Has the 8th American joint committee on cancer TNM staging improved prognostic performance in oral cancer? A systematic review / ¿Ha mejorado la estadificación TNM del octavo comité conjunto estadounidense sobre cáncer? ¿Rendimiento pronóstico en el cáncer oral? Una revisión sistemática

Background: The 8th edition of the American Joint Committee on Cancer (AJCC) classification has introduced two new parameters: depth of invasion (DOI) and extranodal extension (ENE). The aim of this systematic review was to determine whether this 8th edition referred to oral squamous cell carcinoma (OSCC) offers performance superior to that of the 7th edition in relation to overall survival (OS) and disease-specific survival (DSS). Material and Methods: The review was carried out following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The PubMed (MEDLINE), Scopus and Cochrane Library databases were searched covering the period up until April 7th, 2022.Results: Thirteen retrospective cohort studies were finally included. The introduction of DOI and ENE in the 8th edition of the AJCC classification resulted in improved prognostic performance of the classification. Conclusions: Patients with OSCC can be better classified in relation to OS and DSS, while maintaining the simplicity and ease of use of the classification. This allows more appropriate treatment protocols to be applied and affords a better estimation of the prognosis of each patient.(AU)

The use of E-cigarettes as a risk factor for oral potentially malignant disorders and oral cancer: a rapid review of clinical evidence / El uso de cigarrillos electrónicos como factor de riesgo de trastornos orales potencialmente malignos y cáncer oral: una revisión rápida de la evidencia clínica

Background: The popularity of e-cigarettes has increased rapidly in the last decade, particularly among teens andyoung adults, being advertised as a less harmful alternative to conventional tobacco products. However, in vitroand in vivo studies have evidenced a variable quantity of potentially harmful components and some recognizedcarcinogens which may cause DNA damage in oral cells. Additionally, evidence suggests that e-cigarettes mayplay active roles in the pathogenesis of other malignancies, such as lung and bladder cancers. Therefore, this rapidreview aimed to assess the available clinical evidence about using e-cigarettes as a risk factor for oral potentiallymalignant disorders (OPMD) and oral cancer.Material and Methods: A systematic search for English language articles published was performed in PubMed(MEDLINE), Embase, Scopus, and Web of Science. After the study selection process, the authors included twelveclinical studies about OPMD and oral cancer risk in e-cigarette users.Results: The main findings showed the presence of carcinogenic compounds in saliva and morphologic changes,DNA damage, and molecular pathways related to carcinogenesis in the oral cells of e-cigarette users. However,results were inconsistent compared to tobacco smokers and control groups.Conclusions: the current clinical evidence on this topic is limited and insufficient to support using e-cigarettes asa risk factor for OPMD and oral cancer. Nevertheless, dental care professionals should advise patients responsiblyabout the potentially harmful effects of e-cigarettes on the oral mucosa cells. Future long-term and well-designedclinical studies are needed.(AU)

Epidemiological, clinical, and prognostic analysis of oral squamous cell carcinoma diagnosed and treated in a single hospital in Galicia (Spain): a retrospective study with 5-year follow-up / Análisis epidemiológico, clínico y pronóstico del carcinoma oral de células escamosas diagnosticado y tratado en un único hospital de Galicia (España): un estudio retrospectivo con un seguimiento de 5 años

