Abstract Scientific evidence about genetic and molecular changes in oral squamous cell carcinoma (OSCC) among smokers and non-smokers is inconclusive. This systematic review and meta-analysis assessed the effects of tobacco on the DNA of individuals with OSCC based on protein mutations. Electronic searches were conducted on PubMed, Ovid, Web of Science, and Scopus to identify observational studies published up to January/2022. The Joanna Briggs Institute tool was used for the critical appraisal of studies. The certainty of the evidence was evaluated. Twenty-three studies assessing 4,060 individuals (2,967 smokers vs. 1,093 non-smokers) were included in this review. Fifteen groups of proteins/genes were investigated. Analysis of the quality of articles revealed low risk of bias in most studies. The certainty of the evidence was very low. The meta-analysis confirmed no significant difference between smokers and non-smokers with respect to damage to GSTM1 (OR: 0.60; 95%CI: 0.30–1.18), GSTT1 (OR: 1.18; 95%CI:0.49–2.83), hydrolase proteins (Ku70 and Ku80) (OR: 0.74; 95%CI: 0.18–3.05), and transferase proteins (GSTM1, GSTT1, GSTM3) (OR: 0.74; 95%CI: 0.47–1.18). Most of the studies included showed that smokers are more likely to exhibit genetic instability. However, the meta-analysis revealed that smokers do not necessarily have more genetic alterations in the DNA than non-smokers.

Abstract: Tobacco smoking involves a high risk of human malignancies, including oral cancer, because it contains multiple carcinogens that cause genetic instability. Thus, a worse prognosis would be expected for cancer patients who are smokers. The aim of this study was to assess the DNA damage response through the expression of checkpoint kinase 2 (CHK2), H2A histone family member X (H2AX), and P53 among smokers and non-smokers with oral squamous cell carcinoma (OSCC). Associations between immunoexpression of proteins and clinicopathological data and histopathological grading were also analyzed. A total of 35 individuals (18 non-smokers and 17 smokers) with OSCC of the tongue and/or floor of the mouth were included. Immunohistochemistry for H2AX was conducted for the identification of double-strand breaks, CHK2, and P53 to evaluate the expression of this protein in cell cycle regulation. The sample consisted of 22 males and 13 females, with a mean age of 63.9±11.8 years. OSCC of non-smokers were well-differentiated tumors in 50% of the cases, and those of smokers were equally distributed into moderately differentiated and poorly differentiated tumors (35.3% each). Overall, 31 (88.6%) cases were CHK2-positive, 27 (77.1%) were H2AX-positive, and 23 (65.7%) were P53-positive, with no difference between smokers and non-smokers (p > 0.05). No association was found between proteins and clinicopathologic data (p > 0.05). Similarities in CHK2, H2AX, and P53 immunohistochemical staining patterns were observed between smokers and non-smokers, and immunoexpression was not associated with clinicopathological parameters. However, the findings indicated consistent expression of these proteins in OSCC.

Abstract The aim of this study was to investigate the epidemiological and clinical characteristics of chronic inflammatory periapical diseases in different regions of Brazil and to compare with data from the literature. A multicenter study was carried out in four Brazilian referral centers in oral diagnosis. Histopathological records were reviewed, and all cases diagnosed microscopically as periapical granuloma, radicular cyst, and periapical abscess were included. Demographic and clinical data were collected. Descriptive statistics and Pearson’s chi-square test were performed. A total of 10,381 cases of chronic inflammatory periapical diseases were found (13.8% of 74,931 archived specimens) over a period of 65 years. Radicular cysts were the most common lesion (59.9%). Women (56.1%) with a mean age of 37.01 years old (range 13 to 100 ± 14.42) and people of white skin color (59.2%) were the most affected individuals by chronic inflammatory periapical diseases. The lesions were generally asymptomatic (28.1%), located in the maxilla (60.1%), and posterior region (49.8%). The radicular cysts were larger when compared to periapical granulomas (p < 0.001). The disagreement between the clinical and histopathological diagnoses was higher when the final diagnosis was a periapical granuloma (p < 0.001). Chronic inflammatory periapical diseases continue to be common lesions affecting mainly adults. This should be a consequence of the burden of untreated caries in permanent teeth. Women are more affected and radicular cyst was the most common lesion.

