and 6 cases of post-infection LP were found among case reports and case series. 152 cases of post-vaccination LP and 12 cases of post-infection LP were found in retrospective and prospective studies. LP is a rare complication of COVID-19 infection and vaccination that may be mediated by overstimulation of T-cell responses and proinflammatory cytokine production. However, it does not represent a limitation against COVID-19 vaccination, and the benefits of vaccination considerably outweigh the risks.

Oral lichen planus and related lesions. What should we accept based on the available evidence?

Recent new terminologies have been proposed for lesions in the sphere of oral lichen planus (OLP) that theoretically present unique aetiological, clinical, prognostic or management characteristics different from those of the so-called typical forms of OLP. We aimed to critically analyse what concepts and terminologies related to OLP should we accept based on the available evidence. A review of the literature was carried out in order to critically analyse the concepts and terminologies related to OLP. New concepts and terminologies include oral lichenoid lesions; contact lichenoid reactions, drug lichenoid reactions or those in the context of graft-versus-host disease; chronic ulcerative stomatitis; lichen planus pemphigoid; and some lesions that are difficult to categorise, such as OLP with features of proliferative verrucous leukoplakia and lichenoid lesions of the upper labial mucosa. A multidisciplinary, multicontinent working group has recently published a guideline with recommendations for modifying definitions and terminologies associated with a disease, among which a reasoned, evidence-based justification for the proposed change is considered essential. An in-depth analysis of the newly proposed terms for OLP-related lesions shows that many of them are not justified. In this paper, we set out our position on the basis of the existing evidence on the appropriateness of the use of these new terms.

Comparison of CEA and IgG serum levels in oral lichenoid lesions before and after treatment with topical corticosteroids.

Background. Lichen planus is considered a potentially malignant condition with an unknown etiology. This study aimed to determine the carcinoembryonic antigen (CEA) and IgG serum levels in different oral lichenoid lesions before and after treatment with local corticosteroids. Methods. Two groups of 23 individuals, including oral ulcerative lichenoid lesions patients and healthy ones, were evaluated. Toluidine blue staining and biopsy examinations were carried out while visual analog scale (VAS) was used to evaluate symptoms. By applying corticosteroids, CEA and IgG serum levels were determined before and three weeks after intervention and at the end of the study (9 weeks) with ELISA and turbidimetry methods, respectively. Results. Before the intervention, there was no significant difference in CEA serum levels between the control and case groups (P=0.19). Moreover, the CEA serum levels indicated no significant difference before and after treatment in the case group (P=0.30). While IgG serum level was significantly higher before the intervention (P=0.01), it decreased significantly in the case group after treatment (P=0.02). In addition, pain intensity reduced significantly in the case group (P=0.05). According to statistics, 8.2% out of 21.7% of patients with positive staining results exhibited dysplasia signs. Conclusion. However, neither CEA nor IgG serum levels were different in patients diagnosed with or without dysplasia and positive or negative staining results (P>0.05). IgG serum levels and pain severity effectively decreased in the oral ulcerative lichenoid lesions patients treated with local corticosteroids. Therefore, this treatment can be considered an effective and low-complication treatment modality for lichenoid lesions.

A Retrospective Study of 23 Cases: Are Lichenoid Lesions of the Labial Mucosa Induced?

