Made available in DSpace on 2014-07-29T15:25:24Z (GMT). No. of bitstreams: 1 Tese-Edna Manrique.pdf: 787735 bytes, checksum: c22ee105b30898fd35080c35bcd1fc80 (MD5) Previous issue date: 2009-06-30 / Objectives: analyze the performance of the 100% rapid re-screening in detecting falsenegative results of cervical screening cervical, in quality control, after routine screening, using the average time of one and two minutes, according to final diagnosis. Methodology: a total 5,235 smears, classified as negative and unsatisfactory by routine screening, were submitted to 100% rapid re-screening method, using the time average of one and two minutes. In these reviews, the smears classified as unsatisfactory or suspects were subjected to detailed review. The concordant results were considered final diagnosis; the differences were meeting for a consensus that defined the final diagnosis. Results: of 5,235 smears submitted rapid re-screening method, of using the time of one minute and two minutes there was sensitivity and specificity of the final method of 64.3% and 99.2% for the time of one minute and two minutes was 63.8% and 99.5%. In smears, with satisfy adequacy for analysis, the sensitivity and specificity of this method, using the time of one and two minutes, were 64.2%, 98.9%, 61.5% and 99.4% respectively. The smears, with the adequacy of the smears presented for analysis limits, the sensitivity and specificity, using the time of one minute, was 64.7%, 99.9% and for two minutes were 70.6% and 99.8%. Of the total of 5,121 cervical smears, had 958 (18.7%) clinical information, after being submitted to rapid rescreening, using the time of one minute, 18 of those were suspects, of which ten were confirmed by final diagnosis as abnormal. When submitted to rapid re-screening using the time of two minutes, 13 were suspects, nine of these were confirmed by final diagnosis as abnormal. A total 4,163 (81.3%) smears had no clinical information, after being submitted to rapid re-screening, using the time of one minute were 70 suspects, of which 35 were classified as abnormal. When submitted to rapid re-screening using the time of two minutes were 54 suspects, of which 35 were confirmed by final diagnosis as abnormal. A rapid re-screening showed a sensitivity to smear with clinical information, using the time of one minute of 83.3% and for two minutes of 75%. Conclusions: the rapid re-screening method of 100% showed no difference in the detection of falsenegative results using the time of a minute or two. The adequacy of the sample does not influence the detection of false-negative results, using both a time as two minutes, and there was no difference in the detection of false-negative smears with and without clinical information using a time-two minutes and finally, in smears with clinical information / Objetivos: analisar o desempenho da revisão rápida de 100% na detecção de resultados falso-negativos dos exames citopatológicos cervicais, no controle da qualidade, após o escrutínio de rotina, utilizando o tempo médio de um e dois minutos, de acordo com o diagnóstico final. Metodologia: um total 5.235 esfregaços, classificados como negativos e insatisfatórios pelo escrutínio de rotina, foram submetidos à revisão rápida, utilizando os tempos médios de um e dois minutos. Nessas revisões, os esfregaços classificados como insatisfatórios ou suspeitos foram submetidos à revisão detalhada. Os resultados concordantes foram considerados como diagnóstico final, os divergentes foram para reunião de consenso que definiu o diagnóstico final. Resultados: dos 5.235 esfregaços submetidos ao método de revisão rápida utilizando o tempo de um e dois minutos, verificou-se uma sensibilidade e especificidade final desse método de 64,3% e 99,2% para o tempo de um minuto e para dois minutos foi 63,8% e 99,5%. Em esfregaços, com a adequabilidade da amostra satisfatória para análise, a sensibilidade e especificidade desse método, utilizando os tempos de um e dois minutos, foram de 64,2%, 98,9%, 61,5% e 99,4%, respectivamente. Em esfregaços, com a adequabilidade da amostra apresentando limitação para análise, a sensibilidade e especificidade, utilizando o tempo de um minuto, foi de 64,7% e 99,9%, para dois minutos foram de 