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)

Oncologic Significance of Therapeutic Delays in Patients With Oral Cavity Cancer.

Importance: Oral cavity cancer often requires multidisciplinary management, subjecting patients to complex therapeutic trajectories. Prolonged treatment intervals in oral cavity cancer have been associated with poor oncological outcomes, but there has yet to be a study investigating treatment times in Canada. Objective: To report treatment delays for patients with oral cavity cancer in Canada and evaluate the outcomes of treatment delays on overall survival. Design, Setting, and Participants: This multicenter cohort study was performed at 8 Canadian academic centers from 2005 to 2019. Participants were patients with oral cavity cancer who underwent surgery and adjuvant radiation therapy. Analysis was performed in January 2023. Main Outcomes and Measures: Treatment intervals evaluated were surgery to initiation of postoperative radiation therapy interval (S-PORT) and radiation therapy interval (RTI). The exposure variables were prolonged intervals, respectively defined as index S-PORT greater than 42 days and RTI greater than 46 days. Patient demographics, Charlson Comorbidity Index, smoking status, alcohol status, and cancer staging were also considered. Univariate (log rank and Kaplan-Meier) and multivariate (Cox regression) analyses were performed to determine associations with overall survival (OS). Results: Overall, 1368 patients were included; median (IQR) age at diagnosis was 61 (54-70) years, and 896 (65%) were men. Median (IQR) S-PORT was 56 (46-68) days, with 1093 (80%) patients waiting greater than 42 days, and median (IQR) RTI was 43 (41-47) days, with 353 (26%) patients having treatment time interval greater than 46 days. There were variations in treatment time intervals between institutions for S-PORT (institution with longest vs shortest median S-PORT, 64 days vs 48 days; η2 = 0.023) and RTI (institution with longest vs shortest median RTI, 44 days vs 40 days; η2 = 0.022). Median follow-up was 34 months. The 3-year OS was 68%. In univariate analysis, patients with prolonged S-PORT had worse survival at 3 years (66% vs 77%; odds ratio 1.75; 95% CI, 1.27-2.42), whereas prolonged RTI (67% vs 69%; odds ratio 1.06; 95% CI, 0.81-1.38) was not associated with OS. Other factors associated with OS were age, Charlson Comorbidity Index, alcohol status, T category, N category, and institution. In the multivariate model, prolonged S-PORT remained independently associated with OS (hazard ratio, 1.39; 95% CI, 1.07-1.80). Conclusions and Relevance: In this multicenter cohort study of patients with oral cavity cancer requiring multimodal therapy, initiation of radiation therapy within 42 days from surgery was associated with improved survival. However, in Canada, only a minority completed S-PORT within the recommended time, whereas most had an appropriate RTI. An interinstitution variation existed in terms of treatment time intervals. Institutions should aim to identify reasons for delays in their respective centers, and efforts and resources should be directed toward achieving timely completion of S-PORT.

Spatial-temporal analysis of hospitalizations with death caused by oral cancer in Brazil and its correlation with the expansion of healthcare coverage

Background: Oral cancer (OC) is a growing public health problem worldwide. In Brazil, the National Oral Health Policy, implemented in 2004, expanded access to oral health services and prioritized OC care. However, it is not known whether this expansion resulted in a reduction in hospital admissions with death. This study aimed to analyze the proportion of hospital admissions who progressed to death due to OC in Brazil from 2007 to 2019 and its correlation with the coverage of health services. Material and Methods: This study is an ecological, longitudinal, and analytical study of hospital admissions with death due to OC recorded in the Brazilian Hospital Information System. The following analyses were performed: descriptive, spatial (choropleth maps and Moran index), and negative binomial regression, with a hierarchical approach, estimating crude and adjusted regression coefficients (β) and respective 95% confidence intervals (95% CI) (alpha=5%). Results: In 2019, Moran's index (I) of spatial autocorrelation showed a negative association between hospital admissions with death and dentist surgeon/inhabitant rate (I=-0.176), physician/inhabitant rate (I=-0.157), family health strategy (FHS) coverage (I=-0.080), oral health team (OHT) coverage (I= -0.129), dental specialty centers (DSC)/inhabitant rate (I= -0.200), and oncology bed/inhabitant rate (I= -0.101). In the adjusted regression analysis, the proportion of hospitalizations with deaths caused by OC was higher in Brazilian states with a lower medical ̸inhabitant ratio (β= -0.014; p=0.040), a lower dentists/inhabitant ratio (β= -0.720; p=0.045), a lower number of DSC (β= -0.004; p<0.000), a lower amount paid per hospitalization (β= -10.350; p<0.001), and a lower number of biopsies (β= -0.00008; p=0.010). The proportion of hospitalizations that progressed to death showed a positive association with the number of days of hospitalization (β= 0.00002; p=0.002). (AU)

Spatial-temporal analysis of hospitalizations with death caused by oral cancer in Brazil and its correlation with the expansion of healthcare coverage.