Abstract Head and neck radiotherapy causes quantitative and qualitative changes in saliva. The objective of this case-control study was to evaluate the salivary biomarkers associated with bone remodeling and tissue repair in patients submitted to radiotherapy for head and neck cancer treatment, compared with non-irradiated individuals. Total unstimulated saliva was collected for ELISA assay analysis of receptor activator for nuclear factor κ B (RANK) and its ligand (RANK-L), osteoprotegerin, matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2, vascular endothelial growth factor, and epidermal growth factor. Statistics were performed, and revealed that salivary RANK (p = 0.0304), RANK-L (p = 0.0005), matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2 (p = 0.0067), vascular endothelial growth factor (p = 0.0060), and epidermal growth factor (p < 0.0001) were reduced in patients, compared with the control group. Osteoprotegerin did not differ between the groups (p = 0.3765). Salivary biomarkers did not differ according to radiotherapy completion time (p > 0.05). In conclusion, the lower output of the salivary molecules – essential for bone remodeling and tissue repair – may disrupt tissue homeostasis and play a role in the pathogenesis of the radiotherapy-induced deleterious effects in the oral cavity.

Resumo Introdução: Um ressurgimento da sífilis no Brasil tem sido relatado nos últimos anos. Objetivo: Investigar a frequência, as características demográficas e clínicas dos pacientes com sífilis adquirida com envolvimento oral que receberam atendimento médico em um centro de referência em medicina oral em um hospital público brasileiro. Método: Estudo retrospectivo, abrangeu 12 anos, feito para identificar tendências de mudança na sífilis. Registros médicos de todos os pacientes diagnosticados com sífilis adquirida que receberam atendimento médico na clínica de medicina oral do hospital de 2005 a 2016 foram revisados e os dados demográficos e clínicos foram coletados. Resultados: Foram diagnosticas 85 pacientes com sífilis adquirida, com um aumento significativo no número de casos nos últimos 5 anos. A idade dos pacientes variou de 16 a 76 anos, com pico na terceira e quarta décadas; 48 casos eram do sexo masculino (56,5%) e 37 do sexo feminino (43,5%). A maioria das lesões orais apareceu como úlceras ou placas únicas, os lábios e a língua representaram os locais mais afetados. Todos os casos foram positivos para Venereal Disease Research Laboratory e Fluorescent Treponemal Antibody Absorption Test e o tratamento foi feito com penicilina G benzatina na maioria dos casos (84,7%). Conclusão: A frequência da sífilis oral tem aumentado com o tempo e as lesões orais podem representar uma pista diagnóstica; portanto, os profissionais de saúde bucal devem ser conscientizados e devidamente treinados na tentativa de desenvolver um alto grau de suspeição clínica no diagnóstico da sífilis.

Abstract Introduction: A resurgence of syphilis in Brazil has been reported in recent years. Objective: With this in mind, the present study sought to investigate the frequency, demographics, and clinical characteristics of patients with acquired syphilis with oral involvement who received medical care at an Oral Medicine Reference Center in a Brazilian Public Hospital. Methods: A retrospective study, spanning a period of 12 years, was performed to identify changing trends in syphilis over time. Medical records from all patients diagnosed with acquired syphilis who received medical care at the Hospital's Oral Medicine Clinic from 2005 to 2016 were reviewed, and the demographic and clinical data were collected. Results: A total of 85 patients had been diagnosed with acquired syphilis, with a significant increase in the number of cases over the past 5 years. Patients ranged from 16 to 76 years of age, with a peak in the third and fourth decades. Forty-eight cases affected males (56.5%), while 37 cases affected females (43.5%). Most of the oral lesions appeared as unique ulcers or plaques, with the lips and tongue representing the most affected sites. All cases were positive for Venereal Disease Research Laboratory or Fluorescent Treponemal Antibody Absorption, and treatment was performed with Penicillin G benzathine in most cases (84.7%). Conclusion: The frequency of oral syphilis has been rising over time and oral lesions may well represent a diagnostic clue; therefore, oral health professionals must be made aware and properly trained in an attempt to develop a high degree of clinical suspicion in the diagnosis of syphilis.