70,6% e 99,8%. Do total de 5.121 esfregaços citopatológicos, 958 (18,7%) tinham informações clínicas, após serem submetidos à revisão rápida, utilizando o tempo de um minuto, 18 desses foram suspeitos, dos quais 10 foram confirmados pelo diagnóstico final como alterados. Quando submetidos à revisão rápida, utilizando o tempo de dois minutos, 13 foram suspeitos, entre eles, nove foram confirmados pelo diagnóstico final como alterados. Um total de 4.163 (81,3%) esfregaços não tinha informações clínicas, após serem submetidos à revisão rápida, utilizando o tempo de um minuto, 70 foram suspeitos, dos quais 35 foram classificados como alterados. Quando submetidos à revisão rápida, utilizando o tempo de dois minutos, 54 foram suspeitos, dos quais 35 foram confirmados pelo diagnóstico final como alterados. A revisão rápida apresentou uma sensibilidade, para esfregaços com informações clínicas, utilizando o tempo de um minuto de 83,3% e para dois minutos de 75%. Conclusões: o método de revisão rápida de 100% não apresentou diferença na detecção de resultados falso-negativos utilizando o tempo de um ou dois minutos. A adequabilidade da amostra não influencia na detecção de resultados falso-negativos, utilizando tanto o tempo de um como dois minutos, bem como não houve diferença na detecção de resultados falso-negativos em esfregaços com e sem informações clínicas através do método de revisão rápida, utilizando o tempo de um e dois minutos.

Introdução: O câncer do colo do útero é um problema de saúde publica, é uma importante causa de morbidade e mortalidade em mulheres de todo mundo. O rastreamento com a citologia de Papanicolaou, quando realizado periodicamente demonstrou ser eficaz na redução de incidência e mortalidade em países desenvolvidos. O rastreamento com unidade móvel de prevenção é uma estratégia para o diagnóstico precoce do câncer do colo do útero. Objetivo: Avaliar os resultados do programa de rastreamento com busca ativa e unidade móvel na detecção precoce do câncer do colo do útero na população das zonas urbana e rural de Barretos. Casuística e Métodos: Estudo retrospectivo, descritivo, com 16.849 mulheres na zona urbana e 1.055 na zona rural de Barretos. O projeto inclui visitas domiciliares repetidas de um profissional de saúde da unidade móvel do Hospital de Câncer de Barretos (HCB), entrevista e coleta de Papanicolaou. Mulheres com diagnóstico citológico de ASC-US, ASC-H, lesões intraepiteliais e carcinoma invasivo, foram convocadas para colposcopia e todas as mulheres com histopatológico de carcinoma foram tratadas e permanecem em seguimento no HCB. Os resultados deste programa foram comparados com dados do registro sobre câncer do colo do útero do Departamento Regional de Saúde V (DRS-V) e da Fundação Oncocentro de São Paulo (FOSP), do mesmo período. Resultados: Na zona urbana 10.350 (61,4%) mulheres foram examinadas e realizaram o exame de Papanicolaou, com taxa de cobertura de 62,9% nas mulheres em idade alvo (25 a 60 anos) do programa brasileiro. Foram identificados 35 casos de carcinoma, sendo 77,1% de carcinoma espinocelular in situ. A idade média foi 41,9 anos, 81,4% das mulheres examinadas eram das classes socioeconômicas D e E, e 88,6% apresentavam exame prévio de Papanicolaou. Na zona rural, 1.055 (100%) mulheres foram entrevistadas, examinadas e realizaram o exame de Papanicolaou, com taxa de cobertura de 74,4% na idade alvo. Foram identificados 6 casos de carcinoma, sendo 83,3% de carcinoma espinocelular in situ. A idade média foi de 39,8 anos, 86,7% nas classes socioeconômicas D e E, e 81,0% das mulheres apresentavam exame de Papanicolaou prévio. Analisamos os dados do programa de rastreamento do HCB e comparamos com os dados, em relação ao estadiamento, da DRS-V e FOSP, no mesmo período. Está análise mostrou que houve uma prevalência de lesões in situ em relação às invasivas no programa de rastreamento do HCB quando comparado à DRS-V (p=0,005) e à FOSP (p<0,001). Conclusões: O rastreamento com busca ativa e unidade móvel é um método efetivo no diagnóstico precoce do câncer do colo do útero / Introduction: Uterine cervical cancer is a public health problem and an important cause of morbidity and mortality among women worldwide. Screening using the