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.

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.

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.

Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization.

BACKGROUND: Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. We aimed to evaluate the causal effect of sexual behaviour on the risk of OPC using Mendelian randomization (MR). METHODS: Genetic variants robustly associated with age at first sex (AFS) and the number of sexual partners (NSP) were used to perform both univariable and multivariable MR analyses with summary data on 2641 OPC cases and 6585 controls, obtained from the largest available genome-wide association studies (GWAS). Given the potential for genetic pleiotropy, we performed a number of sensitivity analyses: (i) MR methods to account for horizontal pleiotropy, (ii) MR of sexual behaviours on positive (cervical cancer and seropositivity for Chlamydia trachomatis) and negative control outcomes (lung and oral cancer), (iii) Causal Analysis Using Summary Effect estimates (CAUSE), to account for correlated and uncorrelated horizontal pleiotropic effects, (iv) multivariable MR analysis to account for the effects of smoking, alcohol, risk tolerance and educational attainment. RESULTS: In univariable MR, we found evidence supportive of an effect of both later AFS (IVW OR = 0.4, 95%CI (0.3, 0.7), per standard deviation (SD), p = < 0.001) and increasing NSP (IVW OR = 2.2, 95%CI (1.3, 3.8) per SD, p = < 0.001) on OPC risk. These effects were largely robust to sensitivity analyses accounting for horizontal pleiotropy. However, negative control analysis suggested potential violation of the core MR assumptions and subsequent CAUSE analysis implicated pleiotropy of the genetic instruments used to proxy sexual behaviours. Finally, there was some attenuation of the univariable MR results in the multivariable models (AFS IVW OR = 0.7, 95%CI (0.4, 1.2), p = 0.21; NSP IVW OR = 0.9, 95%CI (0.5 1.7), p = 0.76). CONCLUSIONS: Despite using genetic variants strongly related sexual behaviour traits in large-scale GWAS, we found evidence for correlated pleiotropy. This emphasizes a need for multivariable approaches and the triangulation of evidence when performing MR of complex behavioural traits.

Causes of death in former asbestos-cement workers in the state of São Paulo, Brazil.

BACKGROUND: In low- and middle-income countries, such as Brazil, studies on the causes of death in asbestos-exposed workers are scarce. METHODS: A cohort study was performed involving 988 males who had worked in the asbestos-cement industry in the state of São Paulo, with a total of 12,217 person-years of observation between 1995 and 2016. The standardized mortality ratio (SMR) stratified by age was calculated as the ratio between the observed rate and the expected rate in the state of São Paulo. RESULTS: Increased SMRs were observed for overall mortality (SMR 1.1, 95% confidence interval [CI], 0.98-1.23) and mortality due to pleural malignant neoplasms (MN) (SMR, 69.4; 95% CI, 22.55-162.1), asbestosis (SMR, 975.7; 95% CI, 396.4-2031), peritoneal MN (SMR, 5.0; 95% CI, 0.13-27.78), laryngeal MN (SMR, 1.4; 95% CI, 0.30-4.20), and pulmonary MN (SMR, 1.5; 95% CI, 0.82-2.64). CONCLUSION: The present study highlights the damage caused by asbestos exposure and reinforces the existing evidence of a causal association between exposure and increased mortality due to pleural MN, pulmonary MN, and asbestosis.

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

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.

Geographic heterogeneity in the prevalence of human papillomavirus in head and neck cancer.

Human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC), although strongly divergent results have been reported regarding the prevalence of HPV16 in different countries, whether this represents important differences in etiology remains unclear. Applying rigorous protocols for sample processing, we centrally evaluated 1,420 head and neck tumors (533 oropharynx, 395 oral cavity and 482 larynx) from studies conducted in the US, Europe and Brazil for mucosal HPV DNA and p16INK4a expression to evaluate regional heterogeneity in the proportion of HPV16-associated OPSCC and other head and neck cancer, and to assess covariates associated with the risk of HPV16-positive OPSCC. While majority of OPSCC in the US (60%) were HPV16-positive, this proportion was 31% in Europe and only 4% in Brazil (p < 0.01). Similar differences were observed for other head and neck tumors, ranging from 7% in the US and 5% in Europe, to 0% in South America. The odds of HPV16-positive OPSCC declined with increasing pack years of smoking (OR: 0.75; 95% CI: 0.64-0.87) and drink years of alcohol use (OR: 0.64; 95% CI: 0.54-0.76). These results suggest that while the contribution of HPV16 is substantial for the oropharynx, it remains limited for oral cavity and laryngeal cancers.

The design and rationale of an interdisciplinary, non-prescriptive, and Health at Every Size®-based clinical trial: The "Health and Wellness in Obesity" study.

BACKGROUND: This manuscript describes the design and rationale of a clinical trial that aims to investigate the multiple physiological, attitudinal, nutritional, and behavioral effects of a new interdisciplinary intervention based on the Health at Every Size® (HAES®) approach in obese women. METHODS: This will be a prospective, 7-month, randomized (2:1), mixed-method clinical trial. Obese women will be recruited and randomly allocated into two groups. The intervention group (I-HAES®; proposed n = 40) will undertake a novel HAES®-based intervention. Participants will take part in an exercise program, nutrition counseling sessions, and philosophical workshops, all aligned with the principles of the HAES® approach. The control group (CTRL; proposed n = 20) will participate in a program using a traditional HAES®-based group format, characterized by bimonthly lectures about the same topics offered to the experimental group, encouraging the adoption of a healthy lifestyle. The following multiple quantitative outcomes will be assessed pre and post intervention: health-related quality of life, cardiovascular risk factors, anthropometric assessments, physical activity level, physical capacity and function, and psychological and behavioral assessments. Qualitative analysis will be used to evaluate the experiences of the participants throughout the intervention, as assessed by focus groups and semi-structured interviews. CONCLUSIONS: The interdisciplinary research team leading this study has varied and complementary expertise. The knowledge arising from this study will help to guide new interdisciplinary interventions with the potential to holistically improve the health of obese individuals. This trial is registered at Clinicaltrials.gov (NCT02102061).