Abstract Cytokines and chemokines have a fundamental role in the maintenance of inflammation and bone response, which culminate in the development of chronic periapical lesions. Regulatory (Treg) and Th17 cytokines play a key role in regulating the immune response involved in this process. The aim of this study was to investigate the role of Treg and Th17 cells in chronic inflammatory periapical disease, by comparing the expression of the immunoregulatory mediators TGF-β, IL-10, CCL4, and the proinflammatory IL-17 and CCL20 in the periapical tissue of teeth with pulp necrosis, with and without associated chronic lesions. Eighty-six periapical tissue samples were obtained from human teeth. The samples were divided into three groups: pulp necrosis with a periapical lesion (n=26); pulp necrosis without a periapical lesion (n=30), and control (n=30). All samples were submitted to histopathological analysis and cytokine and chemokine measurement through ELISA. Statistical analyses were done with Kruskal-Wallis and Mann-Whitney tests and Spearman correlation. The group with pulp necrosis and a periapical lesion showed a higher expression of CCL4 and TGF-β in comparison with pulp necrosis without a lesion. CCL20 was higher in the group with a periapical lesion when compared to the control. In all groups there was a weak positive correlation between IL-17/CCL20, IL-10/CCL4, and IL-17/TGF-β. Both types of cytokines, pro-inflammatory and immunoregulatory, occur simultaneously in periapical tissue. However, a rise in immunosuppressive cytokines and chemokines (CCL4 and TGF-β) in periapical lesions suggests a role of these cytokines in stable periapical disease.

Abstract: The aim of this study was to determine the number of FoxP3+ regulatory T (Treg) cells in the microenvironment of lower lip squamous cell carcinomas (LLSCCs) and to correlate the findings with clinicopathological parameters (tumor size/extent, regional lymph node metastasis, clinical stage, and histopathological grade of malignancy). Fifty cases of LLSCC were selected. Lymphocytes exhibiting nuclear immunostaining for FoxP3 were quantified in 10 microscopic fields at the deep invasive front of LLSCCs. The results were analyzed statistically using the nonparametric Mann-Whitney test and Fisher's exact test. FoxP3+ lymphocytes were observed in all cases studied. The number of these cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (p > 0.05). Low-grade tumors contained a larger number of FoxP3+ lymphocytes than high-grade tumors (p = 0.019). Tumors with an intense inflammatory infiltrate exhibited a larger number of Treg cells (p = 0.035). On the other hand, the number of FoxP3+ lymphocytes was smaller in tumors arranged in small cell clusters (p = 0.003). No significant differences in the number of FoxP3+ lymphocytes were observed according to the degree of keratinization (p = 0.525) or nuclear pleomorphism (p = 0.343). The results suggest the participation of Treg cells in immune and inflammatory responses in the microenvironment of LLSCCs. These cells may play a more important role in early stages rather than in advanced stages of lip carcinogenesis.

Abstract The objective of this study was to analyze the presence of tumor-associated macrophage (TAM) subpopulations M1 and M2 in squamous cell carcinoma of the lower lip (SCCLL) by immunohistochemitry, and to evaluate the possible role of these subtypes in the development of regional lymph node metastasis and their association with clinical and pathological parameters. Forty-two cases of SCCLL were divided into two groups (21 with and 21 without regional lymph node metastasis). The histopathological grade of malignancy was determined and the material was submitted to double staining with anti-CD68/anti-CD163 and anti-CD68/anti-HLA-DR monoclonal antibodies. The results were analyzed statistically using the Wilcoxon signed-rank and Spearman correlation tests. The M1 and M2 subpopulations were observed in all cases studied. No significant difference was observed between the quantities of M1 and M2 TAMs regarding tumor size (p > 0.05). A significantly larger number of M2 compared to M1 TAMs was observed in tumors without regional lymph node metastasis, tumors in early stages, and low-grade tumors (p < 0.05). No significant difference between the numbers of M1 and M2 TAMs was observed in tumors with regional lymph node metastasis, tumors in advanced stages, and high-grade tumors (p > 0.05). There was a positive weak correlation between M1 and M2 TAMs (r = 0.361; p = 0.019). The results suggest a more important role of M2 TAMs in early stages than advanced stages of lip carcinogenesis. The progression of SCCLL does not seem to be related to an imbalance of macrophage polarization in the microenvironment of these tumors.

A lesão liquenóide oral relacionada ao amálgama, condição rara na prática odontológica, constitui importante diagnóstico diferencial no grupo das leucoplasias orais. Relatam-se dois casos que apresentaram rápida resolução clínica após a substituição das restaurações de amálgama.

Amalgam-related oral lichenoid lesion, a rare disorder in dental practice, is an important differential diagnosis among oral leukoplastic lesions. We report two cases with rapid clinical resolution following the replacement of amalgam fillings.