Papanicolaou cytological test, when done repeatedly, has been shown to be effective for reducing the incidence and mortality of this disease in developed countries. Screening with an active search using a mobile unit is a strategy for early diagnosis of uterine cervical cancer. Objective: To evaluate the results from a screening program with an active search using a mobile unit for early detection of uterine cervical cancer among the populations in the urban and rural zones of Barretos. Sample and Methods: This was a retrospective descriptive study on 16,849 women in the urban zone and 1,055 in the rural zone of Barretos. The project included repeated home visits by a healthcare professional from the mobile unit of Barretos Cancer Hospital (HCB), interviews and collection of Papanicolaou smears. Women with a cytological diagnosis of ASC-US, ASC-H, intraepithelial lesions and invasive carcinoma were called in for colposcopy examinations. All the women with a histopathological diagnosis of carcinoma were treated and remained under follow-up by HCB. The results were compared with data from the uterine cervical cancer records of the Fifth Regional Health Department (DRS-V) and the Oncocenter Foundation of São Paulo (FOSP), covering the same period. Results: From the urban zone, 10,350 Papanicolaou smears (61.4%) were collected, with a coverage rate of 62.9% of the women at the target age for the Brazilian program. There were 35 cases of carcinoma, of which 77.1% were in situ squamous cell carcinoma. The womens mean age was 41.9 years; 81.4% were in socioeconomic classes D and E; and 88.6% had had a previous Papanicolaou examination. In the rural zone, 1,055 Papanicolaou smears (100.0%) were collected, with a coverage rate of 74.4% of the women at the target age. There were six cases of carcinoma, of which 83.3% were in situ squamous cell carcinoma. The womens mean age was 39.8 years; 86.7% were in socioeconomic classes D and E; and 81.0% had had a previous Papanicolaou examination. We analyzed the data from the HCB screening program in comparison with the staging data from DRS-V and FOSP, over the same period. There were statistically significant differences in the proportions of in situ and invasive carcinoma found in the HCB screening program in relation to DRS-V (p = 0.0046) and in relation to FOSP (p < 0.001). This analysis showed that there was higher prevalence of in situ lesions than of invasive lesions in the HCB screening program. Conclusions: Screening with an active search using a mobile unit is an effective method for early diagnosis of uterine cervical cancer

Este trabalho teve como objetivo avaliar a integralidade no cuidado ao CCU em um município de grande porte populacional e com tecnologia de distinta complexidade disponível. Foi utilizada uma metodologia mista (quanti-quali). Para a abordagem quantitativa utilizou-se a base de dados secundários referentes à citologias e biópsias do sistema de informação municipal e regional. A análise e os testes estatísticos foram realizados pelo software PASW statistic 17.0. A abordagem qualitativa foi realizada por meio de entrevistas semi-estruturadas com usuárias, profissionais e representantes da gestão. Os dados qualitativos foram submetidos a uma análise de conteúdo realizada com o software NVivo 9.0. Na análise dos dados secundários, identificou-se que a cobertura de Papanicolau é insuficiente, sendo concentrada em mulheres mais jovens. As biópsias realizadas são equivalentes à quantidade de citologias alteradas. Os diagnósticos mais graves, tanto de citologias quanto de biópsias, prevalecem em mulheres com idade mais avançada. A abordagem qualitativa indica como potencialidades: o acolhimento, o acesso breve a serviços de média e alta complexidade, o papel ativo da gestão municipal de saúde e como fragilidades: a dificuldade para marcação das consultas na atenção básica, a falta de preparo dos profissionais para dar o diagnóstico, a contra referência tardia por parte do serviço terciário, o incentivo ao uso do Pronto-Atendimento e a formação focada na especialidade. Constata-se neste estudo que os principais gargalos para efetivação da integralidade no município investigado estão concentrados no primeiro nível de atenção à saúde / This study aimed to analyze the completeness in the Cervical Cancer care in a city with a large population and with enough technology health equipment available to the people. It was used a mixed methodology (quantitative and qualitative). For the quantitative approach it was used the database regarding cytology and biopsy exams registered in the city. The analysis and statistical tests were performed by the statistic software SPSS 17.0. A qualitative approach was performed through interviews with users, professionals and members of the health system. Qualitative data were submitted to content analysis performed by the software NVivo 9.0. In the analysis of the content, it was found that coverage of Pap test is insufficient and is concentrated in younger women. The biopsies are equivalent to the amount of the cytology with abnormal results. The severe diagnosis, from both cytology and biopsies, are prevalent in older women. A qualitative approach indicates potentialities: the good reception of the patient, the fast access from both medium and high complexity health services, the active role of municipal health. Weaknesses: the difficulty in scheduling an appointment with a doctor, lack of training to inform the patient about the diagnosis, the encouragement to use emergency care and the overspecialization of the health professionals. It appears from this study that the main gaps for having a complete integrate healthcare system in the investigated city are concentrated in the first level of health care

O Câncer Cervical é um importante problema de saúde pública, causando aproximadamente 270 milhões de mortes anuais. Atualmente, esse câncer é o segundo mais comum em mulheres no mundo, com os maiores índices de incidência ocorrendo nos países em desenvolvimento. O Câncer cervical tem como agente etiológico o Papilomavírus Humano (HPV). O vírus possui DNA circular duplo com genes que codificam oito proteínas, E1, E2, E4, E5, E6, E7 (não estruturais), e L1 e L2 (estruturais) que formam o capsídio viral. A proteína L1 quando produzida em sistema heterólgo de expressão tem a capacidade de auto-arranjo em partículas semelhantes ao vírus chamadas de VLPs (\"Vírus like Particles\"), que são a base das vacinas profiláticas disponíveis, Gardasil® e Cervarix®. Neste trabalho, foram produzidas VLPs da proteína L1 do HPV-16 na levedura metilotrófica Pichia pastoris utilizando dois tipos de vetores de expressão para leveduras, um epissomal e outro integrativo, para os trabalhos de purificação. Inicialmente as amostras obtidas ao final da purificação apresentaram degradação e agregação da proteína L1, além de contaminantes. O protocolo de purificação foi modificado e as amostras obtidas no final do processo de purificação não apresentaram degradação e nem agregação da proteína L1, embora ainda tenha sido detectada a presença de contaminantes e, portanto, as amostras obtidas estavam semi-purificadas. Uma segunda abordagem para o desenvolvimento de uma vacina alternativa foi realizada, na qual foram produzidos candidatos vacinais baseados na proteína L2 do Papilomavírus Humano (L2 do HPV-16, L2 do HPV-18 e L2 Multimérica), e também foram expressas proteínas fusionadas ao domínio ZZ de Staphylococcus aureus, utilizado neste caso como adjuvante. Em geral as proteínas de fusão, ainda que apresentando a fusão em sua forma funcional, geraram uma fraca indução de anticorpos IgG e de anticorpos neutralizantes. Pode-se observar uma produção de anticorpos neutralizantes contra pseudovírus homólogos e heterólogos que dependeu da combinação com os adjuvantes utilizados. Numa tentativa de maximizar a eficiência imunológica dos antígenos utilizados, um novo ensaio de imunização foi realizado com uma formulação conjunta contendo três proteínas (L2 do HPV-16, L2 do HPV-18 e L2 Multimérica), sendo também avaliadas as propriedades de três adjuvantes. A combinação da formulação vacinal com os adjuvantes gerou altos níveis de anticorpos L2-específicos, destacando-se as formulações com o hidróxido de alumínio/MPLA e com a vacina celular Pertussis low. Com a utilização desses adjuvantes, os níveis de anticorpos permaneceram elevados a longo termo. Pode-se observar a imunogenicidade de cada um dos antígenos dependeu