BACKGROUND: Oral cancer (OC) is a growing public health problem worldwide. In Brazil, the National Oral Health Policy, implemented in 2004, expanded access to oral health services and prioritized OC care. However, it is not known whether this expansion resulted in a reduction in hospital admissions with death. This study aimed to analyze the proportion of hospital admissions who progressed to death due to OC in Brazil from 2007 to 2019 and its correlation with the coverage of health services. MATERIAL AND METHODS: This study is an ecological, longitudinal, and analytical study of hospital admissions with death due to OC recorded in the Brazilian Hospital Information System. The following analyses were performed: descriptive, spatial (choropleth maps and Moran index), and negative binomial regression, with a hierarchical approach, estimating crude and adjusted regression coefficients (ß) and respective 95% confidence intervals (95% CI) (alpha=5%). RESULTS: In 2019, Moran's index (I) of spatial autocorrelation showed a negative association between hospital admissions with death and dentist surgeon/inhabitant rate (I=-0.176), physician/inhabitant rate (I=-0.157), family health strategy (FHS) coverage (I=-0.080), oral health team (OHT) coverage (I= -0.129), dental specialty centers (DSC)/inhabitant rate (I= -0.200), and oncology bed/inhabitant rate (I= -0.101). In the adjusted regression analysis, the proportion of hospitalizations with deaths caused by OC was higher in Brazilian states with a lower medical ̸inhabitant ratio (ß= -0.014; p=0.040), a lower dentists/inhabitant ratio (ß= -0.720; p=0.045), a lower number of DSC (ß= -0.004; p<0.000), a lower amount paid per hospitalization (ß= -10.350; p<0.001), and a lower number of biopsies (ß= -0.00008; p=0.010). The proportion of hospitalizations that progressed to death showed a positive association with the number of days of hospitalization (ß= 0.00002; p=0.002). CONCLUSIONS: Increased health care coverage has decreased serious hospital admissions with deaths caused by OC in Brazil.

Neck management of pathological N1 oral squamous cell carcinoma: a retrospective study.

This study was performed to compare the effects of neck dissection procedures on the prognosis of patients with pathological N1 (pN1) oral squamous cell carcinoma (OSCC), analyse factors affecting the prognosis, and provide a neck management strategy for clinical N1 (cN1) oral cancer. The study patients were divided into two groups according to the neck dissection: a selective neck dissection (SND) group (n = 85) and a radical or modified radical neck dissection (RND/MRND) group (n = 22). There was no statistically significant difference in recurrence rates at local, regional, and distant sites between the SND and RND/MRND groups. The 5-year overall survival was 68.3% for SND and 65.2% for RND/MRND patients (P = 0.590), while the 5-year disease-specific survival was 70.4% for SND and 75.7% for RND/MRND patients (P = 0.715). Histological grade and postoperative radiotherapy were independent predictors of the outcome for SND patients. For histological grade II/III cases, 5-year overall survival (P = 0.004) and disease-specific survival (P = 0.002) outcomes differed significantly between patients treated with and without postoperative radiotherapy, with worse survival for patients not treated with radiotherapy. Therefore, SND appears appropriate for cN1 OSCC patients, and postoperative radiotherapy is recommended for those with histological grade II or III tumours.

A Novel Autophagy-Related Prognostic Risk Model and a Nomogram for Survival Prediction of Oral Cancer Patients.

BACKGROUND: This study is aimed at constructing a risk signature to predict survival outcomes of ORCA patients. METHODS: We identified differentially expressed autophagy-related genes (DEARGs) based on the RNA sequencing data in the TCGA database; then, four independent survival-related ARGs were identified to construct an autophagy-associated signature for survival prediction of ORCA patients. The validity and robustness of the prognostic model were validated by clinicopathological data and survival data. Subsequently, four independent prognostic DEARGs that composed the model were evaluated individually. RESULTS: The expressions of 232 autophagy-related genes (ARGs) in 127 ORCA and 13 control tissues were compared, and 36 DEARGs were filtered out. We performed functional enrichment analysis and constructed protein-protein interaction network for 36 DEARGs. Univariate and multivariate Cox regression analyses were adopted for searching prognostic ARGs, and an autophagy-associated signature for ORCA patients was constructed. Eventually, 4 desirable independent survival-related ARGs (WDR45, MAPK9, VEGFA, and ATIC) were confirmed and comprised the prognostic model. We made use of multiple ways to verify the accuracy of the novel autophagy-related signature for survival evaluation, such as receiver-operator characteristic curve, Kaplan-Meier plotter, and clinicopathological correlational analyses. Four independent prognostic DEARGs that formed the model were also associated with the prognosis of ORCA patients. CONCLUSIONS: The autophagy-related risk model can evaluate OS for ORCA patients independently since it is accurate and stable. Four prognostic ARGs that composed the model can be studied deeply for target treatment.

The Benefit of Postoperative Radiotherapy and Extending Neck Dissection in pT1-2 Oral Squamous Cell Carcinoma With a Single Ipsilateral Cervical Lymph Node Metastasis (pN1).

