BACKGROUND:Oral lichen planus (OLP) is a chronic immune-mediated disorder with malignant potential. However, its real-world clinical course remains incompletely characterized. This study aimed to describe the natural clinical-histopathological trajectory of OLP in a single tertiary centre and to identify factors associated with dysplasia and malignant transformation over time. METHODS:We conducted a single-centre retrospective cohort study including patients diagnosed with OLP and followed between 2007 and 2024 at the Oral Medicine Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS. Demographic, clinical (red vs. white phenotype and lesion distribution), microbiological (Candida spp.), therapeutic, and histopathological variables were collected across follow-up. Univariate and multivariable logistic regression models were used to evaluate factors associated with dysplasia and malignant transformation. RESULTS:Among 308 screened patients, 246 met inclusion criteria (173 women, 70.3%; mean age 63.2 ± 15.0 years) with a mean follow-up of 55.5 ± 37.0 months. At baseline, Candida spp. colonization was detected in 55 patients (22.4%) and was more frequent in red-type OLP than white-type lesions (33.3% vs. 17.0%; OR 2.44, 95% CI 1.32-4.53; p = 0.005). During follow-up, 33 patients (13.4%) developed fungal infection despite an initially negative swab. Epithelial dysplasia emerged in 42 patients (17.1%). In multivariable analysis, dysplasia was independently associated with increasing age (OR 1.06, 95% CI 1.03-1.10; p = 0.0001) and red-type OLP(OR 2.24, 95% CI 1.10-4.55; p = 0.026). Eight patients (3.25%) developed infiltrative OSCC after a mean interval of 28.3 months from OLP diagnosis (range 4-55). CONCLUSIONS:In this long-term single-centre cohort, OLP frequently evolved through dysplasia during follow-up, and malignant transformation occurred in a minority of patients. Older age and red-type phenotype characterized patients more likely to develop dysplasia, while malignant transformation was more frequent in the case of previously documented dysplastic lesions, in keeping with the notion of dysplasia as a step along the carcinogenic pathway, older age, and diffuse lesions.
BACKGROUND:Aurora Kinase A (AURKA), a highly conserved and potent kinase, is frequently overexpressed in diverse cancers. However, its role in the malignant transformation (MT) of oral mucosa remains poorly understood. This study investigated the expression pattern of AURKA and evaluated the therapeutic potential of its inhibitor in oral leukoplakia (OLK), the most representative oral potentially malignant disorder. METHODS:Immunohistochemistry was performed on clinical samples (21 normal controls, 27 OLK, 23 MT of OLK) to examine AURKA expression and its correlation with clinicopathological characteristics. The inhibitory effect of targeting AURKA on tumor proliferation was verified in vitro using two oral squamous cell carcinoma (OSCC) cell lines. Additionally, the chemopreventive effect of the AURKA inhibitor Alisertib on MT was assessed using a 4-nitroquinoline oxide (4NQO)-induced mouse OLK model. RESULTS:AURKA expression levels positively correlated with the malignant progression of OLK. Significantly higher AURKA expression percentages were observed in non-homogeneous lesions (10.39% ± 4.28% vs. 3.53% ± 4.22% homogeneous, p < 0.001), lesions ≥ 2 cm2 (11.19% ± 4.55% vs. 4.69% ± 4.36% < 2 cm2, p < 0.01), and lesions with high-risk dysplasia (12.10% ± 4.04% vs. 4.59% ± 4.12% low-risk dysplasia, p < 0.001). Targeting AURKA significantly inhibited the proliferation of OSCC cells in vitro. Furthermore, Alisertib treatment effectively suppressed oral mucosa carcinogenesis in the 4NQO model. CONCLUSION:Increased AURKA expression may represent an early molecular event in OLK carcinogenesis, and targeting AURKA with alisertib is a candidate for potential applications in the management of OLK.