de sua formulação com os adjuvantes testados. / Cervical cancer is one of the most important problems of public health, causing nearly 270 million deaths annually. Currently, cervical cancer is the second more common type in women worldwide and the highest incidences occuring in developing countries. Human papillomavirus (HPV) are the ethiologic agents of cervical cancer. HPV have a double-stranded circular DNA genome encoding eight viral proteins, E1, E2, E4, E5, E6, E7 (non-structural), and L1, L2 (structural), the last ones forming the viral capsid. L1 protein expressed in heterologous systems self-assembles into VLPs (\"Virus like Particles\"), the base of prophylactic vaccines available commercially, Gardasil and Cervarix. In this work, we produced VLPs of HPV-16 L1 protein in the methylotrophic yeast Pichia pastoris for purification assays. Initially, samples obtained from purification presented degradation and aggregation of L1 protein and also contaminants. The purification protocol was modified and samples obtained in the new process did not present degradation nor aggregation but the presence of some contaminants could still be detected. Therefore, samples obtained were semi-purified. A second approach to the development of an alternative vaccine was performed with the production of vaccine candidates based on the HPV L2 protein (HPV-16 L2, HPV-18 L2 and Multimeric L2) and we also expressed the same proteins fused to Staphyloccocus aureus ZZ domain, using it as an adjuvant. In general, the fused proteins induced low antibodies titer and low neutralizing antibodies titer when compared to other formulations. Neutralizing antibodies elicited against homologous and heterologous pseudovirus depended on the adjuvant used. In another approach, trying to enhance immunologic antigen efficiencies, an immunization assay was performed with a formulation containing L2 HPV- 16, L2 HPV-18 and Multimeric L2 and the properties of three adjuvants were assessed. The vaccine formulations adjuvanted with alum/MPLA and cellular Pertussis low vaccine induced the highest levels of L2-specific antibodies. In addition, the usage of adjuvants maintained the antibody levels in the long term. The immunogenicity of each antigen depends on the adjuvant combination used.

Introdução: O câncer do colo do útero é um problema de saúde publica, é uma importante causa de morbidade e mortalidade em mulheres de todo mundo. O rastreamento com a citologia de Papanicolaou, quando realizado periodicamente demonstrou ser eficaz na redução de incidência e mortalidade em países desenvolvidos. O rastreamento com unidade móvel de prevenção é uma estratégia para o diagnóstico precoce do câncer do colo do útero. Objetivo: Avaliar os resultados do programa de rastreamento com busca ativa e unidade móvel na detecção precoce do câncer do colo do útero na população das zonas urbana e rural de Barretos. Casuística e Métodos: Estudo retrospectivo, descritivo, com 16.849 mulheres na zona urbana e 1.055 na zona rural de Barretos. O projeto inclui visitas domiciliares repetidas de um profissional de saúde da unidade móvel do Hospital de Câncer de Barretos (HCB), entrevista e coleta de Papanicolaou. Mulheres com diagnóstico citológico de ASC-US, ASC-H, lesões intraepiteliais e carcinoma invasivo, foram convocadas para colposcopia e todas as mulheres com histopatológico de carcinoma foram tratadas e permanecem em seguimento no HCB. Os resultados deste programa foram comparados com dados do registro sobre câncer do colo do útero do Departamento Regional de Saúde V (DRS-V) e da Fundação Oncocentro de São Paulo (FOSP), do mesmo período. Resultados: Na zona urbana 10.350 (61,4%) mulheres foram examinadas e realizaram o exame de Papanicolaou, com taxa de cobertura de 62,9% nas mulheres em idade alvo (25 a 60 anos) do programa brasileiro. Foram identificados 35 casos de carcinoma, sendo 77,1% de carcinoma espinocelular in situ. A idade média foi 41,9 anos, 81,4% das mulheres examinadas eram das classes socioeconômicas D e E, e 88,6% apresentavam exame prévio de Papanicolaou. Na zona rural, 1.055 (100%) mulheres foram entrevistadas, examinadas e realizaram o exame de Papanicolaou, com taxa de cobertura de 74,4% na idade alvo. Foram