Recentes avanços em biomarcadores para diagnóstico, prognóstico e avaliação terapêutica no câncer cervical / Recent advances in biomarkers for diagnosis, prognosis, and therapeutic evaluation in cervical cancer

Objetivos: revisar os estudos clínicos acerca de biomarcadores para o câncer cervical publicados nos últimos 10 anos, com foco no diagnóstico, prognóstico e avaliação do tratamento. Metodologia: as bases de dados PubMed, Web of Science e Science Direct foram pesquisadas utilizando os descritores "Uterine Cervical Neoplasms" e "Biomarkers". Foram selecionados os artigos originais publicados em inglês ou português, no período de 2011 a 2021. Após uma triagem pelos títulos e resumos dos artigos, aqueles relacionados ao objetivo do estudo foram lidos integralmente para a decisão final de inclusão na revisão. Os trabalhos que atenderam todos os critérios de seleção tiveram seus dados extraídos, principalmente, no que se refere ao tipo e objetivo do biomarcador proposto, população do estudo, tamanho da amostra, metodologia utilizada e principais desfechos obtidos. Resultados: esta estratégia de busca e seleção resultou em 22 artigos publicados nos últimos 10 anos na temática de interesse. Ocorreu um grande empenho na investigação de biomarcadores séricos para o câncer cervical, com a vantagem de serem minimamente invasivos. Houve destaque para marcadores genéticos e moleculares, como aqueles voltados para a metilação do DNA, detecção de polimorfismos, padrões de expressão de micro-RNA e expressão de genes relacionados à proliferação, imortalização e invasão celular. Conclusão: os dados reunidos encorajam a ampliação das pesquisas para aprimorar e validar a eficiência destes biomarcadores em grandes populações. É evidente o potencial dos biomarcadores como estratégia para melhorar o manejo do diagnóstico e o tratamento do câncer cervical, sendo que a utilização de marcadores genéticos parece ser o futuro dos biomarcadores para o câncer cervical

Aims: to review clinical studies on biomarkers for cervical cancer published in the last 10 years, focusing on the diagnosis, prognosis, and treatment evaluation. Methods: PubMed, Web of Science, and Science Direct databases were searched using the descriptors "Uterine Cervical Neoplasms" and "Biomarkers". Original articles published in English or Portuguese from 2011 to 2021 were selected. After screening by the titles and abstracts of the articles, those related to the objective of the study were read in full for the final decision of inclusion in the review. The studies that met all the selection criteria had their data extracted, especially regarding the type and objective of the biomarker proposed, study population, sample size, methodology used, and main outcomes obtained. Results: this search and selection strategy resulted in 22 articles published in the last 10 years on the topic of interest. There was a great effort to investigate serum biomarkers for cervical cancer, with the advantage of being minimally invasive. There was an emphasis on genetic and molecular markers, such as those focused on DNA methylation, detection of polymorphisms, expression patterns of microRNA, and expression of genes related to cell proliferation, immortalization, and invasion.Conclusions: the data gathered encourage expanded research to improve and validate the efficiency of these biomarkers in large populations. The potential of biomarkers as a strategy to improve the management of cervical cancer diagnosis and treatment is evident, and the use of genetic markers appears to be the future of biomarkers for cervical cancer

Fatores associados ao início do tratamento especializado em tempo inoportuno após diagnóstico do câncer do colo do útero no Estado da Bahia, Brasil / Factores asociados con el inicio del tratamiento especializado en tiempo inadecuado tras un diagnóstico de cáncer de cuello de útero en el estado de Bahía, Brasil / Factors associated with delay in specialized treatment after diagnosis of cervical cancer in Bahia State, Brazil

Este estudo teve o objetivo de analisar os fatores associados ao tratamento especializado em tempo inoportuno após diagnóstico do câncer do colo do útero no Estado da Bahia, Brasil. Trata-se de um estudo de base hospitalar, de corte transversal, realizado com mulheres tratadas em unidades credenciadas ao sistema de Registro Hospitalar de Câncer (RHC) do Estado da Bahia, no período de 2008 a 2017. Foi realizada análise descritiva e regressão logística, construída na modelagem stepwise backward, para estimar as razões de prevalência (RP) bruta e ajustada, sendo consideradas estatisticamente significantes aquelas com o valor de p ≤ 0,05 pelo teste qui-quadrado de Pearson. Foram analisados 9.184 casos, destes, 65% tiveram tratamento em tempo inoportuno (tempo transcorrido entre o diagnóstico e o primeiro tratamento > 60 dias). A prevalência de tratamento em tempo inoportuno apresentou valores mais elevados entre mulheres com 65 anos ou mais (RP = 1,30; IC95%: 1,21-1,39), nenhuma escolaridade (RP = 1,24; IC95%: 1,15-1,33) e estadiamento avançado (RP = 1,17; IC95%: 1,13-1,21). Na maioria dos casos analisados, houve tratamento em tempo inoportuno, com maior prevalência entre as mulheres com mais idade, menor escolaridade e estadiamento clínico do tumor avançado, evidenciando a necessidade de ampliação do acesso aos serviços de tratamento oncológico no Estado da Bahia, em especial para estes grupos que apresentaram pior situação.