OBJECTIVE:TOP2A has been implicated in the progression of multiple malignancies; however, its clinical significance and biological role in OSCC remain poorly understood. This study aimed to comprehensively investigate the expression, prognostic value, biological functions, and molecular mechanisms of TOP2A in OSCC through an integrative, multilevel approach that combined multi-cohort bioinformatics analyses, clinical immunohistochemical validation, and both in vitro and in vivo functional experiments. METHODS:Multi-cohort bioinformatics analyses were first performed to evaluate TOP2A expression, prognostic relevance, and potential downstream signaling pathways. These findings were further validated using clinical OSCC specimens by IHC and western blot analysis. The biological functions of TOP2A were assessed through a panel of in vitro functional assays and in vivo xenograft models. Mechanistically, the involvement of the TGF-β2/Smad pathway was examined by integrating transcriptomic profiling with pathway validation and functional rescue experiments using TGF-β2 overexpression. RESULTS:TOP2A is aberrantly overexpressed in OSCC, and it was associated with shortened overall survival in affected individuals. TOP2A silencing impaired cell proliferation, invasion, migration, and promoted apoptosis, whereas in vivo it inhibited tumor growth. In addition, TOP2A can activate the TGF-β2/Smad pathway and promote the biological behavior of OSCC cells by this pathway. CONCLUSIONS:These findings suggest that TOP2A is upregulated in OSCC and may promote tumor progression via the TGF-β2/Smad signaling pathway. Our results support TOP2A as a potential prognostic biomarker and therapeutic target in OSCC.
BACKGROUND:Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with increasing incidence. Histopathological assessment remains the diagnostic gold standard, but is labor-intensive and affected by a growing shortage of specialized pathologists. Limited availability of annotated data poses a major challenge for AI-based support tools in digital pathology. METHODS:We evaluated the transfer performance of a domain-specific foundation model, Tissue Concepts, compared to standard ImageNet pretraining for HNSCC detection in histopathological whole slide images. A multicentric, retrospective dataset comprising digitized H&E-stained slides from The Cancer Imaging Archive was used (390 slides, 268 HNSCC cases, 112 patients). Tumor regions were annotated by expert pathologists. Model representations were assessed without task-specific fine-tuning using a standardized classifier probe. Sample efficiency was investigated on patch-based and patient-based levels to estimate the number of annotated cases required for robust performance. RESULTS:The foundation model consistently outperformed ImageNet pretraining across all experiments. On a patch-based level, Tissue Concepts achieved substantially higher discrimination performance with minimal training data (AUROC = 0.70 vs. = 0.50 using only 1 patch). On a patient-based level, the foundation model reached robust performance with a limited number of annotated cases (AUROC = 0.90 with 10 cases), whereas ImageNet-based representations showed slightly inferior performance despite substantially larger training sets (AUROC = 0.87 with 50 cases). Performance improvements plateaued beyond 10 cases, indicating diminishing returns with additional annotations. CONCLUSION:Domain-specific foundation models enable competitive HNSCC detection under annotation-scarce conditions. However, performance depends on the representativeness of annotated cases and tumor heterogeneity across anatomical sites and institutions. Further multicenter and prospective studies are required to assess generalizability and integration into routine histopathological workflows.
BACKGROUND:Oral squamous cell carcinoma (OSCC) is a significant public health issue. While tobacco and alcohol are established risk factors, the role of human papillomavirus (HPV) in oral carcinogenesis remains debated. Cancer stem cells (CSCs) are implicated in tumor aggressiveness and therapy resistance. This study investigated the correlation between HPV infection, CSC marker expression (CD44, CD98, ALDH1), and clinicopathological parameters in tongue SCCs. METHODS:A retrospective cohort of 1047 OSCC cases (2013-2018) was reviewed. From 452 tongue SCCs, 83 formalin-fixed paraffin-embedded specimens were randomly selected. HPV DNA detection was performed using qPCR with generic and type-specific primers (HPV 6, 11, 16, 18). Immunohistochemical expression of CD44, CD98, and ALDH1 was evaluated and quantified using digital image analysis (IHC Profiler). Statistical analyses included Kaplan-Meier survival curves, Kruskal-Wallis, Chi-square, and Spearman correlation tests. RESULTS:HPV DNA was detected in 2/83 cases (2.4%): one HPV16-positive and one with co-infection (HPV6/18). CD44 expression was ubiquitously high, with no significant difference between -High and -Positive categories (p > 0.9999), but both were significantly higher than -Low and -Negative scores (p < 0.0001). ALDH1 exhibited a focal staining pattern. The ALDH1-High score was significantly less frequent than -Positive and -Low scores (p < 0.01) and showed a significant positive correlation with both advanced clinical stage (Spearman r: 0.5062; p = 0.0007) and higher tumor grade (Spearman r: 0.3352; p = 0.0322). CD98 was not detected. An inverse correlation was observed between HPV and clinical staging (Spearman r: -0.2377; p = 0.0305); however, due to the low number of HPV-positive cases, this finding must be interpreted with caution. CONCLUSION:Our findings suggest a distinct CSC expression profile in this cohort, characterized by ubiquitous CD44 expression and a rare but highly aggressive ALDH1-High subpopulation, concomitant with low HPV detection. The strong positive correlation of ALDH1-High score with advanced stage and grade highlights its potential role as a key driver of tumor aggression, warranting further investigation as a prognostic marker.
