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The scope of this study is to analyze the prevalence of advanced stage diagnosis of cervical cancer and its association with individual and contextual socioeconomic and healthcare service indicators in Brazil. A cross-sectional study was conducted using cervical cancer cases in women aged 18 to 99 years, from 2006 to 2015, extracted from the Hospital Cancer Registry (HCR) Integrator. Contextual variables were collected from the Atlas of Human Development in Brazil; the National Registry of Health Institutions (NRHI); and the Outpatient Information System. Multilevel Poisson Regression with random intercept was used. The prevalence of advanced stage diagnosis was 48.4%, revealing an association with older age groups (PR 1.06; CI 1.01-1.10), black, brown, and indigenous race/skin color (PR 1.04; CI 1.01-1.07), lower levels of schooling (PR 1.28; CI 1.16-1.40), no marital partner (PR 1.10; CI 1.07-1.13), public referral to the health service (PR 1.07; CI 1.03-1.11), and lower rates of cytological examination (PR 1.08; CI 1.01-1.14). The results reinforce the need for improvements in the national cervical cancer prevention program in areas with low coverage of oncotic cytology.

The advanced stage at diagnosis of colorectal cancer (CRC) may be related to individual factors, socioeconomic conditions, and healthcare service availability. The objective of the study was to analyze the prevalence of advanced stage CRC at the time of diagnosis and its association with individual, contextual, socioeconomic, and healthcare service indicators. An observational, cross-sectional study was conducted, analyzing cases of malignant neoplasms of the colon and rectum in individuals of both sexes, aged between 18 and 99 years, diagnosed between 2010 and 2019 in Brazil (n = 69,047). Data were collected from the Hospital Cancer Registry (HCR), Atlas of Human Development in Brazil, and from the National Registry of Health Institutions (NRHI). A Multilevel Poisson Regression model with random intercept was used. The prevalence of advanced stage CRC at diagnosis was 65.6%. Advanced stage was associated with older age groups prevalence ratio (PR) 4.40 and younger age groups (PR 1.84), low Human Development Index (HDI) (PR 1.22), and low density of family health strategy teams (PR 1.10). The study highlights the unequal distribution of social determinants of health in the diagnosis CRC in Brazil, revealing the need to evaluate and redirect public policies aimed at improving early detection and prevention of CRC in the country., (© 2024. The Author(s).)

Objective: To analyze the relationship between internet search volume and the prevalence of waterpipe use among young Brazilians in 2019., Methods: This was a descriptive study with data from Brazil in 2019, using the relative search volume on waterpipes extracted from Google Trends and the proportion of waterpipe users aged between 15 and 24 years, as measured by the National Health Survey (Pesquisa Nacional de Saúde - PNS), and aged between 13 and 17 years, as measured by the National Adolescent School-based Health Survey (Pesquisa Nacional de Saúde do Escolar - PeNSE). The relationship was assessed by means of Spearman's correlation., Results: The point prevalence of waterpipe use across the Brazilian Federative Units (FUs) showed a moderate (r = 0.51; PNS) to strong correlation (r = 0.74 and r = 0.80; PeNSE) with the relative search volume (p-value < 0.05)., Conclusion: Google Trends can support the monitoring system on waterpipe use in the FUs, providing additional information to existing population-based surveys., Main Results: The search volume for waterpipes by states in Brazil, as measured by Google Trends, showed a moderate to high correlation with the respective proportions of current use and experimentation of waterpipe among the adolescent/young adult population., Implications for Services: The use of Google Trends as a support to the monitoring system for waterpipe consumption in Brazil warrants further exploration in terms of the validity of additional information to existing population surveys., Perspectives: Expanding the use of Google Trends searches to assess its potential in monitoring other health risk products and detecting (or predicting) incidence or seasonality of health-related events.

