Malnutrition as a Risk Factor in the Development of Oral Cancer: A Systematic Literature Review and Meta-Analyses.

This systematic review and meta-analyses aimed to assess whether malnutrition may increase the incidence of oral cancer. Following the PRISMA statement, the research was conducted on PubMed, Scopus, and MEDLINE via OVID without any time restrictions. The risk of bias was assessed, and the quality of evidence for each performed meta-analysis was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Sixty-one articles met the inclusion criteria and seven studies underwent quantitative evaluation. For our meta-analysis on hypovitaminosis B, three studies with a total of 90,011 patients were included. An odds ratio of 2.22 was found. Our meta-analysis on the correlation between vitamin C and oral cancer included one study with a total of 866 patients and the derived odds ratio was 1.06. Our meta-analysis on the relationship between vitamin D deficiency and the incidence of oral cancer included three studies with a total of 12,087 patients and the odds ratio was -2.58. The GRADE system showed a moderate strength of evidence due to the presence of studies with a high risk of bias and high indirectness of the data given. The present findings suggest that an inadequate intake of vitamins, particularly vitamin D, poses a risk for the onset of oral cancer.

Tongue Mucoceles: a retrospective clinic-pathological evaluation of 240 cases.

BACKGROUND: Minor salivary glands can be found in the ventral and anterior part of the tongue; these glands can rarely develop mucoceles that, due to their rarity and their unusual clinical appearance, may present an interesting differential diagnosis. Mucoceles appear as an exophytic, sometimes pedunculated, lesion, which is a feature that is due to the absence of a capsule; thus, the glands are right beneath the mucosa and over the muscle tissue. The aim of this article is to retrospectively present and discuss the anatomy, pathology, clinical features and therapy of several cases of Blandin-Nunh mucoceles collected from two different institutions. METHODS: A retrospective case review was carried out in two university institutions, retrieving all cases of tongue mucoceles from 1999 to today. Two oral pathologists reviewed all the slides, confirming the diagnosis. Demographic data of the patient, anatomic location and clinical appearance were retrieved from clinical charts, together with the type of surgical procedure and possible relapses. RESULTS: A total of 240 cases of tongue mucoceles were gathered from the archives: the mean age was 22 years (DS = 14,7; Range 2-83), 126 were females (52,5%, mean age 22,7 years, DS = 16,5; Range 2-83), and 114 were males (47,5%, mean age 20,9 years, DS = 12,4; Range 3-73); in all cases, a history of trauma was reported. The ventral surface was the most frequent location (224 cases - 93,3%), and in the great majority (235 cases - 97,9%), pathology revealed mucous spillage with a wall formed by fibrous connective and granulation tissue with no epithelium lining the cavity. Superficial mucocele and sclerosing sialoadenitis were the more frequent pathological variants (21 cases - 8,8%). All lesions were treated with excision and enucleation of the servicing gland. The healing was uneventful in all cases, but there were four recurrences and two cases of sensory paraesthesia of the border of the tongue, all in males, except one case of paraesthesia in a female. CONCLUSIONS: Tongue mucoceles must be differentiated from many benign and malignant lesions. For this reason, surgical removal of the lesion and of the associated gland with a pathological exam is mandatory. In fact, the anatomical location of the glands and the possible pathological variants must be considered to reach a correct diagnosis and diminish possible relapses. TRIAL REGISTRATION: CE-Muc_Ton_3/2023.

Sodium-hyaluronate mouthwash on radiotherapy-induced xerostomia: a randomised clinical trial.

INTRODUCTION: Radiotherapy-induced xerostomia (RIX) is one of the most common adverse effects of radiotherapy (RT) in head and neck cancer patients (HNC) and a major determinant of survivors' quality of life. The primary objective was to evaluate the reduction of patients' xerostomia symptoms after the utilisation of a sodium-hyaluronate mouthwash compared to a placebo solution. The secondary objectives were to evaluate the improvement of quality of life and to evaluate the patients' satisfaction. METHODS: The protocol was approved by the ethical committee (Ref. 50,053/19) and registered at ClinicalTrials.gov (ID: NCT05103124). The study was a double-blind randomised clinical trial (RCT) with a crossover design and was conducted at the Fondazione Policlinico Universitario A. Gemelli, Rome. RESULTS: Thirty-two patients completed the study protocol. Lower values of the modified Xerostomia Questionnaire (XQ) were retrieved when comparing the baseline scores to the ones after the treatment, when compared with placebo (Mann-Whitney U test = 0.01); higher values of patients' satisfaction (Likert scale) and modified XQ were retrieved for the sodium-hyaluronate mouthwash (Mann-Whitney U test = 0.001). CONCLUSIONS: This RCT highlights the advantages of treating RIX with the sodium-hyaluronate mouthwash since it seems to be clinically effective in reducing its symptoms, without any reported adverse events. CLINICALTRIALS: gov: NCT05103124 in 17/10/2021.

