Burning Mouth Syndrome (BMS) is a chronic orofacial pain condition characterized by persistent burning sensations in the absence of consistently identifiable pathology. This mismatch between severe symptoms and inconclusive findings challenges conventional diagnostic reasoning, which presumes that subjective complaints reflect underlying biological lesions—leading to repeated investigations, diagnostic delay, and uncertainty about symptom legitimacy. This paper uses BMS as a paradigmatic case to question a core assumption of clinical reasoning: that objective pathology constitutes primary evidence. In this Perspective, drawing on phenomenology and medical anthropology, we argue that when pathology is indeterminate, illness—the lived experience of suffering—must be treated as primary clinical evidence rather than as a secondary expression of disease. We propose a bidirectional conceptual framework in which physiological processes, psychological states, and lived experience interact dynamically, with symptoms actively participating in the maintenance of the condition. This framework explains persistent diagnostic uncertainty, heterogeneous treatment responses, and the clinical significance of validation and meaning-making. Reframing BMS in this way supports earlier recognition, reduces reliance on exclusion-based strategies, and justifies multimodal interventions addressing both biological and experiential dimensions of pain. More broadly, it suggests that clinical reasoning must expand to incorporate lived experience as indispensable evidence wherever pathology is indeterminate.

OBJECTIVE:The aim of this study was to evaluate the effects of photobiomodulation (PBM) at 635 nm on human gingival fibroblast (HGF) behavior in an in vitro wound-healing model. BACKGROUND:PBM has gained increasing interest in periodontal therapy due to its potential to modulate inflammation and stimulate regenerative processes. Despite promising applications, the most effective parameters for periodontal tissue remain unclear, particularly regarding wavelength, energy density, and irradiation frequency. Understanding cellular responses under controlled conditions is essential to define PBM's therapeutic role in periodontal regeneration. METHODS:HGFs were cultured in a wound-healing model and subjected to PBM using a 635 nm diode laser. Cell proliferation, migration, wound closure, and morphology were assessed at 24 and 48 h and compared with untreated controls. To distinguish proliferation from migration, wound closure was also evaluated in the presence of mitomycin C, and metabolic activity was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] at 48 h. RESULTS:PBM significantly accelerated defect closure at 24 h, with higher cell density along the wound margin and increased mitotic figures. By 48 h, wound closure percentages converged between groups. In the presence of mitomycin C, PBM did not significantly enhance migration, indicating that the early wound closure is primarily driven by proliferation. PBM-treated cultures also displayed a more uniform wound margin, suggesting moderated migratory activity. MTT assay confirmed increased metabolic activity in PBM-treated cells at 48 h. CONCLUSIONS:PBM at 635 nm promotes early enhancement of fibroblast growth and gap colonization in vitro, with effects most evident within the first 24 h. These findings suggest that PBM primarily stimulates cell growth rather than migration in the early phase of wound healing and support its potential as an adjunctive tool in gingival and soft tissue repair, particularly in contexts requiring a balance between cellular proliferation and migration.

Large language models (LLMs) are increasingly investigated for abstract screening in sys-tematic reviews, yet it remains unclear whether screening errors attributed to linguistic complexity reflect intrinsic semantic limitations or the decision architecture in which the model is embedded. We investigated how five polarity variants of logically equivalent eli-gibility criteria—affirmative inclusion, antonymic exclusion, predicate negation, verb-level negation, and double negation—affect screening outcomes in a controlled biomedical task. Using 1,000 abstracts derived from a reconstructed Cochrane review corpus (50 eligible TARGET studies; 950 non-targets), we implemented four abstract-visible criteria within a sequential hard-gated pipeline, where failure at any step triggered irreversible exclusion. Under hard gating, linguistic polarity alone produced substantial sensitivity shifts. For GPT-5.1, recall ranged from 0.72 to 0.32 despite identical logical predicates and input da-ta. Replication with GPT-3.5 Turbo yielded a similar polarity-dependent divergence (recall range 0.92–0.18), confirming that the effect generalizes across model generations. TAR-GET losses were highly concentrated at criteria frequently satisfied but inconsistently re-ported in abstracts, consistent with conservative exclusion under evidential un-der-specification. To assess whether this effect was semantic or architectural, we reim-plemented screening using a scoring-based evidence-accumulation framework in which each criterion contributed graded support (YES/NO/UNCLEAR) and inclusion was de-termined by a tunable score threshold. Scoring substantially reduced polarity-driven recall divergence and transformed it into an explicit precision–recall trade-off. These findings indicate that negation sensitivity in LLM screening is strongly mediated by decision ar-chitecture: irreversible Boolean gating amplifies linguistic asymmetries under uncertainty, whereas cumulative scoring preserves uncertainty and enables controllable operating points.