El objetivo de este estudio fue analizar los factores asociados al tratamiento especializado en un tiempo inadecuado, tras el diagnóstico del cáncer de cuello de útero en el estado da Bahía, Brasil. Se trata de un estudio con base hospitalaria, de corte transversal, realizado con mujeres tratadas en unidades acreditadas en el sistema de Registro Hospitalario de Cáncer (RHC) del estado de Bahía, en el período de 2008 a 2017. Se realizó un análisis descriptivo y regresión logística, construida en el modelado stepwise backward, para estimar las razones de prevalencia (RP) bruta y ajustada, siendo consideradas estadísticamente significativas aquellas con el valor de p ≤ 0,05, mediante el test chi-cuadrado de Pearson. Todos los análisis fueron procesados en el programa Stata versión 16.0. Se analizaron 9.184 casos, de estos, un 65% tuvieron tratamiento en un tiempo inadecuado (tiempo transcurrido entre el diagnóstico y el primer tratamiento > 60 días). La prevalencia de tratamiento en tiempo inoportuno presentó valores más elevados entre mujeres con 65 años o más (RP = 1,30; IC95%: 1,21-1,39), ninguna escolaridad (RP = 1,24; IC95%: 1,15-1,33) y estadio avanzado (RP = 1,17; IC95%: 1,13-1,21). En la mayoría de los casos analizados, hubo tratamiento en un tiempo inadecuado, con mayor prevalencia entre las mujeres con más edad, menor escolaridad y estadio clínico del tumor avanzado, evidenciando la necesidad de una ampliación del acceso a los servicios de tratamiento oncológico en el estado de Bahía, en especial para estos grupos que presentaron peor situación.

This study aimed to analyze factors associated with delay in specialized treatment after diagnosis of cervical cancer in the State of Bahia, Brazil. This was a cross-sectional hospital-based study of women treated in accredited units in the Hospital-Based Cancer Registry (HBCR) system in the State of Bahia from 2008 to 2017. A descriptive analysis and logistic regression were performed with backward stepwise modeling to estimate crude and adjusted prevalence ratios (PR), defining statistical significance as p ≤ 0.05 in Pearson's chi-square test. We analyzed 9,184 cases, and 65% had delayed treatment (time between diagnosis and first treatment > 60 days). Delayed treatment was more prevalent among women 65 years or older (PR = 1.30; 95%CI: 1.21-1.39), with no schooling (PR = 1.24; 95%CI: 1.15-1.33), and in advanced stages (PR = 1.17; 95%CI: 1.13-1.21). Most of the cases analyzed had delayed treatment, more prevalent among older women, with less schooling, and advanced tumor stages, highlighting the need to expand access to cancer treatment services in Bahia state, especially for these groups in worse conditions.

Correlations between alterations of T-helper 17 cells and treatment efficacy after concurrent radiochemotherapy in locally advanced cervical cancer (stage IIB-IIIB): a 3-year prospective study / 中华医学杂志(英文版)

BACKGROUND@#Recently, T-helper 17 (Th17) cells have been proved to play an important role in promoting cervical cancer. But, till now, few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments. This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer (LACC) patients before and after concurrent chemoradiotherapy (cCRT) and to analyze the correlations between the alterations in Th17 cells and treatment efficacy.@*METHODS@#A prospective study with 49 LACC (International federation of gynecology and obstetrics [FIGO] stage IIB-IIIB) patients and 23 controls was conducted. Patients received the same cCRT schedule and were followed up for 3 years. Circulating Th17 cells (CD3+CD8- interleukin [IL]-17+ T cells) and related cytokines IL-17, transforming growth factor-β (TGF-β), IL-10, IL-23, IL-6, and IL-22 were detected before and after cCRT. Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS).@*RESULTS@#We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study. The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls, and it significantly decreased after cCRT (P < 0.05). After cCRT, patients were divided into two groups based on the average of the Th17 cells declined. The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times. Compared with the control patients, LACC patients had higher IL-6, IL-10, IL-22, TGF-β levels and a lower IL-23 level (P < 0.05). After cCRT, IL-6, IL-10, IL-17, IL-23 level significantly increased and TGF-β level significantly decreased compared with the levels before cCRT (P < 0.05).@*CONCLUSION@#Circulating Th17 cells in the LACC patients (FIGO stage IIB-IIIB) were higher than those in the controls, but they generally decreased after cCRT. A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.

Immunonutrition in cervical cancer: immune response modulation by diet

ABSTRACT In the development of cervical cancer (CC), the immune response plays an essential role, from the elimination of human papillomavirus (HPV) infection to the response against the tumor. For optimal function of the immune response, various factors are required, one of the most important being an adequate nutrition. The complex interaction between nutrients and microbiota maintains the immune system in homeostasis and in case of infection, it provides the ability to fight against pathogen invasion, as occurs in HPV infection. The purpose of this article is to describe the role of diet, food, and specific nutrients in the immune response from the onset of infection to progression to precancerous lesions and CC, as well as the role of diet and nutrition during oncological treatment. The immunomodulatory role of microbiota is also discussed. A detailed analysis of the evidence leads us to recommend a nutritional pattern very similar to the Mediterranean diet or the prudent diet for an optimal immune response. Moreover, pre- and probiotics favorably modulate the microbiota and induce preventive and therapeutic effects against cancer.

Immunotherapy treatment against cervical cancer

ABSTRACT Cervical cancer (CC) is one of the most common gynecological tumors and an important health problem, especially in developing countries. The vast majority of patients in early stages are cured of the disease with surgical treatment and with concomitant chemoradiotherapy in locally advanced stages. However, in patients with recurrent, persistent, or metastatic cervical CC, the effectiveness of treatment is limited, except for the combination of chemotherapy based on platinum doublets plus bevacizumab, the treatment that has achieved the best results to date. Programmed cell death-1/PD ligand-1 (PD-1/PD-L1) inhibitors could be a novel and cutting-edge therapeutic option to improve clinical outcomes in this group of patients. Thus far, there are a few Phase I/II clinical trials that have assessed the usefulness of pembrolizumab and nivolumab in this group of patients; these include the KEYNOTE 028, KEYNOTE 158, and CHECKMATE 358 trials, in which clinical benefit has been proven with PD-1/PD-L1 inhibitors in recurrent, persistent, or metastatic CC, as second-line treatment. There are also some ongoing trials that could provide further evidence on the PD-1/PD-L1 pathway as a therapeutic target in CC. In this review, we will focus on the usefulness of these PD-1/PDL1 inhibitors in CC, as well as on trials that are still in the recruitment phase, to confirm their effectiveness in this clinical setting.