Hemangioma, malformação vascular e variz são lesões vasculares benignas comuns na região de cabeça e pescoço. Estudos sobre a prevalência dessas lesões em boca são escassos. O objetivo deste estudo foi estimar a prevalência e realizar um levantamento de dados clínicos de hemangioma, malformação vascular e variz de boca. Dados clínicos dessas lesões foram consultados em fichas clínicas do arquivo do Serviço de Diagnóstico Oral da Universidade Federal de Minas Gerais, Brasil, no período de 1992 a 2002. Uma análise descritiva foi realizada. Foram obtidas neste período de 10 anos 2.419 fichas clínicas. Cento e cinqüenta e quatro (6,4%) casos foram categorizados como hemangioma, malformação vascular e variz de boca. Variz de boca foi a lesão mais freqüente (65,6%). Mulheres foram mais acometidas pelos hemangiomas e varizes de boca. Malformação vascular e variz de boca foram mais prevalentes na 7ª e 6ª décadas de vida, respectivamente. A localização prevalente do hemangioma e da variz de boca foi a superfície ventral da língua, e da malformação vascular, os lábios. Hemangioma de boca foi tratado com escleroterapia em 54,5% dos casos e a malformação vascular com escleroterapia e cirurgia em 19,4% cada. Este estudo sugere que lesões vasculares benignas são alterações incomuns na mucosa bucal e nos maxilares.

Hemangioma, vascular malformation and varix are benign vascular lesions, common in the head and neck regions. Studies about the prevalence of these lesions in the oral cavity are scarce. The aim of this study was to estimate the prevalence of and to obtain clinical data on oral hemangioma, vascular malformation and varix in a Brazilian population. Clinical data on those lesions were retrieved from the clinical forms from the files of the Oral Diagnosis Service, School of Dentistry, Federal University of Minas Gerais, Brazil, from 1992 to 2002. Descriptive analysis was performed. A total of 2,419 clinical forms in the 10-year period were evaluated, of which 154 (6.4%) cases were categorized as oral hemangioma, oral vascular malformation or oral varix. Oral varix was the most frequent lesion (65.6%). Females had more oral hemangioma and oral varix than males. Oral vascular malformation and oral varix were more prevalent in the 7th and 6th decades, respectively. Oral hemangioma and oral varix were more prevalent in the ventral surface of the tongue and oral vascular malformation, in the lips. Oral hemangioma was treated with sclerotherapy (54.5%), and vascular malformation was managed with sclerotherapy and surgery (19.4% each). The data of this study suggests that benign vascular lesions are unusual alterations on the oral mucosa and jaws.

A análise quantitativa das AgNORs e a imunomarcação para o PCNA têm sido empregadas de forma independente na avaliação da proliferação celular de vários tumores, e, em muitos casos, têm mostrado correlação positiva. Entretanto poucos trabalhos têm avaliado, em um mesmo corte histológico, a relação entre PCNA e AgNOR. O objetivo deste trabalho foi otimizar a técnica de dupla marcação com a finalidade de se estudar simultaneamente a correlação entre PCNA e AgNOR no carcinoma adenóide cístico (CAC) de glândulas salivares menores. Foram selecionados 16 casos de CAC classificados de acordo com o subtipo histológico. A análise quantitativa das AgNORs foi feita por meio de análise de imagens. As AgNORs foram contadas em cem núcleos PCNA positivos e em cem núcleos PCNA negativos. O número médio de AgNOR nos núcleos PCNA positivos foi 2,14 ± 0,77, e, nos núcleos PCNA negativos, 1,97 ± 0,79, entretanto esta diferença não se mostrou estatisticamente significante (p = 0,2537). Nosso trabalho não mostrou correlação entre o número de AgNOR e a imunomarcação para o PCNA em CAC quando estes marcadores foram demonstrados simultaneamente através da dupla marcação. Quanto à técnica, o uso do microondas melhorou a coloração da AgNOR, permitindo uma redução no tempo de incubação com a solução de prata e uma melhor individualização das AgNORs, o que facilitou os procedimentos de contagem.

No previous studies have simultaneously assessed the relationship between AgNORs and PCNA expression in salivary gland tumors. We describe a method to demonstrate both PCNA and AgNORs in the same slice of routinely processed tissue. We also evaluated the effect of microwaving on the AgNORs reaction. Sixteen cases of adenoid cystic carcinoma (ACC) were selected and the double staining technique was performed in order to quantify the number of AgNORs in PCNA-positive and negative cells. The best results were obtained when AgNOR was performed after the immunostaining. The microwave oven heating improved the AgNORs staining. Our results did not show a statistical difference between the mean number of AgNORs in PCNA-negative and positive cells. There is no association between PCNA and AGNOR in ACC when they are assessed by double-staining.