Cancer Stem Cells in Oral Squamous Cell Carcinoma: A Narrative Review on Experimental Characteristics and Methodological Challenges.

Cancer stem cells (CSCs) represent a subpopulation of cancer cells that are believed to initiate and drive cancer progression. In animal models, xenotransplanted CSCs have demonstrated the ability to produce tumors. Since their initial isolation in blood cancers, CSCs have been identified in various solid human cancers, including oral squamous cell carcinoma (OSCC). In addition to their tumorigenic properties, dysregulated stem-cell-related signaling pathways-Wnt family member (Wnt), neurogenic locus notch homolog protein (Notch), and hedgehog-have been shown to endow CSCs with characteristics like self-renewal, phenotypic plasticity, and chemoresistance, contributing to recurrence and treatment failure. Consequently, CSCs have become targets for new therapeutic agents, with some currently in different phases of clinical trials. Notably, small molecule inhibitors of the hedgehog signaling pathway, such as vismodegib and glasdegib, have been approved for the treatment of basal cell carcinoma and acute myeloid leukemia, respectively. Other strategies for eradicating CSCs include natural compounds, nano-drug delivery systems, targeting mitochondria and the CSC microenvironment, autophagy, hyperthermia, and immunotherapy. Despite the extensive documentation of CSCs in OSCC since its first demonstration in head and neck (HN) SCC in 2007, none of these novel pharmacological approaches have yet entered clinical trials for OSCC patients. This narrative review summarizes the in vivo and in vitro evidence of CSCs and CSC-related signaling pathways in OSCC, highlighting their role in promoting chemoresistance and immunotherapy resistance. Additionally, it addresses methodological challenges and discusses future research directions to improve experimental systems and advance CSC studies.

Salivary Profile Analysis Based on Oral Cancer Risk Habits: An Observational Cross-Sectional Study.

BACKGROUND: In Indonesia, cultural practices such as betel quid chewing, smoking, and alcohol consumption are prevalent. These practices are known risk factors for oral cancer and may influence the salivary profile, which is essential for maintaining oral health. PURPOSE: To compare the salivary profiles of individuals with and without risk factors for oral cancer. METHODS: The study included 49 individuals identified as having risk factors for oral cancer. Unstimulated saliva samples were collected. Various parameters were measured, including salivary pH, flow rate (FR), thickness, color, turbidity, and the levels of IL-1ß and IL-8. Data were analyzed using Chi-square and t-tests. RESULTS: A significant difference was found in salivary IL-1ß levels between the two groups (p = 0.009), with higher levels observed in individuals with oral cancer risk factors. Notably, the salivary IL-1ß concentrations showed significant differences between the smoking group (p = 0.021; OR = 2.94) and the alcohol-drinking group (p = 0.007; OR = 4.96) compared to the control group. However, no significant differences were observed between the groups in terms of salivary viscosity, color, turbidity, flow rate, acidity, or IL-8 levels (p > 0.05). CONCLUSION: Individuals with risk factors for oral cancer exhibit distinct salivary IL-1ß profiles compared to those without such risk factors, particularly those who practice alcohol drinking.

Enhanced Knowledge Inversed Attitude of Oral Cancer Risk Habit Associated With Sociocultural: A Quantitative and Qualitative Pilot Study.

Aim: In 2023, the global incidence of oral cancer reached 54,540 new cases, with risk factors including smoking (S), alcohol consumption (A), and betel quid chewing (BQC). The knowledge and attitudes about these risk factors impact this practice, particularly in communities that follow local traditions. The aim of this study was to determine the level of knowledge and attitude regarding risk factors for oral cancer on Flores Island, East Indonesia. Materials and Methods: This was an analytical observational study with a cross-sectional design using quantitative and qualitative approaches. Structured questionnaires and focus group discussions (FGDs) were conducted with the community, local government, and dentists to obtain data; quantitative analysis was performed using regression; and qualitative analysis was performed using themes. Results: Of 542 participants (men 66.42 %; women 33.57 %), 64.4% had a high level of knowledge and a low level of attitude for S = 62.5%, A = 66.7%, and BQC = 50.0%. There was a correlation between knowledge and attitudes about S (P = 0.009) and BQC (P = 0.011). The FGDs yielded 14 subjects (five men and nine women) with three themes of knowledge (betel nut ingredients, causes of cancer, and impacts of habits) and three themes of attitude (type of habit, desire to stop, and oral cancer prevention programs). On the basis of FGDs, most of the subjects already knew the causes of oral cancer, but the desire to stop and prevent oral cancer was difficult. Conclusion: The population on Flores Island has a high level of knowledge but a low level of attitude. Nevertheless, it is difficult to minimize or eliminate oral cancer-risk behaviors due to their cultural and socioeconomic conditions.