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.

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.

Machine learning for predicting survival of colorectal cancer patients.

Colorectal cancer is one of the most incident types of cancer in the world, with almost 2 million new cases annually. In Brazil, the scenery is the same, around 41 thousand new cases were estimated in the last 3 years. This increase in cases further intensifies the interest and importance of studies related to the topic, especially using new approaches. The use of machine learning algorithms for cancer studies has grown in recent years, and they can provide important information to medicine, in addition to making predictions based on the data. In this study, five different classifications were performed, considering patients' survival. Data were extracted from Hospital Based Cancer Registries of São Paulo, which is coordinated by Fundação Oncocentro de São Paulo, containing patients with colorectal cancer from São Paulo state, Brazil, treated between 2000 and 2021. The machine learning models used provided us the predictions and the most important features for each one of the algorithms of the studies. Using part of the dataset to validate our models, the results of the predictors were around 77% of accuracy, with AUC close to 0.86, and the most important column was the clinical staging in all of them.

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.

Do tobacco and alcohol modify protective effects of diet on oral carcinogenesis?

Recent systematic reviews concluded that the frequent consumption of fruits and vegetables is inversely associated with the risk of oral cancer. We assessed this association, specifically comparing results obtained to nonsmokers and smokers, as well to nondrinkers and drinkers. We conducted a case-control study involving 296 patients with oral squamous cell carcinoma (cases) attended in 3 major hospitals of São Paulo, Brazil, paired with 296 controls, recruited from outpatient units of the same hospitals. Multivariate models assessed the effect of fruits and salads according to smoking and drinking. The intake of fruit was associated with the prevention of the disease in the specific assessment among light [odds ratio (OR) = 0.46; 95% confidence interval (CI) = 0.27-0.78) and heavy (OR = 0.30; 95% CI = 0.14-0.65) smokers. The same was observed for vegetables consumption. For nonsmokers, no fruit (OR = 50; 95% CI = 0.22-1.12) or vegetable (for tomato, OR = 0.53; 95% CI = 0.31-0.93) was associated with reduced risk of oral and oropharyngeal cancer. Similar results were found in the stratified analysis according to drinking status with OR = 0.51 (95% CI = 0.30-0.87) and 0.18 for fruits (95% CI = 0.07-0.45), respectively, for light and heavy drinkers. This observation suggests that the protective effect of fruit and salad intake may modulate the deleterious effects from tobacco and alcohol.

[Consumption of animal-derived foods and mouth and oropharyngeal cancer]. / Consumo de alimentos de origem animal e câncer de boca e orofaringe.

OBJECTIVE: Evaluate the relationship between animal-derived foods and mouth and oropharyngeal cancer. METHODS: Hospital-based case-control study matched by sex and age (± 5 years) with data collected between July of 2006 and June of 2008. The sample contained 296 patients with mouth and oropharyngeal cancer and 296 patients without a cancer history who were treated in four hospitals in the City of São Paulo, State of São Paulo, Brazil. A semistructured questionnaire was administered to collect data regarding socioeconomic condition and harmful habits (tobacco and alcoholic beverage consumption). To assess eating habits, a qualitative questionnaire that asked about the frequency of food consumption was used. The analysis was rendered by means of multivariate logistic regression models that considered the existing hierarchy among the characteristics studied. RESULTS: Among foods of animal origin, frequent consumption of beef (OR = 2.73; CI95% = 1.27-5.87; P < 0.001), bacon (OR = 2.48; CI95% = 1.30-4.74; P < 0.001) and eggs (OR = 3.04; CI95% = 1.51-6.15; P < 0.001) was linked to an increased risk of mouth and oropharyngeal cancer, in both the univariate and multivariate analyses. Among dairy products, milk showed a protective effect against the disease (OR = 0.41; CI95% = 0.21-0.82; P < 0.001). CONCLUSIONS: This study affirms the hypothesis that animal-derived foods can be etiologically linked to mouth and oropharyngeal cancer. This information can guide policies to prevent these diseases, generating public health benefits.

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.

Cumulative coffee consumption and reduced risk of oral and oropharyngeal cancer.

We examined the association between coffee consumption and oral cancer in a hospital-based case-control study comprising 143 patients with oral and oropharyngeal squamous cell carcinoma attended at 3 major hospitals in Sao Paulo, Brazil, and 240 controls without cancer, recruited from outpatient units of the same hospitals and matched with cases by sex and age. Associations were assessed by multivariate logistic regression conditioned on sociodemographic and behavioral characteristics. Tobacco smoking, alcohol drinking, and higher intake of bacon and deep-fried foods were directly related to disease; the inverse was observed to family income and salad intake. Coffee consumption and tobacco smoking were partially correlated (Spearman correlation coefficient 0.14 among cases, 0.31 among controls). When adjusted for all covariates, a cumulative coffee consumption higher than 18.0 daily liters × year during lifetime was indicated to be protective against disease (adjusted odds ratio 0.39, 95% confidence interval 0.16-0.94, P = 0.037). This observation may have pharmacological implications for clinical medication of these cancers and is relevant to programs aimed at reducing the burden of disease.

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.