Scaffold architecture profoundly influences tissue regeneration through the mechanical, topographical, and biochemical cues it presents to cells. Yet the relationship between architectural complexity and regenerative performance remains difficult to interpret: geometrically elaborate scaffolds do not necessarily produce more organized tissues, while comparatively simple architectures can exert strong organizational effects. We propose that scaffold-guided tissue organization is better understood through a distinction between geometric complexity and informational dimensionality. We argue that scaffold performance depends less on geometric complexity than on the number of stable, biologically interpretable dimensions available for cellular mechanotransduction. Drawing heuristically on kernel methods in machine learning, we suggest that scaffold architectures can transform poorly structured mechanosensory environments into conditions where alternative organizational trajectories become more distinguishable. Mechanotransduction provides the biological basis for this process, integrating scaffold-derived cues through focal adhesions, cytoskeletal tension, nuclear deformation, and YAP/TAZ signaling. This perspective suggests that scaffold design should be evaluated not only by architectural complexity or biomimetic resemblance, but by its capacity to generate stable and interpretable mechanosensory environments. More broadly, this shifts the design question from how complex a scaffold is to whether its architecture generates stable, cell-readable mechanosensory information.

BACKGROUND:The European Federation of Periodontology (EFP) has developed Clinical Practice Guidelines (CPGs) for the treatment of periodontitis and for the management of peri-implant diseases. In accordance with the 2018 Classification, acute periodontal conditions are characterised by rapid-onset pain or discomfort, tissue destruction and infection. Therefore, the development of a CPG to guide patients and clinicians in their management is justified. AIM:To develop an S2k-level CPG for the management of acute periodontal conditions, necrotising periodontal diseases, periodontal abscesses and acute manifestations of endodontic-periodontal lesions. METHODS:This S2k-level CPG was developed by the EFP, following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process. A rigorous and transparent process included synthesis of relevant research in two commissioned systematic reviews, evaluation of the quality and strength of evidence, formulation of specific recommendations and a structured consensus process involving leading experts and a broad base of stakeholders. Recommendations were based on the best available evidence, combined with structured expert consensus, particularly in areas where direct evidence remains scarce. RESULTS:The S2k-level CPG for the management of acute periodontal conditions presents a structured approach, grouping the recommendations in three successive steps: (1) confirming diagnosis, following the case definitions of the 2018 classification; (2) initial treatment, to control the acute condition including pain and active tissue destruction; and (3) subsequent treatments, to manage the pre-existing conditions and prevent the risk of disease recurrence and/or control the potential sequelae. CONCLUSION:The present S2k-level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective interventions in the management of acute periodontal conditions.

