Luís Monteiro

Head and neck cancer (HNC) remains a major therapeutic challenge due to high recurrence rates, limited efficacy of current treatments, and the frequent emergence of therapeutic resistance. Curcumin and its analogs have gained increasing interest as adjuvant compounds capable of potentiating the efficacy of conventional anticancer strategies, including chemotherapy with cisplatin, paclitaxel, and 5-fluorouracil, as well as radiotherapy. This review summarizes preclinical and translational evidence investigating combination approaches involving curcumin-based compounds and standard therapies in HNC models, highlighting their synergistic effects on tumor growth inhibition, apoptosis induction, modulation of therapy resistance mechanisms, and mitigation of treatment-related toxicity. Strategies aimed at overcoming the pharmacokinetic limitations of curcumin, including nanoformulations, co-delivery systems, and targeted delivery platforms, are also discussed. By integrating current evidence, this review highlights the translational potential of curcumin and its analogs as adjuvant agents in multimodal HNC therapy, while identifying current gaps in clinical validation, and outlining future directions for improving therapeutic efficacy and safety.

Tumor-associated macrophages are key components of the tumor microenvironment in oral carcinogenesis; however, their role is not yet fully understood. We aimed to characterize the expression of macrophage (M) markers across the spectrum of oral carcinogenesis, including oral leukoplakias (OL) and oral squamous cell carcinomas (OSCCs). This immunohistochemical study analyzed the macrophage density (cells/mm²) based on the expression of CD68 (pan-macrophage), CD163 (M2), and CD80 (M1) in 81 samples, including healthy mucosa (n = 16), OL (n = 30), and OSCC (n = 35), in both epithelial and subepithelial compartments. All markers showed a progressive increase across the study groups, with significantly higher densities in OSCC than in healthy mucosa (p < 0.001), consistently higher in the subepithelial compartment. CD163 was the most expressed marker (increasing from 78.96 cells/mm² in healthy mucosa to 300.56 cells/mm² in OSCC), whereas CD80 was the least abundant, particularly in OSCC (35.66 cells/mm² in healthy tissue to 188.49 cells/mm² in OSCC). No significant associations were observed between biomarker expression and clinicopathological variables. These results support the involvement of macrophages during oral carcinogenesis, particularly CD163+ (M2) cells, and highlight the potential prognostic and therapeutic relevance of these markers.

Head and neck cancer (HNC), particularly oral squamous cell carcinoma (OSCC), remains a major clinical challenge due to its aggressive behavior, high recurrence rates, and frequent resistance to conventional therapies. Natural compounds, especially curcumin and its derivatives, have gained increasing attention as potential anticancer agents due to their ability to target multiple molecular pathways involved in tumor progression. This review critically evaluates the current preclinical and translational evidence supporting curcumin and its derivatives as monotherapeutic agents in HNC, with particular emphasis on oral cancer. We integrate the available evidence to assess the biological rationale, therapeutic potential, and current limitations of curcumin-based approaches. The molecular mechanisms underlying their antitumor activity are discussed, including modulation of EGFR/ERK and PI3K/Akt signaling pathways, inhibition of NF-κB and STAT3 activation, induction of apoptosis, regulation of oxidative stress, and suppression of epithelial–mesenchymal transition and tumor invasiveness. In addition, we address the impact of curcumin on the tumor microenvironment and its role in overcoming intrinsic cellular resistance mechanisms. The review also highlights advances in drug delivery strategies, such as nanoformulations, that are designed to improve curcumin’s bioavailability and therapeutic efficacy. By critically integrating current evidence, this review highlights both the promise and the challenges associated with curcumin-based monotherapy in HNC, emphasizing the need for more robust and clinically relevant studies to support future translation.