Incidencia del cáncer de cuello uterino y sobrevida de pacientes en Manizales, Colombia, 2008-2012 / Cervical cancer incidence and patient survival in Manizales, Colombia, 2008-2012

RESUMEN Objetivo: Estimar la incidencia de cáncer de cuello uterino y sobrevida de pacientes con esta enfermedad según subtipo histológico y estadios en Manizales, Colombia para el periodo 2008-2012, y comparar cambios en la sobrevida con el quinquenio anterior. Materiales y métodos: A partir de datos poblacionales, se estandarizaron las tasas de incidencia según la edad para cada subtipo histológico. Se realizó un seguimiento activo y pasivo para determinar el estado vital y la causa de muerte a 60 meses. Se ajustaron funciones de Kaplan-Meier y modelos de Cox para estimar la sobrevida global y según covariables. Resultados: Se presentaron 217 casos nuevos para una incidencia media de 17,8 por 100000 mujeres-año. Hubo mayor frecuencia de estadios III-IV en pacientes de nivel socioeconómico medio y bajo. La sobrevida a cinco años fue de 68,9%; la edad (>70 años) se asoció con menor sobrevida (p<0,001). El riesgo de fallecer fue 90% mayor en pacientes con muestra histológicas no diferenciadas o desconocidas comparado con el carcinoma escamocelular (hazard ratio [HR] 1,9; IC 95%: 1,1-3,3); 1,7 veces mayor para personas mayores de 70 años (HR 2,7; IC 95%: 1,6-4,8); y tres veces mayor para estadio III (HR 4,3; IC 95%: 1,8-10,2) y siete veces mayor para estadio IV (HR 8,7; IC 95%: 3,6-20,1) en comparación con el estadio I. Conclusión: La incidencia de cáncer del cuello uterino en Manizales es similar a la global y a la continental, y fue más baja que otras ciudades colombianas con características similares. Hubo mayor frecuencia de estadios avanzados en mujeres de bajo nivel socioeconómico. La sobrevida se asoció con la edad, el subtipo histológico y la estadificación.

ABSTRACT Objective: To estimate the cervical cancer incidence and survival rates by histological subtype and stage in Manizales, Colombia during 2008-2012; and to compare the survival rate to the one from the previous five years. Materials and methods: Using population-based data, incidence rates by age were standardized for each histological subtype. Active and passive follow-up was performed to determine vital status and cause of death at 60 months. The Kaplan-Meier method and Cox models were adjusted to estimate overall survival by each covariant. Results: A total of 217 new cases were observed; with a mean incidence of 17.8 per 100,000 woman-years. Stages III-IV were more frequently observed in patients of medium and low socioeconomic status. At 5 years, the survival rate was 68.9%; ages over 70 years were associated with lower survival rates (p<0.001). Risk of death was 90% higher in patients with undifferentiated or unknown histological samples, when compared with those with squamous cell carcinoma (HR 1.9, 95% CI: 1.1-3.3). Likewise, the risk of death was 1.7 times higher for patients aged over 70 years (HR 2.7, 95% CI 1.6-4.8); and it was also found to be 3 times higher for stage III (HR 4.3, 95% CI: 1.8-10.2) and 7 times higher for stage IV (HR 8.7, 95% CI: 3.6-20.1), when compared with stage I. Conclusion: The incidence rate of cervical cancer in Manizales was found to be similar to the global and continental rates and lower than those from other Colombian cities with similar characteristics. Advanced stages were more frequent in women of low socioeconomic status. Survival was associated with age, histological subtype and staging.

Efectos de la enfermedad y tratamiento en la calidad de vida sexual de la mujer con cáncer cérvico uterino / Effects of the disease and treatment in the quality of sexual life of women with cervical uterine cancer

El cáncer cérvico uterino (CaCu) corresponde al 10% de los cánceres femeninos, se describe prevenible y con viabilidad de curación, no obstante, con la optimización de las terapias las sobrevivientes superan los cinco años en el 70% de los casos, evidenciando efectos adversos producto principalmente del tratamiento que deterioran la calidad de vida e impactan sobre su sexualidad. OBJETIVO: Identificar efectos de la enfermedad y tratamiento que comprometen la calidad de vida sexual de la mujer con CaCu. METODOLOGÍA: Revisión de artículos originales entre los años 2010 y 2019 desde las bases de datos Pubmed, Scopus, Scielo, Google Académico, Science Direct, Elsevier, Redalyc, Springer Link, Wiley Online Library, Dialnet y Ovid, seleccionando 51 artículos de 90 en inglés, español y portugués a texto completo, que reportaran efectos físicos y psicosociales que comprometieran la calidad de vida sexual de mujeres con CaCu. RESULTADOS: La sexualidad de estas mujeres es impactada por efectos físicos, relacionadas con el estadio de la enfermedad y tratamiento como dispareunia, anorgasmia, alteraciones digestivas, urinarias, insomnio, inapetencia, linfedema y neuropatía periférica. Desde el ámbito psicosocial manifiestan efectos sobre su autoestima, depresión e inseguridad en la permanencia del vínculo de pareja. Emerge la comunicación sexual de pareja como condición categórica en el nivel de afectación de la calidad de vida sexual. CONCLUSIONES: la sexualidad de la mujer con CaCu está comprometida por efectos físicas y psicosociales secundarias principalmente al tratamiento recibido. La comunicación sexual de pareja surge como interviniente para superar estos efectos y debe considerarse en la atención profesional.