Background: About half of cancer deaths in Brazil occur among individuals of working-age (under 65 years for men, under 60 for women), resulting in a substantial economic impact for the country. We aimed to estimate the years of potential productive life lost (YPPLL) and value the productivity lost due to premature deaths from cancer between 2001 and 2015 and the projected to 2030., Methods: We used the Human Capital Approach to estimate the productivity losses corresponding to YPPLL for cancer deaths in working age people (15-64 years). Mortality data were obtained from the Mortality Information System from 2001 to 2015 and projected between 2016 and 2030. Economic data were obtained from the Continuous National Household Sample Survey and forecasted to 2030. Productivity lost was calculated as the monetary value arising from YPPLL in Int$(2016)., Results: Between 2001 and 2030, a total of 2.3 million premature deaths from all cancers combined were observed and forecasted in Brazil (57% men, 43% women), corresponding to 32 million YPPLL and Int$141.3 billion in productivity losses (men: Int$102.5 billion, women: Int$38.8 billion). Between 2001 and 2030, among men, lung (Int$ 12.6 billion), stomach (Int$ 10.6 billion) and colorectal (Int$ 9.4 billion) cancers were expected to contribute to the greatest productivity losses; and among women, it will be for breast (Int$ 10.0 billion), cervical (Int$ 6.4 billion) and colorectal (Int$ 3.2 billion) cancers., Conclusions: Many preventable cancers result in high lost productivity, suggesting measure to reduce smoking prevalence, alcohol consumption, physical inactivity and inadequate diet, improving screening programs and increasing vaccination coverage for human papillomavirus and hepatitis B would have a positive impact on the economy, as well as reducing morbidity and mortality from cancer., Competing Interests: Declaration of Competing Interest This study was funded by the MSD Independent Oncology Policy Grant Program. The sponsor was not involved in the study design, in collection, analysis and interpretation of data; in the writing of the manuscript and in the decision to submit the manuscript for publication. IARC disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: This study aimed to evaluate the cost-effectiveness of anti-epidermal growth factor receptor (cetuximab and panitumumab) or anti-vascular endothelial growth factor (bevacizumab) monoclonal antibodies associated with conventional chemotherapy (CT) (fluorouracil and leucovorin with irinotecan) as a first-line treatment for unresectable metastatic colorectal cancer., Methods: A partitioned survival analysis model was adopted to simulate direct health costs and benefits comparing therapeutic options in a 10 years' time horizon. Model data were extracted from the literature and costs were obtained from Brazilian official government databases. The analysis considered the perspective of the Brazilian Public Health System; costs were measured in local currency (BRL) and benefits in quality-adjusted life-years (QALY). A 5% discount rate was applied to costs and benefits. Alternative willingness-to-pay scenarios, varying from 3 to 5 times the cost-effectiveness threshold established in Brazil, were estimated. The results were presented incremental cost-effectiveness ratio (ICER), and both deterministic and probabilistic sensitivity analyses were performed., Results: The most cost-effective choice would be the association of CT with panitumumab, with an ICER of $58 330.15/QALY compared with isolated CT. The second-best option was CT with bevacizumab and panitumumab, with an ICER of $71 195.40/QALY compared with panitumumab alone. Although having higher costs, the second-best option was the most effective. Both strategies were cost-effective in part of the Monte Carlo iterations, considering the 3× threshold., Conclusions: The therapeutic option CT + panitumumab + bevacizumab represents the most significant effectiveness gain in our study. It is the second-lowest cost-effectiveness, and this option includes monoclonal antibodies association for patients with and without KRAS mutation., (Copyright © 2023 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective:  Similar to Human Papillomavirus (HPV) genotypes, different lineages of a genotype also have different carcinogenic capabilities. Studies have shown that specific genotype lineages of oncogenic HPV are associated with variable risks for the development of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer. The present study aimed to analyze the genetic diversity of the HPV16 genotype in women with CIN2/CIN3 and cervical cancer, from the northeast region of Brazil., Methods:  A cross-sectional multicenter study was conducted in the northeast region of Brazil, from 2014 to 2016. This study included 196 cases of HPV16 variants (59 and 137 cases of CIN2/CIN3 and cervical cancer, respectively). The difference of proportion test was used to compare patients with CIN2/CIN3 and cervical cancer, based on the prevalent HPV16 lineage ( p  < 0.05)., Results:  According to the histopathological diagnosis, the percentage of lineage frequencies revealed a marginal difference in the prevalence of lineage A in CIN2/CIN3, compared with that in cervical cancer ( p  = 0.053). For lineage D, the proportion was higher in cancer cases (32.8%), than in CIN2/CIN3 cases (16.9%), with p  = 0.023., Conclusion:  HPV16 lineage A was the most frequent lineage in both CIN2/CIN3 and cervical cancer samples, while lineage D was predominant in cervical cancer, suggesting a possible association between HPV16 lineage D and cervical cancer., Competing Interests: The authors have no conflict of interest to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: Cancer staging information in Hospital Cancer Registries (HCR) is essential for cancer care quality evaluations. This study aimed to analyze the completeness of cervical cancer staging in Brazilian HCR and identify individual and contextual factors associated with unknown staging., Methods: The outcome analyzed was missing or unknown staging (Malignant Tumor Classification System and/or International Federation of Gynecology and Obstetrics) in 2006-2015. Individual data on cancer cases were collected from the HCR Integrator. Contextual variables were collected from the Atlas of Human Development in Brazil, the National Registry of Health Facilities, and the Outpatient Information System. The random intercept multilevel Poisson regression model was performed to identify the factors associated with the outcome., Results: The prevalence of unknown staging data was 32.4% (95% confidence interval [CI], 32.1-32.7). Women aged 18-29 years (prevalence ratio [PR], 1.48; 95% CI, 1.42-1.54), referred by the public health system (PR, 1.16; 95% CI, 1.11-1.21), living in states with a low density of oncologists (PR, 1.70; 95% CI, 1.62-1.79), and with a low cytopathological testing rate (PR, 1.69; 95% CI, 1.57-1.82) showed a higher prevalence of unknown tumor staging data. A lower level of education (PR, 0.91; 95% CI, 0.84-0.98) was associated with complete staging data., Conclusions: Individual and contextual factors were associated with missing staging data. It is necessary to improve information on cancer in the HCRs by improving the awareness and training of Brazilian cancer care professionals., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To cross-validate estimates of the size of the illicit cigarette trade based on the results of four different survey methods., Methods: In 2018/2019, four non-industry-funded, large-scale studies were conducted in selected Brazilian cities: packs discarded in household garbage/PDG (1 city), packs littered in the streets/PLS (5 cities), a phone survey of tobacco users' purchase behaviors/VIGITEL (5 cities), and a face-to-face household survey of tobacco users' purchase behaviors/FTF-household (2 cities). The proportions of illicit cigarettes consumed were based on the price paid by smokers in their last purchase (VIGITEL or FTF-household) and/or direct observation of brand names and health warnings (PDG, PLS or FTF-household)., Results: Based on PLS, the share of packs that avoided taxation ranged from 30.4% (95% CI 25.6% to 35.7%) in Rio de Janeiro to 70.1% (95% CI 64.6% to 75.0%) in Campo Grande; and PDG conducted in Rio de Janeiro found an even lower proportion point estimate of illicit cigarette use (26.8%, 95% CI 25.1% to 28.6%). In FTF-household, the share of illicit cigarette consumption based on the self-reported price ranged from 29.1% (95% CI 22.4% to 35.7%) in Rio de Janeiro to 37.5% (95% CI 31.2% to 43.7%) in São Paulo, while estimates based on pack observation ranged from 29.9% (95% CI 23.3% to 36.5%) in Rio de Janeiro to 40.7% (95% CI 34.3% to 47.0%) in São Paulo. For all cities, VIGITEL presented the lowest levels of illicit consumption, and most illicit brands were produced in Paraguay., Conclusions: Small differences in the estimated levels of illicit trade across methods were found, except for the phone survey. The cross-validation of estimates from independent studies is important to help effectively implement tobacco excise tax policy in Brazil and other low-income and middle-income countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The illicit trade of tobacco products, by enabling access to cheaper cigarettes, favors smoking initiation and hinders its cessation, minimizing the effects of price policy and taxes on reducing the demand for tobacco. This is especially the case among populations with lower income and schooling, where smoking is concentrated. Its confrontation requires multisectoral actions, aligned with the World Health Organization Framework Convention on Tobacco Control, supported by estimates of the illicit trade magnitude and the analysis of its characteristics. This study analyzes, based on samples of household solid waste collected in 2018 in the city of Rio de Janeiro, Brazil, the conformity of discarded cigarette packages with criteria for their regular commercialization in Brazil, classifying them as legal or illegal. The evaluation was also carried out for the 15 Planning Areas (PA) of the municipality. The Social Progress Index (SPI) was chosen to represent heterogeneities among PA. The average percentage of illegal cigarette packs found was 26.79%, ranging from 3.36% to 46.29% among PA. The PAs with high illegality presented lower Social Progress Index and lower percentages of legal cigarette packages with a price equal to or greater than BRL 7.25. Among the illegal packages, 98.07% were manufactured in Paraguay. The study contributes methodologically to measure the consumption of illegal cigarettes in the second economic capital of Brazil, supporting the National Tobacco Control Policy in the struggle against illicit trade of tobacco products and in the effective implementation of the pricing and tax policy on these products.