Background: Oral cancer is a common neoplasm worldwide, mostly corresponding to squamous cell carcinoma(OSCC). Unfortunately, its overall prognosis remains poor, with no improvement in recent decades. In this study,we have analysed the epidemiological, clinical, and prognostic characteristics of OSCC on patients of a specificSpanish region (Galicia), in order to improve its prognosis and apply effective preventive and early diagnosismeasures.Material and Methods: We retrospectively analysed 243 cases of OSCC, diagnosed and treated in a single hospitalcentre in Galicia between 2010 and 2015 (minimum of 5 years of evolution). Overall and specific survival werecalculated (Kaplan-Meier) and associated variables were identified (log rank test and Cox regression).Results: The mean age of the patients was 67 years, with the majority being male (69.5%), smokers (45.9%) andalcohol consumers (58.6%), who lived in non-urban areas (79.4%). Cases diagnosed at advanced stages entailedthe 48.1% of the sample, and 38.7% of cases relapsed. The 5-year overall and disease-specific survival rates were39.9% and 46.1%, respectively. Patients who consumed tobacco and alcohol had a worse prognosis. OSCC casesreferred to hospital by specialist dentists had a better prognosis, as those who were previously diagnosed with anoral potentially malignant oral disorder (OPMD) or received dental care during OSCC treatmen. Conclusions: In view of these findings, we conclude that OSCC in Galicia (Spain) still has a very poor overall prog-nosis, which is mainly related to the advanced age of the patients and the late diagnosis. Our study highlights thebetter survival of OSCC in relation to the referring health professional, the presence of a previous OPMD and thedental care after diagnosis. This demonstrates the importance of dentistry as a health profession involved in the earlydiagnosis and multidisciplinary management of this malignant neoplasm.(AU)

Clinical practice guideline of the Spanish society of oral surgery for dental care in patients with oral cancer / Guía de práctica clínica de la sociedad española de cirugía bucal para el cuidado dental en pacientes con cáncer oral

Background: Oral cancer is the sixteenth most common malignant neoplasm worldwide, with a high mortalityrate, greater than 50% at five years, and high morbidity. The effect of oncological treatment in the oral cavity isbroad and has multiple levels, therefore knowing these effects and preventing them is essential for avoiding anincrease in the oral pathology related with oncological therapy, maintaining the quality of life of the patient, andimproving the efficacy of the treatment itself.Material and Methods: A group of experts belonging to the fields of Dentistry, Maxillofacial Surgery and Oncol-ogy of the University of Seville and the Virgen del Rocío University Hospital of Seville in collaboration with theUniversity of Valencia, University of Barcelona, and University of the Basque Country, developed this ClinicalPractice Guideline for the proper clinical management of patients diagnosed with oral cancer. The clinical ques-tions were formulated in PICO format. The databases consulted were Medline/PubMed and Embase/Elsevier. Thesystematic reviews published on the topic were identified on Tripdatabase, Cochrane Library and CRD (Centre forReviews and Dissemination). The recommendations were prepared based on the GRADE methodology.Results: Various recommendations were defined, derived from the 21 PICO questions, referring to prevention,treatment and care for alterations arising from the pathology of oral cancer itself and its treatment.Conclusions: The preparation of this clinical practice guideline allows recommendations to be generated basedon the scientific evidence available, on dentistry actions in patients with oral cancer and undergoing oncologicaltreatment, which may be of use to the multidisciplinary team treating this type of patient.(AU)

Proliferative verrucous leukoplakia/multifocal leukoplakia in patients with and without oral submucous fibrosis / Leucoplasia verrugosa proliferativa/leucoplasia multifocalen pacientes con y sin fibrosis submucosa oral

Background: Oral submucous fibrosis (OSF) and proliferative verrucous leukoplakia (PVL) are established as oralpotentially malignant disorders. Dual pathology of the two conditions is not commonly encountered in clinicalpractice. This study aims to present a case series of multifocal leukoplakia in patients with and without OSF tooutline the clinical behavior and challenges in the management of this high-risk group in clinical practice.Material and Methods: We retrospectively analyzed cases of six Indian patients (four with OSF) managed over aperiod of 5.5 to 13 years at the Government Dental College, Nagpur. Patient data consisting of age, gender, med-ical history, habits, clinical findings, and biopsy reports were recorded at the initial visit. During follow-up visits,the clinicopathological data were reassessed. When surgical intervention failed to arrest the disease or whensurgery was contraindicated metronomic therapy with Folitrax 15 mg once a week and Celecoxib 100mg twicedaily was initiated.Results: All patients developed PVL after the initial pathology diagnosis of OSF or oral leukoplakia. Initial lesionswere either homogenous or non-homogenous leukoplakia. All patients developed multiple recurrences, regional orsystemic metastasis. Despite thorough interventions, the patients died of, or with the disease.Conclusions: The occurrence of two or more oral potentially malignant disorders poses challenges in patient man-agement and possibly presents a higher risk of malignant transformation. More clinical trials are necessary to as-sess the benefits of metronomic therapy for patients diagnosed with aggressive PVL concurrently found with OSF.(AU)