Objective: The aim was to evaluate the diagnostic accuracy and temporal reproducibility of multimodal large language models (LLMs) in the image-based diagnosis of oral mucosal lesions. Materials and Methods: The study included 100 anonymized clinical photographs of oral mucosal conditions obtained from the archive of the Department of Oral Medicine, School of Dental Medicine, University of Zagreb. Images were categorized into four subgroups: physiological variations, benign mucosal lesions, oral potentially malignant disorders, and oral cancer (25 images each). Three multimodal LLMs (ChatGPT-5.1 Plus, Gemini 3 Pro, and Perplexity Pro) analyzed each image using an identical prompt and were required to provide a single most probable diagnosis based solely on visual features. To evaluate temporal reproducibility, the entire evaluation was repeated in three independent testing cycles conducted at one-month intervals. Diagnostic accuracy was compared using chi-square tests, while intra-model agreement across cycles was assessed using Fleiss’ kappa. Results: Gemini demonstrated the highest diagnostic accuracy, reaching 78% correct responses in cycles 2 and 3, significantly outperforming ChatGPT (55–57%) and Perplexity (28–31%) (p < 0.00001). Subgroup analyses showed similar trends, with Gemini achieving the highest accuracy across most lesion categories. Intra-model agreement across cycles was moderate for ChatGPT (κ = 0.525), fair for Gemini (κ = 0.338) and Perplexity (κ = 0.409). Gemini also showed the highest proportion of responses that remained correct across all three cycles (51%). Conclusions: Multimodal LLMs demonstrate promising diagnostic capabilities in the image-based assessment of oral mucosal lesions; however, variability in reproducibility highlights the need for cautious clinical implementation and further validation.

Background: Artificial intelligence (AI) is expected to play an increasingly important role in medicine and dentistry. While its diagnostic potential has been tested in various medical fields, limited research exists on its applications within oral medicine diagnoses using clinical images. Objective: This pilot study aimed to evaluate the diagnostic accuracy of ChatGPT, Gemini, and Copilot in identifying benign, potentially malignant, and malignant oral lesions. Methods: A cross-sectional study was conducted using clinical images from three categories: benign oromucosal conditions, oral potentially malignant disorders, and malignant oral lesions. Results: ChatGPT evaluated all images and consistently outperformed Copilot—and in some cases Gemini—across multiple diagnostic questions, with statistically significant advantages particularly in the cancer subgroup. Copilot showed the weakest performance, with high rates of missing evaluations and significantly lower proportions of correct responses in several analyses. Across both full-dataset and adjusted analyses, ChatGPT demonstrated the highest diagnostic performance overall. Diagnostic accuracy metrics for malignancy suspicion was similar for ChatGPT and Gemini. Several limitations such as sample size, lack of reproducibility testing and inability of some AI models to process images must be taken into account when interpreting the results. Conclusions: AI tools show promise but cannot yet replace clinical expertise. Further research and development are needed to improve the accuracy and applicability of AI diagnostic tools.

Objective: We aim to investigate the association between oral hygiene habits, including frequency of toothbrushing and regularity of dental check‐ups, and oral cancer risk. Materials and Methods: A systematic review and meta‐analysis was developed following the PRISMA and the MOOSE guidelines. We searched electronic databases until 4th December 2024 (CRD42021242709). Results: A total of 15 studies were included. Overall, the results indicated that poor oral hygiene habits are potential risk factors for oral cancer. Compared to brushing once/day or more, toothbrushing < 1/day or never significantly increased the risk for oral cancer, with an OR of 1.85 (95% CI, 1.06–3.22). Toothbrushing < 2/day compared with ≥ 2/day also showed a positive association with oral cancer risk, with an OR of 1.32 (95% CI, 1.17–1.48). Irregular dental check‐ups, defined as less than once a year or never, also significantly increased oral cancer risk (OR, 1.58; 95% CI, 1.29–1.92). Conclusion: Infrequent toothbrushing and irregular dental check‐ups are risk factors for oral cancer. Toothbrushing twice or more daily and visiting a dentist once a year could be recommended to reduce oral cancer risk. The study reinforces the importance of good oral health as a preventive measure in the control of oral cancer.