identificados 6 casos de carcinoma, sendo 83,3% de carcinoma espinocelular in situ. A idade média foi de 39,8 anos, 86,7% nas classes socioeconômicas D e E, e 81,0% das mulheres apresentavam exame de Papanicolaou prévio. Analisamos os dados do programa de rastreamento do HCB e comparamos com os dados, em relação ao estadiamento, da DRS-V e FOSP, no mesmo período. Está análise mostrou que houve uma prevalência de lesões in situ em relação às invasivas no programa de rastreamento do HCB quando comparado à DRS-V (p=0,005) e à FOSP (p<0,001). Conclusões: O rastreamento com busca ativa e unidade móvel é um método efetivo no diagnóstico precoce do câncer do colo do útero / Introduction: Uterine cervical cancer is a public health problem and an important cause of morbidity and mortality among women worldwide. Screening using the Papanicolaou cytological test, when done repeatedly, has been shown to be effective for reducing the incidence and mortality of this disease in developed countries. Screening with an active search using a mobile unit is a strategy for early diagnosis of uterine cervical cancer. Objective: To evaluate the results from a screening program with an active search using a mobile unit for early detection of uterine cervical cancer among the populations in the urban and rural zones of Barretos. Sample and Methods: This was a retrospective descriptive study on 16,849 women in the urban zone and 1,055 in the rural zone of Barretos. The project included repeated home visits by a healthcare professional from the mobile unit of Barretos Cancer Hospital (HCB), interviews and collection of Papanicolaou smears. Women with a cytological diagnosis of ASC-US, ASC-H, intraepithelial lesions and invasive carcinoma were called in for colposcopy examinations. All the women with a histopathological diagnosis of carcinoma were treated and remained under follow-up by HCB. The results were compared with data from the uterine cervical cancer records of the Fifth Regional Health Department (DRS-V) and the Oncocenter Foundation of São Paulo (FOSP), covering the same period. Results: From the urban zone, 10,350 Papanicolaou smears (61.4%) were collected, with a coverage rate of 62.9% of the women at the target age for the Brazilian program. There were 35 cases of carcinoma, of which 77.1% were in situ squamous cell carcinoma. The womens mean age was 41.9 years; 81.4% were in socioeconomic classes D and E; and 88.6% had had a previous Papanicolaou examination. In the rural zone, 1,055 Papanicolaou smears (100.0%) were collected, with a coverage rate of 74.4% of the women at the target age. There were six cases of carcinoma, of which 83.3% were in situ squamous cell carcinoma. The womens mean age was 39.8 years; 86.7% were in socioeconomic classes D and E; and 81.0% had had a previous Papanicolaou examination. We analyzed the data from the HCB screening program in comparison with the staging data from DRS-V and FOSP, over the same period. There were statistically significant differences in the proportions of in situ and invasive carcinoma found in the HCB screening program in relation to DRS-V (p = 0.0046) and in relation to FOSP (p < 0.001). This analysis showed that there was higher prevalence of in situ lesions than of invasive lesions in the HCB screening program. Conclusions: Screening with an active search using a mobile unit is an effective method for early diagnosis of uterine cervical cancer

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection in the U.S., where one HPV-related cancer is diagnosed every 20 minutes. The most common HPV-related cancer is cervical cancer, with an estimated incidence of 12,000 cases annually, a third of which lead to death. Cervical cancer disparately affects women of ethnic minority groups and geographically isolated regions, such as Appalachia. Tennessee ranks third highest in cervical cancer incidence in the country. Many cases of cervical cancer could be prevented through vaccination against HPV, however, vaccination rates for females in Tennessee are among the lowest in the country. This mixed-methods study included an in-depth exploration of the factors that influence HPV vaccine acceptance in Appalachian Tennessee. Healthcare providers, mothers of