Relationship between transcriptional expression of pyruvate dehydrogenase and local control of disease in patients with oral cavity carcinomas / Relación entre la expresión transcripcional de piruvato deshidrogenasa y el control local de la enfermedad en pacientes con cáncer en la cavidad oral

Background The altered cellular metabolism is one of the hallmarks of the cancer cells, favoring the process of aerobic glycolysis, known as the Warburg effect. The pyruvate dehydrogenase (PDH) complex is one of the elements involved in this metabolic process. The present study aims to evaluate the relationship between the transcriptional expression of PDHB and the risk of local recurrence in patients with oral cavity carcinomas. Methods We determined the transcriptional expression of PDHB in biopsies from 41 patients with oral cavity carcinomas treated with surgery. The PDHB expression was categorized according to the local control of the disease with a recursive partitioning analysis. Results During the follow-up period 13 patients (31.7%) had a local recurrence of the tumor. Considering local disease control as the dependent variable, the recursive partitioning analysis classified the patients in two categories according to high (n=16, 39.0%) or low (n=25, 61.0%) PDHB expression. Five-year local recurrence-free survival for patients with high PDHB expression was 84.8% (95% CI: 65.2-100%), and for patients with low expression it was 54.3% (95% CI: 34.3–74.2 %) (P=0.034). The results of multivariate analysis showed that patients with a low PDHB expression had a 4.90 times higher risk of local recurrence of the tumor (95% CI: 1.02–22.68, P=0.042). Conclusion There is a relationship between the metabolic characteristics of the tumor and its aggressiveness. According to our results, patients with oral cavity carcinomas with low transcriptional expression levels of PDHB have a significantly higher risk of local tumor recurrence. (AU)

Antecedentes La alteración del metabolismo celular es una de las características distintivas de las células cancerígenas, y favorece el proceso de la glucólisis aeróbica, conocido como efecto de Warburg. El complejo de piruvato deshidrogenasa (PDH) es uno de los elementos implicados en este proceso metabólico. El objetivo del presente estudio es evaluar la relación entre la expresión transcripcional de PDHB y el riesgo de recidiva local en los pacientes con cáncer en la cavidad oral. Métodos Determinamos la expresión transcripcional de PDHB en biopsias de 41 pacientes con cáncer en la cavidad oral tratados con cirugía. Se categorizó la expresión de PDHB de acuerdo con el control local de la enfermedad, con un análisis de partición recursiva. Resultados Durante el periodo de seguimiento, trece pacientes (31,7%) tuvieron una recidiva local del tumor. Considerando el control de la enfermedad local como variable dependiente, el análisis de partición recursiva clasificó a los pacientes en dos categorías, de acuerdo con la expresión de PDHB alta (n=16, 39%) o baja (n=25, 61%). La tasa de supervivencia libre de enfermedad a cinco años con expresión alta de PDHB fue del 84,8% (95% IC: 65,2–100%), siendo del 54,3% (95% IC: 34,3–74,2%) (P=0,034) para los pacientes con expresión baja. Los resultados del análisis multivariante reflejaron que los pacientes con expresión baja de PDHB tuvieron un riesgo 4,90 veces mayor de recidiva local del tumor (95% IC: 1,02–22,68, P=0,042). Conclusión Existe una relación entre las características metabólicas del tumor y su agresividad. Conforme a nuestros resultados, los pacientes con cáncer en la cavidad oral y bajos niveles transcripcionales de PDHB tienen un riesgo significativamente mayor de recidiva local del tumor. (AU)