BACKGROUND/AIM: We compared postoperative radiotherapy (PORT) to surgery only (SO), and supraomohyoidal neck dissection (SOHND) to modified radical neck dissection (MRND) in patients with pT1-T2 squamous cell carcinomas of the oral cavity (OSCC) and a single cervical lymph node metastasis (pN1) in terms of overall survival (OS), oral cancer specific survival (OCSS), and regional recurrence-free survival (RRFS), in a prospective cohort study. PATIENTS AND METHODS: We included patients with pT1-T2 pN1 OSCC with no distant metastasis and estimated the survival probabilities using the Kaplan-Meier method and calculated hazards ratios (HR) for PORT vs. SO and MRND vs. SOHND using adjusted Cox regression models. RESULTS: A total of 51 patients (26 SO vs. 25 PORT, 9 SOHND vs. 42 MRND) were evaluated. Patients who received PORT were more likely to be younger and healthier. OS at 5 years was 41% and 87% in the SO and PORT groups, respectively. OS at 5 years was 52% and 67% in the in the SOHND and MRND groups, respectively. Both OCSS and RRFS were improved by PORT. Extending neck dissection was not associated with improved OS (HR = 0.83). CONCLUSION: PORT is associated with preferable OS, OCSS, and RRFS in pT1-2 pN1 oral cancer and should be recommended regularly.

Prospective Phase II Open-Label Randomized Controlled Trial to Compare Mandibular Preservation in Upfront Surgery With Neoadjuvant Chemotherapy Followed by Surgery in Operable Oral Cavity Cancer.

PURPOSE: The objective of this study was to explore the potential role and safety of neoadjuvant chemotherapy (NACT) in tumor shrinkage and resultant mandibular preservation in oral cancers compared with conventional surgical treatment. METHODS: This study was a single-center, randomized, phase II trial of treatment-naive histologically confirmed squamous cell carcinoma of the oral cavity with cT2-T4 and N0/N+, M0 (American Joint Committee on Cancer, seventh edition) stage, necessitating resection of the mandible for paramandibular disease in the absence of clinicoradiologic evidence of bone erosion. The patients were randomly assigned (1:1) to either upfront surgery (segmental resection) followed by adjuvant treatment (standard arm [SA]) or two cycles of NACT (docetaxel, cisplatin, and fluorouracil) at 3-week intervals (intervention arm [IA]), followed by surgery dictated by postchemotherapy disease extent. All patients in the IA received adjuvant chemoradiotherapy, and patients in the SA were treated as per final histopathology report. The primary end point was mandible preservation rate. The secondary end points were disease-free survival and treatment-related toxicity. RESULTS: Sixty-eight patients were enrolled over 3 years and randomly assigned to either SA (34 patients) or IA (34 patients). The median follow-up was 3.6 years (interquartile range, 0.95-7.05 years). Mandibular preservation was achieved in 16 of 34 patients (47% [95% CI, 31.49 to 63.24]) in the IA. The disease-free survival (P = .715, hazard ratio 0.911 [95% CI, 0.516 to 1.607]) and overall survival (P = .747, hazard ratio 0.899 [95% CI, 0.510 to 1.587]) were similar in both the arms. Complications were similar in both arms, but chemotherapy-induced toxicity was observed in the majority of patients (grade III: 14, 41.2%; grade IV: 11, 32.4%) in the IA. CONCLUSION: NACT plays a potential role in mandibular preservation in oral cancers with acceptable toxicities and no compromise in survival. However, this needs to be validated in a larger phase III randomized trial.

Performance and survival outcomes of defect-driven versus specimen-driven method of frozen section intraoperative margin assessment in oral cancers.

Margin status is one of the most important prognostic factors in oral cancers. Intraoperative frozen section (FS) can be performed to ensure a margin-negative resection, however the method of FS assessment is debatable. The aim of this study was to compare the defect-driven (DDA) versus specimen-driven (SDA) approach for intraoperative assessment of tumour margins in oral cancer resections and their impact on loco-regional recurrence and survival. The primary study endpoint was margin status determined from the final histopathological examination report. Secondary endpoints were disease recurrence and survival. This retrospective cohort study compared the two methods of FS in terms of their performance and survival outcomes. All oral squamous cell carcinoma patients who underwent surgery as the primary treatment from January 2018 to February 2019 were included. The involved margin rate was slightly lower with SDA than DDA (7.5% vs 11.8%), however the difference was not statistically significant. The recurrence rate was higher with DDA (19/51, 37.2%) than SDA (14/53, 26.4%), although this was not statistically significant. Local recurrence-free survival (DDA 62% vs SDA 75%; P = 0.653) and overall survival (DDA 76% vs SDA 78%; P = 0.300) at 18 months of follow-up were comparable. There was no significant difference in sensitivity or specificity of intraoperative FS for margin assessment between SDA and DDA. The type of intraoperative FS technique used did not affect loco-regional recurrence or overall survival.

