Submitted by William Justo Figueiro (williamjf) on 2015-07-17T21:35:41Z No. of bitstreams: 1 28c.pdf: 1664499 bytes, checksum: e38ac91534a8d10f05977f5835c56e81 (MD5) / Made available in DSpace on 2015-07-17T21:35:41Z (GMT). No. of bitstreams: 1 28c.pdf: 1664499 bytes, checksum: e38ac91534a8d10f05977f5835c56e81 (MD5) Previous issue date: 2014 / Nenhuma / Esta dissertação é composta por dois artigos, um artigo de revisão sistemática da literatura e um artigo empírico. No primeiro estudo, buscou-se realizar uma revisão sistemática da literatura internacional sobre intervenções clínicas que utilizam o modelo do senso comum. Foram selecionados cinco artigos de um total de 170 encontrados. Os resultados mostraram que os estudos são de intervenções psicológicas diversas e com foco em portadores de doenças crônicas e na prevenção delas em indivíduos saudáveis. No segundo estudo buscouse desenvolver, aplicar e avaliar um protocolo de intervenção utilizando a psicoeducação e o Modelo do Senso Comum no intuito de aumentar o conhecimento em mulheres saudáveis quanto ao câncer de colo de útero, ajustar a percepção de risco, promover e fortalecer condutas de autocuidado e ajustar a percepção da doença. Método: delineamento misto, quase experimental, com a avaliação pré e pós-intervenção com mulheres usuárias de uma Unidade Básica de Saúde de uma capital do sul do Brasil. Os instrumentos utilizados foram: Questionário sociodemográfico, Escala de Avaliação das Capacidades de Autocuidado (ASAA), Brief Illness Perception Questionaire (Brief IPQ), Questionário Percepção de Risco, Folder sobre o câncer de colo de útero. Resultados: a intervenção possibilitou que as mulheres ajustassem a percepção sobre a doença, aumentando a percepção de risco e, com isso, diminuindo a percepção de ameaça da doença. / This essay is divided in two articles. One is based on a systematic literature review and the other is an empirical article. The aim of the first study was to conduct a systematic review of the international literature about psychological interventions based on the Common Sense Model. Five arcticles were selected from a total of 170 found. The results have shown that most of the studies are about psychological interventions focused on the the management of patients with chronical diseases and on the prevention of those diseases in healthy individuals. The second study aims to develop, apply and evaluate an intervention protocol using psychoeducation based on the Common Sense Model, with the purpose to acquire knowledge on cervical cancer, adjust risk perception, promote and enhance selfcare and change illness perception. Method: quasi-experimental design, with evaluation pre and post-intervention with women that use a health care center. The instruments were: Sociodemographic questionnaire, Self-Care Evaluation Scale (ASA-A), Brief Illness Perception Questionnaire (Brief IPQ), Risk Perception Questionnaire, Leaflet about cervical cancer. Results: The intervention allowed women to adjust their perception about the disease, increasing risk perception and reducing the perceived threat of the disease.

O câncer do colo do útero (CCU) é passível de prevenção e tratamento, quando detectado precocemente e seguido do efetivo tratamento. Ainda assim, é o terceiro tipo mais comum entre as mulheres no mundo e mantém-se como a quarta causa de morte por câncer em mulheres no Brasil. Em países desenvolvidos observou-se diminuição importante da incidência e mortalidade por CCU nas últimas décadas, principalmente após a implantação de programas organizados de rastreamento. Estes programas pressupõem uma rede de atenção coordenada de serviços, capazes de oferecer desde o rastreamento populacional com foco e cobertura no grupo mais suscetível até a garantia de tratamento de qualidade quando necessário. A oferta de exames citológicos do colo do útero tem sido uma importante estratégia para o controle deste câncer na população feminina no Brasil. Entretanto supõe-se que um percentual significativo de mulheres, com exames alterados no rastreamento, que são encaminhadas para avaliação colposcópica para confirmação diagnóstica não chega a fazê-la, e o sistema de saúde também não é eficiente para controlar adequadamente esse evento. Nesta direção, estudo observacional, tipo coorte histórica, foi realizado com usuárias de um serviço de Atenção