BACKGROUND:Nanocarrier-based drug delivery systems enable the co-administration of antifungal agents, enhancing pharmacological efficacy and creating synergistic effects. This study aimed to evaluate the biocompatibility and antifungal properties of chitosan nanoparticles co-loaded with nystatin and carvacrol against Candida albicans. METHODS:Chitosan nanoparticles were synthesized and loaded with nystatin and carvacrol. Their antifungal activity was evaluated by determining the minimum inhibitory concentration (MIC) and checkerboard synergy assays, while antibiofilm activity was measured using a microtiter plate crystal violet assay. Biocompatibility was assessed through hemolysis testing of human red blood cells (HRBCs) and MTT cytotoxicity assays on human foreskin fibroblasts (HFF). RESULTS:The nanoparticles exhibited an average hydrodynamic diameter of 70 ± 1.2 nm with favorable polydispersity (0.21 ± 0.03). The MIC of co-loaded nanoparticles was significantly lower than that of single-drug loaded nanoparticles, and checkerboard assays confirmed strong synergy (FICI 0.16-0.5). Sub-MIC concentrations markedly reduced biofilm formation. At 1000 μg/mL, drug-loaded nanoparticles induced < 5% hemolysis, compared with 15.7% ± 2.7% for blank chitosan nanoparticles. HFF cell viability exceeded 90% across concentrations up to 1000 μg/mL at 24-72 h. CONCLUSION:Co-loading nystatin and carvacrol into chitosan nanoparticles yielded a synergistic antifungal and antibiofilm effect against C. albicans, coupled with excellent hemocompatibility and minimal cytotoxicity, highlighting its potential as a topical therapeutic for oral candidiasis particularly where resistance to azoles is rising. Further in vivo studies are warranted.
BACKGROUND/AIMS:Risk prediction models (RPMs) based on histopathological analysis of oral epithelial dysplasia (OED) are increasingly used to stratify patients with oral potentially malignant disorders (OPMDs) and support personalized management. This systematic review and meta-analysis evaluated artificial intelligence (AI)-based models compared with conventional human microscopy for predicting malignant transformation (MT). METHODS:A total of 32 studies published between 1998 and 2026 were included (9 AI-based and 23 human-based), focusing on OED in oral leukoplakia (OL), erythroleukoplakia, and erythroplakia. AI approaches addressed prediction or prognostic tasks using machine learning (ML), deep learning (DL), or hybrid methods, with multilayer perceptron and random forest among the most frequently used algorithms. RESULTS:Meta-analysis demonstrated strong discriminative performance for AI models (pooled odds ratio [OR] = 12.64; 95% CI: 5.65-28.26; I2 = 57%). Human evaluation also confirmed a significant association between OED and MT (OR = 3.42; 95% CI: 2.07-5.68), with substantial heterogeneity (I2 = 85%). AI-based models showed higher specificity and more consistent performance, while sensitivity remained comparable to human assessment. CONCLUSIONS:Overall, AI-based RPMs demonstrate promising and more reliable discriminative ability, primarily by improving decision precision rather than detection rates. However, further standardization, external validation, and larger multicentric datasets are required for clinical implementation.