Clinical outcomes of teeth adjacent to the site of mandibulotomy or mandibulectomy in patients with head and neck cancer: results from a multidisciplinary mono-institutional head and neck tumor board.

INTRODUCTION: The aim of this case series was to evaluate the necrosis of teeth adjacent to the site of mandibulotomy or mandibulectomy in a cohort of patients suffering from head and neck cancers. METHODS: Fourteen patients who underwent segmental mandibulectomy or paramedian mandibulotomy for oral, oropharynx or major salivary gland cancer and a total of 23 teeth were included in this case series. Twelve patients underwent adjuvant head and neck radiotherapy. Cold sensitivity pulp testing and/or electric pulp testing were performed on teeth at the margin of mandibulectomy and on teeth adjacent to mandibulotomy after surgery. A "positive" response was considered the healthy state, and "negative" was considered the diseased state of the tooth. RESULTS: The 10 patients who underwent mandibulotomy had 12 teeth with a negative response. The 4 patients treated by mandibulectomy had two positive and three negative responses to cold and electric pulp tests. Fifteen out of 23 teeth (65.2%) showed a negative response to sensitivity testing. CONCLUSIONS: Tooth necrosis seems to be a common event after mandibulectomy and mandibulotomy. CLINICAL RELEVANCE: To avoid post-surgery complications, performing root canal therapy before surgery on the teeth adjacent to the surgical site could be an appropriate strategy.

Is Systemic Immunosuppression a Risk Factor for Oral Cancer? A Systematic Review and Meta-Analysis.

Even if the relationship between immunosuppression and increased incidence of systemic cancers is well known, there is less awareness about the risk of developing oral cancer in immunosuppressed patients. The aim of this review was to evaluate the association between immunosuppression and the development of oral cancer. Two authors independently and, in duplicate, conducted a systematic literature review of international journals and electronic databases (MEDLINE via OVID, Scopus, and Web of Science) from their inception to 28 April 2023. The assessment of risk of bias and overall quality of evidence was performed using the Newcastle-Ottawa Scale and GRADE system. A total of 2843 articles was identified, of which 44 met the inclusion criteria and were included in either the qualitative or quantitative analysis. The methodological quality of the included studies was generally high or moderate. The quantitative analysis of the studies revealed that immunosuppression should be considered a risk factor for the development of oral cancer, with a percentage of increased risk ranging from 0.2% to 1% (95% CI: 0.2% to 1.4%). In conclusion, the results suggest that a constant and accurate follow-up should be reserved for all immunosuppressed patients as a crucial strategy to intercept lesions that have an increased potential to evolve into oral cancer.

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO.

OBJECTIVES: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. METHODS: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. RESULTS: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). CONCLUSIONS: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. CLINICAL RELEVANCE: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients.

Oral Candida and psoriasis: Is there association? A systematic review and trial sequential analysis.

To assess (i) the prevalence of oral colonization by Candida spp. in patients with psoriasis and (ii) the prevalence of oral lesions associated with Candida spp. in patients with psoriasis and identify the risk factors for oral lesions. A systematic review was conducted in accordance with PRISMA criteria. The PROSPERO registration code is CRD42019127178. PubMed, Scopus and Web of Science were used as search engines. Meta-analyses and trial sequential analyses were performed. Among the 5805 retrieved records, nine articles were included. Among 530 psoriatic patients, 255 patients had an oral Candida spp. colonisation with an odds ratio (OR) = 3.44 (95% CI:2.38-5.00). Among 490 psoriatic patients, 43 patients developed oral Candida spp. lesions with an OR = 5.31 (95% CI:1.04-27.23). Among the patients without the main predisposing factors for infections, psoriatic patients had a higher OR (3.48, 95% CI: 2.0-6.0) for Candida spp. colonization, but not for Candida spp. infection, when compared with healthy controls (p-value > 0.05). Meta-analysis showed a higher risk of Candida spp. colonisation in patients with psoriasis. Patients who received immunosuppressive therapies were also at higher risk of developing oral lesions. Further studies are needed to understand these associations.

Oral Candida spp. Colonisation Is a Risk Factor for Severe Oral Mucositis in Patients Undergoing Radiotherapy for Head & Neck Cancer: Results from a Multidisciplinary Mono-Institutional Prospective Observational Study.

