Barriers to early diagnosis and management of oral cancer in Latin America and the Caribbean.

OBJECTIVE: This study aimed to explore perceived barriers to early diagnosis and management of oral cancer, as well as potential pathways for improvement in Latin America and the Caribbean (LAC). METHODS: This cross-sectional study used a self-administered online questionnaire created via the Research Electronic Data Capture platform. The survey was distributed to health professionals trained in Oral Medicine, Oral Pathology, Oral and Maxillofacial Surgery, and Dentists with clinical and academic expertise in oral potentially malignant disorder (OPMD) and oral cancer. Data obtained were systematically organized and analyzed descriptively using Microsoft Excel. RESULTS: Twenty-three professionals from 21 LAC countries participated. Major barriers included the limited implementation of OPMD and oral cancer control plans (17.4%), low compulsory reporting for OPMD (8.7%) and oral cancer (34.8%), unclear referral pathways for OPMD (34.8%) and oral cancer (43.5%), and a shortage of trained professionals (8.7%). Participants endorsed the utility of online education (100%) and telemedicine (91.3%). CONCLUSION: The survey highlights major perceived barriers to early diagnosis and management of OPMD and oral cancer in LAC, as well as potential avenues for improvement.

The role of occupation in SARS-CoV-2 infection within a Brazilian municipality: A test-negative case-control study.

OBJECTIVE: To investigate the association between occupation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections within a Brazilian municipality. METHODS: In this test-negative study, cases and controls were randomly selected among individuals aged 18-65 years that were registered in a primary health care program in São Caetano do Sul, Brazil. Those who had collected samples for RT-PCR testing between April 2020 and May 2021 were randomly selected to compose the case (positive for SARS-CoV-2) and control (negative for SARS-CoV-2) groups, frequency-matched by sex, age group, and month of sample collection. Complementary data were collected through phone interviews. We estimated the residual effect of occupation on SARS-CoV-2 infection using multiple conditional logistic regression models incrementally adjusted for confounding variables. RESULTS: 1724 cases and 1741 controls who reported being at work at the time of RT-PCR collection were included. Cases were mainly females (52.9%), Whites/Asians (73.3%), and unvaccinated against COVID-19 (46.6%). Compared to other university-level professionals, the highest odds of having COVID-19 were found for workers in police and protective services (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.27-3.84), healthcare and caregiving (OR 1.90; 95% CI 1.34-2.68), and food retail and production (OR 1.88; 95% CI = 1.14-3.11), after adjustment for age, sex, education, means of transport, household crowding, and COVID-19 vaccination. CONCLUSION: Occupation played an important role in SARS-CoV-2 infection. Food retail and production, health care and caregiving, and police and protective services showed the highest odds of SARS-CoV-2 infection.

Spatial Clusters of Cancer Mortality in Brazil: A Machine Learning Modeling Approach.

Objectives: Our aim was to test if machine learning algorithms can predict cancer mortality (CM) at an ecological level and use these results to identify statistically significant spatial clusters of excess cancer mortality (eCM). Methods: Age-standardized CM was extracted from the official databases of Brazil. Predictive features included sociodemographic and health coverage variables. Machine learning algorithms were selected and trained with 70% of the data, and the performance was tested with the remaining 30%. Clusters of eCM were identified using SatScan. Additionally, separate analyses were performed for the 10 most frequent cancer types. Results: The gradient boosting trees algorithm presented the highest coefficient of determination (R 2 = 0.66). For total cancer, all algorithms overlapped in the region of Bagé (27% eCM). For esophageal cancer, all algorithms overlapped in west Rio Grande do Sul (48%-96% eCM). The most significant cluster for stomach cancer was in Macapá (82% eCM). The most important variables were the percentage of the white population and residents with computers. Conclusion: We found consistent and well-defined geographic regions in Brazil with significantly higher than expected cancer mortality.

Survival inequalities in head and neck cancers: A hospital-based cohort study.