Cervical uterine cancer (CaCu) corresponds to 10% of female cancers, it is described as preventable and with viability of cure, however, with the optimization of therapies the survivors exceed five years in 70% of the cases, evidencing adverse effects mainly due to the treatment that deteriorates the quality of life and impact on their sexuality. OBJECTIVE: To identify the effects of the disease and treatment that compromises the quality of sexual life of women with CaCu. METHODOLOGY: Review of original articles between 2010 and 2019 from Pubmed, Scopus, Scielo, Google Scholar, Science Direct, Elsevier, Redalyc, Springer Link, Wiley Online Library, Dialnet, and Ovid databases, selecting 51 articles out of 90 in English, Spanish, and Portuguese in full text, which reported physical and psychosocial effects that compromises the quality of sexual life of women with CaCu. RESULTS: The sexuality of these women is impacted by physical effects, related to the stage of the disease and treatment, such as dyspareunia, anorgasmia, digestive and urinary disorders, insomnia, inappetence, lymphedema and peripheral neuropathy. From the psychosocial perspective, they show effects on their self-esteem, depression and insecurity in the permanence of the couple's relationship. Sexual communication between couples is emerging as a categorical condition in the level of affectation of the quality of sexual life. CONCLUSIONS: The sexuality of women with CaCu is compromised by physical and psychosocial effects mainly secondary to the treatment received. Couple's sexual communication emerges as an intervention to overcome these effects and should be considered in professional care.

Is surgical treatment an option for locally advanced cervical cancer in the presence of central residual tumor after chemoradiotherapy?

Abstract Objective To evaluate the outcomes of surgical treatment in patients with chemoradiotherapy (CRT)-resistant and locally advanced cervical cancer (LACC). Methods Patients with LACC who underwent surgery due to resistance to CRT between 2005 and 2015 were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) related factors were analyzed. Results A total of 23 patients were included in the study and the median age was 51 years old. A total of 14 patients (60.8%) experienced recurrence; among these recurrences, 8 of them were local, 5 were distant, 1 was both distant and local. A total of 9 patients (39%) died. The Median DFS and OS durations were 15 and 32 months, respectively. A total of 17 patients (74%) had undergone simple hysterectomy, 4 (17%) radical hysterectomy, and 2 (9%) total pelvic exenteration. Postoperative grade 3 and 4 complications were seen in 12 patients (52%). Macroscopic tumor presence in the pathology specimen was associated with distant recurrence and positive surgical margins with local recurrence (Log-Rank test p = 0.029 and p = 0.048, respectively). The only factor associated with OS was surgical margin positivity (Log-Rank test p = 0.008). The type of surgery, grades 3 and 4 postoperative complications, brachytherapy, and tumor histology were not associated with recurrence. Conclusion In patients with LACC, hysterectomy is an option in the presence of a central residual tumor after CRT. However, the risk of grades 3 and 4 complications of performed surgery is high. The presence of macroscopic tumor in the pathology specimen and positive surgical margins are poor prognostic factors. The goal of the surgeon should be to achieve a negative surgical margin. It does not seem important if the surgery is simple or radical.

Fatores limitadores e facilitadores para o controle do câncer de colo de útero: uma revisão de literatura / Cervical cancer control limiting factors and facilitators: a literature review

Resumo Este artigo revisa os fatores limitadores e facilitadores do acesso aos serviços públicos de saúde no Brasil na área da atenção ao câncer de colo de útero (CCU). Nesta revisão, foram utilizadas a base de dados bibliográficos Medline (interface com Biblioteca Virtual de Saúde/BVS e PubMed) e os portais Lilacs e SciELO. Buscou-se publicações referentes ao período 2011-2016, a partir do uso de termos específicos das fontes consultadas, relativos a 'neoplasias do colo do útero' e 'acesso aos serviços de saúde'. Foram inicialmente encontrados 704 artigos, mas, considerando os critérios adotados, foram selecionados 31 artigos, dos quais foram incluídos 19. Foram mencionados aspectos facilitadores do acesso como ampla cobertura do exame Papanicolaou e de biopsias equivalente ao número de preventivos alterados. Entretanto, aspectos limitadores de acesso como periodicidade inadequada do Papanicolau, dificuldades para agendamento de consultas e exames, alto índice de estadiamento avançado e atrasos no diagnóstico e no início de tratamento, também foram apresentados.

Abstract This paper reviews the limiting factors and facilitators of access to Brazilian cervical cancer care public health services. This review employed bibliographic database Medline (interface with the Virtual Health Library/BVS and PubMed) and Lilacs / SciELO portals. We sought publications for the period 2011-2016 based on the use of specific terms from the sources consulted, regarding "cervical neoplasms" and "access to health services". We found 704 papers initially, which were shortlisted to 31 following adopted criteria, which were further reduced to 19 papers to make up the final selection. Access facilitating aspects such as wide coverage of the Pap smear test and coverage of biopsies equivalent to the number of altered prevention tests were mentioned. However, access limiting aspects such as inadequate Pap smear's periodicity, difficulties in scheduling appointments and exams, high rate of advanced staging and delays in diagnosis and treatment onset were also reported.

Estimation of the costs of invasive cervical cancer treatment in Brazil: A micro-costing study / Estimativa dos custos do tratamento do câncer do colo do útero invasivo no Brasil: um estudo de microcustos

Abstract Objective Themain objective of the present study was to estimate the annual treatment costs of invasive cervical cancer (ICC) per patient at an oncology center in Brazil from a societal perspective by considering direct medical, direct nonmedical, and indirect costs. Methods A cost analysis descriptive study, in which direct medical, direct nonmedical, and indirect costs were collected using a microcosting approach, was conducted between May 2014 and July 2016 from a societal perspective. The study population consisted of women diagnosed with ICC admitted to a tertiary hospital in Recife, state of Pernambuco, Brazil. The annual cost per patient was estimated in terms of the value of American Dollars (US$) in 2016. Results From a societal perspective, the annual ICC treatment cost per patient was US $ 2,219.73. Direct medical costs were responsible for 81.2% of the total value, of which radiotherapy and outpatient chemotherapy had the largest share. Under the base-case assumption, the estimated cost to the national budget of a year of ICC treatment in the Brazilian population was US$ 25,954,195.04. Conclusion We found a high economic impact of health care systems treating ICC in a poor region of Brazil. These estimates could be applicable to further evaluations of the cost-effectiveness of preventing and treating ICC.