Background Lichen planus (LP) is a pathology that affects the skin and the mucosa. The lips are rarely involved but represent a diagnostic challenge in those cases. Oral lichenoid lesions (OLL) are defined as lesions that resemble oral lichen planus (OLP) but do not fully meet the clinical and/or histologic criteria for OLP. This study aimed to present our case series and to study the correlation between the location of the lesion and the dental factor (resin composite, amalgams, crowns, abrasive teeth, and mandibular crossbite) that could cause the lesion. Methods We conducted a retrospective observational study of 23 patients with LP/OLL of the lips treated in the Department of Oral Mucosal Pathology of the Department of Stomatology and Maxillofacial Surgery of the Pitié-Salpêtrière Hospital in Paris between January 2017 and February 2021. We noted the location of the lesion (upper, lower, or both lips), medical history, treatments, smoking habits, and the aspect of the teeth facing the lesion. Patients received a local corticoid treatment and were monitored via follow-up. Results Sixteen patients had lesions on the upper lip, two on the lower lip, and five on both lips, and most patients (n = 14, 60.1%) had a dental factor facing the lesion (e.g., abrasive teeth, resin composites, dental crowns, and mandibular crossbite). Six patients received clobetasol propionate, and 15 patients received a preparation combining betamethasone and benzocaine (Orabase, ConvaTec, Deeside, UK). Fourteen patients returned for post-treatment follow-up consultations approximately two months after treatment. Seven patients saw clinical improvement, five had partial improvement, and two had no improvement. Conclusions Lesions of the labial mucosa appear to be a rare condition in LP/OLL. The difference between LP and OLL can be difficult, even with histological analysis. Its pathogenesis remains unknown, although some studies found evidence of lichenoid reactions of the lips in contact with dental composite restorations. In our study, 14 of our patients had a dental factor facing the lesions. However, our study failed to show a correlation between the presence of an inducing factor and the lesion. In a future study, the potential effect of dental inducing factor removal could be studied. This topic requires further investigations, particularly regarding the inducing factor and the optimal therapeutic approach.

Lichenoid areas may arise in early stages of proliferative verrucous leukoplakia: A long-term study of 34 patients.

BACKGROUND: Proliferative verrucous leukoplakia is considered an uncommon oral potentially malignant disorder with a high malignant transformation rate. The objective of this paper was to define its cancer incidence and related risk factors. METHODS: A retrospective audit of 34 patients diagnosed with proliferative verrucous leukoplakia from a university-based unit, during the period from 1995 to 2019 was performed. The mean number of visits was 23 ± 18.6. The follow-up was divided into four-time intervals to evaluate the clinical presentation, number of lesions, dysplasia grade, and malignant transformation rate. RESULTS: The majority of patients were females 29 (85.3%), with verrucous component (77.8%), with a gingival presentation (31.8%), and with a preceding lichenoid area (44.1%). Eleven patients (32.4%) were affected by oral cancer during the follow-up, developing a total of 15 carcinomas. The mean age of malignant transformation was 67.2 ± 12.9 years, particularly 8 ± 8.5 from the onset of the lesions. Warty forms presented a higher mean estimate for malignant transformation (15.2 years, 95% confidence interval 4.4-26 years) than nodular forms (1.9 years, 95% confidence interval 1.9-1.9) (p = 0.019). Patients with an initial proliferative verrucous leukoplakia diagnosis suffered a higher risk of malignancy, particularly 15.55 times (95% confidence interval 1.69-143.17; p = 0.015) than those who did present a preceding area with lichenoid morphology. CONCLUSION: Proliferative verrucous leukoplakia presented a high malignant transformation rate and sometimes displayed preceding oral lichenoid areas in early stages. Further studies are needed to understand the impact of these lichenoid areas in proliferative verrucous leukoplakia progression.

Oral Potentially Malignant Disorders: Etiology, Pathogenesis, and Transformation Into Oral Cancer.

Among oral diseases, oral cancer is a critical health issue due to its life-threatening potential. Globocan, in its 2020 report, estimated ∼0.37 million new cases of oral cancer, with the majority of them coming from the Asian continent. The WHO has anticipated a rise in the incidences of oral cancer in the coming decades. Various factors, such as genetic, epigenetic, microbial, habitual, and lifestyle factors, are closely associated with oral cancer occurrence and progression. Oral lesions, inherited genetic mutations (dyskeratosis congenital syndrome), and viral infections (HPV) are early signs of oral cancer. Lesions with dysplastic features have been categorized under oral potentially malignant disorders (OPMDs), such as oral leukoplakia, erythroplakia, oral submucous fibrosis (OSMF), and proliferative verrucous leukoplakia, are assumed to have a high risk of malignancy. The incidence and prevalence of OPMDs are recorded as being high in South-Asian countries. Early detection, prevention, and treatment of OPMDs are needed to prevent its malignant transformation into oral cancer. Many advanced diagnostic techniques are used to predict their progression and to assess the risk of malignant transformation. This communication provides insight into the importance of early detection and prevention of OPMDs.