The repertoire of mutational signatures in tobacco- and non-tobacco-induced oral cancer

The use of tobacco products is one of the established contributors toward the development and spread of oral cancer. Additionally, recent research has indicated oral microbiome, infections with Human papilloma virus (HPV), Epstein–Barr virus (EBV), Candida as significant contributing factors to this disease along with lifestyle habits. Deregulation of cellular pathways envisaging metabolism, transcription, translation, and epigenetics caused by these risk factors either individually or in unison is manifold, resulting in the increased risk of oral cancer. Globally, this cancer continues to exist as one of the major causes of cancer-related mortalities; the numbers in the developing South Asian countries clearly indicate yearly escalation. This review encompasses the variety of genetic modifications, including adduct formation, mutation (duplication, deletion, and translocation), and epigenetic changes evident in oral squamous cell carcinoma (OSCC). In addition, it highlights the interference caused by tobacco products in Wnt signaling, PI3K/Akt/mTOR, JAK-STAT, and other important pathways. The information provided also ensures a comprehensive and critical revisit to non-tobacco-induced OSCC. Extensive literature survey and analysis has been conducted to generate the chromosome maps specifically highlighting OSCC-related mutations with the potential to act as spectacles for the early diagnosis and targeted treatment of this disease cancer (AU)

DNA oxidative damage in oral cancer: 8-hydroxy-2´-deoxyguanosine immunoexpression assessment

Background: The development and establishment of oral squamous cell carcinoma are confined to carcinogenesis, which involves oxidative stress via oxygen-free radical production as a hydroxyl radical (HO•), considered the most important cause of oxidative damage to basic biomolecules since it targets DNA strands. 8-Hydroxy-2´- deoxyguanosine (8-OHdG) is considered a free radical with a promutagenic capacity due to its ability to pair with adenosine instead of cytosine during replication. Material and Methods: We collected 30 paraffin-embedded tissue samples of OSCC from patients treated between 2013 and 2018. We recorded risk habits, disease stage, disease free survival and death with at least 3 years of followup. 8-Hydroxyguanosine was evaluated by immunohistochemistry and subsequently classified as weak-moderate or strong positive expression. Additionally, we noted whether it was expressed in the cytoplasm and/or nucleus. Results: Most of the cases expressed 8-OHdG with a strong intensity (80%). All neoplastic cells were preferentially stained in only the cytoplasm (70.0%), but nuclear positivity was found in 30%, independent of the intensity. Based on the location in the cytoplasm and/or nucleus, tumors >4 cm showed a high frequency (95.5%) of 8-OHdG expression in only the cytoplasm, with a significant difference (p value ≤ 0.001). Additionally, overall survival was affected when immunoexpression was present in the cytoplasm and nucleus because all deaths were in this group were statistically significant (p value = 0.001). Conclusions: All tumors showed DNA oxidative damage, and 8-OHdG was preferentially expressed in the cytoplasm. This finding was associated with tumor size and, when present in the nucleus, might also be related to death. (AU)

Reducing the anxiety of patients undergoing an oral biopsy by means of graphic novels: an open-label randomized clinical trial

Background: The use of graphic novels is a trending topic in health communication as a new form of visual storytelling which explores narratives of health care, cancer, healing, and disability. The objective of the present study was to evaluate - for the first time in the literature - the effect of graphic novels in reducing the anxiety of patients waiting for an incisional biopsy in an oral oncology setting. Material and Methods: This open-label randomized clinical trial comprised 50 patients with a clinical suspicion of oral potentially malignant disorders. Twenty-five patients were randomly allocated to the test group, and a colourful graphic novel was provided. Subsequently, the Beck Depression Inventory and the Depression Anxiety Stress Scales-21 were administered to all 50 recruited patients, after which a biopsy was performed on each patient. Results: No statistically significant difference was observed between the test and control groups for the variables regarding the demographic data (p>0.2). There was a significant difference after the introduction of the graphic novel, regardless of which questionnaire was used. The graphic novel demonstrated an improvement in the ability of the test group to tolerate anxiety while waiting for an oral biopsy in both psychological tests (p<0.05). Conclusions: In light of these initial positive results, the authors of this study would like to suggest the use of graphic novels in oral oncology, dentistry, and medicine with the aim of reducing patient anxiety. (AU)

