Search Results (13)

Leukoplakia is a condition marked by white patches on the inner surfaces of the oral cavity. Its potential to progress to oral squamous cell carcinoma underscores the need for effective screening and early diagnosis procedures. We employed NMR-based salivary and tissue metabolomics to identify potential biomarkers for leukoplakia and dysplastic leukoplakia. Univariate and multivariate methods were used to evaluate the NMR-derived metabolite concentrations. The salivary metabolite profile of leukoplakia exhibited specific alterations compared to healthy controls. These metabolic changes were more pronounced in cases of dysplastic lesions. Multivariate ROC curve analysis, based on a selection of salivary metabolites, ascribed high diagnostic accuracy to the models that discriminate between dysplastic and healthy cases. However, NMR analysis of tissue biopsies was ineffective in extracting metabolic signatures to differentiate between lesional, peri-lesional, and healthy tissues. Our pilot study employing a metabolomics-based approach led to the development of salivary models that represent a complementary strategy for clinically detecting leukoplakia. However, larger-scale validation is required to fully evaluate their diagnostic potential and to effectively stratify leukoplakia patients according to dysplasia status. Full article

Background: Periodontal disease is an inflammatory, chronic, and multifactorial disease. The objective of this study is to analyze the association between periodontal disease and some disorders such as papillomas (benign lesions), lichen planus (a chronic immune-mediated disorder), leukoplakia (potentially malignant lesions), and oral cancer (malignant lesions). Methods: For this study, 42 patients were recruited whose supragingival and subgingival plaque was qualitatively analyzed using a phase-contrast microscope, which allowed for the detection of compatible bacterial flora (immobile and composed mainly of cocci) indicative of periodontal health and incompatible bacterial flora (mobile and composed mainly of spirochetes) indicative of periodontal pathology. Patients with incompatible bacterial flora were then subjected to a laser-assisted periodontal treatment with irrigation with hydrogen peroxide within the periodontal pockets (a non-surgical laser-assisted periodontal protocol which is referred to as dye-free photodynamic therapy). Results: Based on the 42 patients recruited, there was no association between oral cavity lesions and periodontal pathogenic bacteria. Four of them were found to have incompatible bacterial flora. Indeed, it was found that almost all the patients had been previously instructed in the proper techniques of home oral hygiene, and more than half of them reported that they carried out periodic check-ups by a dental hygienist. Of the four patients with signs and symptoms of periodontitis, two stated a willingness to undergo the non-surgical laser-assisted periodontal protocol and showed improvements in periodontal indices such as CAL, PPD, and BoP. Conclusions: hygienists and dentists are determining factors in the prevention of periodontal disease and for the maintenance of good oral health. Full article

Precancerous cells in the oral cavity may appear as oral potentially malignant disorders, but they may also present as dysplasia without visual manifestation in tumor-adjacent tissue. As it is currently not possible to prevent the malignant transformation of these oral precancers, new treatments are urgently awaited. Here, we generated precancer culture models using a previously established method for the generation of oral keratinocyte cultures and incorporated CRISPR/Cas9 editing. The generated cell lines were used to investigate the efficacy of a set of small molecule inhibitors. Tumor-adjacent mucosa and oral leukoplakia biopsies were cultured and genetically characterized. Mutations were introduced in CDKN2A and TP53 using CRISPR/Cas9 and combined with the ectopic activation of telomerase to generate cell lines with prolonged proliferation. The method was tested in normal oral keratinocytes and tumor-adjacent biopsies and subsequently applied to a large set of oral leukoplakia biopsies. Finally, a subset of the immortalized cell lines was used to assess the efficacy of a set of small molecule inhibitors. Culturing and genomic engineering was highly efficient for normal and tumor-adjacent oral keratinocytes, but success rates in oral leukoplakia were remarkably low. Knock-out of CDKN2A in combination with either the activation of telomerase or knock-out of TP53 seemed a prerequisite for immortalization. Prolonged culturing was accompanied by additional genetic aberrations in these cultures. The generated cell lines were more sensitive than normal keratinocytes to small molecule inhibitors of previously identified targets. In conclusion, while very effective for normal keratinocytes and tumor-adjacent biopsies, the success rate of oral leukoplakia cell culturing methods was very low. Genomic engineering enabled the prolonged culturing of OL-derived keratinocytes but was associated with acquired genetic changes. Further studies are required to assess to what extent the immortalized cultures faithfully represent characteristics of the cells in vivo. Full article

Despite the profession placing great emphasis on oral potentially malignant disorders (OPMDs) as a gateway for early recognition and consequently better outcomes for oral cancer, the death rates for lip and oral cavity cancer have remained stagnant for three decades. Evidence shows that only a small fraction of oral cancers are in fact preceded by OPMDs, and that most OPMDs have an annual transformation rate of less than 1%. As OPMDs encompass a very heterogeneous group of oral conditions, it could be argued that only patients with oral mucosal diseases bearing a substantial risk of malignant transformation warrant close surveillance and treatment, these include proliferative leukoplakia, erythroplakia, non-homogeneous leukoplakia, as well as diseases presenting with severe dysplasia at biopsy. In this narrative review, I discuss the intricate epidemiology of the malignancies that we colloquially refer to as oral cancer, explore the limitations of focusing on OPMDs to reduce the incidence and mortality of oral cavity cancer, and argue that a may-be cancer label represents overdiagnosis for most OPMDs. Full article