Breast cancer presents high incidence and mortality rates, being considered an important public health issue. Analyze the spatial distribution pattern of late stage diagnosis and mortality for breast cancer and its correlation with socioeconomic and health service offer-related population indicators. Ecological study, developed with 161 Intermediate Region of Urban Articulation (IRUA). Mortality data were collected from the Mortality Information System (MIS). Tumor staging data were extracted from the Hospital Cancer Registry (HCR). Socioeconomic variables were obtained from the Atlas of Human Development in Brazil; data on medical density and health services were collected from the National Registry of Health Institutions (NRHI) and Supplementary National Health Agency. Global Moran's Index and Local Indicator of Spatial Association (LISA) were utilized to verify the existence of territorial clusters. Multivariate analysis used models with global spatial effects. The proportion of late stage diagnosis of breast cancer was 39.7% (IC 39.4-40.0). The mean mortality rate for breast cancer, adjusted by the standard world population was 10.65 per 100,000 women (± 3.12). The proportion of late stage diagnosis presented positive spatial correlation with Gini's Index (p = 0.001) and negative with the density of gynecologist doctors (p = 0.009). The adjusted mortality rates presented a positive spatial correlation with the Human Development Index (p<0.001) and density of gynecologist doctors (p<0.001). Socioeconomic and health service offer-related inequalities of the Brazilian territory are determinants of the spatial pattern of breast cancer morbimortality in Brazil., Competing Interests: The authors have declared that no competing interests exist.