Tendência Temporal da Mortalidade por Câncer de Boca e da Cobertura de Atenção Primária no Estado do Rio de Janeiro / Temporal trend of Mortality by Oral Cancer and Coverage of Primary Attention in the State of Rio de Janeiro Tendencia / Temporal de la Mortalidad por Cáncer Bucal y la Cobertura de Atención Primaria de Salud en el Estado de Río de Janeiro

Introdução: O câncer de boca é comumente diagnosticado de forma tardia, comprometendo a qualidade de vida dos indivíduos ou os levando a óbito. Objetivo: Verificar a tendência temporal da mortalidade por câncer de boca no Estado do Rio de Janeiro e da cobertura da Estratégia Saúde da Família (ESF) e de equipes de saúde bucal (ESB). Método: Estudo ecológico com análise da tendência temporal da mortalidade por câncer de boca, entre 1999 e 2018, e da cobertura da ESF e ESB, no período de 2002 a 2018, no Estado e Regiões de Saúde. Utilizou-se a regressão linear generalizada de Prais-Winsten no cálculo das tendências para o Estado, cada Região de Saúde, sexo, faixa etária e localização do tumor. Resultados: Houve tendência de mortalidade por câncer de boca decrescente no Estado e nas Regiões Metropolitana I e II; nas demais Regiões de Saúde, foi estacionária. As tendências dos óbitos em homens, das faixas etárias 40 a 59 anos e 80 anos ou mais, foram decrescentes. Na localização do tumor, houve tendência decrescente entre óbitos por outras partes e partes não especificadas (C06) e uma tendência crescente na mortalidade por câncer de base de língua (C01). Na cobertura de ESF e ESB, na maioria das Regiões de Saúde e no Estado, a tendência foi crescente. Conclusão: A tendência decrescente na mortalidade por câncer de boca e a tendência crescente de ESF e ESB, no Estado do Rio de Janeiro, não foram observadas em todas as Regiões de Saúde

Introduction: Oral cancer is usually diagnosed late, compromising the individuals' quality of life or causing death. Objective: Check the time trend of mortality by oral cancer in the State of Rio de Janeiro and the coverage of the Family Health Strategy (FHS) and oral health teams (OHT). Method: Ecological study with analysis of the time trend of mortality by oral cancer, between 1999 to 2018 and the coverage of the FHS and OHT, in the period from 2002 to 2018, in the State and Health Regions. Generalized linear regression of Prais-Winsten to calculate trends for the state, each Health Region, sex, age group and tumor location was utilized. Results: Declining trends in mortality by oral cancer in the State and in the Metropolitan I and II Regions. In the other Health Regions, it was stationary. The trends of deaths in men, aged 40 to 59 years and 80 years or more were decreasing. In the location of the tumor, there was a decreasing trend among deaths in other and unspecified parts (C06) and a raising trend in mortality by cancer of the Tongue Base (C01). In the coverage of FHS and OHT in most Health Regions and in the State, the trend was rising. Conclusion: Declining trend in oral cancer mortality and the raising trend of FHS and OHT in the State of Rio de Janeiro was not observed for all Health Regions

Introducción: El cáncer de boca suele diagnosticarse de forma tardía, comprometiendo la calidad de vida de los individuos o llevándolos a la muerte. Objetivo: Verificar la tendencia temporal de mortalidad por cáncer bucal en el Estado de Río de Janeiro y la cobertura de la Estrategia de Salud de la Familia (ESF) y los equipos de salud bucal (ESB). Método: Estudio ecológico con análisis de la tendencia temporal de mortalidad por cáncer bucal, entre 1999 y 2018 y la cobertura de ESF y ESB, en el período de 2002 a 2018, en el Estado y Regiones de Salud. Regresión lineal generalizada de Prais-Winsten en el cálculo de tendencias para el Estado, cada región sanitaria, sexo, grupo de edad y ubicación del tumor. Resultados: Tendencia decreciente de la mortalidad por cáncer bucal en el Estado y Metropolitano I y II. En las demás Regiones Sanitarias, fue estacionario. Las tendencias de muertes en hombres, de 40 a 59 años y 80 años o más, estaban disminuyendo. En la localización del tumor, hubo una tendencia decreciente entre las muertes por otras partes y partes no especificadas (C06) y una tendencia creciente en la mortalidad por cáncer de Base de la Lengua (C01). En la cobertura de la ESF y ESB en la mayoría de Regiones Sanitarias y en el Estado, la tendencia fue en aumento. Conclusión: Tendencia decreciente de mortalidad por cáncer bucal y tendencia creciente de ESF y ESB en Estado de Río de Janeiro no se observó en todas Regiones Sanitarias

Tendências de Mortalidade por Câncer Bucal no Brasil por Regiões e Principais Fatores de Risco / Trends in Oral Cancer Mortality in Brazil by Region and main Risk Factors / Tendencias de la Mortalidad por Cáncer Bucal en Brasil por Región y Principales Factores de Riesgo