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. Full article

Malignant transformation of oral lichen planus (OLP) into oral squamous cell carcinoma is considered as one of the most serious complications of OLP. For the early detection of oral cancer in OLP follow-up, accurate localization of the OLP center is still difficult but often required for confirmatory biopsy with histopathological examination. Optical coherence tomography (OCT) offers the potential for more reliable biopsy sampling in the oral cavity as it is capable of non-invasively imaging the degenerated oral layer structure. In this case-series study with 15 patients, features of clinically classified forms of OLP in OCT cross-sections were registered and correlated with available histologic sections. Besides patients with reticular, atrophic, erosive and plaque-like OLP, two patients with leukoplakia were included for differentiation. The results show that OCT yields information about the epithelial surface, thickness and reflectivity, as well as the identifiability of the basement membrane and the vessel network, which could be used to complement the visual clinical appearance of OLP variants and allow a more accurate localization of the OLP center. This forms the basis for further studies on OCT-assisted non-invasive clinical classification of OLP, with the aim of enabling decision support for biopsy sampling in the future. Full article

Betel quid and areca nut are complex mixture carcinogens, but little is known about whether their derived single-agent arecoline or arecoline N-oxide (ANO) is carcinogenic, and the underlying mechanisms remain unclear. In this systematic review, we analyzed recent studies on the roles of arecoline and ANO in cancer and strategies to block carcinogenesis. In the oral cavity, flavin-containing monooxygenase 3 oxidizes arecoline to ANO, and both alkaloids conjugate with N-acetylcysteine to form mercapturic acid compounds, which are excreted in urine, reducing arecoline and ANO toxicity. However, detoxification may not be complete. Arecoline and ANO upregulated protein expression in oral cancer tissue from areca nut users compared to expression levels in adjacent normal tissue, suggesting a causal relationship between these compounds and oral cancer. Sublingual fibrosis, hyperplasia, and oral leukoplakia were diagnosed in mice subjected to oral mucosal smearing of ANO. ANO is more cytotoxic and genotoxic than arecoline. During carcinogenesis and metastasis, these compounds increase the expression of epithelial–mesenchymal transition (EMT) inducers such as reactive oxygen species, transforming growth factor-β1, Notch receptor-1, and inflammatory cytokines, and they activate EMT-related proteins. Arecoline-induced epigenetic markers such as sirtuin-1 hypermethylation, low protein expression of miR-22, and miR-886-3-p accelerate oral cancer progression. Antioxidants and targeted inhibitors of the EMT inducers used reduce the risk of oral cancer development and progression. Our review findings substantiate the association of arecoline and ANO with oral cancer. Both of these single compounds are likely carcinogenic to humans, and their mechanisms and pathways of carcinogenesis are useful indicators for cancer therapy and prognosis. Full article

Oral leukoplakia, which presents as white lesions in the oral cavity, including on the tongue, is precancerous in nature. Conservative treatment is preferable, since surgical removal can markedly reduce the patient’s quality of life. In the present study, we focused on the flavonoid apigenin as a potential compound for preventing carcinogenesis, and an apigenin-loaded mucoadhesive oral film was prepared using a three-dimensional (3D) bioprinter (semi-solid extrusion-type 3D printer). Apigenin-loaded printer inks are composed of pharmaceutical excipients (HPMC, CARBOPOL, and Poloxamer), water, and ethanol to dissolve apigenin, and the appropriate viscosity of printer ink after adjusting the ratios allowed for the successful 3D printing of the film. After drying the 3D-printed object, the resulting film was characterized. The chemopreventive effect of the apigenin-loaded film was evaluated using an experimental rat model that had been exposed to 4-nitroquinoline 1-oxide (4NQO) to induce oral carcinogenesis. Treatment with the apigenin-loaded film showed a remarkable chemopreventive effect based on an analysis of the specimen by immunohistostaining. These results suggest that the apigenin-loaded mucoadhesive film may help prevent carcinogenesis. This successful preparation of apigenin-loaded films by a 3D printer provides useful information for automatically fabricating other tailored films (with individual doses and shapes) for patients with oral leukoplakia in a future clinical setting. Full article