Large language models (LLMs) are increasingly investigated for abstract screening in systematic reviews, yet it remains unclear whether screening errors attributed to linguistic complexity arise from intrinsic semantic sensitivity or from its interaction with decision architecture. We examined how five polarity variants of logically equivalent eligibility criteria-affirmative inclusion, antonymic exclusion, predicate negation, verb-level negation, and double negation-affect screening outcomes in a controlled biomedical task. Using 1000 abstracts from a reconstructed Cochrane review corpus (50 TARGET; 950 non-targets), we implemented four abstract-visible criteria within a sequential hard-gated pipeline, where failure at any step triggered irreversible exclusion. Under hard gating, linguistic polarity alone produced substantial and statistically significant variation in recall. For GPT-5.1, recall ranged from 0.72 to 0.32 despite identical logical predicates and input data. Replication with GPT-3.5 Turbo yielded a similar divergence (0.92-0.18), confirming generalization across model generations. TARGET losses were concentrated at criteria typically satisfied but inconsistently reported in abstracts, indicating conservative exclusion under evidential under-specification. To assess whether this effect is semantic or architectural, we reimplemented screening using a scoring-based evidence-accumulation framework in which each criterion contributed graded support and inclusion was determined by a tunable threshold. Under scoring, recall increased across all variants and converged within a high-sensitivity regime, while residual polarity effects were attenuated but remained detectable. Linguistic differences shifted from structural recall collapse to controlled precision-recall trade-offs. These findings show that negation sensitivity is strongly mediated by decision architecture. Irreversible gating amplifies local uncertainty into false-negative exclusion, whereas cumulative scoring preserves uncertainty and enables controllable operating thresholds.

This manuscript examines how distinct epistemic attitudes toward singularity and generality have been articulated in medical writing across different historical contexts, offering a conceptual and meta-historical analysis of two enduring genres in biomedical literature: the individualized case report and the systematically aggregated clinical trial. Hippocratic case narratives are considered as a particularly lucid articulation of a mode of inquiry that privileges detailed observation of individual patients, while medieval Aristotelian natural philosophy exemplifies a contrasting emphasis on regularity, intelligibility, and general explanation. Renaissance medical and philosophical traditions are treated as a mediating moment in which attention to anomaly, wonder, and singularity was explicitly re-legitimized within learned medicine. These historically situated articulations are not presented as stages in a progressive narrative, but as recurrent epistemic orientations that are repeatedly reconfigured under different theoretical, institutional, and technological conditions. The paper argues that the tension between attention to exceptional cases and the pursuit of generalizable knowledge continues to structure modern biomedical writing, where case reports remain essential for identifying rare, novel, or anomalous phenomena, while clinical trials formalize strategies for producing reproducible, population-level evidence.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive and antiangiogenic therapies. Laser-based approaches, including photobiomodulation therapy (PBMT) and erbium laser-assisted surgery, have been proposed as adjunctive interventions to improve healing and clinical outcomes. This consensus-based review aimed to synthesize evidence from systematic reviews and meta-analyses evaluating laser-based therapies in the prevention and treatment of MRONJ, and to translate these findings into clinical recommendations developed by the World Federation for Laser Dentistry (WFLD) and the Polish Society for Laser Dentistry (PTSL).The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and Joanna Briggs Institute (JBI) guidance, and was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO). An electronic search of the PubMed/MEDLINE, Embase, Scopus, and Cochrane Library databases was conducted for systematic reviews and meta-analyses published between January 2015 and October 2025. Study selection, data extraction and methodological assessment were performed independently by 3 reviewers.Eighty-five records were identified, and 14 reviews met the inclusion criteria. These included several hundred primary studies, mainly observational studies and case series. Laser-based interventions were primarily used as adjuncts to conventional MRONJ management. Photobiomodulation therapy was associated with pain reduction and improved soft tissue healing, while erbium-doped yttrium aluminum garnet (Er:YAG) laser-assisted surgery enabled the precise removal of necrotic bone. Combined protocols showed generally favorable trends. However, substantial heterogeneity in study design, laser parameters and outcome definitions precluded quantitative synthesis.Laser-based therapies may provide beneficial adjunctive effects in MRONJ management, particularly within multimodal treatment strategies. However, the strength of these conclusions is limited due to substantial heterogeneity in study design, laser protocols and outcome reporting.