BACKGROUND: We investigated whether the socioeconomic status (SES) influenced survival rates in oropharynx cancers (OPC), oral cavity cancers (OCC), and larynx cancers (LC) in Brazilian patients. METHODS: This hospital-based cohort study assessed the age-standardized 5-year relative survival (RS) using the Pohar Perme estimator. RESULTS: Overall, we identified 37 191 cases, and 5-year RS were 24.4%, 34.1%, and 44.9% in OPC, OCC, and LC, respectively. In multiple Cox regression, the highest risk of death occurred in the most vulnerable social strata for all subsites-that is, illiterates or patients relying on publicly funded healthcare services. Disparities increased over time by 34.9% in OPC due to the rising of survival rates in the highest SES, whereas they reduced by 10.2% and 29.6% in OCC and LC. CONCLUSIONS: The potential inequities were more significant for OPC than for OCC and LC. It is urgent to tackle social disparities to improve prognoses in highly unequal countries.

Covid-19 hospital mortality using spatial hierarchical models: cohort design with 74,994 registers.

OBJECTIVE: To investigate the relationship between covid-19 hospital mortality and risk factors, innovating by considering contextual and individual factors and spatial dependency and using data from the city of São Paulo, Brazil. METHODS: The study was performed with a spatial hierarchical retrospective cohort design using secondary data (individuals and contextual data) from hospitalized patients and their geographic unit residences. The study period corresponded to the first year of the pandemic, from February 25, 2020 to February 24, 2021. Mortality was modeled with the Bayesian context, Bernoulli probability distribution, and the integrated nested Laplace approximations. The demographic, distal, medial, and proximal covariates were considered. RESULTS: We found that per capita income, a contextual covariate, was a protective factor (odds ratio: 0.76 [95% credible interval: 0.74-0.78]). After adjusting for income, the other adjustments revealed no differences in spatial dependence. Without income inequality in São Paulo, the spatial risk of death would be close to one in the city. Other factors associated with high covid-19 hospital mortality were male sex, advanced age, comorbidities, ventilation, treatment in public healthcare settings, and experiencing the first covid-19 symptoms between January 24 and February 24, 2021. CONCLUSIONS: Other than sex and age differences, geographic income inequality was the main factor responsible for the spatial differences in the risk of covid-19 hospital mortality. Investing in public policies to reduce socioeconomic inequities, infection prevention, and other intersectoral measures should focus on lower per capita income, to control covid-19 hospital mortality.

Cumulative Coffee Consumption as a Protective Factor for Head and Neck Cancer in Brazil.

There is still no consensus in the literature regarding the role of coffee in head and neck cancer. Thus, we sought to analyze the cumulative consumption of coffee as a protective factor in the genesis of head and neck cancer in Brazil, one of the main coffee producing countries, from January 2011 to February 2017. We carried out a case-control study in 5 referral centers for head and neck cancer with 839 cases and 842 non-cancer hospital controls matched by sex, data collection center and age group. The results of logistic regression analysis showed that the cumulative consumption of >2 cups of coffee per day is an important protective factor (OR: 0.73, 95% CI: 0.5-0.9) against head and neck cancer. Smoking increased the risk by 22 times (OR: 22.19; 95% CI: 13.7-35.8) in individuals who smoke more than 50 packs per year, and the habit of ingesting more than 155 ml of alcohol per day represented approximately twice as high risk (OR: 2.20; 95% CI: 1.4-3.4). In summary, this study suggests that coffee consumption is associated with a lower chance of head and neck cancer.

Covid-19 hospital mortality using spatial hierarchical models: cohort design with 74, 994 registers

ABSTRACT OBJECTIVE To investigate the relationship between covid-19 hospital mortality and risk factors, innovating by considering contextual and individual factors and spatial dependency and using data from the city of São Paulo, Brazil. METHODS The study was performed with a spatial hierarchical retrospective cohort design using secondary data (individuals and contextual data) from hospitalized patients and their geographic unit residences. The study period corresponded to the first year of the pandemic, from February 25, 2020 to February 24, 2021. Mortality was modeled with the Bayesian context, Bernoulli probability distribution, and the integrated nested Laplace approximations. The demographic, distal, medial, and proximal covariates were considered. RESULTS We found that per capita income, a contextual covariate, was a protective factor (odds ratio: 0.76 [95% credible interval: 0.74-0.78]). After adjusting for income, the other adjustments revealed no differences in spatial dependence. Without income inequality in São Paulo, the spatial risk of death would be close to one in the city. Other factors associated with high covid-19 hospital mortality were male sex, advanced age, comorbidities, ventilation, treatment in public healthcare settings, and experiencing the first covid-19 symptoms between January 24 and February 24, 2021. CONCLUSIONS Other than sex and age differences, geographic income inequality was the main factor responsible for the spatial differences in the risk of covid-19 hospital mortality. Investing in public policies to reduce socioeconomic inequities, infection prevention, and other intersectoral measures should focus on lower per capita income, to control covid-19 hospital mortality.