BACKGROUND:Associations between microbial dysbiosis and malignancies of the pancreatobiliary system have been described in recent studies. As a result of the limited number of studies that have been done specifically on the malignancies of the biliary tract, information regarding oral, biliary and tumour-related microbial alterations was combined to provide an overview of the microbial changes that may occur. METHODS:Studies that involved observations on the composition or presence of dysbiosis of the microbiota from oral (saliva, oral rinse, dental plaque) or other non-oral specimens (bile, pancreatic tissue, duodenal tissue and bacteria-derived extracellular vesicles from plasma) in patients with pancreatobiliary malignancies were considered. The risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS) for case-control study designs and the JBI Checklist for cross-sectional studies. RESULTS:There were a total of 16 studies involving 1426 participants that were conducted using both case-control and cross-sectional study designs. Samples were collected from saliva, oral wash, bile, pancreatic and duodenal tissues and bacterial extracellular vesicles isolated from plasma samples. The most common method used was 16S rRNA sequencing, and two used shotgun metagenomics. In all the studies, patients with pancreatobiliary cancers, especially PDAC, had a significantly higher abundance of opportunistic microbes like Streptococcus, Veillonella, Fusobacterium, Prevotella and a lower abundance of commensal bacteria like Neisseria and Corynebacterium. There was overlap of microbial profile in the oral cavity and tumour/bile compartments in a few studies. CONCLUSIONS:Although the current data is preliminary and observational in nature, there are consistent findings linking microbiota dysbiosis with cancers of the pancreatobiliary region within both oral and non-oral body sites. Causality has not been established yet. The use of microbial signatures as a basis for biomarker development is a promising research direction.
BACKGROUND:Oral Medicine is that specialist branch of dentistry concerned with the diagnosis, prevention, and predominantly non-surgical management of medically-related disorders and conditions affecting the oral and maxillofacial region, in particular oral mucosal disease and orofacial pain, as well as the oral health care of medically complex patients. Published national curricula for postgraduate Oral Medicine training exist in the United Kingdom (UK General Dental Council, 2010; revised 2023) and the United States (American Academy of Oral Medicine competency framework, 2015), and an international competency consensus was established by the Sixth World Workshop on Oral Medicine (2015). Despite this international momentum, no equivalent nationally published, competency-aligned postgraduate curriculum has been established for the Australasian region. This manuscript describes the development and structure of a contemporary 3-year Doctor of Clinical Dentistry (DClinDent) curriculum for Oral Medicine specialist training, developed by the Oral Medicine Academy of Australasia (OMAA) and aligned with the OMAA Essential Competencies (2026). METHODS:The curriculum was developed through a joint collaboration of all program convenors and heads of training of DClinDent (Oral Medicine) programs in Australia and New Zealand, together with the OMAA Curriculum Working Group, informed by the OMAA Essential Competencies (2026), benchmarked against the UK GDC Oral Medicine Specialty Training Curriculum (2023) and the internationally validated competencies from the Sixth World Workshop on Oral Medicine (2015), and structured according to a spiral learning framework. The curriculum was endorsed by the OMAA Credentialing and Peer Review Subcommittee in 2026. The program is divided into three progressive phases: Foundations (Year 1), Development (Year 2), and Consolidation (Year 3). RESULTS:The curriculum encompasses five competency domains-Professionalism; Communication and Social Skills; Critical Thinking; Scientific and Clinical Knowledge; and Patient Care-mapped across all 3 years. The integration of cultural awareness and safety is an important feature across all phases of the curriculum. Year 1 establishes core scientific, clinical, and professional foundations. Year 2 develops clinical expertise across all Oral Medicine domains with increasing diagnostic independence. Year 3 prepares trainees for autonomous specialist practice, including complex case management, research thesis completion, and professional leadership. Minimum clinical case targets, portfolio-based assessment, and a conjoint Fellowship of the Oral Medicine Academy of Australasia (FOMAA) exit examination are integral to program completion. CONCLUSIONS:This curriculum provides a nationally applicable, competency-aligned framework for Oral Medicine postgraduate training in Australasia. It addresses recognized gaps in specialty-specific graduate medical education and offers a replicable model for programs seeking harmonization with Australasian and international Oral Medicine training standards.