Perfect maintenance of the soft tissue and bone level at the implant site substantially influences the long-term surgical success and esthetic and functional results of prosthetic rehabilitation. Hyaluronic acid (HA) is a glycosaminoglycan, that is a long linear polymer chain formed by the repetition of disaccharide units, in turn composed of alternating molecules of glucuronic acid and N-acetylglucosamine joined together by glycosidic and hydrogen bonds. HA in oral surgery improves wound healing by stimulating clot formation, inducing angiogenesis, increasing osteogenesis, preserving the viability of periodontal ligament fibroblasts and gingival fibroblasts, and accelerating bone regeneration through chemotaxis, proliferation, and subsequent differentiation of mesenchymal cells. The cross-linking process, which modifies the three-dimensional structure of the HA chains, gives the product a higher molecular weight and, consequently, a greater density, slower reabsorption, and longer lasting action. Laser photobiomodulation (laser PBMT) promotes wound healing by inducing cell proliferation, anti-inflammatory responses, pain relief, and scar formation inhibition. The present paper describes the clinical case of a 72-year-old male patient who, due to a large vestibular bone defect in Zone 1.1, required bone regeneration. The aim of this case report was to propose a combination of cross-linked hyaluronic acid (xHyA) and laser PBMT to support bone and soft tissue regeneration in areas of severe periodontal compromise and tissue defects.

OBJECTIVE:To map the literature on management of surgical margins for oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL). METHODS:Searches were performed in five electronic databases and gray literature. Studies involving patients undergoing any type of surgical excision of OL or PVL were included. Data extraction focused on surgical technique, margin size, method of margin delineation, and recurrence outcome. Margin size was categorized in centimeters. RESULTS:Ninety-one studies were included. More than half of the studies (54.9%) did not report the width of surgical margins. Among those that did, margins between > 2 and < 3 mm were the most frequently reported (19.7%). Notably, 94.5% of the studies did not specify the criteria used to determine the margin width. Furthermore, 76.9% failed to describe the method used to delineate lesion margins. High recurrence was observed in 15.1% of OL cases with surgical margins ≤ 2 mm and in 40% of PVL cases with margins > 2 to ≤ 3 mm. Lesions with margins between 3 and 5 mm showed a lower recurrence rate. CONCLUSION:We identified a lack of standardization in the reporting of surgical margins. Excision with 5 mm of clinically healthy tissue should be considered the optimal approach for the surgical management.

OBJECTIVE:To evaluate whether the age at diagnosis of oral squamous cell carcinoma (OSCC) has changed over time and to assess whether stage at presentation has varied across decades. METHODS:A systematic review was conducted according to PRISMA guidelines (PROSPERO registration: CRD420251048070). MEDLINE, Scopus, and Web of Science were searched. Studies reporting age at diagnosis and/or stage distribution of OSCC were included. RESULTS:Twenty-nine studies (15,911 subjects) were included. A primary meta-analysis of 11 eligible studies (n = 3527) yielded a pooled mean age at diagnosis of 57.42 years (95% CI: 54.51-60.33). A sensitivity analysis (8 studies with sample size ≥ 100 patients, total = 3322) produced a pooled estimate of 55.61 years (95% CI: 52.32-58.91), suggesting a potentially meaningful shift toward younger age at diagnosis in larger cohorts. Early-stage disease (I-II) accounted for 54.2% of cases and advanced-stage disease (III-IV) for 45.8%. Variability in staging systems (AJCC/UICC editions) and reporting formats limited direct cross-decade comparisons. CONCLUSIONS:Current evidence is compatible with a modest, population-dependent trend toward younger age at diagnosis in selected contemporary cohorts. Standardized staging, harmonized reporting, and age-stratified risk-factor analyses are needed to clarify whether emerging young-onset OSCC reflects changing exposure profiles, distinct tumor biology, or both. TRIAL REGISTRATION:PROSPERO Registration: CRD420251048070.