Socio-demographic profiles and obstetrics outcomes of pregnant women with epilepsy in a vulnerability State, Brazil.

INTRODUCTION: The socio-demographic profile of pregnant women in low- and middle- income countries is characterized by low educational attainment and unemployment, leading to social and economic morbidity. characterized by limited opportunities for education, employment, and marriage, which are strongly related to the stigmatization of the disease. The study of the socio- profile and obstetric outcomes of pregnant women with epilepsy in Alagoas, Brazil, may help understand this scenario and facilitate the development of public policy strategies to reduce local morbidity. OBJECTIVES: We aimed to describe the sociodemographic profile of pregnant women with epilepsy and obstetric outcomes in Alagoas, Brazil. METHODS: This cohort study was based on medical records of pregnant women with epilepsy in Brazilian high-risk maternity hospitals from 2008 to 2020. The following data were collected: age, race, education, marital status, occupation, number of pregnancies, delivery, and abortion. The inclusion criteria were pregnant women with and without epilepsy (control group) aged < 40 years. RESULTS: The prevalence of PWWE was 0.49% (n = 224/44,917). Cesarean delivery was more frequent in PWWE than in pregnant women without epilepsy (adjusted odds ratio [OR] = 22.0; 95% confidence interval [CI] = 14.35-33.73; p<0,01). Abortion was associated with PWWE (OR adjusted = 1.72; 95% CI = 1.13-2.61; p = 0.01). Pregnant women in the countryside were more likely to develop epilepsy than those born in the capital (OR = 1.55; 95% CI = 1.12-2.14; p <0.01). CONCLUSION: The PWWE socio-demographic profile of the Alagoas had a predominance of brown- colored skin, single status, homemakers, and illiteracy with a high proportion residing in the interior of the state. The obstetrics data show a higher incidence of cesarean deliveries and miscarriages.

Examining socio-economic factors to understand the hospital case fatality rates of COVID-19 in the city of São Paulo, Brazil.

BACKGROUND: Understanding differences in hospital case fatality rates (HCFRs) of coronavirus disease 2019 (COVID-19) may help evaluate its severity and the capacity of the healthcare system to reduce mortality. METHODS: We examined the variability in HCFRs of COVID-19 in relation to spatial inequalities in socio-economic factors, hospital health sector and patient medical condition across the city of São Paulo, Brazil. We obtained the standardized hospital case fatality ratio adjusted indirectly by age and sex, which is the ratio between the HCFR of a specific spatial unit and the HCFR for the entire study area. We modelled it using a generalized linear mixed model with spatial random effects in a Bayesian context. RESULTS: We found that HCFRs were higher for men and for individuals ≥60 y of age. Our models identified per capita income as a significant factor that is negatively associated with the HCFRs of COVID-19, even after adjusting for age, sex and presence of risk factors. CONCLUSIONS: Spatial analyses of the implementation of these methods and of disparities in COVID-19 outcomes may help in the development of policies for at-risk populations in geographically defined areas.

Agreement and validity of asbestos-related cancers in the hospital information system of the Brazilian Unified Health System. / Concordância e validade dos diagnósticos de cânceres associados ao asbesto no sistema de informação hospitalar do Sistema Único de Saúde.

OBJECTIVE: To estimate the degree of agreement and validity of diagnoses of asbestos-related malignant neoplasms registered in the Hospital Information System of the Brazilian Unified Health System (SIH/SUS), in comparison to the Hospital Cancer Registries of the State of São Paulo (HCR/SP). METHODS: Deaths with records of malignant neoplasms associated with asbestos were identified and extracted from SIH/SUS between 2007 and 2014. Deaths in cases registered in the HCR/SP were extracted for the same period. The databases were linked using software Link Plus. A single ICD-10-coded diagnosis selected from each system was analyzed. The proportion of agreement, and the sensitivity, specificity and predictive values were estimated. RESULTS: 19,458 pairs were found with records in both bases. The proportion of agreement was high, ranging from 92.4% for the unknown primary site, to 99.7% for cancer of the pleura. The Kappa Index ranged from 0.05 (95%CI 0.04 - 0.07) for cancer of the pleura to 0.85 (95%CI 0.84 - 0.87) for lung cancer. Sensitivity varied from 0.08 (95%CI 0.01 - 0.25) for cancer of the pleura, to 0.90 (95%CI 0.90 - 0.91) for lung cancer. CONCLUSION: Diagnosis of asbestos-related malignancies reached higher levels of agreement and validity when common. Rare diagnoses showed low accuracy in SIH/SUS.