Introdução: O câncer bucal ainda é destacado como preocupante problema de saúde pública. Objetivo: Verificar a tendência de mortalidade por câncer bucal por Região brasileira e fatores de risco, avaliando o intervalo de tempo entre o diagnóstico e o tratamento. Método: Estudo com dados secundários do DATASUS (taxa de mortalidade e tempo para tratamento) e do Vigitel (consumo de álcool e cigarro); análises de séries temporais e correlações entre taxas de mortalidade (2010-2019) e consumo de álcool e cigarro (2010-2019), para idade superior a 40 anos, e análise descritiva do tempo entre diagnóstico e tratamento. Resultados: Houve aumento da tendência de câncer bucal por Regiões e sexo, com predominância para o sexo masculino. A variação percentual anual (VPA) da ingestão de álcool e o uso de cigarro foram considerados estacionários na maioria das Regiões analisadas. Ao correlacionar as variáveis, verificou-se correlação estatisticamente significativa entre taxa de mortalidade (2010-2019) e percentual de consumo de álcool (p=0,011; r=0,957), percentual de consumo de cigarro (p=0,019; r=0,936) e taxa bruta de mortalidade em homens (2019) (p=0,005; r=0,97). Verificou-se que, na maioria dos casos (74%), o tempo para início do tratamento é de mais de 60 dias. Conclusão: Embora o consumo de álcool e o tabagismo sejam fatores de risco para o câncer bucal, o presente estudo concluiu que houve aumento da mortalidade por câncer e os fatores de risco analisados permaneceram estacionários. O início de tratamento foi maior do que 60 dias a partir do diagnóstico. Palavras-chave: neoplasias bucais/mortalidade; tabagismo; consumo de bebida alcoólica; estudos de séries temporais; saúde pública

Introduction: Oral cancer still stands out as a concerning public health issue. Objective: Verify the trend of oral cancer mortality by Brazilian regions and risk factors, evaluating the time interval between diagnosis and treatment. Method: Study with secondary data from DATASUS (mortality rate and time to treatment) and Vigitel (alcohol and cigarette use). Time series analyzes and correlations were performed among mortality rates (2010-2019) and alcohol and cigarette use (2010-2019) for over 40 years of age. Descriptive analysis of the time between diagnosis and treatment was also performed. Results: There was an increase in the tendency to oral cancer by region and sex, with a predominance of males. The annual percentage change (APC) of alcohol intake and cigarette use was considered stationary in most regions analyzed. When correlating the variables, there was a statistically significant correlation for mortality rate (2010-2019) and percentage of alcohol use (p=0.011; r=0.957), percentage of cigarette use (p=0.019; r=0.936) and crude mortality rate in men (2019) (p=0.005; r=0.97). It was found that most cases (74%) take more than 60 days to start treatment. Conclusion: Although alcohol and tobacco use are risk factors for oral cancer, the present study showed an increase in cancer mortality and stationary for the risk factors analyzed. The beginning of the treatment was over 60 days after diagnosis

Introducción: El cáncer oral todavía se destaca como un problema de salud pública preocupante. Objetivo: Verificar la tendencia de la mortalidad por cáncer bucal por región brasileña y factores de riesgo, evaluando el intervalo de tiempo entre el diagnóstico y el tratamiento. Método: Estudio con datos secundarios de DATASUS (tasa de mortalidad y tiempo de tratamiento) y Vigitel (consumo de alcohol y cigarrillos). Se realizaron análisis de series de tiempo y correlaciones entre las tasas de mortalidad (2010-2019) y el consumo de alcohol y cigarrillos (2010-2019) para los mayores de 40 años. También se realizó un análisis descriptivo del tiempo transcurrido entre el diagnóstico y el tratamiento. Resultados: Hubo un incremento en la tendencia al cáncer bucal por región y sexo, con predominio del sexo masculino. El cambio porcentual anual (APV) de la ingesta de alcohol y el consumo de cigarrillos se consideró estacionario en la mayoría de las regiones analizadas. Al correlacionar las variables, hubo una correlación estadísticamente significativa para tasa de mortalidad en hombres (2010- 2019) y porcentaje de consumo de alcohol para hombres (p=0,011; r=0,957), porcentaje de consumo de cigarrillos en hombres (p=0,019; r=0,936) y tasa bruta de mortalidad en hombres (2019) (p=0,005; r=0,97). Se encontró que la mayoría de los casos (74%) demoran más de 60 días en comenzar el tratamiento. Conclusión: Aunque el consumo de alcohol y el tabaquismo son factores de riesgo para el cáncer oral, el presente estudio mostró un aumento en la mortalidad por cáncer y estacionario para los factores de riesgo analizados. Hubo un alto porcentaje de inicio del tratamiento durante 60 días después del diagnóstico

Tendência Temporal e Distribuição Espacial da Mortalidade por Câncer de Boca em Sergipe / Temporal Trend and Spatial Distribution of Oral Cancer Mortality in Sergipee / Tendencia Temporal y Distribución Espacial de la Mortalidad por Cáncer de Boca en Sergip

Introdução: Anualmente, no Brasil, 15 mil pessoas são diagnosticadas com câncer de boca, e quase metade delas morre. Sergipe está entre os sete Estados brasileiros com maiores índices. Objetivo: Analisar a tendência temporal e a distribuição espacial da mortalidade por câncer de boca em Sergipe entre 2007 e 2016. Método: Estudo ecológico de série temporal de base populacional, utilizando técnicas de análise espacial. Os dados de mortalidade foram obtidos no Sistema de Informação sobre Mortalidade (SIM). A análise das tendências temporais foi realizada no modelo de regressão de Joinpoint por meio da regressão de Poisson. Foram realizadas análises espaciais utilizando o estimador de intensidade Kernel e os índices de Moran Global e Local. Resultados: Foram analisadas 543 mortes por câncer de boca. Os casos mais frequentes ocorreram em homens (74%), com idade média de 64 anos e baixa escolaridade. As taxas de mortalidade global (variação percentual anual ‒ APC=2,5; IC 95% 0,9-6,7) e masculina (APC=2,96; IC 95% 1,2-5,6) aumentaram. Houve também uma tendência crescente de mortalidade por câncer na língua (APC=10,05; IC 95% 3,8-16,7). A mortalidade relacionada a outras localizações anatômicas foi estável. Houve concentração de óbitos nas Regiões Metropolitana, Centro-Sul e Centro-Agreste. Conclusão: Durante o período analisado, a taxa de mortalidade geral mostrou uma tendência crescente, com concentração nas Regiões Centro-Sul, Central e Metropolitana, sendo necessário manter medidas de prevenção e controle contra o câncer de boca em todo o Estado de Sergipe