INTRODUCTION:Biomimetics offers promising tools to improve wound healing in difficult clinical conditions. Polynucleotides (PN) show high potential for tissue repair in oral and periodontal surgery, by relying on the body's inherent self-healing capabilities. The aim of the present study was to elucidate in vitro the effects of Odonto-PN (O-PN) and Regenfast (REG), two PN-based compounds, on oral tissue repair. METHODS:We employed 3D spheroid cultures and cell scratch assays to simulate wound healing in vitro, assessing cell migration and morphology under normal conditions and following mitomycin-induced inhibition of cell growth. RESULTS:Both O-PN and REG supported early cell viability and spheroid disassembly. O-PN supported the initial outgrowth of fibroblasts, whereas REG enhanced sustained cell migration at later time points. In scratch assays, REG effectively facilitated defect closure - even under mitomycin treatment - and induced a more elongated, migratory cell phenotype. CONCLUSIONS:These findings suggest that both O-PN and REG can favorably modulate fibroblast function to support wound repair. While O-PN fosters early activation and cell viability, REG exerts potent pro-migratory effects that may be particularly useful for complex periodontal regeneration. Their selective use could provide valuable adjuncts in clinical protocols aimed at restoring delicate oral structures, such as the interdental papillae.

Background: Systematic reviewers face a growing body of biomedical literature, making early-stage article screening increasingly time-consuming. In this study, we assessed six large language models (LLMs)—OpenHermes, Flan T5, GPT-2, Claude 3 Haiku, GPT-3.5 Turbo, and GPT-4o—for their ability to identify randomized controlled trials (RCTs) in datasets of increasing difficulty. Methods: We first retrieved articles from PubMed and used all-mpnet-base-v2 to measure semantic similarity to known target RCTs, stratifying the collection into quartiles of descending relevance. Each LLM then received either verbose or concise prompts to classify articles as “Accepted” or “Rejected”. Results: Claude 3 Haiku, GPT-3.5 Turbo, and GPT-4o consistently achieved high recall, though their precision varied in the quartile with the highest similarity, where false positives increased. By contrast, smaller or older models struggled to balance sensitivity and specificity, with some over-including irrelevant studies or missing key articles. Importantly, multi-stage prompts did not guarantee performance gains for weaker models, whereas single-prompt approaches proved effective for advanced LLMs. Conclusions: These findings underscore that both model capability and prompt design strongly affect classification outcomes, suggesting that newer LLMs, if properly guided, can substantially expedite systematic reviews.

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.

Oral tongue squamous cell carcinoma is the most prevalent cancer of the oral cavity. To date, the mainstay management for carcinoma in situ of the oral cavity is the surgical radical removal of the neoplastic tis-sue. This paper describes a new approach in the management of an in situ carcinoma of the tongue margin, treated surgically by the use of Nd:YAG laser, the application of cross-liked hyaluronic acid (xHyA) gel and the placement of a resorbable porcine pericardium membrane (PPM). The case involves a 49-years old male patient with no history of smoking and alcohol use, who presented a non-homogeneous leukoplakia of the right tongue border. The biopsy revealed high-grade lichenoid dysplasia, corresponding to severe epithelial dysplasia or carcinoma in situ (Tis), characterized by full-thickness dysplasia without stromal invasion. The case shows that the combined use of Neodimium laser surgery, xHyA gel and PPM is a viable option for promoting soft tissue regeneration in the oral cavity, enabling excellent clinical results in terms of healing medium-sized surgical defects. In addition, compared with other options for the reconstruction of surgical defects of the tongue, the clinical use of the association between these two materials has several biological advantages due to the absence of donor sites and high patient tolerability.

Oral lichen planus (OLP) is a chronic T-cell-mediated autoimmune disease, with low potential for malignant transformation. Its etiology remains unclear, necessitating immunohistochemical and molecular-level studies to enhance diagnosis and management. Thirteen patients diagnosed with OLP and 13 healthy controls (HCs) were enrolled from three centers. Mucosal tissue samples collected during diagnostic biopsies and unstimulated whole saliva samples were analysed. A comprehensive approach was taken, with high-resolution magic angle spinning (HR-MAS) 1H-NMR spectroscopy performed on biopsies and liquid 1H-NMR spectroscopy on saliva samples to identify potential biomarkers correlated with OLP. Multivariate analyses effectively distinguish OLP patients from HC based on metabolic profiles, with key metabolites contributing to the separation. In tissue, triglycerides were significantly elevated in OLP biopsies, whereas amino acids such as glutamate, glutamine, taurine, glycine and alanine were significantly decreased in OLP tissues compared with controls (p < 0.05). Salivary analysis revealed significant alterations in compounds of bacterial origin-such as isobutyrate, isocaproate, isovalerate and agmatine-suggesting dysbiosis in OLP patients. The metabolic alterations identified highlight the roles of oxidative stress and lipid metabolism in OLP pathogenesis and suggest potential biomarkers for OLP diagnosis. These findings provide new insights into the molecular mechanisms of OLP, which may have important clinical implications for future diagnostic and therapeutic strategies.