Oral cancer knowledge in adults evaluated through a phone survey in the context of the SARS-CoV2 health emergency in Colombia

Background: in Colombia, oral cancer is the eighth most common type of cancer, with an estimated survival rate of 52%. Lack of knowledge about oral cancer and its risk factors is associated with late detection. Material and Methods: a descriptive cross-sectional study was carried out on 268 patients attending the School of Dentistry of the University of Antioquia clinics, to whom a validated 47-question questionnaire was applied by phone during the COVID-19 pandemic (2020 and 2021). Data were analyzed using the SPSS software. Results: the mean age was 58.9. 58.6% of the participants had heard of oral cancer, 42% acquire knowledge from the media, and 96.7% considered screening necessary. Most of the patients expressed not feeling worried (54.5%), fearful (59.7%), or anxious (56.3%) in the case of being submitted to an examination for early detection of oral cancer. A correlation between low socioeconomic status and educational level with less knowledge of oral cancer was found. The dimensions of experience and attitude towards screening were not associated with sociodemographic variables. Conclusions: There is little knowledge about oral cancer, especially in low socioeconomic and educational status, although this does not occur in the dimensions of attitude and experience toward screening. In contrast, patients participating in this study presented high knowledge about oral cancer risk. This population recognizes the situations most related to the development of cancer. This level of knowledge was similar for the demographic conditions except for people with no education, who presented less knowledge of the risks. The need for educational campaigns on oral cancer knowledge is reaffirmed, especially in socially disadvantaged groups, considering that there would be no barriers related to screening. (AU)

The development of radioresistant oral squamous carcinoma cell lines and identification of radiotherapy-related biomarkers

Background In the treatment of oral squamous cell carcinoma (OSCC), radiation resistance remains an important obstacle to patient outcomes. Progress in understanding the molecular mechanisms of radioresistance has been limited by research models that do not fully recapitulate the biological features of solid tumors. In this study, we aimed to develop novel in vitro models to investigate the underlying basis of radioresistance in OSCC and to identify novel biomarkers. Methods Parental OSCC cells (SCC9 and CAL27) were repeatedly exposed to ionizing radiation to develop isogenic radioresistant cell lines. We characterized the phenotypic differences between the parental and radioresistant cell lines. RNA sequencing was used to identify differentially expressed genes (DEGs), and bioinformatics analysis identified candidate molecules that may be related to OSCC radiotherapy. Results Two isogenic radioresistant cell lines for OSCC were successfully established. The radioresistant cells displayed a radioresistant phenotype when compared to the parental cells. Two hundred and sixty DEGs were co-expressed in SCC9-RR and CAL27-RR, and thirty-eight DEGs were upregulated or downregulated in both cell lines. The associations between the overall survival (OS) of OSCC patients and the identified genes were analyzed using data from the Cancer Genome Atlas (TCGA) database. A total of six candidate genes (KCNJ2, CLEC18C, P3H3, PIK3R3, SERPINE1, and TMC8) were closely associated with prognosis. Conclusion This study demonstrated the utility of constructing isogenic cell models to investigate the molecular changes associated with radioresistance. Six genes were identified based on the data from the radioresistant cells that may be potential targets in the treatment of OSCC (AU)