Primária à Saúde (APS) em Porto Alegre, RS, Brasil. O objetivo principal foi avaliar o programa de rastreamento desenvolvido neste serviço, principalmente em relação ao seguimento dos casos positivos identificados no rastreamento. Todas as mulheres que apresentavam lesões precursoras de câncer do colo do útero, no exame citológico (CP), entre 2001-2007, foram elegíveis para o estudo e acompanhadas até agosto de 2011. Avaliou-se a condição prévia de rastreamento, o diagnóstico/tratamento e o seguimento. Para a análise da qualidade do cuidado foram considerados o alcance dos atributos da APS (acesso, longitudinalidade e coordenação dos cuidados) e a efetividade do tratamento e do acompanhamento subsequente. A ausência de CP anterior estava associada à detecção de alteração de maior grau. A maioria das mulheres (94%) foi encaminhada para avaliação ginecológica, sendo que 97% delas compareceram a consulta. O tempo mediano entre as datas do CP alterado e a consulta no serviço de referência foi de 25 dias. Houve a confirmação do diagnóstico em 80% das mulheres que fizeram histologia. Após tratamento, 89% apresentaram CP normal, sendo que 66% têm seguimento subsequente realizado na APS. Estimamos que a vigilância em saúde com auxílio da busca ativa contribuiu para melhorar o acesso e a adesão aos cuidados. Este serviço trabalha para controle do CCU há mais de 20 anos, e as taxas de mortalidade por este câncer são menores do que as encontradas em Porto Alegre. O maior alcance da longitudinalidade e coordenação dos cuidados, características de um serviço orientado pela APS, pode ter relação com estes resultados. / Cervical cancer is preventable and treatable depending on its early detection followed by effective treatment. Even so, it is the third type of cancer more common among women in the world. In Brazil is the fourth cause of death due to cancer among women. In developed countries, an important decrease in incidence and mortality of cervical cancer has been observed in the last decades, mainly after the implementation of organized screening programs. Such programs are responsible for a network of services capable to offer population screening focusing on more susceptible groups, and including the warranty of high quality treatment when necessary. The offer of cytological exams of the uterine cervix has been an important strategy to control this cancer among Brazilian women. However, it is estimated that a significant proportion of women with abnormal screening exams who are referred to colposcopy to diagnostic confirmation do not perform such exam, and the health system is not efficient enough to control this event. In this perspective, a historical cohort study was performed, including women who attended a Primary Care Service in Porto Alegre city, southern Brazil. The main objective was to evaluate the screening program developed in this service, especially regarding the follow-up of positive cases identified during screening. All women who presented cervical cancer precursor lesions in the cytological exam between 2001 and 2007, were eligible for the study and they were followed-up until august 2011. The women condition prior to screening, diagnostic/treatment and follow-up was evaluated. To analyze the quality of care were considered the scope of the Primary Care attributes (access, longitudinality and coordination of care) and effectiveness of treatment and subsequent follow-up. The absence of a previous cytological exam was associated to the detection of a high grade abnormality. The majority of women (94%) were sent to gynecological evaluation and 97% attended the appointment. The median time between the date of the abnormal cytological exam and the appointment was 25 days. There was diagnostic confirmation through biopsy in 80% of the studied women. After treatment, 89% presented normal cytological exam, being 66% performed in the Primary Care Service. It’s estimated that a health surveillance with active search contributed to improve the access and adhesion to the follow-up. This service works to control the cervical cancer for more than 20 years, and the mortality rates of this cancer are lower than those reported for the whole city of Porto Alegre. The greatest extent of longitudinality and coordination of care, characteristics of a service-driven APS, may be related to these results.