Introduction: Annually, in Brazil, 15 thousand individuals are diagnosed with oral cancer and almost half of them die. Sergipe is among the seven Brazilian states with the highest rates. Objective: To analyze the temporal trend and the spatial distribution of oral cancer mortality in Sergipe between 2007 and 2016. Method: Population-based time series ecological study, using techniques of spatial analysis. Mortality data were obtained from the Mortality Information System (SIM). The analysis of temporal trends was performed with the Joinpoint regression model using Poisson regression. Spatial analyzes were carried out using the Kernel intensity estimator and the Moran Global and Local indexes. Results: 543 oral cancer deaths were analyzed. The most frequent cases were in men (74%), with an average age of 64 years and low education. The overall and male's mortality rates (annual percent change ‒ APC=2.5; 95% CI 0.9-6.7 and APC=2.96; 95% CI 1.2- 5.6), respectively, increased. There was also an increasing trend of mortality by tongue cancer (APC=10.05; 95% CI 3.8-16.7). Mortality related to other anatomical locations was stable. There was a concentration of deaths in the Metropolitan, Midsouth and Mid-rural regions. Conclusion: During the period investigated, the general mortality rate showed an increasing trend, with concentration in the Midsouth, Mid and Metropolitan regions, and it is necessary to maintain preventive and control measures against oral cancer throughout the State of Sergipe

Introducción: Cada año en Brasil, 15.000 personas son diagnosticadas con cáncer de boca y casi la mitad de ellas mueren. Sergipe es uno de los siete Estados brasileños con las tasas más altas. Objetivo: Analizar la tendencia temporal y la distribución espacial de la mortalidad por cáncer de boca en Sergipe entre 2007 y 2016. Método: Estudio ecológico de series temporales basadas en la población, utilizando técnicas de análisis espacial. Los datos de mortalidad se obtuvieron del Sistema de Información sobre Mortalidad (SIM). Poisson realizó el análisis de las tendencias de tiempo en el modelo de regresión de Punto de unión. Fueron realizadas análisis espaciales utilizando el estimador de intensidad del Kernel y los índices Moran Global y Local. Resultados: Se analizaron un total de 543 muertes por cáncer de boca. Los casos más frecuentes se dieron en hombres (74%), con una edad media de 64 años y baja escolaridad. Aumentaron las tasas de mortalidad global (porcentual cambio anual ‒ PCA=2,5; IC 0,9-6,7) y masculinas (PCA=2,96; IC 95% 1,2-5,6). También hubo una tendencia creciente de mortalidad por cáncer en la lengua (PCA=10,05; IC 95% 3,8-16,7). La mortalidad relacionada con otros lugares anatómicos fue estable. Hubo una concentración de muertes en las regiones Metropolitana, Central-Sur y Centro-Agreste. Conclusión: Durante el período analizado, la tasa general de mortalidad mostró una tendencia creciente, con concentración en las Regiones Centro-Sur, Centro y Metropolitano, y es necesario mantener medidas de prevención y control contra el cáncer de boca en todo el Estado de Sergipe

The prognostic and clinical significance of IFI44L aberrant downregulation in patients with oral squamous cell carcinoma.

BACKGROUND: It is a basic task in high-throughput gene expression profiling studies to identify differentially expressed genes (DEGs) between two phenotypes. RankComp, an algorithm, could analyze the highly stable within-sample relative expression orderings (REOs) of gene pairs in a particular type of human normal tissue that are widely reversed in the cancer condition, thereby detecting DEGs for individual disease samples measured by a particular platform. METHODS: In the present study, Gene Expression Omnibus (GEO) Series (GSE) GSE75540, GSE138206 were downloaded from GEO, by analyzing DEGs in oral squamous cell carcinoma based on online datasets using the RankComp algorithm, using the Kaplan-Meier survival analysis and Cox regression analysis to survival analysis, Gene Set Enrichment Analysis (GSEA) to explore the potential molecular mechanisms underlying. RESULTS: We identified 6 reverse gene pairs with stable REOs. All the 12 genes in these 6 reverse gene pairs have been reported to be associated with cancers. Notably, lower Interferon Induced Protein 44 Like (IFI44L) expression was associated with poorer overall survival (OS) and Disease-free survival (DFS) in oral squamous cell carcinoma patients, and IFI44L expression showed satisfactory predictive efficiency by receiver operating characteristic (ROC) curve. Moreover, low IFI44L expression was identified as risk factors for oral squamous cell carcinoma patients' OS. IFI44L downregulation would lead to the activation of the FRS-mediated FGFR1, FGFR3, and downstream signaling pathways, and might play a role in the PI3K-FGFR cascades. CONCLUSIONS: Collectively, we identified 6 reverse gene pairs with stable REOs in oral squamous cell carcinoma, which might serve as gene signatures playing a role in the diagnosis in oral squamous cell carcinoma. Moreover, high expression of IFI44L, one of the DEGs in the 6 reverse gene pairs, might be associated with favorable prognosis in oral squamous cell carcinoma patients and serve as a tumor suppressor by acting on the FRS-mediated FGFR signaling.