Resumo Objetivo O objetivo principal do presente estudo foi estimar os custos anuais por paciente do tratamento do câncer do colo do útero (CCU) invasivo em um centro de oncologia no Brasil, sob a perspectiva da sociedade, considerando os custos diretos médicos, diretos não médicos e indiretos. Métodos Foi realizado um estudo descritivo de análise de custos, no qual os custos médicos diretos, não médicos diretos e indiretos foram coletados por meio de uma abordagem de microcustos, realizado entre maio de 2014 e julho de 2016 sob a perspectiva da sociedade. A população do estudo foi composta por mulheres diagnosticadas com CCU invasivo internadas em um hospital terciário em Recife, PE, Brasil. O custo anual por paciente foi estimado emtermos de dólares americanos (US$) para o ano de 2016. Resultados O custo anual do tratamento do CCU invasivo sob a perspectiva da sociedade foi de US$ 2.219,73 por paciente. Os custos médicos diretos foram responsáveis por 81,2% do valor total, dos quais a radioterapia e a quimioterapia ambulatorial tiveram a maior participação. Sob o pressuposto do caso base, o custo estimado para o orçamento nacional de um ano de tratamento do CCU invasivo na população brasileira foi de US$ 25.954.195,04. Conclusão Foi encontrado um alto impacto econômico dos sistemas de saúde para o tratamento do CCU invasivo em uma região pobre do Brasil. Essas estimativas poderão ser aplicáveis emavaliações adicionais do custo-efetividade da prevenção e tratamento do CCU.

Percursos e obstáculos na Rede de Atenção à Saúde: trajetórias assistenciais de mulheres em região de saúde do Nordeste brasileiro / Healthcare trajectories and obstacles faced by women in a health region in Northeast Brazil / Itinerarios y obstáculos en la Red de Atención de Salud: trayectorias asistenciales de mujeres en la región de salud del Nordeste brasileño

Resumo: O artigo tem como objetivo avaliar a organização e o acesso à Rede de Atenção à Saúde em uma região de saúde, na perspectiva das usuárias. Foram construídas trajetórias assistenciais de mulheres com lesão intraepitelial escamosa de alto grau do colo do útero, adscritas a diferentes modalidades de atenção primária à saúde (APS) de zonas urbana e rural, em municípios do interior e da sede de região de saúde do Nordeste do Brasil. As mulheres utilizavam a APS como serviço de busca regular para ações preventivas e assistenciais, mas reportaram barreiras de acesso para consultas médicas, sobretudo nas zonas rurais. Avaliações positivas foram vinculadas ao acolhimento e à representação da unidade básica de saúde/unidade de saúde da família (UBS/USF) como lócus disponível para cuidados. Percepção de baixa resolutividade da APS esteve ligada à demora para o agendamento das referências, abastecimento irregular/insuficiente de medicamentos e rotatividade de médicos. As mulheres indicaram dificuldade de acesso à atenção especializada, mais evidente nos municípios do interior da região, com utilização de serviços públicos e privados. Todas as usuárias da sede da região realizaram exames de confirmação diagnóstica e cirurgia pelo Sistema Único de Saúde. Apoio de familiares, amigos e políticos atravessaram as trajetórias assistenciais. Comunicação interprofissional foi quase inexistente e entre profissional/usuária, precária. A rede regionalizada apresentou-se desarticulada e com fluxos desordenados, não garantindo acesso oportuno às usuárias dos municípios do interior e apresentando dificuldades adicionais àquelas da área rural, mesmo no município sede, desvelando a incompletude dos arranjos regionais e a manutenção de desigualdades de acesso inter e intramunicipal.

Abstract: The article aims to assess organization and access to the Healthcare Network in a health region, from the perspective of female users. Healthcare trajectories were constructed for women with high-grade cervical squamous intraepithelial lesions, covered by different modalities of primary health care (PHC) in urban and rural areas, in municipalities in the interior, and in the capital city of the Northeast health region, Brazil. Women used PHC as their regular service for prevention and care, but reported barriers to access to medical appointments, especially in rural areas. Positive assessments were associated with positive reception by the health service and representation of the basic health unit or family health unit as the available locus for care. A perception of low case-resolution capacity in PHC was associated with delays in scheduling referrals, irregular/insufficient supply of medicines, and physician turnover. Women reported difficulty in access to specialized care, especially in municipalities in the interior, with the use of public and private services. All the users in the capital city of the health region underwent confirmatory diagnostic tests and surgeries in the Brazilian Unified National Health System (SUS). Support from family members, friends, and local politicians were part of the healthcare trajectories. Interprofessional communication was nearly non-existent and health professional-patient communication was precarious. The regionalized network appeared disconnected and with confusing flows in terms of guaranteeing timely access for users in municipalities in the interior and with additional difficulties for those in rural areas, even in the capital city, revealing incompleteness in regional arrangements and persistence of inter- and intra-municipal inequalities in access.