BACKGROUND: This study aims to find a correlation between Candida spp. oral colonisation prior to radiotherapy (RT) and (i) the development of severe oral mucositis (OM) (grade 3/4) and (ii) early development of severe OM (EOM). METHODS: The protocol was registered on ClinicalTrials.gov (ID: NCT04009161) and approved by the ethical committee of the 'Fondazione Policlinico Universitario Gemelli IRCCS' (22858/18). An oral swab was obtained before RT to assess the presence of Candida spp. Severe OM occurring before a dose of 40 Gy was defined as EOM. RESULTS: No patient developed G4 OM, and only 36/152 patients (23.7%) developed G3 OM. Tumour site and lymphocytopenia were risk factors for severe OM (OR for tumour site: 1.29, 95% CI: 1-1.67, p = 0.05; OR for lymphocytopenia: 8.2, 95% CI: 1.2-55.8, p = 0.03). We found a correlation between Candida spp. and EOM (OR: 5.13; 95% CI: 1.23-21.4 p = 0.04). Patients with oral colonisation of Candida spp. developed severe OM at a mean dose of 38.3 Gy (range: 28-58; SD: 7.6), while negative patients did so at a mean dose of 45.6 Gy (range: 30-66; SD: 11.1). CONCLUSIONS: Candida spp. in the oral cavity appears to be a predictive factor of EOM.

Oral juvenile xanthogranuloma: An unusual presentation in an adult patient and a systematic analysis of published cases.

OBJECTIVE: The purpose of this study was to describe an unusual case of intraoral juvenile xanthogranuloma (JXG) and to perform a systematic review to investigate the available literature regarding oral JXGs. STUDY DESIGN: We present a new case of oral JXG arising in a 36-year-old Italian woman and conducted a systematic literature review in PubMed, Web of Science, and Scopus, according to the PRISMA guidelines. RESULTS: Our review of the English-language literature yielded 34 cases of oral JXG, which included our case report. CONCLUSIONS: JXG is a non-Langerhans cell histiocytosis. Oral JXG has been reported, but it is a rare manifestation. Because of the rarity of oral lesions and possible variations in the clinical and histologic presentation, the correct diagnosis can be challenging, requiring a careful clinical and histopathologic evaluation with adjuvant immunohistochemical studies.

Osteoradionecrosis of the Jaws Due to Teeth Extractions during and after Radiotherapy: A Systematic Review.

Teeth extractions before or after radiotherapy (RT) could be procedures at high risk for osteoradionecrosis (ORN) onset. This systematic review was performed to investigate the ORN incidence following teeth extractions during and after RT for head and neck (H&N) cancer and to evaluate any other possible risk factor. METHODS: This systematic review was conducted according to PRISMA protocol, and the PROSPERO registration number was CRD42018079986. An electronic search was performed on the following search engines: PubMed, Scopus, and Web of Science. A cumulative meta-analysis was performed. RESULTS: Two thousand two hundred and eighty-one records were screened, and nine were finally included. This systematic review revealed an ORN incidence of 5.8% (41 patients out of 462, 95% CI = 2.3-9.4); 3 ORN developed in the maxilla. No other clinical risk factors were detected. CONCLUSION: Post-RT teeth extractions represent a major risk factor for ORN development, especially in the mandible, with a diminishing trend in the last years. Further research on other possible risk factors might improve this evidence.

Saprochaete clavata Infection in Immunosuppressed Patients: Systematic Review of Cases and Report of the First Oral Manifestation, Focusing on Differential Diagnosis.

Background: Saprochaete clavata infection is an emerging issue in immunosuppressed patients, causing fulminant fungaemia. The purpose of this systematic review of cases is to retrieve all cases of S. clavata infection and describe oral lesions as the first manifestation of S. clavata infection. Methods: We report the first case of intraoral S. clavata infection in Acute Myeloid Leukemia (AML) affected subject, presenting as multiple grayish rapidly growing ulcerated swellings, and provide a review of all published cases of infection caused by S. clavata, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, conducted by searching SCOPUS, Medline, and CENTRAL databases. Only articles in English were considered. Individual patient data were analyzed to identify risk factors for S. clavata infection. Results: Seventeen of 68 retrieved articles were included in the review reporting data on 96 patients (mean age 51.8 years, 57 males and 38 females). Most cases were disseminated (86) with a 60.2% mortality rate. Ninety-five were hematological patients, with AML being the most common (57 cases). Conclusions:S. clavata infection in immunosuppressed patients has a poor prognosis: middle-age patients, male gender and Acute Myeloid Leukemia should be considered risk factors. In immunosuppressed patients, the clinical presentation can be particularly unusual, imposing difficult differential diagnosis, as in the reported case.

Psychological profile and unexpected pain in oral lichen planus: A case-control multicenter SIPMO studya.