O câncer cervical é uma neoplasia muito prevalente na população feminina e está associado à infecção pelo papilomavírus humano (HPV). As oncoproteínas E6 e E7 de HPV de alto risco são as principais responsáveis pelas alterações celulares que levam ao desenvolvimento deste tipo tumoral. A dipeptidil peptidase IV (DPPIV/CD26) é uma enzima que exerce importantes funções relacionadas à progressão tumoral. Diversos estudos demonstram alterações na expressão e atividade desta proteína em diferentes tipos de câncer. Tendo em vista a relação entre a DPPIV/CD26 e o câncer, e que ainda não existem estudos relacionando esta proteína ao câncer cervical, neste estudo inicialmente investigamos a expressão e atividade da DPPIV/CD26 em linhagens celulares de carcinoma cervical humano (SiHa, HeLa e C33A) e em queratinócitos imortalizados (HaCaT). Nossos resultados demonstram uma baixa expressão da DPPIV/CD26 nas linhagens celulares estudadas, sendo praticamente indetectável na linhagem HeLa. Foi verificada a atividade enzimática dipeptidilpeptidásica tanto ligada à membrana quanto solúvel em todas as linhagens. Na presença do inibidor de DPPIV/CD26 (fosfato de sitagliptina) observamos que a linhagem SiHa apresentou um aumento na migração celular, e assim sugerimos que ao menos em parte a migração nesta linhagem é regulada pela atividade enzimática da DPPIV/CD26. A fim de investigar a relação da expressão da DPPIV/CD26 com as oncoproteínas E6 e E7 do HPV, avaliamos sua expressão em queratinócitos normais e transduzidos com estas oncoproteínas. Verificamos que queratinócitos expressando E6 de HPV de alto risco apresentam uma redução na expressão da DPPIV/CD26, e esta regulação parece ser dependente da degradação da p53. Considerando que as linhagens celulares estudadas apresentam baixa expressão e atividade da DPPIV/CD26, para melhor compreender a importância da expressão desta proteína, nós induzimos a superexpressão da DPPIV/CD26 em linhagem de câncer cervical (HeLa) para posterior avaliação dos efeitos em diferentes mecanismos tumorais. Os resultados demonstram uma redução no crescimento de células expressando DPPIV/CD26, sendo este efeito independente da atividade enzimática. Além disso, foi demonstrado que a indução da expressão de DPPIV/CD26 não afeta os mecanismos de migração e adesão celular na linhagem HeLa. Sendo assim, acreditamos que o esclarecimento do papel da DPPIV/CD26 no contexto do câncer cervical possibilita que novas abordagens diagnósticas e terapêuticas sejam implementadas no futuro. / Cervical cancer is a very prevalent neoplasm in female population and is associated with human papillomavirus (HPV) infection. The high risk HPV E6 and E7 oncoproteins are responsible for cellular alterations that lead to the development of this tumor type. The dipeptidyl peptidase IV (DPPIV/CD26) is an enzyme that exerts important functions related to tumor progression. Several studies have shown changes in the expression and activity of this protein in different types of cancer. Considering the relationship between DPPIV/CD26 and cancer, and that there are still no studies relating this protein to cervical cancer, in the present study we first investigated the DPPIV/CD26 expression and activity in human cervical carcinoma cell lines (SiHa, HeLa and C33A) and in immortalized keratinocytes (HaCaT). Our results demonstrate a low DPPIV/CD26 expression in the studied cell lines, being almost undetectable in HeLa cell line. The dipeptidylpeptidasic enzymatic activity was verified both membrane bound and in the soluble form in all cell lines. In the presence of the DPPIV/CD26 inhibitor (sitagliptin phosphate) we observed that SiHa cell line showed an increase in cell migration, thus we suggest that at least in part cell migration in this cell line is regulated by DPPIV/CD26 enzymatic activity. In order to investigate the relationship between DPPIV/CD26 expression and HPV E6 and E7 oncoproteins, we evaluated the expression of this protein in normal keratinocytes or transduced with these oncoproteins. We have found that keratinocytes expressing high-risk HPV E6 present a reduction in DPPIV/CD26 expression, and this regulation appears to be dependent on p53 degradation. Considering that the cell lines studied have low DPPIV/CD26 expression and activity, in order to better understand the importance of the expression of this protein, we induced the DPPIV/CD26 overexpression in a cervical cancer cell line (HeLa) for further evaluation of the effects on different tumor mechanisms. The results demonstrate a reduction in cell growth of DPPIV/CD26 expressing cells, being this effect independent of the enzymatic activity. In addition, it has been demonstrated that the induction of DPPIV/CD26 expression does not affect the cell migration and adhesion mechanisms in the HeLa cell line. Thus, we believe that the elucidation of the DPPIV/CD26 role in the context of cervical cancer enables new diagnostic and therapeutic approaches to be implemented in the future.