Background and Objectives: Dentists play a very important part in the early identification of oral cancer lesions. This aspect of dental practice depends on the knowledge acquired during the faculty years. The aim of this study was to assess dental students’ and residents’ levels of awareness in terms of oral cancer. Materials and Methods: The cross-sectional study was conducted at the Faculty of Dental Medicine within the “Grigore T. Popa” University of Medicine and Pharmacy in Iasi, on a sample of 197 students in the fourth and the fifth years and first year residents in general dentistry. To assess their knowledge, a questionnaire was created containing 22 questions about the risk factors for oral cancer, with a focus on HPV infection. Results: Most participants correctly identified smoking, alcohol, and the HPV infection as risk factors and leukoplakia and erythroplasia as potentially malignant lesions. At the opposite site, aspects considered as unsatisfactory focused on the palpation of lymphatic nodules, a procedure largely carried out by 41.6% of the fourth year students, the counseling only of the patients at risk performed by 59.7% of residents, the lack of knowledge about the prevention of oral cancer through anti-HPV immunization found in 39.7% of the fifth year students. Other incorrect answers focused on other types of suspicious lesions, such as actinic cheilitis, as well as certain areas in the oral cavity subject to the frequent onset of oral cancer, such as buccal mucosa. Conclusions: Although the fifth year students and residents have better knowledge than the fourth year students, the gaps in terms of knowledge and practice encountered in all three categories of participants require a reevaluation of the academic curriculum and the focus on the building of the skills necessary for the correct screening of oral cancer. Full article

Lesions commonly associated with HIV infection include oral candidiasis, herpes simplex infection, oral Kaposi’s sarcoma, hairy leukoplakia, periodontal diseases (linear gingival erythema and necrotizing ulcerative periodontitis), xerostomia, human papillomavirus-associated warts, aphthous ulcers, non-Hodgkin’s lymphoma, histoplasmosis, carcinoma, exfoliative cheilitis, and HIV salivary gland disease. Non-Hodgkin’s lymphoma (NHL) is the most common cancer in people living with HIV (PLWH), and the incidence is increased for aggressive B-cell NHL. Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy that is often unresponsive to chemotherapy and usually has a poor prognosis. We hereby present the case of a patient with a recent history of COVID-19 infection who was diagnosed with HIV and NHL, with manifestations in the oral cavity and a favorable evolution after the introduction of antiviral therapy, specific chemotherapy, and radiotherapy. Dental expertise is necessary for the appropriate management of oral manifestations of HIV infection or AIDS, and lymphoma should be included in the differential diagnosis of any oral lesions. Full article

We reviewed the current published literature on the impact of oral microbiota on oral cavity leukoplakia (OLK), aiming at clarifying its role in disease transformation. The analysis unveiled that bacterial richness and diversity in the oral cavity tend to be decreased in OLK compared to healthy controls, with a reduction in the prevalent commensals, such as Streptococci, and elevation of anaerobes. Moreover, Fusobacterium nucleatum, Porphyromonas gingivalis and Prevotella intermedia are recurrent findings, and they already have been linked to periodontal disease. These microbial community changes may also represent a marker for the transition from OLK to oral squamous cell carcinoma. Unfortunately, the reviewed studies present several limitations, making an objective comparison difficult. To overcome these biases, longitudinal studies are necessary. Full article

Saliva is a highly versatile biological fluid that is easy to gather in a non-invasive manner—and the results of its analysis complement clinical and histopathological findings in the diagnosis of multiple diseases. The objective of this review was to offer an update on the contribution of salivary biomarkers to the diagnosis and prognosis of diseases of the oral cavity, including oral lichen planus, periodontitis, Sjögren’s syndrome, oral leukoplakia, peri-implantitis, and medication-related osteonecrosis of the jaw. Salivary biomarkers such as interleukins, growth factors, enzymes, and other biomolecules have proven useful in the diagnosis and follow-up of these diseases, facilitating the early evaluation of malignization risk and the monitoring of disease progression and response to treatment. However, further studies are required to identify new biomarkers and verify their reported role in the diagnosis and/or prognosis of oral diseases. Full article

Periodontal diseases are multiperspective problems resulting from numerous and diverse exposures that influence the process of initiation or progression of disease. The negative influence of tobacco smoking on oral health is well documented. The aim of the study was to analyze three SNPs in vitamin D receptor gene—rs7975232 (ApaI), rs2228570 (FokI) and rs1544410 (BsmI)—combined with oral health assessment—pH, gingival index, dry mouth, periodontitis, dry socket, redness of oral cavity mucosa, leukoplakia—in a group of cigarette smokers and in non-smokers. Moreover, the possibility of interactions between these polymorphisms and smoking was examined. When comparing the smokers and non-smokers groups, we noticed that rs1544410 heterozygotes were significantly more frequent in the first group, and for the second, both homozygotes were more frequent. Additionally, we observed the impact of interaction between the rs7975232 genotype and smoking status on gingival index. Current smoking was also associated with all analyzed oral health measures except for leucoplakia. Correlation between pH and age in both smokers and non-smokers was also present. Results of our analysis indicate that in our study group lifestyle and aging were leading factors associated with worse oral health status. However, the impact of genetic variants, and also the impact of their interaction with smoking on analyzed parameters was also visible. These results show great possibilities for all levels of prevention of oral diseases by means of education based on evidence-based medicine, but also for incorporating genetic testing and early interventions into this process for predisposed individuals. Full article