Monica Pentenero

Objective: To assess the psychometric performance of the Hamilton Anxiety Rating Scale (HAM‐A) and Hamilton Depression Rating Scale (HAM‐D) in patients with oral lichen planus (OLP) according to clinical phenotype. Methods: This multicenter SIPMO case–control study included 395 participants: 132 patients with keratotic OLP (K‐OLP), 131 with non‐keratotic OLP (NK‐OLP), and 132 healthy controls (HCs). Internal consistency was assessed with Cronbach's alpha and item discrimination with item–total correlations. HAM‐A and HAM‐D scores were compared between OLP patients and HCs; phenotype‐specific hierarchical regressions identified variables associated with anxiety and depressive symptoms. Results: HAM‐A and HAM‐D showed satisfactory internal consistency in K‐OLP and NK‐OLP patients (HAM‐A α = 0.877 and 0.858; HAM‐D α = 0.768 and 0.766, respectively). Patients with OLP had significantly higher HAM‐A and HAM‐D scores than age‐ and sex‐matched controls without oral mucosal disease ( p = 0.018 and p = 0.002, respectively). The strongest item–total correlations involved depressed mood, tension, insomnia, and somatic symptoms. Poor sleep quality was independently associated with psychological burden, and pain intensity independently predicted anxiety severity in NK‐OLP patients. Conclusions: HAM‐A and HAM‐D showed satisfactory psychometric performance in OLP and may support psychological assessment. Somatic and sleep‐related symptoms were closely associated with psychological distress.

Aims: To evaluate the attitudes of Italian dental students towards HIV‐infected patients and explore factors influencing discriminatory behaviour. Methods: This observational, multicentric survey analysed responses from dental students across Italian Dental Schools. The questionnaire covered demographic data, interactions with HIV‐positive patients, knowledge of HIV infection, and adherence to preventive protocols. Results: A total of 470 questionnaires were analysed. Thirty two students (6.8%) reported discriminatory attitudes, with the highest prevalence in Northern Italy (9.8%), compared to 6.5% in Central Italy and 0.9% in Southern Italy ( p = 0.006). Nearly half of the respondents (231/470) had been asked to treat HIV‐positive patients, with requests significantly more frequent in Northern Italy (65.4%) than in Central (43.8%) and Southern Italy (22.7%) ( p = 0.001). Students who treated HIV‐positive patients as first operators demonstrated a higher likelihood of discriminatory behaviour (OR = 43.9, 95% CI: 5.9–327.8, p = 0.009) compared to second operators (OR = 13.4, 95% CI: 1.47–121.7, p = 0.02). Stress perception during these treatments correlated with discriminatory attitudes (ANOVA test, p = 0.008). Despite these findings, most students showed strong knowledge about HIV, with 99.8% identifying correct transmission routes and 85.6% aware of post‐exposure prophylaxis. Additionally, 91.8% expressed interest in further education on HIV‐dentistry topics. Conclusions: The findings suggest that Italian dental students are generally well‐prepared to treat HIV‐positive patients without discrimination. Practical training fosters confidence, as evidenced by the high willingness to provide care even among students with no prior experience in treating HIV‐positive individuals. However, geographic disparities and the influence of stress on discriminatory behaviour highlight areas for improvement in dental education.

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.

Introduction: The tumor microenvironment (TME) plays a crucial role in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). Despite progress, the mechanisms behind the TME‐epithelial cell interaction remain unclear. Cancer‐associated fibroblasts (CAFs), the most abundant cells in the TME, require further study.Material and Methods: We conducted a scoping review, searching for clinical and vivo studies that discuss the role of CAFs in OSCC and OPMDs progression.Results: From 1152 PubMed results, 29 studies met the inclusion criteria. CAFs, identified as αSMA+ cells, interact with the TME and epithelial cells by secreting various molecules. In OSCC, CAF signals contribute to a pro‐tumorigenic environment, and CAF numbers positively correlate with tumor grade, size, stage, aggressiveness, and mortality. While limited data exist on CAFs in OPMDs, they seem linked to malignant transformation risk.Discussion: CAFs are critical in OSCC pathophysiology, but the complex intercellular mechanisms are not fully understood. Currently, CAFs are not part of clinical decision‐making, but emerging evidence suggests they could represent a promising new approach in managing OSCC and OPMDs.Conclusion: Future research should aim to gain a deeper understanding of how CAFs contribute to OSCC progression and their role in OPMDs pathophysiology.

Background/Objectives: Tumor-infiltrating lymphocytes (TILs) play a crucial role in the tumor microenvironment (TME), influencing the progression, prognosis, and response to treatment in oral squamous cell carcinoma (OSCC) and its precursors, oral potentially malignant disorders (OPMDs). This scoping review assesses the current literature on TILs in the TME of OSCC and OPMDs, aiming to identify trends and gaps in the research. Methods: A comprehensive search was performed in PubMed, using the following query terms: “Tumor Microenvironment AND (mouth neoplasms OR oral lichen OR leukoplakia OR oral lichenoid OR dysplasia OR GVHD OR lupus)”. Based on the inclusion criteria, we selected in vivo human original research and clinical observational studies that focused on TILs within the TME of OSCC and OPMDs. Results: Out of 1152 results in PubMed, 58 studies were selected and analyzed. These studies investigated various TILs, including T cells, B cells, and natural killer (NK) cells. Of these, 47 studies focused on the OSCC TME, 4 examined the OPMDs ME, and 7 compared OSCC TME and OPMDs ME. Discussion: While TILs in OSCC have been extensively studied, research on infiltrating lymphocytes in OPMDs is still limited. In OSCC, CD8+ T cells, T helper 1 cells, and NK cells are associated with strong antitumor activity, whereas CD4+ T cells, including T helper 2 and regulatory T cells, are linked to protumoral effects. B cells remain less explored due to their low frequency in the TME. In OPMDs, trends suggest an increase in activated CD8+ T cells in OLP and lower NK cell numbers compared to OSCC, which may contribute to malignant transformation. Understanding the spatial distribution and activation status of TILs within the TME is essential for deciphering their role. The variability in TIL composition highlights the complexity of the TME. Conclusions: Current knowledge remains preliminary, though it highlights the crucial role of TILs in carcinogenesis and OSCC. A more in-depth understanding could improve diagnostic and therapeutic strategies, including the assessment of the risk of malignant transformation in OPMDs.