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-02-18T09:24:00Z No. of bitstreams: 2 Dissertação - Ariadne Ferreira Amaral - 2014.pdf: 1513948 bytes, checksum: a8f7e328246d685685d791753c3b29da (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-02-18T09:26:40Z (GMT) No. of bitstreams: 2 Dissertação - Ariadne Ferreira Amaral - 2014.pdf: 1513948 bytes, checksum: a8f7e328246d685685d791753c3b29da (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2016-02-18T09:26:40Z (GMT). No. of bitstreams: 2 Dissertação - Ariadne Ferreira Amaral - 2014.pdf: 1513948 bytes, checksum: a8f7e328246d685685d791753c3b29da (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-03-14 / The quality of cytopathology womb cervix test is important to ensure the functionality of an organized screening program. Objectives: Evaluate the impact of training of health professionals involved in the screening for cervical cancer in basic health units. Methods: Intervention study developed based on information from the requisition forms of cytopathology tests of women attending seven basic health units in the city of Goiânia-GO. The variables were the woman personal data, anamnesis, clinical examination and the identification of responsible professional for the collection, in the request form for the cytopathology womb cervix test. 21,344 requisition forms were analyzed, of these, 10,672 forms are related the period from January 2007 to April 2009, before the training, and the other 10,672 are for the period July 2010 to December 2012, after the training. Evaluating the impact of training was conducted by comparing the information contained in the requisition forms of cytopathology tests. The training conducted with health professionals was related to filling in the requisition form, collection of cytopathology test, adequacy of the sample, representation of the epithelium and conducts clinics for screening of cervical cancer having as reference the standards of the Ministry of Health. To evaluate the results of the training we used a Pearson chi-square test with significance level p < 0.05. Results: After the training there was a significant increased frequency of school completion, from 67.2% to 92.6% (p < 0.001), the telephone from 78.9% to 98.7% (p < 0.001). Cervical inspection from 86.8% to 96.6% (p < 0.001), and STDs suggestive signs, from 80.8% to 93.5% (p < 0.001). There was a reduction in the exam frequency of less than one year (p < 0.001) and one year of intervals (p < 0.001). There was a reduction in the frequency of Pap smear testing in women under 25 years of age, from 22.0% to 17.9% (p < 0.001). There was a significant increase in the proportion of satisfactory samples from 70.4% to 80.2% (p < 0.001). It was observed a reduction of obscuring factors. The desiccation frequency was 2.9% before training and 2.0% after training (p < 0.001). There was an increase in the frequency representation of endocervical cells from 79.5% to 88.5% (p < 0.001).Conclusions: After the training conducted with health professionals observed a significant improvement in completing the requisition form and Pap smear testing as the frequency and age, recommended by the Ministry of Health. Regarding the Abstract adequacy of the sample there was an increase of satisfactory samples, reducing obscuring factors and better representation of squamous and glandular epithelium. / A qualidade do exame citopatológico do colo do útero é importante para garantir a funcionalidade de um programa de rastreamento organizado. Objetivos: Avaliar o impacto da capacitação dos profissionais de saúde envolvidos no rastreamento do câncer do colo do útero em unidades básicas de saúde. Metodologia: Estudo de intervenção desenvolvido com base nas informações dos formulários de requisição dos exames citopatológicos das mulheres atendidas em sete unidades básicas de saúde do município de Goiânia-GO. As variáveis estudadas foram os dados pessoais da mulher, anamnese, exame clínico e identificação do profissional responsável pela coleta, contidas no formulário de requisição do exame citopatológico do colo do útero. Foram analisados 21.344 formulários de requisição, destes, 10.672 formulários são referentes ao período de janeiro de 2007 a abril de 2009, antes da capacitação, e os outros 10.672 são referentes ao período de julho de 2010 a dezembro de 2012, após a capacitação. A avaliação do impacto da capacitação foi realizada por meio da comparação das informações contidas nos formulários de requisição dos exames citopatológicos. A capacitação realizada com os profissionais de saúde foi relacionada ao preenchimento do formulário de requisição, coleta do exame citopatológico, adequabilidade da amostra, representação do epitélio e condutas clínicas para o rastreamento do câncer do colo do útero, tendo como referencial as normas vigentes do Ministério da Saúde. Para avaliar o resultado da capacitação utilizou-se o teste Qui-quadrado de Pearson com nível de significância de 5%. Resultados: Após a capacitação houve aumento significativo da frequência de preenchimento da escolaridade, de 67,2% para 92,6% (p<0,005), do telefone, de 78,9% para 98,7% (p<0,001). Da inspeção do colo, de 86,8% para 96,6% (p<0,001), e sinais sugestivos de DSTs, de 80,8% para 93,5% (p<0,001). Houve redução da frequência de realização do exame no intervalo menor que um ano (p<0,001) e de um ano (p<0,001). Houve redução da frequência de realização do exame citopatológico em mulheres com menos de 25 anos de idade, de 22,0% para 17,9% (p<0,001). Houve um aumento significativo da proporção de amostras satisfatórias, de 70,4% para 80,2% (p<0,001). Verificou-se redução da ocorrência de fatores obscurecedores. A frequência de dessecamento foi de 2,9% antes da capacitação e de 2,0% após a Resumo capacitação (p<0,001). Houve um aumento da frequência de representação de células endocervicais, de 79,5% para 88,5% (p<0,001). Conclusões: Após a capacitação realizada com os profissionais de saúde observou-se uma melhora significativa no preenchimento do formulário de requisição e na realização do exame citopatológico conforme a periodicidade e faixa etária preconizadas pelo Ministério da Saúde. Em relação à adequabilidade da amostra observou-se aumento das amostras satisfatórias, redução dos fatores obscurecedores e melhor representação dos epitélios escamoso e glandular.