Management of oral mucositis: a systematic review.

INTRODUCTION: Oral mucositis is one of the most common complications following chemotherapy and/or head and neck radiotherapy. Various treatments for oral mucositis have been proposed. However, there has still been no review of the most frequent and most effective type of therapy to treat oral mucositis. This systematic review aims to determine the most frequent and effective types of therapy to treat and reduce the severity of oral mucositis. EVIDENCE ACQUISITION: The literature search was carried out using PRISMA guidelines. Publications included from 2010 to June 2021 with a clinical trial, prospective, and retrospective observational research design. The following databases were used: PubMed, Cochrane Library, and Wiley Online Library. The search was for limited articles published in English, which were screened and analyzed by three authors. The risk of bias of each study was also assessed by three authors simultaneously, using different types of instruments depending on its study design. EVIDENCE SYNTHESIS: Forty-seven of 1274 journals were included. From 3577 subjects, oral mucositis was more common in males than females (2.12: 1), with a mean age of 56.39 (18-90 years). The most commonly used types of therapy are low-level laser therapy (396 subjects) and lysozyme-based compounds (314 subjects). Meanwhile, the most effective type of therapy is low-level laser therapy. CONCLUSIONS: Low-level laser therapy is the most commonly used oral mucositis therapy and is also the most effective in reducing the degree of oral mucositis and associated pain.

Image collection and annotation platforms to establish a multi-source database of oral lesions.

OBJECTIVE: To describe the development of a platform for image collection and annotation that resulted in a multi-sourced international image dataset of oral lesions to facilitate the development of automated lesion classification algorithms. MATERIALS AND METHODS: We developed a web-interface, hosted on a web server to collect oral lesions images from international partners. Further, we developed a customised annotation tool, also a web-interface for systematic annotation of images to build a rich clinically labelled dataset. We evaluated the sensitivities comparing referral decisions through the annotation process with the clinical diagnosis of the lesions. RESULTS: The image repository hosts 2474 images of oral lesions consisting of oral cancer, oral potentially malignant disorders and other oral lesions that were collected through MeMoSA® UPLOAD. Eight-hundred images were annotated by seven oral medicine specialists on MeMoSA® ANNOTATE, to mark the lesion and to collect clinical labels. The sensitivity in referral decision for all lesions that required a referral for cancer management/surveillance was moderate to high depending on the type of lesion (64.3%-100%). CONCLUSION: This is the first description of a database with clinically labelled oral lesions. This database could accelerate the improvement of AI algorithms that can promote the early detection of high-risk oral lesions.

Barriers to early detection and management of oral cancer in the Asia Pacific region.

OBJECTIVE: Oral cancer is amenable to early detection but remains a prominent cause of mortality in the Asia Pacific region. This study aimed to identify barriers to early detection and management of oral cancer in the Asia Pacific region. METHODS: A mixed-methods approach was employed triangulating findings from a survey and focus groups. The survey was conducted among seven representative members of the Asia Pacific Oral Cancer Network (APOCNET) across six countries. Focus groups were conducted to gain deeper insights into the findings of the survey. RESULTS: The identified barriers were a lack of national cancer control strategies and cancer registries and the limited availability of trained health care professionals. Overcoming these challenges in the Asia Pacific region where resources are scarce will require collaborative partnerships in data collection and novel approaches for continuous professional training including eLearning. Further, to overcome the lack of trained health care professionals, innovative approaches to the management of oral potentially malignant lesions and oral cancer including telemedicine were suggested. CONCLUSION: The findings of this study should be taken into account when charting national cancer control plans for oral cancer and will form the basis for future collaborative studies in evaluating effective measures to improve oral cancer detection and management in low- and middle-income countries.

Characteristics of Current Betel Quid/Chewing Tobacco Users, Smokers and Dual Users in Indonesia: An Analysis of GATS 2011 Data.

Background: Indonesia has the third largest population of smokers in the world, however, little is known about the use of chewing tobacco/betel quid in Indonesia. This paper describes the characteristics of chewing tobacco/betel quid users in Indonesia, to understand the user population and inform future research. Methods: The 2011 Indonesia GATS included 8,176 adults ages 15 and older. These data are weighted to be nationally representative. Weighted descriptive statistics and multivariate logistic regression were run using SAS 9.4. Results: Estimated national prevalence for exclusive chewing tobacco/betel quid use was 0.9%, for exclusive smoked tobacco use was 33.9% and for dual use was 0.8%. Multivariate logistic regression analyses showed that exclusive chewing tobacco/betel quid users were significantly more likely to be female, and to be older adults (45-64); while smokers are more likely to be male and younger (25-44). Conclusions/Importance: These results provide information on the different characteristics of users by product type, and show that users' demographics vary by their product of choice. This study helps to inform researchers and practitioners of the burden of chewing tobacco/betel quid use in Indonesia. These data, especially specific data on chewing tobacco/betel quid use patterns, are limited in this context, and this knowledge can help to identify populations who need quit tobacco interventions.