Background/Objectives: The early detection of oral squamous cell carcinoma (OSCC), especially when in the presence of oral potentially malignant disorders (OPMDs), may be challenging and would assist in improving poor OSCC survival rates reported in the literature. We conducted a systematic review to evaluate the utility of adjunctive aids that could assist during clinical examination of the oral cavity to identify suspicious mucosal lesions. Methods: Three databases (CENTRAL, PubMed/MEDLINE, Embase) were screened, limiting results from 2015 to November 2025. Inclusion criteria were: articles written in English; investigating the diagnostic accuracy of diagnostic visual aids compared to conventional oral examination under white light in the assessment of oral mucosal lesions. Extracted data were analysed narratively. Studies not reporting diagnostic accuracy using biopsy results as the gold standard were excluded. Results: The search produced 137 articles; after removing duplicates, 105 were screened through inclusion/exclusion criteria, leading to 17 papers included in the review. Eight articles investigated diagnostic accuracy of narrow band imaging (NBI), seven visually enhanced lesion scopes (VELscopes), one Glasses for Oral Cancer Curing Light Exposed Screening (GOCCLES), one ViziLite chemiluminescence system, and two toluidine blue (TB). Conclusions: High study heterogeneity and lack of randomized clinical trials limit the conclusions of this review. In this context, among the investigated visual aids for expert use, NBI (sensitivity 85–100%, specificity 75–98%) emerges as the most promising tool (VELscope sensitivity 76–87.1%, specificity 21.4–90%; GOCCLES 66%, 48%; ViziLite 77.3%, 27.8%, TB 56.8–91%, 65.3–68%), due to its ability to highlight sub epithelial vascular abnormalities, considered as early indicators of dysplastic or neoplastic progression even. None of the investigated visual aids seem suited for screening purposes/use by the general dentist.

Oral cancer represents a major cause of death mainly due to the existence of important gaps in the knowledge of and subsequent interventions in these neoplasms, including many factors, such as the late diagnosis of neoplastic lesions and a lack of treatment options, that contribute to the poor survival of these patients

An abnormal upper labial frenum (ULF) can represent a potentially harmful gingival insertion located between the central incisors. Lasers, particularly the Er:YAG laser, have been described for ULF frenectomy and offer several promising advantages. The aim of this study was to evaluate the usefulness of Er:YAG laser frenectomy using the "tunnelization technique" for the elimination of an abnormal upper labial frenum. This cohort study evaluated ULF frenectomy using the tunnelling technique with an Er:YAG laser in a cohort of 20 patients treated between January 2011 and December 2024. The ULFs were morphologically and clinically characterized before and after the procedure. No intraoperative complications were observed during the frenectomy, apart from moderate intraoperative bleeding in 12 patients (60%), with no sutures required in any case. Postoperatively, analgesic medication was required by only 2 patients (10%) for mild pain. At the 3-month follow-up, a significant reduction was observed in both frenulum size (P<0.001) and interincisal diastema (P=0.008). All incisive papillae were preserved without any defects. Er:YAG laser frenectomy using the tunneling technique proved to be a suitable option, resulting in the immediate preservation of the incisive papilla and a reduction in ULF size and position, without significant associated complications.

Oral vascular anomalies, though benign, may impact comfort and aesthetics, particularly in visible or functional areas. Laser therapies have gained prominence due to their precision, minimal invasiveness, and favourable outcomes. This study aimed to analyse the laser treatment modalities for oral vascular anomalies and their respective outcomes in a population of the north of Portugal. This retrospective study analysed 111 vascular anomalies in 95 patients treated between January 2011 and May 2025 in the University Clinics of IUCS - CESPU. Data on demographics, type and location of vascular anomalies, treatment (Nd:YAG, CO₂, or diode laser), and outcomes were collected. Venous lakes were the most frequent diagnosis (n=77;69.4%) and lip was the most common location (n=81;73%). Induced photocoagulation (IPC) (n=79;71.2%), essentially with Nd:YAG, was the predominant technique. Recurrence was observed in 4 cases (3.6%), healing occurred mostly ≤21 days (n=88; 79.3%), scar tissue was present in 10 cases (9%), pain was reported in 29 patients (26.1%) (mean of 0.85±0.14), and satisfaction was high (n=103; 92.8%). No major complications were observed. Logistic regression analysis showed that larger vascular anomalies were associated with delayed healing (P=0.009) and scar formation correlated with presence of pain (one day after intervention) (P=0.03) and recurrence (P=0.039). Laser-based management in particular, IPC, is a safe, effective, and well tolerated option for the treatment of small oral vascular anomalies. Prospective studies are encouraged to optimize protocols and standardize the technique.