BACKGROUND:RANTES, a chemokine involved in regulating inflammatory responses, has been implicated in the pathogenesis of various diseases, including oral lichen planus (OLP). In this condition, the interaction between C-C motif ligand 5 (CCL5) and CC motif chemokine receptor 5 (CCR5) may contribute to the destruction of basal keratinocytes and an imbalance of Th1 cells, leading to chronic inflammation. OBJECTIVES:This systematic review aimed to evaluate expression of the CCL5 in the serum and relevant cell types of patients with oral lichen planus and oral lichenoid lesions (OLLs) compared to controls. METHODS:We searched the following databases: Medline (Ovid), CENTRAL (Cochrane Library), Embase (Ovid), CINAHL (EBSCO), and Web of Science Core Collection, up to May 2026. Study quality and risk of bias were assessed using the Joana Briggs Institute tools. RESULTS:Five studies (227 participants) met the inclusion criteria. The findings indicated a marked upregulation of CCL5 in the serum, T-lymphocytes, and fibroblasts of OLP/OLL patients compared to controls. However, these results were weakened by high risk of bias in statistical analysis, reporting, and confounding factors, along with significant heterogeneity in methodology and diagnostic criteria. CONCLUSION:CCL5 may play a role in the pathogenesis of OLP/OLLs by promoting T-cell infiltration, correlating positively with disease severity, and presenting itself as a potential therapeutic target. However, the low-quality evidence due to the high risk of bias identified in the majority of included studies highlights the need for further research to confirm the immunomodulatory role of CCL5 in OLP/OLLs pathogenesis.
BACKGROUND:Burning mouth syndrome (BMS) is a chronic pain disorder frequently associated with clinical and psychological comorbidities, the treatment of which continues to represent a therapeutic challenge. Clonazepam is widely used in its management, although reported results vary depending on the route of administration. This review mapped how clinical-psychological characteristics were reported across clonazepam studies and explored whether outcome patterns differed by administration route within a synthesis without meta-analysis (SWiM) framework. METHODS:A systematic review was carried out in accordance with the PRISMA 2020 guidelines and the SWiM framework. We searched PubMed, Scopus, and Web of Science for studies up to October 2025, including clinical and observational studies evaluating the use of clonazepam in people with BMS. Therapeutic response was defined as a ≥ 30% reduction in baseline symptoms. RESULTS:We included 20 studies (n = 1042 patients; 85% women; mean age: 62 years). Patients presented with frequent systemic comorbidities, such as high blood pressure, diabetes mellitus, and thyroid disorders, along with a high prevalence of anxiety and depression. Eleven studies evaluated topical clonazepam, eight the systemic route, and one a mixed regimen. Using a vote-counting approach, topical clonazepam reported a ≥ 30% reduction in pain in 9 of 11 studies and ≥ 50% in 5 of 11; however, the studies showed substantial heterogeneity in diagnostic criteria, design, dosage, duration of treatment, pain assessment tools, and methodological quality. In this context, the results should be interpreted as a descriptive synthesis and not as definitive comparative evidence between routes of administration. CONCLUSION:Topical clonazepam showed a more consistent trend toward clinically meaningful symptom improvement; however, comparative effectiveness and phenotype-related effect modification cannot be inferred from the available evidence. Clinical-psychological characteristics could constitute a relevant element in therapeutic decision-making, although their value as a predictive guide requires confirmation in future studies with standardized methodologies.