The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma

Background: Oral squamous cell carcinoma (OSCC) has high morbidity and mortality rates while oral verrucous carcinoma (OVC), an uncommon variant of OSCC, exhibits a distinct biological behavior. CLIC4 protein plays a role in the cell cycle and apoptosis regulation and participates in the myofibroblasts transdifferentiation process, which are the main cells of the tumor stroma. This study analyzed the immunoexpression of CLIC4 and α-SMA in 20 OSCC cases and 15 OVC cases. Material and methods: A semiquantitative analysis of CLIC4 and α-SMA immunoexpression was performed in the parenchyma and stroma. Nuclear and cytoplasmic reactivity was analyzed separately for the CLIC4 immunostaining. The data were submitted to Pearson's chi-square and Spearman's correlation tests (p ≤ 0.05). Results: In the CLIC4 analysis, there was a significant difference in the immunoexpression of this protein between OSCC and OVC stroma (p < 0.001). It was observed a higher expression of α-SMA in the OSCC stroma. There was a positive and significant correlation between CLIC4 and α-SMA immunoexpression in the OVC stroma (r = 0,612; p = 0,015). Conclusions: The decrease or absence of nuclear CLIC4 immunoexpression in the neoplastic epithelial cells and the increase of its expression in the stroma may influence the difference in biological behavior between OSCC and OVC. (AU)

Estimating the direct costs of oral cancer in Spain: a retrospective hospital data analysis

Background: Studies on the costs incurred from cancer in Spain are scarce and have focused on the most prevalent types such as colorectal, breast, and lung cancer. The aim of this study was to calculate the direct costs associated with the diagnostic, treatment and follow-up procedures for oral cancer in Spain. Material and methods: Applying a bottom-up approach, we retrospectively analyzed the medical records of a cohort of 200 patients with oral cancer (C00-C10), diagnosed and treated in Spain between 2015 and 2017. For each patient, we collected their age, sex, degree of medical impairment (American Society of Anesthesiologists [ASA] classification), tumor extent (TNM classification), relapses and survival during the first 2 years of follow-up. The final calculation of the costs is expressed in absolute values in euros as the percentage of the gross domestic product per capita and in international dollars (I$). Results: The total cost per patient rose to €16,620 (IQR, €13,726; I$11,634), and the total direct cost at the national level was €136,084,560 (I$95,259,192). The mean cost for oral cancer represented 65.1% of the gross domestic product per capita. The costs for the diagnostic and therapeutic procedures were determined by the ASA grade, tumor size, lymph node infiltration and presence of metastases. Conclusions: The direct costs for oral cancer are considerable compared with other types of cancer. In terms of gross domestic product, the costs were similar to those of countries neighboring Spain, such as Italy and Greece. The main determinants of this economic burden were the patient's degree of medical impairment and tumor extent. (AU)

Role of selected salivary inflammatory cytokines in the diagnosis and prognosis of oral squamous cell carcinoma. A Systematic Review and Meta-analysis

Background: Oral squamous cell carcinoma (OSCC) is gradually increasing its incidence in our society. Unfortunately, this entity is diagnosed at an advanced stage in most patients, a fact that implies greater difficulty in its treatment and a worse prognosis. This systematic review aims to assess whether the cytokines IL-6, IL-8 and TNF-α are potential salivary biomarkers that allow early diagnosis of cancer. Material and methods: An electronic search was performed in three databases (Pubmed, Scopus and Web of Science). We used the following keywords: "salivary cytokines", "saliva cytokines", "salivary interleukins", "biomarkers", "oral squamous cell carcinoma" and "diagnosis", combined with the Boolean operators "AND" and "OR". Results: 128 publications were found and finally 23 articles were included in the review and 15 in the meta-analysis. It has been observed that the majority of OSCC patients express higher salivary concentrations of IL-6, IL-8 and TNF-α compared to the control (CL) and premalignant lesion (OPML) groups. It has also been observed that the different premalignant lesions do not have statistically significant differences in the salivary concentration of the cytokines, and on the other hand, differences have been observed between the different TNM stages. The meta-analysis has shown that the difference in concentration of IL-6, IL-8 and TNF-α is statistically significant between the CL group and the OSCC, and also between the CL group and OPML. Conclusions: There is sufficient evidence to affirm that IL-6, IL-8 and TNF-α are useful salivary cytokines in the early diagnosis and prognosis of OSCC. Although future studies are necessary to establish greater reliability of these biomarkers and thus be able to develop a valid diagnostic test. (AU)