abstract: Biomarkers find a wide variety of applications in oncology from risk assessment to diagnosis and predicting and monitoring recurrence and response to therapy. Developing clinically useful biomarkers for cancer is faced with several challenges, including cancer heterogeneity and factors related to assay development and biomarker performance. Circulating biomarkers offer a rapid, cost-effective, and minimally-invasive window to disease and are ideal for population-based screening. Circulating immune biomarkers are stable, measurable, and can betray the underlying antigen when present below detection levels or even no longer present. This dissertation aims to investigate potential circulating immune biomarkers with applications in cancer detection and novel therapies. Over 600,000 cancers each year are attributed to the human papillomavirus (HPV), including cervical, anogenital and oropharyngeal cancers. A key challenge in understanding HPV immunobiology and developing immune biomarkers is the diversity of HPV types and the need for multiplexed display of HPV antigens. In Project 1, nucleic acid programmable protein arrays displaying the proteomes of 12 HPV types were developed and used for serum immunoprofiling of women with cervical lesions or invasive cervical cancer. These arrays provide a valuable high-throughput tool for measuring the breadth, specificity, heterogeneity, and cross-reactivity of the serologic response to HPV. Project 2 investigates potential biomarkers of immunity to the bacterial CRISPR/Cas9 system that is currently in clinical trials for cancer. Pre-existing B cell and T cell immune responses to Cas9 were detected in humans and Cas9 was modified to eliminate immunodominant epitopes while preserving its function and specificity. This dissertation broadens our understanding of the immunobiology of cervical cancer and provides insights into the immune profiles that could serve as biomarkers of various applications in cancer. / Dissertation/Thesis / Doctoral Dissertation Molecular and Cellular Biology 2018

O câncer de colo do útero é o segundo tumor mais frequente entre as mulheres brasileiras, os tratamentos disponíveis trazem complicações de curto a longo prazo e estudos que avaliam a qualidade de vida destas mulheres ainda são escassos no Brasil. Isto é justificado pela falta de instrumentos específicos e validados para esta finalidade em língua portuguesa (Brasil). Neste estudo objetivou-se testar as propriedades psicométricas dos questionários EORTC QLQ-CX24 e FACT-CX em uma amostra de mulheres brasileiras com câncer do colo do útero. O estudo é metodológico e foi realizado com 100 mulheres tratadas no Hospital de Câncer de Barretos, por meio de três avaliações (no início do estudo, 15 dias e 18 a 24 meses após o início). Foi testada a consistência interna (alfa de Cronbach), reprodutibilidade (coeficiente de correlação intraclasse), validade convergente (correlação com o questionário SF-36 e com o questionário EORTC QLQ-C30), a validade discriminante pelo estadiamento, tipo de tratamento e autoclassificação de saúde e a responsividade pelo método de distribuição dos dados, além da análise da facilidade de compreensão das questões e dos questionários. Confirmou-se a confiabilidade do questionário EORTC QLQ-CX24, a reprodutibilidade foi baixa nas escalas de preocupação sexual, atividade sexual e prazer sexual, bons resultados observou-se ao avaliar a validade convergente e discriminante. A análise da responsividade não confirmou todas as hipóteses. Ao avaliar o questionário FACT-CX, por meio da consistência interna, exceto pela escala de bem-estar emocional, as demais apresentaram valores de Alpha de Cronbach superiores a 0,70. A reprodutibilidade foi satisfatória nas cinco escalas que compõem o FACT- CX. Na análise da validade convergente, somente as escalas de bem-estar físico e bem-estar emocional mostrou boa correlação com as escalas do SF-36. Em geral, o questionário revelou boa validade discriminante, principalmente em relação a autoclassificação da saúde. Resultado satisfatório encontrou-se na análise da responsividade. Em geral observou-se um bom grau de entendimento das questões e dos questionário. Concluindo os questionários desenvolvidos para medir a QVRS em mulheres com câncer de colo do útero EORTC QLQ-CX24 e FACT-CX obtiveram resultados aceitáveis recomendando-se que outros estudos testem a responsividade por outros métodos / Cervical cancer is the second most common tumor among Brazilian women. Available treatments bring short and long-term complications, and studies assessing the quality of life of these women are still rare in Brazil. Such situation is warranted by the lack of specific and validated tools in (Brazilian) Portuguese for such a purpose. The goal of this study was to test the psychometric properties of EORTC QLQ-CX24 and FACT-CX questionnaires in a sample of Brazilian women affected by cervical cancer. This is a methodological study and it was conducted on 100 women treated at the Barretos Cancer Hospital by way of three assessments (at baseline, 15 days and 18 to 24 months after the onset). We tested the internal consistency (Cronbach\'s alpha), reproducibility (intraclass correlation coefficient), convergent validity (correlation with the SF-36 questionnaire and the EORTC