OBJETIVO: Estimar o grau de concordância e validade dos diagnósticos de neoplasias malignas relacionadas à exposição ao asbesto registrados no Sistema de Informação Hospitalar do Sistema Único de Saúde (SIH/SUS), em comparação aos Registros Hospitalares de Câncer do Estado de São Paulo (RHC/SP). MÉTODOS: Óbitos com registros de neoplasias malignas associadas ao asbesto foram identificados e extraídos do SIH/SUS entre 2007 e 2014. Óbitos nos casos de câncer registrados na base do RHC/SP foram extraídos para o mesmo período. Essas bases foram unidas pelos mesmos indivíduos empregando-se o software Link Plus. Um único diagnóstico codificado pela CID-O3 ou CID-10 selecionado de cada sistema foi analisado. A proporção de concordância e a sensibilidade, especificidade e valores preditivos foram estimados. RESULTADOS: Encontraram-se 19.458 pares com registros nas duas bases. A proporção de concordância foi elevada, variando de 92,4% para a localização primária desconhecida a 99,7% para o câncer de pleura. O índice Kappa variou de 0,05 (IC95% 0,04 - 0,07) para o câncer de pleura a 0,85 (IC95% 0,84 - 0,87) para o câncer de pulmão. A menor sensibilidade foi de 0,08 (IC95% 0,01 - 0,25), para o câncer de pleura, e a maior de 0,90 (IC95% 0,90 - 0,91), para o câncer de pulmão. CONCLUSÃO: Diagnósticos de neoplasias malignas associadas ao asbesto alcançaram maiores níveis de concordância e validade quando comuns. Os diagnósticos mais raros apresentaram baixa acurácia no SIH/SUS.

The role of metformin on lung cancer survival: the first systematic review and meta-analysis of observational studies and randomized clinical trials.

PURPOSE: To assess the effects of metformin use on lung cancer (LC) survival according to summarized results from observational studies (OBs) and randomized clinical trials (RCTs). METHODS: We systematically searched electronic databases and, to our knowledge, for the first time, RCTs were included in a systematic review and meta-analysis about the role of metformin on LC survival. We carried out meta-analyses separately for OBs and RCTs. Analyses for overall survival (OS) concerning OBs were stratified by studies with and without time-dependent approach. Subgroup analyses were adopted for OBs to identify the sources of heterogeneity. Included studies were assessed for quality. RESULTS: We identified ten OBs and four RCTs. For OBs, metformin use was associated with improved OS for LC patients. Only two studies used time-dependent approach in which a higher ratio was found when compared to the non-use of the time-dependent analysis in eight studies. OBs were classified as high quality but the risk of bias was "unclear" in eight OBs due to absence of the time-dependent analysis. For RCTs, metformin use was not beneficial for OS and neither for progression-free survival. Heterogeneous quality was found among RCTs. Sources of bias that could alter significantly the results or raise doubts were identified in RCTs. CONCLUSION: Time-dependent analysis should be considered an appropriate strategy for OBs focused on the metformin use for LC patients' survival, and further studies applying this approach are required. More well-designed RCTs are needed to provide consistent results for the association between metformin use and LC survival.

Homeobox gene amplification and methylation in oral squamous cell carcinoma.

OBJECTIVES: Investigate the DNA copy number and the methylation profile of the homeobox genes HOXA5, HOXA7, HOXA9, HOXB5, HOXB13, HOXC12, HOXC13, HOXD10, HOXD11, IRX4 and ZHX1, and correlate them with clinicopathological parameters and overall survival. MATERIAL AND METHODS: DNA from OSCC samples and surgical margins were submitted to DNA amplification by qPCR and to DNA methylation analysis using a DNA Methylation PCR Array System. RESULTS: HOXA5, HOXB5 and HOXD10 were amplified in surgical margins while HOXA9, HOXB13 and IRX4 were amplified in OSCC. HOXD10 demonstrated hypermethylation in half of the tumor while ZHX1 did not show hypermethylation. No correlation of DNA copy number or methylation with clinicopathological parameters or survival was observed. CONCLUSION: HOXA9, HOXB13 and IRX4 genes appears to be regulated by amplification and HOXD10 by methylation in OSCC. Further studies are needed to determine the role of these events in OSCC development.