Perineural invasion predicts poor survival and cervical lymph node metastasis in oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) usually invades peripheral nerves through a process known as perineural invasion (PNI), recognized as an adverse factor considered for the administration of postoperative adjuvant therapy. The aim of this study was to assess the impact of PNI on survival and cervical lymph node metastasis in a cohort of OSCC patients. Material and methods: Presence, location and extension of PNI were assessed in a cohort of 57 paraffin-embedded OSCC resections. Clinico-pathological variables were obtained from each case. Five-year overall survival (OS) and 5-year disease-specific survival (DSS) curves were constructed according to the Kaplan-Meier method and compared with log-rank test. The Cox proportional hazard model was used to assess the role of PNI as an independent risk factor related to poor survival, and a binary logistic regression was performed to estimate the predictive value of PNI for regional lymph node metastasis. Results: PNI was observed in 49.1% of the cases, affecting only small nerves. Peritumoral PNI was the most common location, and multifocal PNI the most frequent extent. Most PNI positive cases had cervical metastasis (p=0.001), and PNI was more frequent in stages III-IV than in I-II (p=0.02). The five-year OS and the 5-year DSS decreased in PNI positive and peritumoral PNI cases. PNI was an independent risk factor for poor 5-year OS and poor 5-year DSS. The odds for cervical lymph node metastasis were of 6.076 (p=0.006) and 10.257 (p=0.007) for PNI and Tumor budding (TB) positive cases, respectively. Conclusions: PNI is a frequent finding in OSCC and an independent risk factor for poor OS and DSS. PNI and TB are both risk factors associated to an increased likelihood for the development of lymph node metastasis. Therefore, we suggest further investigations to test the combined PNI-TB scoring system in risk stratification models for OSCC. (AU)

Gingival neoplasms: a multicenter collaborative study of 888 patients in Brazil

Background: To evaluate the prevalence and clinicopathological features of a large series of gingival neoplasms in Brazil. Material and methods: All gingival benign and malignant neoplasms were retrieved from the records of six Oral Pathology Services in Brazil, during a 41-year period. Clinical and demographic data, clinical diagnosis, and histopathological data were collected from the patients' clinical charts. For statistical analysis, the chi-square, median test of independent samples and the U Mann-Whitney tests were used, considering a significance of 5%. Results: From 100,026 oral lesions, 888 (0.9%) were gingival neoplasms. There were 496 (55.9%) males, with a mean age of 54.2 years. Most cases (70.3%) were malignant neoplasms. Nodules (46.2%) and ulcers (38.9%) were the most common clinical appearance for benign and malignant neoplasms, respectively. Squamous cell carcinoma (55.6%) was the most common gingival neoplasm, followed by squamous cell papilloma (19.6%). In 69 (11.1%) malignant neoplasms, the lesions were clinically considered to be inflammatory or of infectious origin. Malignant neoplasms were more common in older men, appeared with larger size, and with a time of complaint shorter than benign neoplasms (p<0.001). Conclusions: Benign and malignant tumors may appear as nodules in gingival tissue. In addition, malignant neoplasms, especially squamous cell carcinoma, should be considered in the differential diagnosis of persistent single gingival ulcers. (AU)

The lateral cervical stria approach to selective neck dissection: a preliminary study