The advanced-stage diagnosis of breast cancer reveals the inequalities associated with socioeconomic conditions and the offer of health services. This study analyzes the prevalence of advanced breast cancer and its relationship with individual and contextual socioeconomic indicators and offer of health service. A cross-sectional study is presented herein, on the assessment of malignant breast neoplasms in women diagnosed between 2006 and 2015 (n = 195,201). Data were collected from the Hospital Cancer Registry (HCR), Atlas of Human Development in Brazil, and from the National Registry of Health Institutions (NRHI). A multilevel Poisson Regression was carried out with random intercept. The prevalence of advanced breast cancer diagnosis was 40.0%. Advanced staging was associated with younger age groups (PR 1.41), race/nonwhite (PR 1.13), lower education levels (PR 1.38), and public access to health services (PR 1.25). There was also an association with a low density of mammographic equipment (PR 1.08), and with low indices of local social inequality (PR 1.33) and human development (PR 0.80). This study maps and highlights the causes related to inequalities in the diagnosis of advanced breast cancer in Brazil, and presents essential data to reorient public policies and health-related actions to strengthen the control of breast cancer in Brazil.

Introduction: The human papillomavirus (HPV) E5 gene encodes a small and highly hydrophobic oncoprotein that affects immune evasion, cell proliferation, loss of apoptotic capacity and angiogenesis in tumors. E5 shows an affinity for biological membranes and was associated with an increase of epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) signaling through the accumulation of EGFR in cellular membranes. Due to the frequent integration of the HPV genome into the host cell genome, E5 is frequently not transcribed in cervical tumors., Aim: In this study we looked forward to verifying whether the potential expression of E5 protein in human papillomavirus 16 positive (HPV16 + ) and human papillomavirus 18 positive (HPV18 + ) cervical tumors was associated with levels of EGFR and vascular endothelial growth factor A (VEGFA) transcription and with patients overall survival., Results: Association between the presence of E5 transcripts and viral genome disruption was observed for HPV16 + and HPV18 + tumors. Association was not observed between tumors potentially capable of translating E5 and EGFR or VEGFA transcriptional levels. Similarly, the capability of translating E5 and overall survival in patients with HPV16 + squamous cell carcinoma tumors stage ≥ IB2 were not associated., Conclusion: The likely presence of E5 transcripts was neither associated to a higher activity of the EGFR-VEGFA pathway nor to the overall survival of patients with HPV16 + squamous cell carcinoma in stages ≥ IB2., (© 2019 Wiley Periodicals, Inc.)