Protein disulfide isomerase family A member 3 expression is upregulated in tissue-derived extracellular vesicles in oral lichen planus and oral lichenoid lesions.

OBJECTIVES: The aim of this study was to identify the tissue-derived extracellular vesicles immunogen involved in the pathogenesis of oral lichen planus (OLP) and its variation oral lichenoid lesions (OLL). DESIGN: Six pooled tissue-derived extracellular vesicles from participants with OLP/OLL and three from healthy controls were isolated and enriched. The extracellular vesicles were characterized with transmission electronic microscopy, nanoparticle tracking analysis and western blotting. Proteins from extracellular vesicles were identified with proteomics analysis and differentially expressed proteins (DEPs) were further identified with a 2-fold (p < 0.05) increase or a 0.5-fold decrease. RESULTS: A total of 1805 peptides and 141 proteins were identified. Ten DEPs were further identified, with five upregulated proteins of fibrinogen alpha chain, lamin isoform A, 40S ribosomal protein, protein disulfide isomerase family A member 3 (PDIA3) and elongation factor 1-alpha 1, and five downregulated proteins of plakophilin-1, katanin p80 repeat-containing subunit B1, collagen alpha-3 chain, mitochondrial 2-oxoglutarate/malate carrier protein and guanine nucleotide-binding protein subunit gamma-12. PDIA3 was found to be immune-associated and to be involved in the antigen processing and presentation pathway. The upregulation of PDIA3 was confirmed in a verification cohort composed of three pairs of OLP/OLL-extracellular vesicles and healthy controls-extracellular vesicles with western blotting. CONCLUSIONS: Protein disulfide isomerase family A member 3 in extracellular vesicles may play a significant role in the local immune responses and the pathogenesis of oral lichen planus and oral lichenoid lesions.

Comparative Analyses of Clinical Features, Histopathology, and CD123 Immunohistochemistry of Oral Lupus Erythematosus, Lichen Planus, and Other Lichenoid Lesions.

BACKGROUND: Oral lupus erythematosus (OLE) and oral lichen planus (OLP) are among the common causes of oral lichenoid lesions (OLLs). The differential diagnosis among causes of OLLs, particularly between OLE and OLP, is challenging as they have significant clinical and histopathological overlap. OBJECTIVES: To compare and summarize the clinical, histopathological, and direct immunofluorescence (DIF) findings between OLE, OLP, and other OLLs and to explore the diagnostic value of CD123 immunohistochemistry. METHODS: A retrospective study on patients with OLE, OLP, and other OLLs was performed between January 2014 and December 2019. The baseline characteristics, the clinical, histopathological, and DIF features, as well as CD123 immunohistochemistry for plasmacytoid dendritic cells (PDCs) were statistically analyzed and compared between groups. RESULTS: Of 70 patients, 12 had OLE, 39 had OLP, and 19 had other OLLs. Oral erosions/ulcers were the most common findings in all three groups. Red macules, telangiectases, and discoid plaques were more common in OLE patients, while OLP cases were typified by reticulated patches (p < 0.05). Additionally, white patches were found more often in other OLLs than in both OLE and OLP (p = 0.002). Histologically, mucosal atrophy, basal vacuolization, and perivascular infiltrate were observed in OLE, whereas OLP specimens possessed mucosal hyperplasia, hypergranulosis, and compact orthokeratosis (p < 0.05). Mucosal spongiosis was a histologic feature that favored other OLLs over OLE and OLP (p < 0.001). Data on DIF were nonspecific for all three conditions. For immunohistochemical staining, the median number of total CD123+ PDCs was observed to be higher in OLE than OLP in the mucosal-submucosal junction (MSJ) (p = 0.021), the superficial perivascular area (p = 0.026), and the superficial and deep perivascular areas (p = 0.001). Likewise, PDCs in clusters ≥2+ were seen in significantly higher numbers on OLE than OLP along the MSJ (p = 0.002), the superficial perivascular area (p < 0.001), as well as the superficial and deep perivascular areas (p = 0.011). CD123+ PDCs were found to be significantly more numerous in both OLE and OLP than other OLLs in all of the abovementioned areas (all p < 0.05). CONCLUSION: While there are some differences in the clinicopathological features between OLE, OLP, as well as other OLLs, a significant overlap remains. The quantity and distribution pattern of CD123 immunohistochemical staining has a diagnostic implication in differentiating OLE from OLP and other OLLs.