The Predictive Model of Oral Squamous Cell Survival Carcinoma: A Methodology of Validation.

BACKGROUND: Cancer is primarily caused by smoking, alcohol, betel quit, a series of genetic alterations, and epigenetic abnormalities in signaling pathways, which result in a variety of phenotypes that favor the development of OSCC. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, accounting for 80-90% of all oral malignant neoplasms. Oral cancer is relatively common, and it is frequently curable when detected and treated early enough. The tumor-node-metastasis (TNM) staging system is used to determine patient prognosis; however, geographical inaccuracies frequently occur, affecting management. OBJECTIVE: To determine the additional relationship between factors discovered by searching for sociodemographic and metastasis factors, as well as treatment outcomes, which could help improve the prediction of the survival rate in cancer patients. Material and Methods. A total of 56 patients were recruited from the ambulatory clinic at the Hospital Universiti Sains Malaysia (USM). In this retrospective study, advanced computational statistical modeling techniques were used to evaluate data descriptions of several variables such as treatment, age, and distant metastasis. The R-Studio software and syntax were used to implement and test the hazard ratio. The statistics for each sample were calculated using a combination model that included methods such as bootstrap and multiple linear regression (MLR). RESULTS: The statistical strategy showed R demonstrates that regression modeling outperforms an R-squared. It demonstrated that when data is partitioned into a training and testing dataset, the hybrid model technique performs better at predicting the outcome. The variable validation was determined using the well-established bootstrap-integrated MLR technique. In this case, three variables are considered: age, treatment, and distant metastases. It is important to note that three things affect the hazard ratio: age (ß 1: -0.006423; p < 2e - 16), treatment (ß 2: -0.355389; p < 2e - 16), and distant metastasis (ß 3: -0.355389; p < 2e - 16). There is a 0.003469102 MSE for the linear model in this scenario. CONCLUSION: In this study, a hybrid approach combining bootstrapping and multiple linear regression will be developed and extensively tested. The R syntax for this methodology was designed to ensure that the researcher completely understood the illustration. In this case, a hybrid model demonstrates how this critical conclusion enables us to better understand the utility and relative contribution of the hybrid method to the outcome. The statistical technique used in this study, R, demonstrates that regression modeling outperforms R-squared values of 0.9014 and 0.00882 for the predicted mean squared error, respectively. The conclusion of the study establishes the superiority of the hybrid model technique used in the study.

Elective neck dissection improves the survival of patients with T2N0M0 oral squamous cell carcinoma: a study of the SEER database.

BACKGROUND: Treatment of clinical N0 neck tumours is controversial in early-stage oral squamous cell carcinoma (OSCC), possibly because T1N0M0 and T2N0M0 merge together at early stages. The purposes of this study were to compare survival outcomes only for T2N0M0 cases based upon treatment elective neck dissection versus neck observation. METHODS: T2N0M0 OSCC cases were identified in the Surveillance, Epidemiology, and End Results database of the United States National Cancer Institute between 2004 and 2015. Survival curves for different variable values were generated using Kaplan-Meier estimates and compared using the log-rank test. Variables that achieved significance at P < 0.05 were entered into multivariable analyses via the Cox proportional hazards multivariate regression. RESULTS: A total of 2857 patients were selected, and 2313 cases were available for disease specific survival (DSS). The 5-year and 10-year overall survival (OS) were 66.7 and 46% for patients receiving elective neck dissection (END), respectively, and 56.4 and 37.2% for patients with neck observation (P < 0.0001). The 5-year and 10-year DSS were 73.6 and 64% for the END group, respectively, versus 64.5 and 54.5% for the neck observation group (P < 0.0001). More importantly, performing END was independently associated with favourable DSS and OS for patients with T2N0M0 OSCC [hazard ratio (HR) = 0.769, P = 0.0069 for DSS; HR = 0.829, P = 0.0031 for OS, neck observation group as reference] according to multivariate survival analysis. CONCLUSION: END is recommended for T2N0M0 OSCC cases and it is associated with improved DSS and OS.