Objectives: To assess the number of new cases of Medication-Related Osteonecrosis of the Jaw (MRONJ) among patients with osteoporosis and other non-malignant bone diseases in Northwestern Italy between 2007 and 2022. Methods: MRONJ cases were collected from referral centers in a population of 4.5 million. We analysed the number of new MRONJ cases per year, type of disease, administered drugs, duration of therapy (when available), and onset time of disease. Results: We analysed 198 cases (out of 1071 total MRONJ cases); diseases included osteoporosis (87%), rheumatoid arthritis (5%), their association (4%), Paget’s disease, and other various diseases (4%). Patients received bisphosphonates alone (74%), or denosumab alone (6%), or a sequence of different drugs (20%). The number of new cases increased over five years from 2 (2003–2007) to 51 (2008–2012), 65 (2013–2017), and 79 (2018–2022), and the percentage increased from 1% to 14%, 20%, and 29% of the total cases. Conclusions: The number of new MRONJ cases per year among patients with non-malignant diseases is rapidly increasing all around the world, though underestimation cannot be excluded. In this study, we describe epidemiological and clinical characteristics of patients, and the drug most frequently involved in MRONJ cases in our region over a long period, allowing a comprehensive view of the progression of the disease. Greater collaboration among specialists is needed for correct and early diagnosis to improve measures potentially reducing disease incidence and to limit quality of life deterioration in patients with osteoporosis and other non-malignant diseases.

Background: This prospective observational study investigated the determinants of malignant transformation (MT) in localized oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL).Methods: Demographic, clinical, histological, and DNA ploidy status data were collected at enrolment. Survival analysis was performed (MT being the event of interest).Results: One‐hundred and thirty‐three patients with OL and 20 patients with PVL entered the study over 6 years (mean follow‐up 7.8 years). The presence of OED, DNA ploidy, clinical presentation, and lesion site were associated with MT in patients with OL in a univariate analysis. In a multivariate model, OED was the strongest predictor of MT in patients with OL. Adding DNA ploidy increased the model's predictive power. None of the assessed predictors was associated with MT in patients with PVL.Conclusions: DNA ploidy might identify a subset OL with low risk or minimal risk of MT, but it does not seem to be a reliable predictor in patients with PVL.

PTEN hamartoma tumor syndrome (PHTS), is a spectrum of disorders caused by mutations of PTEN, in which non-cancerous growths, called hamartomas, develop in different areas of the body, often including the oral mucosa. PHTS also implies a recognized increased risk of malignancies, as PTEN is a tumor suppressor gene capable of inhibiting progression of several cancers. One of the main and most common clinical manifestation of PHTS are gingival overgrowths presenting as warty lumps. The current study describes patients with gingival or mucosal enlargements leading to the diagnosis of PHTS associated to novel PTEN pathogenic variants. Patients referred to us for gingival lumps suggestive of PHTS associated overgrowths were submitted to genetic analysis in the PTEN gene. Two related and two unrelated patients were investigated. PTEN novel pathogenic variant was found in all of them. Two patients also fulfilled diagnostic criteria of Cowden syndrome (CS). Mucocutaneous lesions, and particularly diffuse gingival overgrowths, are both early and major clinical signs revealing a potential diagnosis of PHTS. Further genetic and clinical assessments are needed in order to confirm and clarify the diagnosis within the PHTS spectrum, including, among others, the CS. A correct interpretation of oral clinical features potentially associated to PHTS is mandatory for diagnosis and a surgical approach can be useful just in case of impairment of periodontal health or for aesthetic needs. The increased risk of malignancies associated to PHTS makes a correct diagnosis pivotal to set up an appropriate lifelong surveillance, aiming at secondary cancer prevention.

The management of oral potentially malignant disorders (OPMD) including oral leukoplakia (OL) is not currently structured according to agreed guidelines. The current report presents survey data gathered from Oral Medicine Practitioners (OMPs) in Europe and Australia and is aimed to investigate attitudes and practice in the diagnosis, risk stratification and treatment of OL. In the presence of a clinical provisional diagnosis of OL, respondents reported always undertaking biopsy in 83% of cases, with most OMPs also relying on diagnostic adjuncts. The potential for malignant transformation is almost invariably assessed through epithelial dysplasia status, with other biomarkers described in the literature used less often. Active treatment of OL was considered mandatory by 20% of OMPs, while others reserve treatment for selected cases only. OMPs are mostly driven to active treatment by lesion‐related features which are frequently jointly considered including lesion site, clinical appearance and dysplasia status. Inconsistent assessment was observed regarding mild dysplasia, lesion size, presence of unavoidable trauma, exposure to tobacco and patient age. Frequently observed geographical variations were seldom statistically significant. In agreement with previous surveys, a lack of consensus around the management of OL was observed, supporting claims from learned academies and societies for treatment guidelines aiming to reduce inter‐practitioner variability.