Periodontics is a complex field characterized by a constantly growing body of research, which poses a challenge for researchers and stakeholders striving to stay abreast of the evolving literature. Traditional bibliometric surveys, while accurate, are labor-intensive and not scalable to meet the demands of such rapidly expanding domains. In this study, we employed BERTopic, a transformer-based topic modeling framework, to map the thematic landscape of periodontics research published in MEDLINE from 2009 to 2024. We identified 31 broad topics encompassing four major thematic axes—patient management, periomedicine, oral microbiology, and implant-related surgery—thereby illuminating core areas and their semantic relationships. Compared with a conventional Latent Dirichlet Allocation (LDA) approach, BERTopic yielded more contextually nuanced clusters and facilitated the isolation of distinct, smaller research niches. Although some documents remained unlabeled, potentially reflecting either semantic ambiguity or niche topics below the clustering threshold, our results underscore the flexibility, interpretability, and scalability of neural topic modeling in this domain. Future refinements—such as domain-specific embedding models and optimized granularity levels—could further enhance the precision and utility of this method, ultimately guiding researchers, educators, and policymakers in navigating the evolving landscape of periodontics.

The relentless growth of biomedical literature poses a significant challenge for systematic reviews, where manually screening thousands of studies can be very laborious. In this study, we explored the performance of large language models (LLMs) to assist in identifying randomized controlled trials (RCTs) pertaining to periodontal regeneration interventions. Starting from a recent review on Emdogain and bone grafts, we identified a target set of RCTs fulfilling its key inclusion criteria and then retrieved a larger pool of thematically related PubMed articles using the query “periodontal regeneration.” Each article was embedded using all-mpnet-base-v2, and the resulting vectors were compared against the mean embedding of the target set to group articles into quartiles of descending relevance. Various LLMs (Open Hermes, Flan T5, GPT-2, GPT-3.5 turbo and GPT-4o) were then tasked with classifying each article in the 4 datasets as “Accepted” or “Rejected.” By comparing their predictions, we calculated classification performance metrics. Overall, the results show that different LLM respond differently to prompt strategies and can effectively perform this task (or sub-tasks), confirming the potential role of these tools to expedite systematic reviews.

OBJECTIVES:This multicentre case-control study aimed to investigate the potential association between oral lichen planus (OLP) and extraoral cancers. The secondary objective included the identification of risk factors for this association. METHODS:The study was conducted between January 2023 and June 2024 and included 21 Italian Oral Medicine centres affiliated with the Italian Society of Oral Medicine (SIPMO). The study protocol was approved by the Ethics Committee of Università Cattolica del Sacro Cuore (Prot. ID 4073) and registered at clinicaltrials.gov (ID NCT06449248). RESULTS:In total, 1650 participants were enrolled (550 OLP and 1100 non-OLP patients) matched for age and sex. OLP patients showed a significantly higher prevalence of extra-oral cancers (19.8%) compared to controls (12.4%) with a 1.79 OR (1.34-2.39, p < 0.05). Moreover, erosive OLP (n = 32/120, 26.7%, p < 0.01) and plaque-like variants (n = 27/114, 23.7%, p < 0.04) seem to have a slightly increased risk of extra-oral cancer. CONCLUSIONS:Patients with OLP had a higher risk of developing extraoral cancer; moreover, erosive and plaque-like forms could be considered at higher risk. Potential pathogenic mechanisms involve an interplay between chronic inflammation, immune dysregulation and carcinogenesis. Therefore, the directionality of such association remains unclear, underscoring the need for prospective studies to clarify causality and temporal dynamics.