Global incidence trends in head and neck cancer for HPV-related and -unrelated subsites: A systematic review of population-based studies.

In head and neck cancer (HNC), some subsites are associated with human papillomavirus (HPV) infection, whereas others are unrelated. Although studies have demonstrated the heterogeneity of HPV prevalence worldwide, its impacts on incidence trends in HNC are unknown. This systematic review examined the incidence trends for HPV-related HNC subsites, exploring patterns by geographic region, age group, sex, and race/ethnicity. We searched for publications on PubMed, Embase, and Scopus. Eligible articles included population-based studies that analyzed incidence trends for subsites classified as a proxy for HPV infection in HNC (hereafter referred to as HPV-related subsites). We retrieved 3,948 non-duplicate records, of which 31 were eligible articles, representing 18 countries and spanning almost fifty years. Overall, the incidence of HPV-related HNC subsites rose, while most of the HPV-unrelated subsites declined or remained stable. For HPV-related HNC subsites, incidence trends increased regardless of age group, highlighting a distinct global pattern between sexes. Also, similar peaks in increased risk were observed in recent cohorts from both Australia and the United States. There is a dramatic shift in the global trends of HNCs, characterized by the emerging burden in HNC for HPV-related subsites.

Inequalities in lung cancer mortality trends in Brazil, 2000-2015.

The present study was conducted to evaluate the socioeconomic inequality related to lung cancer mortality rates and trends between 2000 and 2015 according to gender in Brazil. We retrieved the death records for cases of lung cancer (ICD-10 C33 C34) from 2000 to 2015 in adults age 30 years and older in Brazilian Regions from official databases (DATASUS) and corrected for ill-defined causes. The Prais-Winsten regression method and Pearson correlation were applied. The results were considered statistically significant when p < 0.05. The correlation between the lung cancer mortality rates and the HDI decreased when the rates for the first and last years of the historical series were compared in men (r = 0.77; r = 0.58) and women (r = 0.64; r = 0.41). However, the correlation between the trends in the lung cancer mortality rates and the HDI was negative in men (r = - 0.76) and women (r = - 0.58), indicating larger reductions (or smaller additions) among the Federative Units with the highest HDI, in contrast to trends reflecting a greater increase in those with the lowest HDI. Our results suggest a relevant inequality in the trends of mortality from lung cancer in Brazil.

Association between oral hygiene and head and neck cancer in Brazil.

INTRODUCTION: Poor oral hygiene, regular use of mouthwash and absence of visits to the dentist could correspond to potential risk factors for the development of head and neck cancer. OBJECTIVE: The objective of this study was to determine whether oral hygiene is associated with the occurrence of oral cavity and head and neck cancer in a Brazilian sample. METHOD: The variables of oral hygiene condition, such as toothbrushing frequency, dental loss, need and use of prosthesis, and regular visit to the dentist in a case-control study were analyzed in patients from five hospitals in the state of São Paulo, Brazil, paired by gender and age, from the multicenter project Genoma do Câncer de Cabeça e Pescoço (GENCAPO). RESULTS: The most frequent malignancies in the 899 patients included were those of the tongue border (11.41%) and tongue base (10.92%). The multivariable statistical analysis found odds ratio values: Brushing once 0.33 (95%CI 0.25 - 0.44); Brushing twice 0.42 (95%CI 0.35 - 0.52); Flossing always 0.19 (95%CI 0.13 - 0.27); Flossing sometimes 0.19 (95%CI 0.15 - 0.24); Bleeding 2.40 (95%CI 1.40 - 4.09); Prosthesis 1.99 (95%CI 1.54 - 2.56); Visiting the dentist 0.29 (95%CI 0.22 - 0.37); Good hygiene 0.21 (95%CI 0.17 - 0.27); Regular hygiene 0.20 (95%CI 0.15 - 0.25); number of missing teeth (6 or more) 3.30 (95%CI 2.67 - 4.08). CONCLUSION: These data showed that, in the population studied, indicators of good hygiene such as brushing teeth and flossing were protective factors for mouth and head and neck cancer, while bleeding and many missing teeth were risk factors.