Resumen: El artículo tiene como objetivo evaluar la organización y el acceso a la Red de Atención de Salud en una región de salud, desde la perspectiva de las usuarias. Se construyeron trayectorias asistenciales de mujeres con una lesión intraepitelial escamosa de alto grado en el cuello del útero, adscritas a diferentes modalidades de atención primaria de salud (APS) de zonas urbanas y rurales, en municipios del interior y de la sede de región de salud del Nordeste, Brasil. Las mujeres utilizaban la APS, como servicio de búsqueda regular para acciones preventivas y asistenciales, pero informaron sobre barreras de acceso para consultas médicas, sobre todo en las zonas rurales. Las evaluaciones positivas se vincularon con la acogida y la representación de la unidad básica de salud/ unidad de salud familiar (UBS/USF) como un lugar disponible para cuidados. La percepción de baja resolutividad de la APS estuvo vinculada a la tardanza para las citas con el especialista, suministro irregular/insuficiente de medicamentos y rotatividad de médicos. Las mujeres indicaron dificultades de acceso a la atención especializada, aún más evidentes en los municipios del interior de la región, con utilización de servicios públicos y privados. Todas las usuarias de la sede de la región realizaron exámenes de confirmación diagnóstica y cirugía a través del Sistema Unico de la Salud. El apoyo de familiares, amigos y políticos se cruzó con las trayectorias asistenciales. La comunicación interprofesional fue casi inexistente y entre profesional-usuaria precaria. La red regionalizada se presentó desarticulada y con flujos desordenados, no garantizando el acceso oportuno a las usuarias de los municipios del interior, y presentando dificultades adicionales para las procedentes del área rural, incluso en el municipio sede, desvelando lo incompleto de los acuerdos regionales y la existencia de desigualdades de acceso inter- e intramunicipal.

"Ter câncer mudou minha vida": cartografia de Luiza na micropolítica das redes de cuidado oncológico / "Having cancer changed my life": Luiza's cartography in the micropolitics of cancer care networks

Resumo Garantir cuidado integral à saúde de mulheres com câncer cérvico-uterino ainda é um desafio para a Saúde Coletiva, embora se evidencie o enraizamento de políticas, práticas e saberes na conformação de redes oncológicas de cuidado. Este estudo apostou na necessidade de mergulhar nas experimentações da micropolítica do cuidado para conhecer as nuances do fenômeno investigado. Ao fundamentar-se no aporte teórico-metodológico de Deleuze e Guattari, objetivou-se cartografar linhas de composição da produção de cuidado oncológico, na cidade de São Luís-MA, tendo como dispositivo a rede da usuária-guia Luiza. Investigaram-se 28 participantes através de entrevistas em profundidade e rodas de conversas. Como resultado, desenhou-se uma rede vulnerável, fragmentada e centralizada no cuidado biomédico, tendo um hospital que acolhe demandas da doença e uma atenção primária que abandona prevenção e promoção de saúde. Destaca-se a importância de conhecer a mulher com câncer atrelada à comunidade, à religiosidade e aos vínculos familiares. Ter câncer mudou a vida de Luiza e demandou conexões para além do biomédico. Essa cartografia convoca à percepção dos gargalos existentes na produção de redes oncológicas, convidando a quebrar muros tecnoassistenciais e criar enfrentamentos centrados na promoção de saúde e qualidade de vida.

Abstract Ensuring comprehensive health care for women with cervical-uterine cancer remains a challenge for public health, although evidence of the established policies, practices and knowledge in shaping of cancer care networks. This study focused on the need to deepen in the micropolitics of care experiments to know the nuances of the investigated phenomenon. Based on the theoretical and methodological approach of Deleuze and Guattari, it aimed to map the composition lines of cancer care production in the city of São Luis-MA, Brazil, using the network of the guide-user Luiza as a device. Twenty-eight participants were investigated through in-depth interviews and conversation groups. As a result, a vulnerable, fragmented, centralized network of biomedical care was designed, with a hospital that welcomes demands of the disease, and primary care that abandons prevention and health promotion. The importance of knowing women with cancer linked to the community, religiosity and family ties is highlighted. Having cancer changed Luiza's life and required connections beyond the biomedical sphere. This cartography calls for the perception of narrowing in the production of cancer care networks, inviting the breaking of techno-assistance walls and creating confrontations focused on health promotion and quality of life.

Trajetórias assistenciais de usuárias pela APS em uma região de saúde: trânsito livre, pontos de lentidão e parada / Care trajectories of users with precursor lesions of cervical cancer by primary health care in a health region: free transit, length and stop points

Resumo O artigo objetiva avaliar o acesso e a organização das ações da Atenção Primária à Saúde (APS) utilizando o câncer do colo do útero (CCU) como evento traçador. Foram construídas trajetórias assistenciais de mulheres com diagnóstico de lesão de alto grau do colo uterino, adscritas a Unidades Básicas de Saúde Tradicionais e Unidades de Saúde da Família, de zonas urbana e rural, em municípios do interior e na sede de uma região de saúde da Bahia. As mulheres indicam dificuldade de acesso às consultas médicas na APS, sobretudo na zona rural. Além dos obstáculos para agendamento do citopatológico, a maioria relata não receber convocação para sua realização e não participar de atividades educativas sobre o tema. As ações de controle do CCU na APS são restritas à realização do citopatológico, avaliação do resultado e encaminhamento para rede especializada, sem seguimento do cuidado e com falhas na comunicação profissional-usuária. Foram identificadas barreiras no acesso à APS, em geral, e para controle do CCU relacionadas ao escopo de ações, principalmente nas unidades localizadas no município com menor disponibilidade de serviços, na zona rural e nas UBS tradicionais.