SHH Expression Is Significantly Associated With Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a highly invasive malignancy with poor prognosis. Recent reports suggest that Sonic Hedgehog (SHH) plays a key role in tumor progression and worsens the response to therapy, possibly through an association with a cancer stem cell (CSC) phenotype. The objective of our study was to investigate the relationship between SHH expression and CSC markers in OSCC. MATERIALS AND METHODS: A total of 67 OSCC specimens were immunostained for SHH and CSC markers using specific antibodies and expression was correlated with clinicopathological parameters. RESULTS: SHH expression was significantly correlated with CD133 (p=0.026, r=0.272) and SRY-box transcription factor 2 (SOX2; p<0.001, r=0.793). SHH and SOX2 expression were associated with worse survival in OSCC (p=0.003 and p=0.003, respectively). In multivariate analysis SHH and CD44 were independent prognostic biomarkers in patients with OSCC (p=0.001 and p=0.008, respectively). CONCLUSION: Our study revealed that SHH overexpression is closely associated with CSC markers, contributing to tumor progression and worse outcomes of patients with OSCC.

Multicenter Retrospective Study of Weekly Cetuximab Plus Paclitaxel for Recurrent or Metastatic Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: This study was conducted to compare the efficacy and safety of the weekly cetuximab plus paclitaxel (wCmab-PTX) regimen with those of the EXTREME regimen in patients with recurrent or metastatic oral squamous cell carcinoma (R/M OSCC). PATIENTS AND METHODS: This multicenter retrospective study involved a chart review of the clinical records of R/M OSCC patients treated with wCmab-PTX in each institution between January 2013 and December 2017. Data were collected, and the efficacy, safety, and treatment outcomes were analyzed. RESULTS: The best overall response and disease control rates were 48.4% and 61.3%, respectively. The median PFS and OS were 6 and 13 months, respectively. There was no significant difference in prognosis with or without previous platinum administration. The grade 3-4 adverse events were leukopenia (16.1%), followed by acne-like rash (12.9%), and neutropenia (9.7%). All adverse events, excluding more than grade 3 infusion reactions, were tolerable and manageable. CONCLUSION: wCmab-PTX may be considered as a treatment option for R/M patients with OSCC that is refractory to platinum-based chemotherapy, or progressive disease after receiving chemotherapy.

Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OCSCC) is a prevalent surgically treated subset of head and neck cancer with frequent recurrence and poor survival. Immunotherapy has demonstrated efficacy in recurrent/metastatic head and neck cancer. However, whether antitumor responses could be fostered by neoadjuvant presurgical immunotherapy remains unclear. Using a Simon's two-stage design, we present results of a single-arm phase-II trial where 12 patients with stage II-IVA OCSCC received 3 to 4 biweekly doses of 3 mg/kg nivolumab followed by definitive surgical resection with curative intent. Presurgical nivolumab therapy in this cohort shows an overall response rate of 33% (n = 4 patients; 95% CI: 12%-53%). With a median follow up of 2.23 years, 10 out of 12 treated patients remain alive. Neoadjuvant nivolumab is safe, well-tolerated, and is not associated with delays in definitive surgical treatment in this study. This work demonstrates feasibility and safety for incorporation of nivolumab in the neoadjuvant setting for OCSCC (ClinicalTrials.gov: NCT03021993).

Estimating LOCP cancer mortality rates in small domains in Spain using its relationship with lung cancer.

The distribution of lip, oral cavity, and pharynx (LOCP) cancer mortality rates in small domains (defined as the combination of province, age group, and gender) remains unknown in Spain. As many of the LOCP risk factors are preventable, specific prevention programmes could be implemented but this requires a clear specification of the target population. This paper provides an in-depth description of LOCP mortality rates by province, age group and gender, giving a complete overview of the disease. This study also presents a methodological challenge. As the number of LOCP cancer cases in small domains (province, age groups and gender) is scarce, univariate spatial models do not provide reliable results or are even impossible to fit. In view of the close link between LOCP and lung cancer, we consider analyzing them jointly by using shared component models. These models allow information-borrowing among diseases, ultimately providing the analysis of cancer sites with few cases at a very disaggregated level. Results show that males have higher mortality rates than females and these rates increase with age. Regions located in the north of Spain show the highest LOCP cancer mortality rates.

Perineural invasion/lymphovascular invasion double positive predicts distant metastasis and poor survival in T3-4 oral squamous cell carcinoma.

Postoperative adjuvant therapy has been indicated by advanced T classification for T3-4 oral squamous cell carcinoma (OSCC) and the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) in treatment for T3-4 OSCC remains unclear. Ninety-eight cumulative patients with T3-4 OSCC who underwent curative surgery between Jan 2002 and Dec 2010 were recruited and analyzed. Twenty-seven (27.6%) patients were PNI/LVI double positive. PNI/LVI double positive demonstrated independent predictive values for higher neck metastasis (LN+), higher distant metastasis (DM) and low 5-year disease-specific survival (DSS) rates (p < 0.001, p = 0.017, and p < 0.001, respectively) after controlling for other pathologic features of the primary tumors. A high DM rate of 33.3% was noted in PNI/LVI double-positive patients. Among the PNI/LVI double negative, single positive to double positive subgroups, increasing LN+, DM rates and decreasing DSS rate were observed. Among the 44 LN+ patients, PNI/LVI double positive remained associated with a markedly high DM rate of 42.9% and a poor 5-year DSS of 27.7%. PNI/LVI double positive plays important roles in prognostication and potential clinical application for T3-4 OSCC by independently predicting LN+, DM, and poor DSS, and can be used as a good marker to select DM high-risk patients for novel adjuvant therapy trials.