BACKGROUND:Oral cancer is a significant global public health issue, with high morbidity and mortality often linked to late diagnosis. This study evaluated a 12-year oral cancer screening program in northern Portugal to characterize its implementation and outcomes, identifying predictors of lesion detection. The program's outcomes were analyzed to assess its feasibility and contribution to early detection. METHODS:A retrospective analysis of screening program data from 2012 to 2024 was conducted. Participants were recruited through community outreach and selection of high-risk groups in primary care settings. A standardized oral/oropharyngeal examination protocol was used to classify lesions as benign, suspicious, or malignant based on clinical examination. Demographic data and risk factors were recorded, and individuals with suspicious or malignant lesions were referred for specialized evaluation. RESULTS:A total of 10 433 participants were screened (median age 63 years; 64% female). Oral lesions were detected in 16.7%, with 6.1% classified as suspicious and 0.2% malignant. Current smoking (OR = 1.65; p < 0.001), former smoking (OR = 1.27; p = 0.010), and previous oncological disease (OR = 1.74; p < 0.001) were associated with lesion detection on multivariable logistic regression. Overall, 16.4% of participants were referred for specialized consultation. CONCLUSION:This large-scale screening program successfully reached a broad population, identifying a substantial number of potentially malignant lesions. The association with known risk factors supports the need for targeted screening strategies. Further research should integrate diagnostic confirmation, evaluate long-term patient outcomes, and assess cost-effectiveness to refine oral cancer screening policies and healthcare resource allocation.
Objective Oral squamous cell carcinoma (OSCC) is highly recurrent and metastatic; EP300 drives tumorigenesis, but its mechanism is unclear.Materials and Methods EP300 expression was profiled in OSCC via databases, RT-PCR, and Western blot. Knockdown effects on proliferation (CCK-8, colony), cell cycle, and apoptosis (flow cytometry) were measured. EP300-Notch interplay was probed with Valproic acid, a Notch signaling activator (VPA) rescue assays.Results Our experimental results showed that EP300 was upregulated in OSCC Cell Lines. In addition, bioinformatics analysis showed that EP300 upregulation was significantly associated with poor prognosis of OSCC. Prior research and bioinformatics analyses have demonstrated a close relationship between EP300 and the activation of the notch signaling pathway in OSCC. After EP300 knockdown in OSCC cells treated with VPA, our results indicated that VPA could partially reverse the effects of EP300 knockdown on cell proliferation, cell cycle, apoptosis, and EMT processes in OSCC Cells.Conclusion In this study, we observed that EP300 knockdown suppressed the Notch signaling pathway, consequently inhibiting OSCC cell proliferation, the cell cycle, and EMT while also promoting apoptosis. These findings suggest that EP300 is crucial for OSCC cell growth and development.
BACKGROUND:Head and neck squamous cell carcinoma is a heterogeneous disease with poor survival outcomes. Bcl-xL regulates tumor cell survival and apoptosis and has been associated with metastasis and poor prognosis, although its overall role remains undeciphered. METHODS:We systematically evaluated the prognostic value of Bcl-xL in head and neck squamous cell carcinoma following PRISMA 2020 guidelines. We identified 2241 reports from seven databases, of which 20 original studies with overall good quality (REMARK) and low bias (QUIPS) were included. RESULTS:An association between Bcl-xL levels and survival was rarely observed. However, high Bcl-xL levels correlated with increased risk of lymph node metastasis in 40% of studies. A study on oral tongue cancer identified a significant correlation between high Bcl-xL levels and decreased survival and lymph node metastasis. CONCLUSIONS:Current evidence does not support Bcl-xL as a general prognostic marker in head and neck squamous cell carcinoma. Nevertheless, Bcl-xL may have prognostic relevance in oral tongue cancer if further studies confirm the original finding.
BACKGROUND:The Oral Epithelial Dysplasia Informational Needs Questionnaire (ODIN-Q) was developed to assess the informational needs of patients with oral epithelial dysplasia (OED), a precancerous disorder associated with an increased risk of malignant transformation. This study aimed to evaluate the responsiveness of the ODIN-Q following an educational intervention using a written patient information leaflet about OED. METHODS:A prospective pre-post observational study was conducted at the Oral Medicine Unit at University College London Hospitals, between March 2023 and March 2025. Fifty patients with histologically confirmed OED completed the previously validated ODIN-Q before and after reading the leaflet. Differences between pre- and post-reading ODIN-Q scores were analysed using descriptive statistics and Cohen's d to determine effect sizes and responsiveness. RESULTS:Fifty participants (29 females, 21 males; mean age = 65 years) were included in the analysis. Overall ODIN-Q scores increased from 2.44 to 2.71, with a small overall effect size (d = 0.30; 95% CI: 0.01-0.59). The highest responsiveness was observed in the medical system and access to information domain (+0.42; +19%; d = 0.49; 95% CI: 0.19-0.79), followed by psychosocial aspects (+0.29; +12%; d = 0.38; 95% CI: 0.09-0.67) and physical aspects (+0.28; +11%; d = 0.36; 95% CI: 0.07-0.65). Other domains showed negligible to small responsiveness (investigative tests: d = 0.11; 95% CI: -0.18-0.40). CONCLUSIONS:The ODIN-Q demonstrates preliminary evidence of responsiveness to changes in patients' informational needs following educational interventions, supporting its potential use as a multidomain measure for evaluating and guiding patient-centred education in OED.