OBJECTIVES: To analyze psychological profiles, pain, and oral symptoms in patients with oral lichen planus (OLP). MATERIALS AND METHODS: 300 patients with keratotic OLP (K-OLP; reticular, papular, plaque-like subtypes), 300 patients with predominant non-keratotic OLP (nK-OLP; erythematosus atrophic, erosive, ulcerative, bullous subtypes), and 300 controls were recruited in 15 universities. The number of oral sites involved and oral symptoms were recorded. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered. RESULTS: The OLP patients, especially the nK-OLP, showed higher scores in the NRS, T-PRI, HAM-D, HAM-A and PSQI compared with the controls (p-value < .001** ). A positive correlation between the NRS, T-PRI, HAM-A, HAM-D, and PSQI was found with the number of oral symptoms and number of oral sites involved. Pain was reported in 67.3% of nK-OLP and 49.7% of K-OLP cases with poor correspondence between the site of lesions and the site of the symptoms. CONCLUSIONS: Mood disorders are frequently associated with OLP with an unexpected symptomatology correlated with the number of oral symptoms and with the extension of disease suggesting a peripheral neuropathy.

Tooth extraction before radiotherapy is a risk factor for developing osteoradionecrosis of the jaws: A systematic review.

OBJECTIVES: The aim of this systematic review was to estimate the osteoradionecrosis rate in patients with head and neck cancer due to teeth extraction performed before radiotherapy and to identify possible risk factors. MATERIAL AND METHODS: PRISMA protocol was used to evaluate and present the results. PubMed, Scopus and Web of Science were used as search engines: English full-length papers of clinical studies, in peer-reviewed journals, were investigated. Cumulative meta-analysis was performed with a random effects model (PROSPERO registration code: CRD42018079986). RESULTS: Among 2,020 records screened, 8 were included in this review. Sixteen of 494 patients who underwent tooth extraction before radiotherapy developed osteoradionecrosis, with an osteoradionecrosis incidence of 2.2% (95% Confidence of Interval = 0.6-3.9, p < .185, I2  = 3,044%). All cases were reported in the mandible. No other clinical risk factor for osteoradionecrosis was detected. CONCLUSIONS: Even if it is generally recommended to remove oral foci before radiotherapy, this systematic review confirmed that teeth extractions before radiotherapy represent a risk factor for osteoradionecrosis; the considerable amount of missing data prevented us from identifying other possible risk factors for osteoradionecrosis onset. Major efforts should be done to perform sounder methodological clinical investigations.

Rate of malignant transformation of oral lichen planus: A systematic review.

OBJECTIVE: The aim of this study was to systematically review the literature to determine: (a) the malignant transformation rate (TR) of oral lichen planus (OLP) and its risk factors; (b) whether or not oral lichenoid lesions (OLL) have a different malignant TR. MATERIALS AND METHODS: PubMed, Scopus, and Web of Science were used as search engines: only observational, full-length, English language studies were investigated. PRISMA protocol was used to evaluate and present results. PROSPERO registration code is CRD42016048529. RESULTS: Among 7,429 records screened, only 21 were included in this review. Ninety-two of 6,559 patients developed oral squamous cell carcinoma, with an overall TR of 1.40% (1.37% for OLP and 2.43% for OLL), an annual TR of 0.20%. Female gender, red clinical forms, and tongue site seem to slightly increase the transformation risk. CONCLUSIONS: This systematic review confirms that both OLP and OLL, the latter with a slightly higher TR, may be considered potentially malignant disorders and suggest that erosive type, female gender and tongue site should be considered as risk factors for OLP transformation. Major efforts should be done to establish strict clinical and histological criteria to diagnose OLP and to perform sounder methodological observational studies.

The association between periodontitis and sleep duration.

AIM: Due to its potential to influence systemic inflammation and oxidative stress, and to predispose to bacterial infections, sleep duration could potentially be a risk factor for periodontitis. The aim of this cross-sectional study was to evaluate if there was in 2012 an association between periodontitis and sleep duration in a representative sample of the South Korean population. MATERIALS AND METHODS: A total of 5812 subjects representative of 39.4 million of adults were examined. Multivariate logistic regressions were applied controlling for age, gender, education, smoking status, alcoholism and consumption frequency of coffee, tea, chocolate and red wine. RESULTS: Compared to the group sleeping ≤5 h/day, the adjusted odds ratios for periodontitis prevalence defined as Community Periodontal Index (CPI) = 4 were OR = 2.46 (95% CI: 1.20-5.06) in the 6 h/day sleepers group, OR = 2.66 (95% CI: 1.35-5.25) in the 7 h/day sleepers group, OR = 2.29 (95% CI: 1.13-4.63) in the 8 h/day sleepers group and OR = 4.27 (95% CI: 1.83-9.97) in the ≥9 h/day sleepers group. The association has shown to be highlighted in middle-aged people, females, non-smokers, lower educated, with lower lead and higher cadmium blood levels and with higher carotene dietary intake ones and to be partially mediated by lipid profile alterations, diabetes, serum Vitamin D levels and WBC count. CONCLUSIONS: A novel, direct and independent association between sleep duration and the prevalence of periodontitis was found. However, it needs to be investigated how the factors influencing the sleep duration affect this association.