To understand the impact of demographic, behavioral and contextual factors on cervical cancer, we examined the profile of women classified according to cervical cancer staging [precursor lesions cervical intraephitelial neoplasia (CIN2/CIN3), early- and advanced-stage cancer]. Patients were identified in the main oncological reference hospital in Pará State, Brazil, from 2013 through 2015. Adjusted prevalence ratios and their respective 95% confidence intervals were estimated using Poisson regression with robust variance. The study included 172 cases of CIN2/CIN3 lesions, 158 of early stage and 552 of advanced stage of cervical cancer. The proportion of gynecological complaints as a reason for clinic visit was 2.3 times higher among patients at an early stage compared with patients with CIN2/CIN3 lesions. Compared with early-stage cancer groups, the prevalence of advanced-stage cancer was higher among older patients, those without paid activity (adjusted prevalence ratio = 1.15; confidence interval 95%: 1.03-1.29), those who never had a Pap test (adjusted prevalence ratio = 1.23; confidence interval 95%: 1.08-1.40), those who were seen at the hospital clinic due to gynecological complaints (adjusted prevalence ratio = 1.48; confidence interval 95%: 1.19-1.85) and those who underwent biopsy in the private care system (adjusted prevalence ratio = 1.12; confidence interval 95%: 1.02-1.22). These differences seem to reflect problems in the health system, low socioeconomic level and poor awareness of the importance of Pap tests among those with a diagnosis of advanced-stage cervical cancer.

Papanicolaou test screening remains an effective approach for the control of cervical cancer. However, for successful control of the disease, patients need to have access to the test results and complete the treatment. The aim of this study was to investigate the factors associated with lack of access to results from the most recent Papanicolaou test in women living in the municipality of Rio de Janeiro who used the Brazilian Unified Health System. Overall prevalence of lack of access to test results was 18.4%. Access to test results was lower for younger women of Black race/skin color origin, those who had difficulties in making an appointment, those who received no information about when to pick up the test results, and those who evaluated the assistance provided by the health professional who collected the Papanicolaou test. Issues related to the organization and infrastructure of the health unit were the most frequently reported cause by the interviewees. The Brazilian Unified Health Service should improve its knowledge of users and service conditions to prevent interruption of the screening flow.

CpG methylation at early promoter of HPV16 DNA, in the 3' end of the Long Control Region (3'LCR), has been associated to the presence of episomal forms of viral genome and, consequently, intact E1 and E2 ORFs. The DNA methylation would block the access of E2 viral protein to the E2 binding sites at early-promoter. However, is still unclear if methylation at 3'LCR of HPV16 DNA can also vary depending of other tumor characteristics in addition to viral DNA physical state. In this study, we evaluate whether the methylation level at the five CpG located at 3'LCR of HPV16 is associated to patient age and E1 and/or E2 ORFs integrity. DNA pyrosequencing was used to measure the methylation level in 69 invasive cervical cancer samples obtained from biopsies of patients attended at Brazilian National Institute of Cancer (INCA). PCR amplifications were performed to assess disruption status of E1 and E2 genes of HPV16. The methylation average per sample ranged widely, from <1 to 88.00%. Presence of intact E1/E2 genes and patient age were positively associated with average methylation in both bivariate analyses (p=0.003 and p=0.006, respectively), and multivariate analysis (p=0.002 and p=0.021, respectively), adjusted for tumor type (squamous cell carcinomas or adenocarcinomas) and HPV16 lineage. These findings showed that presence of intact E1/E2 open reading frames was associated with high levels of DNA methylation, and older patients showed higher levels of methylation than younger ones independently of viral genome disruption., (Copyright © 2017 Elsevier B.V. All rights reserved.)

To evaluate the impact of HPV immunization and possible changes in virus type-specific prevalence associated with cervical cancer, it is important to obtain baseline information based on socioeconomic, educational, and environmental characteristics in human populations. We describe these characteristics and the type-specific HPV distribution in 1,183 women diagnosed with cervical cancer in two Brazilian healthcare institutions located at the Southeastern (Rio de Janeiro/RJ) and the Amazonian (Belém/PA) regions. Large differences were observed between women in these regions regarding economic, educational, and reproductive characteristics. The eight most frequent HPV types found in tumor samples were the following: 16, 18, 31, 33, 35, 45, 52, and 58. Some HPV types classified as unknown or low risk were found in tumor samples with single infections, HPV 83 in RJ and HPV 11, 61, and 69 in PA. The proportion of squamous cervical cancer was lower in RJ than in PA (76.3% versus 87.3%, p < 0.001). Adenocarcinoma was more frequent in RJ than in PA (13.5% versus 6.9%, p < 0.001). The frequency of HPV 16 in PA was higher in younger women ( p < 0.05). The success of a cervical cancer control program should consider HPV types, local health system organization, and sociodemographic diversity of Brazilian regions.