Background: This study aims to propose a lateral cervical stria approach for selective neck dissection (SND) in patients of early-stage oral malignancies. Material and methods: The lateral cervical stria approach was used in 11 patients undergoing SND between December 2020 and March 2022. The surgical incision was located in submandibular cervical stria, with a length of 5.0 cm. The ipsilateral SND was performed according to the pathological type, covering part or all of I-V levels. Perioperative variables including operation time, blood loss, drainage volume, number of lymph node as well as complications were assessed. The score of appearance using the University of Washington Quality of Life Questionnaire (UW-QOL) was recorded 6-month postoperatively. Results: Direct closure of primary lesion was performed in ten patients and a forearm free flap reconstruction was used in one patient. No wound breakdown or infection was found in all cases. The mean operative time of SND was 157.63±27.39 min. The volume of intraoperative blood loss and postoperative drainage was 120.45±36.77 ml and 314.09±98.82 ml, respectively. The mean number of retrieved lymph nodes was 17.89±6.03 (ranging from 12 to 31). Postoperative complications included mild static lower lip deviation (n=1), shoulder discomfort (n=1) and mild auricular paraesthesia (n=1). The mean score of appearance was 86.36±13.06, with 100 scores in 5 patients and 75 scores in 6 patients. Conclusions: The lateral cervical stria approach for SND in early-stage oral malignancies is reliable, achieving to satisfactory functional and aesthetic outcomes. (AU)

CircZNF236 facilitates malignant progression in oral squamous cell carcinoma by sequestering miR-145-5p

Background A number of non-coding circular RNAs (circRNAs) have recently been implicated in the modulation of gene expression in cancer models. We therefore sought to explore if circZNF236 has a role in oral squamous cell carcinoma (OSCC). Methods We first examined circZNF236 expression in 32 pairs of OSCC and noncancerous tissues. We then investigated a functional role for circZNF236 using knockdown and overexpression approaches in OSCC cancer cell lines. Cell counting kit-8, wound healing, Transwell, and flow cytometry were employed to assess circZNF236 function in vitro. The association between circZNF236 and miR-145-5p, or that between miR-145-5p and malignant brain tumor domain containing 1 (MBTD1) was predicted by bioinformatics and demonstrated by dual-luciferase reporter assays, RNA pull-down assays as well as RNA immunoprecipitation (RIP) assays. A mouse OSCC xenograft model was employed to demonstrate the impacts of circZNF236 inhibition on tumor development in vivo. Results OSCC tissues and cells had higher levels of circZNF236 expression compared with normal controls. Furthermore, high circZNF236 levels in patients with OSCC correlated with a poor prognosis. CircZNF236 silencing decreased the malignant properties of OSCC cells and suppressed OSCC tumor formation in the mouse model. We then noticed that miR-145-5p can be regulated by circZNF236, and that circZNF2361 promoted OSCC development by absorbing miR-145-5p and consequently upregulating MBTD1 expression. Conclusion CircZNF236 modulates OSCC via the miR-145-5p/MBTD1 axis. These results support the potential of circZNF236 as a treatment target for OSCC (AU)

Histopathological parameters reported in microinvasive oral squamous cell carcinoma: a systematic review

Background: Microinvasive oral squamous cell carcinoma (OSCCmi) is an incipient stage of oral cancer. Through this systematic review, we aim to assess patterns of histopathological outcomes reported in OSCCmi cases. Material and methods: An online search in major databases was performed without period restriction, and 2,024 publications in English, Spanish and Portuguese were obtained. After screening and eligibility, 4 studies were selected. The risk of bias was assessed using Joanna Briggs Institute Critical Appraisal Checklist. A descriptive synthesis was conducted. Results: All 4 publications included were retrospective, reporting a total of 116 OSCCmi patients, with a male predominance (1.6:1) and a mean age of 55.9 years. The main parameters considered for microinvasion were tumor thickness (TT) (range 4-10mm) and depth of invasion (DOI) (range 0,02-5mm). Definition, cut-off values, and assessment of microscopic features were not standardized. Other relevant measures such as perineural or lymphovascular invasion and pattern of invasive front were barely described, and cytological/architectural characteristics were not discussed. Conclusions: TT and DOI are currently the primary histopathological criteria used to define OSCCmi. Nonetheless, the outcomes of this systematic review showed the absence of standardized quantitative parameters to render the diagnosis of microinvasive OSCC. Therefore, additional studies aiming to standardize histopathological features to diagnose OSCCmi are paramount. (AU)