Deep Learning Predicts the Malignant-Transformation-Free Survival of Oral Potentially Malignant Disorders.

Machine-intelligence platforms for the prediction of the probability of malignant transformation of oral potentially malignant disorders are required as adjunctive decision-making platforms in contemporary clinical practice. This study utilized time-to-event learning models to predict malignant transformation in oral leukoplakia and oral lichenoid lesions. A total of 1098 patients with oral white lesions from two institutions were included in this study. In all, 26 features available from electronic health records were used to train four learning algorithms-Cox-Time, DeepHit, DeepSurv, random survival forest (RSF)-and one standard statistical method-Cox proportional hazards model. Discriminatory performance, calibration of survival estimates, and model stability were assessed using a concordance index (c-index), integrated Brier score (IBS), and standard deviation of the averaged c-index and IBS following training cross-validation. This study found that DeepSurv (c-index: 0.95, IBS: 0.04) and RSF (c-index: 0.91, IBS: 0.03) were the two outperforming models based on discrimination and calibration following internal validation. However, DeepSurv was more stable than RSF upon cross-validation. External validation confirmed the utility of DeepSurv for discrimination (c-index-0.82 vs. 0.73) and RSF for individual survival estimates (0.18 vs. 0.03). We deployed the DeepSurv model to encourage incipient application in clinical practice. Overall, time-to-event models are successful in predicting the malignant transformation of oral leukoplakia and oral lichenoid lesions.

Oral submucous fibrosis presenting with histopathological lichenoid changes as predominant feature: Report of five cases and review of the literature.

Oral submucous fibrosis (OSF) is a precancerous condition of the oral cavity associated with habitual chewing of quid, with a high incidence among populations of the Indian subcontinent and Southeast Asia. Clinically, its initial manifestation may mimic oral lichen planus or lichen sclerosus. If the habit is not halted, the mucosa gets leathery and thickened, and fibrous bands form causing significant morbidity. Microscopically, it is characterized by atrophic epithelium, loss of rete ridges, and hyalinization of lamina propria. Of note, these hallmark histopathological features may be overlooked in the unusual presence of lichenoid interface changes, which may lead to the wrong diagnosis. We present herein five cases in which the rare joint appearance of OSF and lichenoid reaction features posed a diagnostic challenge. Due to its progressive nature and malignant potential, the presence of oral lichenoid changes overlying submucous hyalinization, in the right clinical and demographic setting, should raise suspicion of OSF and prompt actions directed at quid-chewing discontinuation.

Treatment trends in oral lichen planus and oral lichenoid lesions (Review).

Oral lichen planus (OLP) is a chronic inflammatory disease, associated with altered cell-mediated immunological function. It has long-term evolution, repeated exacerbations, sometimes painful and resistant to treatment, even all of these, OLP significantly affects patient's life quality. Not least, OLP is accompanied by an increased risk of malignant transformation. A wide spectrum of therapeutic options is available, but none are curative. In this review, 58 structured studies on the clinical symptomatology and treatment strategy of OLP were analyzed. The literature research was performed according to the criteria of the PRISMA system. This study summarizes current knowledge regarding management of OLP and oral lichenoid lesions, discusses the challenges of choosing an adequate treatment and, in attempt to improve the quality of patient life, trying to describe a therapeutic algorithm that takes into consideration the clinical features of the disease. Current OLP therapy aims at eliminating all mucosal-related lesions, reduce symptomatology and decrease the risk of oral cancer and include corticosteroids, immunomodulatory agents, retinoids, ultraviolet irradiation and/or laser therapy.

Diagnostic Criteria of Oral Lichen Planus: A Narrative Review.