The emerging risk of oropharyngeal and oral cavity cancer in HPV-related subsites in young people in Brazil.

Human papillomavirus (HPV) is responsible for the rise in the incidence of cancer in the oropharynx, tonsils, and base of the tongue (i.e., HPV-related subsites). HPV triggered the changes in the epidemiology of oropharyngeal and oral cavity cancer (OPC/OCC) in Asia, Europe, North America, and Oceania. Hence, the incidence of cancer in HPV-related subsites is augmenting, while that in other HPV-unrelated subsites is decreasing. In South America, although the incidence of HPV-positive tumors has gradually increased, there is an atypically low prevalence of HPV in people with OPC/OCC. To clarify whether this dramatic shift in incidence trends also occurred in this population, we estimated the burden of HPV on the incidence trends of OPCs/OCCs in São Paulo city in Brazil. In this population-based study, we categorized OPCs/OCCs by HPV-related and HPV-unrelated subsites. We used Poisson regression to assess the age-standardized incidence rates (ASRs) stratified by sex and age groups, as well as to examine the age-period-cohort effects. There were 15,391 cases of OPCs/OCCs diagnosed in HPV-related (n = 5,898; 38.3%) and HPV-unrelated (n = 9,493; 61.7%) subsites. Overall, the ASRs decreased for most subsites, for both sexes and for all age groups, except for HPV-related OPC/OCC in young males and females, which increased by 3.8% and 8.6% per year, respectively. In the birth-cohort-effect analysis, we identified an increasing risk for HPV-related OPC/OCC in both sexes in recent birth cohorts; however, this risk was sharply decreased in HPV-unrelated subsites. Our data demonstrate an emerging risk for HPV-related OPC/OCC in young people, which supports prophylactic HPV vaccination in this group.

Lung Cancer Mortality Trends in a Brazilian City with a Long History of Asbestos Consumption.

There are scarce epidemiological studies on lung cancer mortality in areas exposed to asbestos in developing countries. We compared the rates and trends in mortality from lung cancer between 1980 and 2016 in a municipality that made extensive use of asbestos, Osasco, with rates from a referent municipality with lower asbestos exposure and with the rates for the State of São Paulo. We retrieved death records for cases of lung cancer (ICD-9 C162) (ICD-10 C33 C34) from 1980 to 2016 in adults aged 60 years and older. The join point regression and age-period-cohort models were fitted to the data. Among men, there was an increasing trend in lung cancer mortality in Osasco of 0.7% (CI: 0.1; 1.3) in contrast to a mean annual decrease for Sorocaba of -1.5% (CI: -2.4; -0.6) and a stable average trend for São Paulo of -0.1 (IC: -0.3; 0.1). Similar increasing trends were seen in women. The age-period-cohort model showed an increase in the risk of death from 1996 in Osasco and a reduction for Sorocaba and São Paulo State during the same period. Our results point to a need for a special monitoring regarding lung cancer incidence and mortality in areas with higher asbestos exposure.

GLI3 knockdown decreases stemness, cell proliferation and invasion in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is an extremely aggressive disease associated with a poor prognosis. Previous studies have established that cancer stem cells (CSCs) actively participate in OSCC development, progression and resistance to conventional treatments. Furthermore, CSCs frequently exhibit a deregulated expression of normal stem cell signalling pathways, thereby acquiring their distinctive abilities, of which self-renewal is an example. In this study, we examined the effects of GLI3 knockdown in OSCC, as well as the differentially expressed genes in CSC-like cells (CSCLCs) expressing high (CD44high) or low (CD44low) levels of CD44. The prognostic value of GLI3 in OSCC was also evaluated. The OSCC cell lines were sorted based on CD44 expression; gene expression was evaluated using a PCR array. Following this, we examined the effects of GLI3 knockdown on CD44 and ESA expression, colony and sphere formation capability, stem-related gene expression, proliferation and invasion. The overexpression of genes related to the Notch, transforming growth factor (TGF)ß, FGF, Hedgehog, Wnt and pluripotency maintenance pathways was observed in the CD44high cells. GLI3 knockdown was associated with a significant decrease in different CSCLC fractions, spheres and colonies in addition to the downregulation of the CD44, Octamer-binding transcription factor 4 (OCT4; also known as POU5F1) and BMI1 genes. This downregulation was accompanied by an increase in the expression of the Involucrin (IVL) and S100A9 genes. Cellular proliferation and invasion were inhibited following GLI3 knockdown. In OSCC samples, a high GLI3 expression was associated with tumour size but not with prognosis. On the whole, the findings of this study demonstrate for the first time, at least to the best of our knowledge, that GLI3 contributes to OSCC stemness and malignant behaviour. These findings suggest the potential for the development of novel therapies, either in isolation or in combination with other drugs, based on CSCs in OSCC.