Abstract The article aims to evaluate the access and organization of Primary Health Care (PHC) actions using cervical cancer (CCU) as a tracer event. Assistance trajectories of women with diagnosis of high grade cervical lesion were constructed, from Basic Health Units and Family Health Units, urban and rural areas, in the interior municipalities and at the headquarters of a health region of the Bahia. Women indicate difficulty accessing medical consultations in PHC, especially in rural areas. In addition to the obstacles to cytopathological scheduling, most patients report not being called to accomplish it and do not participate in educational activities on the issue. The control actions of the CCU in PHC are restricted to cytopathology, evaluation of the outcome and referral to specialized care, without follow-up care and with failures in professional-user communication. Barriers to access to PHC in general and to CCU control related to the scope of actions were identified, mainly in the units located in the municipality with less availability of services, in the rural area and in the traditional Basic Health Units.

An exploration into the quality of life of women treated for cervical cancer

Background: Cervical cancer mainly occurs among women from the developing world, and women face unique challenges in terms of their disease and treatment. Most women present with advanced cervical cancer and receive the standard curative treatment with external beam radiotherapy and brachytherapy with or without chemotherapy. Objectives: To describe the quality of life (QOL) of women treated for cervical cancer during treatment (M0), at 6 months after completing treatment (M6) and at 12 months after treatment (M12).Methods: A cross-sectional design, calculated sample size (n = 153) and convenience sampling were used. Data were collected through structured interviews, and the EORTC QLQ-C30 and EORTC QLQ CX24 served as data collection instruments. Descriptive statistics were used to analyse the data, and the Kruskal­Wallis H test was used to compare the mean responses across the groups (p ≤ 0.05).Results: The mean age of the respondents was 50.6 years (standard deviation [SD] 11.9). The global health status improved significantly in contrast with the functional scores. Financial difficulties were rampant, especially during the treatment phase. Insomnia and urinary frequency were the most cumbersome problems and remained so even after treatment.Conclusions: Despite an improvement in the global health, cervical cancer and its treatment had a negative influence on the QOL in all domains of lives of these women. Assessing the QOL of patients during treatment and follow-up visits would allow nurses to develop interventions to address distressing problems timeously. In addition, Africa's nurses should assess social functioning and develop programmes to prevent social dysfunction

Postpartum genital melanoma - A case report / Melanoma genital pós-parto - relato de caso

Abstract Melanomas of the female genital tract may occur in the vulva, the vagina, the ovary or the cervix.Pregnancy has been considered an aggravating factor in the evolution and prognosis of melanoma. A 35-year-old female presented with vaginal bleeding 2 months after a term cesarean delivery. An endovaginal ultrasound revealed a lesion in the uterine cervix. The pathological report revealed a small round-cell neoplasm, and the immunohistochemistry confirmed the diagnosis of malignant melanoma. A positron emission tomography revealed an expansive hypermetabolic lesion centered on the cervix, and hypermetabolic lesions in the liver and right kidney. Non-surgical treatment was provided, with biochemotherapy followed by ipilimumab and nivolumab. The patient died one year later. Postpartum vaginal bleeding, even if late-onset, should be investigated, as it may be a pregnancy-associated malignant melanoma, which has a poor prognosis.

Resumo Melanomas do trato ginecológico podem ocorrer na vulva, vagina, ovário ou cérvix. A gravidez é considerada um fator agravante na evolução e prognóstico do melanoma. Uma mulher de 35 anos de idade apresentou sangramento vaginal 2 meses após o parto por cesariana a termo. Uma ultrassonografia endovaginal mostrou lesão no colo uterino. O exame anatomopatológico mostrou uma pequena neoplasia de células redondas, e a imuno-histoquímica confirmou o diagnóstico de melanoma maligno. A tomografia por emissão de pósitrons mostrou lesão hipermetabólica expansiva centrada no colo do útero,e lesões hipermetabólicas no fígado e no rim direito. O tratamento não cirúrgico foi feito com bioquimioterapia seguida de ipilimumab e nivolumab. A paciente morreu um ano depois. Sangramentos vaginais pós-parto,mesmo que tardios,devem ser investigados,pois podem ser um melanoma maligno associado à gravidez, o qual tem um mau prognóstico.

Características clínico-patológicas y sobrevida en mujeres jóvenes con cáncer cervical: análisis retrospectivo del instituto nacional de enfermedades neoplásicas / Clinical-pathological features and survival in young women with cervical cancer: a retrospective analysis from the instituto nacional de enfermedades neoplásicas

RESUMEN Objetivos Determinar las características clínicas, histológicas y los factores pronósticos del cáncer cervical (CC) en pacientes jóvenes peruanas. Materiales y métodos Análisis retrospectivo de pacientes de 35 años de edad o menos diagnosticadas con CC entre el 2008 y el 2012 en el Instituto Nacional de Enfermedades Neoplásicas. Resultados 449 pacientes tenían neoplasias epiteliales. Los tipos histológicos principales fueron: carcinoma de células escamosas (84,9%), adenocarcinoma (11,0%) y carcinoma adenoescamoso (2,4%). El tamaño tumoral promedio fue 4,98 cm. También se identificó anemia (55,7%), creatinina elevada (21,2%) e hidronefrosis (13,8%). El 82,3% de los pacientes presentaron enfermedad localmente avanzada. Los estadios IIB (47,4%) y IIIB (25,8%) fueron los más comunes. La supervivencia global a 5 años fue de 59,5% (I, 90,9%; II, 57,5%; III, 42,7% y IV, 13,3%). La creatinina elevada, la anemia, el tamaño tumoral, el compromiso parametrial y la hidronefrosis fueron factores que afectaron la supervivencia. No se encontró relación significativa entre el tipo histológico y la supervivencia. La presencia de anemia (Hazard Ratio ajustado [HRa]: 2,5; intervalo de confianza al 95% [IC 95%]: 1,6-4,0) y la hidronefrosis (HRa: 1,6; IC 95%: 1,0-4,0) estuvieron independientemente asociados con la supervivencia; asimismo, el compromiso parametrial con (HRa: 3,3; IC 95%: 1,5-7,2) o sin (HRa: 2,6; IC 95%: 1,3-5,3) extensión al hueso pélvico. Conclusiones El cáncer cervical en jóvenes peruanas es diagnosticado en estadios avanzados. La supervivencia global en cada estadio es similar a la reportada en pacientes mayores. Se confirmó la importancia de los factores convencionales relacionados con el pronóstico. La anemia fue un factor de pronóstico independiente importante que requiere mayores investigaciones.