Oral lichen planus (OLP) is a disease with unclear etiology or pathogenesis, categorized by the World Health Organization as oral lichenoid lesions (OLL; interface mucositis or lichenoid mucositis) into a group of potentially malignant disorders. The diagnosis of OLP is challenging because the clinical and histopathologic features are frequently seen in OLP, OLL and/or other mucosal diseases with lichenoid characteristics. Furthermore, OLP has a dynamic nature. Finally, an early and precise diagnosis can play a decisive role, allowing timely treatment and thus improving the patient quality of life. This article summarizes the state-of-the-art regarding OLP and OLL and discusses the challenges faced on making an accurate diagnosis, aiming to provide a practical guideline for the postgraduates and oral physicians in reaching the diagnosis of these lesions.

Malignant transformation risk of oral lichen planus: A systematic review and comprehensive meta-analysis.

OBJECTIVES: To evaluate current evidence on the malignant transformation of oral lichen planus (OLP), oral lichenoid lesions (OLLs), and oral lichenoid reactions (LRs) and to determine the variables with greatest influence on cancer development. MATERIAL AND METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies published before November 2018. We evaluated the quality of studies (QUIPS tool). We carried out meta-analyses to fulfill our objectives. We examined the between-study heterogeneity and small-study effects, and conducted sensitivity studies and subgroup analyses. RESULTS: Inclusion criteria were met by 82 studies (26,742 patients. The combined malignant transformation rate was 1.14% for OLP (95% CI = 0.84-1.49), 1.88% for OLLs (95% CI = 0.15-4.95) and 1.71% for LRs (95% CI = 0.00-5.46). Subgroup analysis revealed a higher malignant transformation rate in studies when the presence of epithelial dysplasia was not an exclusion criterion (p = 0.001), when both clinical and histopathological criteria were used for diagnosis (p < 0.001), when the follow-up was at least 12 months (p = 0.048), and when there was lower risk of potential bias (p = 0.002). Malignant transformation risk factors were: tongue localization (RR = 1.82, 95% CI = 1.21-2.74, p = 0.004), presence of atrophic-erosive lesions (RR = 4.09, 95% CI = 2.40-6.98, p < 0.001), tobacco use (RR = 1.98, 95% CI = 1.28-3.05, p = 0.002), alcohol consumption (RR = 2.28, 95% CI = 1.14-4.56, p = 0.02), and hepatitis C virus infection (RR = 4.46, 95% CI = 0.98-20.22, p = 0.053). CONCLUSIONS: The malignant transformation rates of OLP, OLLs and LRs are underestimated due essentially to restrictive diagnostic criteria, inadequate follow-up periods, and/or low quality of studies.

Severity of oral lichen planus and oral lichenoid lesions is associated with anxiety.

OBJECTIVES: Oral lichen planus (OLP) and oral lichenoid lesions (OLL) are chronic inflammatory diseases whose symptoms can impair patient's quality of life (QoL). Psychological factors seem to play an important role in these diseases. This study aimed to determine the impact of oral health and anxiety levels on the QoL of patients with OLP and OLL. PATIENTS AND METHODS: This was a cross-sectional study composed of OLP and OLL patients and a control group matched by age and sex with no autoimmune/inflammatory or malignant oral lesions. Anxiety levels and oral health impact on QoL were assessed using the Hamilton Anxiety Scale (HAM-A) and the Oral Health Impact Profile-14 (OHIP-14), respectively. The instruments were filled through personal interview before starting the treatment for oral lesions. RESULTS: A total of 87 patients diagnosed with OLP (n = 45) and OLL (n = 42), and 87 controls were included in the study. Statistical differences were observed for the psychic and somatic anxiety dimensions between severities of diseases. Patients with OLP or OLL had higher scores for the OHIP-14 dimensions physiological discomfort and social limitation compared with controls. In addition, higher scores for physical pain, physical disability, social disability, and handicap were detected among patients with greater severity. CONCLUSION: Greater severity of OLP and OLL seems to be associated with increased levels of anxiety, higher scores of oral health impact profile, and decreased QoL. CLINICAL RELEVANCE: Patients with severe OLP/OLL may benefit from additional therapeutic treatments, such as psychological and/or psychiatric management, concomitant to treatment specific to oral lesions.