Effects of a new intervention based on the Health at Every Size approach for the management of obesity: The "Health and Wellness in Obesity" study.

Health at Every Size® (HAES®) is a weight-neutral approach focused on promoting healthy behaviors in people with different body sizes. This study examined multiple physiological, attitudinal, nutritional, and behavioral effects of a newly developed, intensive, interdisciplinary HAES®-based intervention in obese women. This was a prospective, seven-month, randomized (2:1), controlled, mixed-method clinical trial. The intervention group (I-HAES®; n = 39) took part in an intensified HAES®-based intervention comprising a physical activity program, nutrition counseling sessions, and philosophical workshops. The control group (CTRL; n = 19) underwent a traditional HAES®-based intervention. Before and after the interventions, participants were assessed for physiological, psychological, and behavioral parameters (quantitative data) and took part in focus groups (qualitative data). Body weight, body mass index, and waist and hip circumferences did not significantly differ within or between groups (P > 0.05). I-HAES® showed increased peak oxygen uptake and improved performance in the timed-stand test (P = 0.004 and P = 0.004, between-group comparisons). No significant within- or between-group differences were observed for objectively measured physical activity levels, even though the majority of the I-HAES® participants indicated that they were engaged in or had plans to include physical activity in their routines. I-HAES® resulted in improvements in eating attitudes and practices. The I-HAES® group showed significantly improved all Body Attitude Questionnaire subscale and all Figure Rating Scale scores (P ≤ 0.05 for all parameters, within-group comparisons), whereas the CTRL group showed slight or no changes. Both groups had significant improvements in health-related quality of life parameters, although the I-HAES® group had superior gains in the "physical health," "psychological health," and "overall perception of quality of life and health" (P = 0.05, 0.03, and 0.02, respectively, between-group comparisons) domains. Finally, most of the quantitative improvements were explained by qualitative data. Our results show that this new intensified HAES®-based intervention improved participants' eating attitudes and practices, perception of body image, physical capacity, and health-related quality of life despite the lack of changes in body weight and physical activity levels, showing that our novel approach was superior to a traditional HAES®-based program.

Tumour stage and gender predict recurrence and second primary malignancies in head and neck cancer: a multicentre study within the INHANCE consortium.

Recurrence and second primary cancer (SPC) continue to represent major obstacles to long-term survival in head and neck cancer (HNC). Our aim was to evaluate whether established demographics, lifestyle-related risk factors for HNC and clinical data are associated with recurrence and SPC in HNC. We conducted a multicentre study by using data from five studies members of the International Head and Neck Cancer Epidemiology consortium-Milan, Rome, Western Europe, Sao Paulo, and Japan, totalling 4005 HNC cases with a median age of 59 (interquartile range 52-67). Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for recurrence and SPC. During follow-up, 1161 (29%) patients had recurrence and 343 (8.6%) developed SPC. Advanced tumour stage was associated with increased risk of recurrence in HNC overall (HR = 1.76, 95% CI 1.41-2.19). Women with laryngeal cancer had a reduced risk of recurrence compared to men (HR = 0.39, 95% CI: 0.24-0.74). Concerning predictors of SPC, advanced age (HR = 1.02; 95% CI: 1.00-1.04) and alcohol consumption (> 1 drink per day, HR = 2.11; 95% CI: 1.13-3.94) increased the risk of SPC among patients with laryngeal cancer. Additionally, women were at higher risk of SPC, in HNC overall group (HR = 1.68; 95% CI: 1.13-2.51) and oropharyngeal cancer group (HR = 1.74; 95% CI: 1.02-2.98). Tumour stage and male gender (larynx only) were positive predictors of cancer recurrence in HNC patients. Predictors of SPC were advanced age and alcohol use among laryngeal cancer cases, and female gender for oropharyngeal and HNC overall.