ABSTRACT Objective To determine the clinical and histological characteristics and prognostic factors of cervical cancer (CC) in young Peruvian patients. Materials and methods Retrospective analysis of patients younger than 35 years old diagnosed with CC between 2008 and 2012 in the Instituto Nacional de Enfermedades Neoplásicas. Results 449 patients had epithelial neoplasms. The main histological types were: squamous cell carcinoma (84.9%), adenocarcinoma (11.0%) and adenosquamous carcinoma (2.4%). The average tumor size was 4.98 cm. Anemia (55.7%), elevated creatinine (21.2%) and hydronephrosis (13.8%) were also identified. 82.3% of the patients presented locally advanced disease. Stages IIB (47.4%) and IIIB (25.8%) were the most common. Overall 5-year survival was 59.5% (I, 90.9%; II, 57.5%; III, 42.7% and IV, 13.3%). Elevated creatinine, anemia, tumor size, parametrial involvement and hydronephrosis were factors that affected survival. No significant relation was found between histological type and survival. The presence of anemia (adjusted hazard ratio [aHR]: 2.5; 95% confidence interval [CI 95%]: 1.6-4.0) and hydronephrosis (aHR: 1.6; CI 95%: 1.0-4.0) were independently associated with survival; likewise, the parametrial commitment with (aHR: 3.3; CI 95%: 1.5-7.2) or without (aRH: 2.6; CI 95%: 1.3-5.3) extension to the pelvic bone. Conclusions Cervical cancer in young Peruvians is diagnosed in advanced stages. Overall survival in each stage is similar to the reported in older patients. The importance of conventional prognosis- related factors was confirmed. Anemia was an important independent prognostic factor requiring further investigations.

Manejo terapéutico y supervivencia del cáncer de cuello uterino en el Instituto Nacional de Oncología y Radiobiología (2004-2010) / Therapeutic management and survival of cervical cancer at the National Institute of Oncology and Radiobiology (2004-2010)

Introducción: el cáncer de cuello uterino es uno de los principales problemas de la salud pública en el mundo por sus altas tasas de incidencia y mortalidad en la mujer. Objetivos: describir el manejo de las pacientes diagnosticadas con cáncer cérvico uterino admitidas y atendidas en el Instituto Nacional de Oncología y Radiobiología. Método: estudio descriptivo, retrospectivo en una serie de 853 pacientes diagnosticadas con cáncer de cuello uterino (estadios IA-IVA, FIGO 2009). Se realizaron pruebas de hipótesis y análisis de supervivencia. Para la estimación de la supervivencia se utilizó el método estadístico de Kaplan-Meier. Se aplicó la prueba de Long Rank para comparar la supervivencia por estratos. Se consideró como diferencia estadísticamente significativa p< 0,05. Resultados: edad promedio de las pacientes, 49,7 años (DS: ± 13,9), 56,6 por ciento no se habían realizado la citología cervical. El seguimiento citológico, según establece el Programa de Diagnóstico Precoz del Cáncer de Cuello Uterino, se cumplió por 84,1 por ciento de las mujeres pesquisadas; en 15,9 por ciento de los casos, el periodo de seguimiento citológico fue superior a los 3 años. El carcinoma epidermoide fue la variedad histológica más frecuente (88,2 por ciento). Del total de pacientes, 87,1 por ciento fueron diagnosticadas en estadios localmente avanzados (FIGO IB2-IVA). La modalidad terapéutica más empleada fue la quimio radioterapia concurrente. La tasa de supervivencia global al diagnóstico fue de 47,2 por ciento. La mediana de supervivencia fue de 4 años. La edad al diagnóstico y el estadio del tumor mostraron una asociación estadísticamente significativa con la supervivencia global (p< 0,005). Conclusiones: la incidencia y mortalidad de cáncer de cuello uterino, así como su estabilidad en el último quinquenio, exigen la realización de estudios de mayor alcance e investigaciones dirigidas a la evaluación de los programas, sistemas y servicios de salud implicados(AU)

Introduction: cervical cancer is one of the main public health problems in the world due to its high incidence and mortality rates in women. Objective: to describe the management of patients diagnosed with uterine cervical cancer admitted and treated at the National Institute of Oncology and Radiobiology. Method: descriptive, retrospective study in a series of 853 patients diagnosed with cervical cancer (stages IA-IVA, FIGO 2009). Hypothesis testing and survival analysis were performed. The Kaplan-Meier statistical method was used to estimate survival. The Long Rank test was used to compare survival by strata. Statistically significant difference was considered p < 0.05. Results: mean age of the patients, 49.7 years (DS: ± 13.9), 56.6 percent had not performed the cervical cytology. Cytological follow-up, according to the Early Diagnosis Program of Cervical Cancer, was met by 84.1 percent of the women surveyed; in 15.9 percent of the cases, the cytological follow-up period was superior to 3 years. Epidermoid carcinoma was the most frequent histological variety (88.2 percent). Of the total number of patients, 87.1 percent were diagnosed in locally advanced stages (FIGO IB2-IVA). The most commonly used therapeutic modality was concurrent chemo radiotherapy. The overall survival rate at diagnosis was 47.2 percent. The median survival was 4 years. Age at diagnosis and tumor stage showed a statistically significant association with overall survival (p < 0.005). Conclusion: cervical cancer incidence and mortality, as well as its stability over the last five years, require more extensive studies and research aimed at evaluating the health programs, systems and services involved(AU)