BACKGROUND:Early diagnosis is crucial in improving oral cancer outcomes. Patient education materials support timely recognition and management. However, these resources are often written above recommended reading levels, beyond patients' health literacy and limiting accessibility. OBJECTIVES:To assess the readability of available patient information on oral cancer by the NHS, to evaluate three large language models (LLMs; ChatGPT, Claude and Gemini) in simplifying texts while preserving their content, and to propose an improved leaflet based on UK materials, expert review and LLM adjustment to match average UK reading levels. METHODS:Materials were collected from NHS-affiliated websites. Original and LLM-simplified texts were assessed using validated readability tools (FRES, FKGL, GFI, CLI and SMOG). Content fidelity was assessed using character 3-5-g cosine, sentence-content retention and latent semantic analysis (LSA). An expert review was applied to the proposed leaflet. RESULTS:LLM-revisions significantly improved readability across all five indices (p < 0.0001). Mean FRES of original texts was 66.4 ± 7.7, while Claude (81.6 ± 6.2) was the only model to surpass the 80 benchmark. Semantic similarity to source text remained high (LSA means 0.97 ± 0.04, 0.94 ± 0.09 and 0.96 ± 0.08; character 3-5-g cosine 0.85 ± 0.05, 0.80 ± 0.08 and 0.82 ± 0.08 for respective models). Baseline readability of the proposed leaflet was comparable to NHS materials (FRES 65.7); Claude increased this to 81.2. CONCLUSIONS:LLM-based simplification enhanced readability while preserving content fidelity. This approach can help enhance accessibility, particularly for populations disproportionately affected by oral cancer. With human oversight, it could be adopted at the policy level to standardise patient education and reduce health literacy disparities.
Background Cisplatin is a common chemotherapeutic agent for advanced head and neck squamous cell carcinoma (HNSCC), but treatment success is often limited by resistance. Cancer stem cells (CSCs) are known contributors to this cisplatin chemoresistance in HNSCC. The mechanistic target of rapamycin (mTOR) pathway, which is frequently dysregulated in HNSCC, plays a crucial role via the PI3K/AKT/mTOR axis in maintaining CSC populations and promoting cancer proliferation. However, the specific effects of combining rapamycin, an mTOR pathway inhibitor, with chemotherapeutic agents on CSC maintenance and overall tumorigenicity remain unclear.Methods We examined CSC gene expression in HNSCC cell lines (HSC4, SCC25, OT-1109) and evaluated the therapeutic potential of combining rapamycin, an mTOR pathway inhibitor, with cisplatin on CSC using a cell viability assay. The combination was further evaluated in an HSC4 mouse xenograft model. Tumor volume and animal weight were monitored throughout treatment. Xenograft tissue analysis via immunohistochemistry assessed stem cell markers (CD133 and ALDH1A1), proliferation markers (Ki-67), and mTOR pathway inhibition (pS6).Results Administration of low-dose cisplatin enriched the CD133+ cell population but failed to decrease the tumor mass in HNSCC xenografts. In contrast, the combination of cisplatin and rapamycin significantly impeded tumor growth and minimized toxicity, concurrently reducing the population of CD133+ tumor cells.Conclusion These findings suggest that rapamycin enhances the mechanistic efficacy of cisplatin by specifically targeting and reducing cisplatin-induced stemness (CD133+ CSC population). This study proposes a viable combination therapy for HNSCC involving an mTOR inhibitor and a platinum-based drug to overcome CSC-mediated resistance.