QLQ-C30 questionnaire), the discriminant validity by way of staging, type of treatment and health self-classification and responsiveness by the method of data distribution, as well as the analysis of how easy it was their understanding of questions and questionnaires. The reliability of the EORTC QLQ-CX24 questionnaire was confirmed, reproducibility was low in the scales of sexual worry, sexual activity and sexual enjoyment, and good results were observed when evaluating the convergent and discriminant validity. The analysis of responsiveness did not confirm all hypotheses. Upon evaluation of the FACT-CX questionnaire through internal consistency, except for the scale of emotional well-being, the others showed Cronbach\'s alpha values above 0.70. Reproducibility was satisfactory in the five scales comprising FACT-CX. In convergent validity analysis, only the scales of physical well-being and emotional well-being showed good correlation with the scales of the SF-36. In general, the questionnaire demonstrated good discriminant validity, especially in relation to the self-ratings of health. Satisfactory result was found in the analysis of responsiveness. In general there was a good degree of understanding of questions and questionnaires. In conclusion, questionnaires developed to measure HRQOL in women with cervical cancer such as EORTC QLQ-CX24 and FACT-CX achieved acceptable results, and we do recommended that further studies are performed to assess responsiveness by other methods

Perception of cervical cancer screening among Immigrant African women residing in Houston, Texas Esther I. Orji M.Ed., University of Lagos, 2002 B. Ed, Abia State University, 1998 A.C. E. University of Benin, 1990 Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Public Health Walden University August 2016 Disparities in cervical cancer screening participation still exist especially among immigrant and minority women compared to non immigrant populations. Research investigators through multiple studies have explored reasons for non participation in cervical cancer screening among immigrant and minority women. However, there was limited research specifically on how immigrant women of African descent could be empowered to overcome barriers associated with cervical cancer screening in Houston Texas. The purpose of this study was to explore and understand the perceptions of factors which are barriers to perform cervical cancer screening tests among immigrant women of African descent, as well as their beliefs on preventive medicine, and how immigrant women could be empowered in order to overcome barriers associated with cervical cancer screening. The theoretical framework was based on the health belief model. The participants for the study were 20 immigrant women of African descent aged 21-65. A semi-structured interview schedule which comprised of open ended questions was used to collect data on the perspectives of immigrant women towards cervical cancer screening. Data was transcribed verbatim and analyzed thematically. The social change implications of the study can be that immigrant women could be more encouraged to seek access to the appropriate state of the art in cervical cancer screening which could contribute in reducing mortality, morbidity rate, and costs associated with cervical cancer.

Sexual minority women (SMW) demonstrate lower rates of cervical cancer screening than heterosexual women. This is concerning as lesbian and bisexual women tend to engage in higher rates of substance-related cancer risk behaviors, unprotected sex, and tend to have higher body mass indices, all of which are risk factors for cancer development. Another major risk factor, screening avoidance, places SMW at increased risk for the development of high grade cervical lesions in the absence of early detection practices, which is likely to impact overall cervical cancer morbidity in this population. The aim of the present study was to utilize the Health Equity Promotion Model in order to investigate the interplay of medical heterosexism, social and community, behavioral, biological, and social identity/position factors on cervical cancer screening rates in a sample of SMW from a large metro area in the southeastern United States. 145 women who identify as sexual minorities were recruited from local LGBT-friendly venues, events, community organizations, email LISTSERVs, and related social media accounts and were asked to complete a fifteen-minute survey. A series of bivariate correlation, t-test, and multivariate regression analyses were run. Findings from mediation analyses demonstrated that health communication factors mediated the relationship between perceived medical heterosexism and cervical cancer screening outcomes. Further, after accounting for demographic factors, greater provider communication quality, provider trust, eHealth literacy, and ever having an HIV test significantly and differentially predicted cervical cancer screening outcomes in the multivariate models (ps < .05). Findings suggest that health communication factors play an important role in facilitating cervical cancer screenings for SMW, and provider training interventions and policy that focus on reducing medical heterosexism may aid in improving patient-provider relationships in this population.