Tobacco (kretek) smoking, betel quid chewing and risk of oral cancer in a selected Jakarta population.

PURPOSE: This study aimed to determine the association between tobacco consumption (kretek) and betel quid chewing with oral cancer risk. MATERIALS AND METHODS: A total of 81 cases of oral cancers were matched with 162 controls in this hospital-based study. Information on sociodemographic characteristics and details of risk habits (duration, frequency and type of tobacco consumption and betel quid chewing) were collected. Association between smoking and betel quid chewing with oral cancer were analysed using conditional logistic regression. RESULTS: Slightly more than half of the cases (55.6%) were smokers where 88.9% of them smoked kretek. After adjusting for confounders, smokers have two fold increased risk, while the risk for kretek consumers and those smoking for more than 10 years was increased to almost three-fold. Prevalence of betel quid chewing among cases and controls was low (7.4% and 1.9% respectively). Chewing of at least one quid per day, and quid combination of betel leaf, areca nut, lime and tobacco conferred a 5-6 fold increased risk. CONCLUSIONS: Smoking is positively associated with oral cancer risk. A similar direct association was also seen among betel quid chewers.

GSTM1, GSTT1 and CYP1A1 polymorphisms and risk of oral cancer: a case-control study in Jakarta, Indonesia.

PURPOSE: to investigate genetic polymorphisms in GSTM1, GSTT1 and CYP1A1 and the association with the risk of oral cancer in the Jakarta population. METHOD: A total of 81 cases and 162 controls matched for age and sex were selected from 5 hospitals in Jakarta. Sociodemographic data using questionnaires were obtained and peripheral blood samples were collected with informed consent for PCR-RFLP assay. Conditional logistic regression analysis was performed to obtain the association between the risk of oral cancer and GSTM1, GSTT1 and CYP1A1 polymorphisms. RESULTS: GSTM1 and GSTT1 null were slightly overrepresented among cases (60.5% and 45.7% respectively) compared to controls (55.6% and 41.4% respectively), but no statistically significant differences were observed. In contrast, the distribution of CYP1A1 polymorphism was higher among controls compared to cases (52.5 % versus 42.4 %). The odds ratio of null GSTM1 and GSTT1 genotypes was slightly higher compared to wild type genotypes (OR 1.19, 95% CI 0.70-2.02 and OR 1.19, 95% CI 0.72-2.05 respectively). Furthermore, the presence of CYP1A1 polymorphism did not increase the risk of oral cancer (OR 0.70, 95% 0.39-1.25). CONCLUSION: Genetic polymorphisms of GSTM1, GSTT1 and CYP1A1 may not be risk factors for oral cancer in the Jakarta population.

Dietary patterns and risk of oral cancer: a factor analysis study of a population in Jakarta, Indonesia.

A matched case-control, hospital-based study of oral cancer was conducted in Jakarta population. The sample included 81 cases and 162 controls. The purpose of this study was to determine the association between dietary pattern and oral cancer in a Jakarta population using factor analysis. Dietary data were collected using food frequency questionnaire and factor analysis was performed on 15 food groups resulting in four principle factors/components being retained. The first factor "preferred" was characterized by fast food, fermented food, canned food, snacks high in fat and sugar, cooked and raw vegetables, and seafood. The second factor labeled "combination" was loaded by the intake of dairy product, red meat, white meat and fruits. The third factor labeled "chemical related was loaded by processed food and monosodium glutamate and the fourth principle component consisted of drinks and grain was labeled as "traditional". The conditional logistic regression was done using STATA 8 to obtain the odds ratio (OR) of highest tertile of each component retained from factor analysis and the ORs were then adjusted with risk habits. The consumption the highest tertile of the "preferred" pattern increased the risk of oral cancer by two-times compared to the lowest tertile of consumption [adjusted odds ratio (aOR)=2.17; 95% confidence interval (CI)=1.05-4.50]. The chemical related" pattern showed higher risk of about threefold (aOR=2.56; 95% CI=1.18-5.54), while the "traditional" pattern showed an increased of risk by twofold (aOR=2.04; 95% CI=1.01-4.41). In contrast, the "combination" pattern displayed protective effects in relation to oral cancer (aOR=0.50; 95% CI=0.24-1.00). This finding suggests that factor analysis may be useful to determine the diet pattern of a big set of food type and establish the correlation with oral cancer.