Cervical cancer, caused by oncogenic (high risk [hr]) human papillomavirus (HPV) subtypes, is the most common cancer in women in Guatemala and the most common cause of cancer mortality in women aged 15-44 years. Visual inspection with acetic acid (VIA) with onsite cryotherapy “test-and-treat” is recommended for underserved Guatemalan indigenous rural women. This research assessed: 1) hrHPV infection prevalence in women screened by VIA; 2) Sensitivity and specificity of VIA in detecting hrHPV infection and cytologically identified precancerous and cancerous lesions; and 3) Factors associated with hrHPV infection. Analysis of anonymous data collected during VIA clinics in 2013 (N = 205) and 2017 (N = 234) for indigenous women aged 21-65 years in six villages showed 22.6% (95% confidence interval [CI]=18.7%-27.2%) had hrHPV cervical infection. VIA results were abnormal in 5.9% (95%CI=3.8%-8.8%). Only nine VIA exams in 89 women with hrHPV were abnormal (Sensitivity=10.1%, 95%CI=4.7%-18.3%), although abnormal VIA was associated with hrHPV (Prevalence Ratio [PR])=1.8; 95%CI=1.1-3.1; P=.05). Of 221 women who had VIA, hrHPV nucleic acid testing and liquid preparation cytology (equivalent to Papanicolaou or “Pap”) testing, 10 (4.7% [95%CI=2.3%-8.5%]) had abnormal cytological results, including one cancer, four high- and five low-grade squamous intraepithelial lesions. VIA sensitivity and specificity for detection of precancerous cytological abnormalities and cancerous lesions were 20.0% (95%CI=2.5%-55.6%) and 96.0% (95%CI=92.3%-98.3%) respectively. In contrast, hrHPV sensitivity and specificity were 100% (95%CI=71.7%-100%) and 88.7% (95%CI: 83.9%-92.7%). In both years combined, women aged fewer than 29 years or reporting fewer than four pregnancies were more likely to have hrHPV cervical infection (36.8%, 27.3%, respectively) than those who were older or reported more pregnancies (18.7; P=.025, respectively); 60.0% reported some form of modern contraception. Progesterone injections or implant users were more likely to have hrHPV infection (31.9%) than women using other or no contraceptives (19.5%); PR=1.6; 95%CI=1.1-2.4; P=.01). These data suggest that VIA may not be sufficiently sensitive for use in cervical cancer screening. “Test-and-treat” screening using hrHPV real-time testing, as recommended by the World Health Organization may be preferable to VIA, and may be acceptable using self-collected specimens.

O câncer cervical é um dos tipos de câncer mais comuns entre as mulheres, e a infecção persistente pelos HPV-16 e HPV-18 é responsável por 70% dos casos. As vacinas profiláticas disponíveis possuem alta eficácia na prevenção da infecção pelos tipos mais prevalentes de HPV. No entanto, este tipo de abordagem não beneficia mulheres que já apresentam lesões precursoras ou tumores cervicais avançados, e a busca por abordagens terapêuticas para esse tipo de câncer é considerada uma necessidade. A qualidade do antígeno representa um aspecto fundamental para o sucesso de vacinas terapêuticas baseadas em proteínas recombinantes. Neste sentido, os sistemas de expressão em células eucarióticas, como leveduras e células de mamíferos são considerados adequados para a produção de proteínas com aplicação biotecnológica. O objetivo principal deste trabalho contemplou a expressão das proteínas de fusão gDE7E6 do HPV-16 e do HPV-18 e a oncoproteína E7 do HPV-16 em células da levedura Pichia pastoris e expressão da gDE7E6 do HPV-16 e do HPV-18 em células de mamífero HEK293T e CHODG-44 para obtenção de antígenos purificados com futura aplicação em vacinas terapêuticas contra tumores associados ao HPV-16 e HPV-18. Os genes que codificam as proteínas gDE7E6 dos HPV-16 e HPV-18 e da E7 do HPV-16 foram clonados no vetor pPIC9K, os quais foram linearizados por digestão enzimática e utilizados na transformação da P. pastoris. A expressão das proteínas foi analisada nos tempos de 24, 48, 72 e 96 horas, no entanto, não foi observada a produção das proteínas no sobrenadante e nem no lisado celular. Diante desta constatação, iniciamos a expressão das proteínas gDE7E6 do HPV-16 e gDE7E6 do HPV-18 em células de mamíferos HEK293T e CHODG-44. As sequências genéticas das proteínas gDE7E6 do HPV-16 e do HPV-18 foram clonadas no vetor de expressão pNU1 e analisadas por digestão enzimática. Análises de SDS-PAGE e western blot demonstraram a expressão das proteínas gDE7E6 do HPV-16 e do HPV-18 em até 96 horas em células HEK293T. Em paralelo, realizamos a transfecção estável dos plasmídeos contendo as sequencias da gDE7E6 do HPV-16 e gDE7E6 do HPV-18 em células CHO-DG44. Com o intuito de aumentar a expressão das proteínas de interesse na população mista de CHODG-44, realizamos amplificação genômica com metotrexato (MTX), sendo possível observar aumento da expressão das proteínas, conforme aumento gradativo nas concentrações de MTX. Posteriormente, foram feitas tentativas para isolar um clone produtor das proteínas gDE7E6 HPV-16 e HPV-18, através de clonagem por diluição limitante e sistema automatizado, sendo possível isolar um clone para cada construção através de matriz semisólida, confirmado por western blot e citometria de fluxo. Apesar de demonstrar a expressão das proteínas de interesse em sistema de expressão baseado em células de mamífero, o rendimento obtido após a purificação por afinidade ao níquel foi extremamente baixo, o que dificulta a obtenção dos antígenos para fins vacinais. / Cervical cancer is one of the most common cancers among women, and persistent infection with HPV-16 and HPV-18 accounts for 70% of the cases. Available prophylactic vaccines are highly effective in preventing infection by the most prevalent types of HPV. However, this type of approach does not benefit women who already have precursor lesions or advanced cervical tumors, and the search for therapeutic approaches to this type of cancer is considered a necessity. Antigen quality represents a key aspect for the success of therapeutic vaccines based on recombinant proteins. In this sense, expression systems based in eukaryotic cells such as yeast and mammalian cells are considered suitable for the production of proteins with biotechnological applications. The main objective of this work was to express the gDE7E6 fusion proteins HPV-16 and HPV-18 and the E7 oncoprotein HPV-16 in Pichia pastoris and expression of gDE7E6 HPV-16 and HPV-18 in mammalian cells HEK293T and CHODG-44 to obtain purified antigens with future applications in therapeutic vaccines against HPV-16 and HPV-18 associated tumors. The genes encoding the gDE7E6 proteins HPV-16 and HPV-18 and E7 HPV-16 were cloned into the pPIC9K vector, which were linearized by enzymatic digestion and used in the transformation of P. pastoris. Expression of the proteins was analyzed at 24, 48, 72 and 96 hours, however, the production of the proteins in the supernatant and in the cell lysate was not observed. In light of this finding, we initiated the expression of gDE7E6 proteins HPV-16 and HPV-18 in mammalian cells HEK293T and CHODG-44. The genetic sequences of gDE7E6 proteins HPV-16 and HPV-18 were cloned into the pNU1 expression vector and analyzed by enzymatic digestion. SDSPAGE and western blot analyzes demonstrated expression of gDE7E6 proteins HPV-16 and HPV-18 within 96 hours in HEK293T cells. In parallel, we performed stable transfection of plasmids containing gDE7E6 HPV-16 and HPV-18 sequences into CHODG44 cells. In order to increase the expression of the proteins in the mixed population of CHODG-44, we performed genomic amplification with methotrexate (MTX), and it was possible to observe an increase in protein expression, as a gradual increase in MTX concentrations. Therefore, attempts were made to isolate a clone producing gDE7E6 proteins HPV-16 and HPV-18 by limiting dilution and automated system, being possible to isolate one clone for each construct through a semisolid matrix, confirmed by western blot and flow cytometry. Despite observing protein expression in mammalian cell-based expression system, the yield obtained after nickel affinity purification was extremely low, which makes it difficult to obtain the antigens for vaccine purposes.