adolescent girls, and college-aged women were recruited to participate in the study. From October 2016 to January 2017, interviews were conducted with healthcare providers (n=12), focus groups were conducted with mothers (n=13), and a survey was administered to college women (n=479). Interview and focus group sessions were recorded, transcribed and analyzed using a thematic framework. Survey responses were analyzed using descriptive tests, comparison of means, and regression analyses. The predominant barriers to vaccine acceptance identified in the study were: cost and novelty of the vaccine, vaccine safety, lack of school-entry requirement, and the implication of vaccine acceptance on adolescents’ sexual activity. Most negative perceptions towards the vaccine appeared to be propagated by the sociocultural influence on sex and reproductive health communication within the community. Perceived benefits for cancer prevention and receipt of strong and personal provider recommendations facilitated vaccine acceptance. Additionally, college students who reported vaccine acceptance reported discussing sexual health topics with their mothers more often than those who had not been vaccinated. The findings from this study provide foundational insights about the facilitators and barriers of HPV vaccine acceptance in Appalachian Tennessee. Identifying and understanding these factors is crucial to improving HPV vaccination rates and essential to maximizing the primary benefit of the vaccine in addressing the existing cervical cancer disparity in the region.

Thesis (M. A. (Social Work)) --University of Limpopo, 2018 / Cancer of the cervix is second type of cancer among women in developing countries, and a common problem among women of low socio-economic status in rural communities. The spiral increase of the problem is aggravated by some socio-economic, structural, cultural and political factors. Understanding the risk factors associated with the disease is a step forward towards effective prevention and treatment. Numerous studies have been conducted on knowledge and perceptions of cervical cancer however the information on cervical cancer is still not reaching the majority of women. The study explored the perceptions and attitudes of rural women of Matebeleng village towards cervical cancer, the risk factors, screening tests and the HPV vaccines. A qualitative exploratory case study was conducted. Self-reported data was collected from 22 women. Two focus groups of 7 and 9 and 6 face-face individual interviews were conducted using a semi-structured interview guide. Data was analysed thematically. The research findings revealed that the majority of women in the rural area where the study was conducted never heard of cervical cancer and only few received inadequate information. Few highlighted some of the risk factors but some information was incorrect. Very few participants had only once been screened and the majority have never been tested for cervical cancer. Some became aware of the vaccine through the consent forms from school even though they did not exactly understand the content. The sources of information were the radio, health clinic and random women. The concerns of those who were screened were lack of feedback from the clinic nursing staff after the test, lack of adequate preparation and information before been screened to allay fear and doubt of the unknown and lack of reach out programmes to rural communities. The methods of disseminating information to rural women in their distinct contexts should be examined. Conventional traditional ways of reaching out to rural women could perhaps produce improved results through the integrated approach involving multi-disciplinary teams in educating communities. Key Words: Perceptions, attitudes, rural-based women, cervical cancer, risk factors, screening tests, HPV vaccine

Introduction : Depuis 2007, la vaccination contre les infections à papillomavirus humains (HPV) est recommandée en complément du dépistage du cancer du col utérin (CCU). Cependant, au vu de la faible couverture vaccinale en France, l’impact épidémiologique de la vaccination est discuté, ainsi que le choix de la population cible et les moyens déployés pour son adhésion à la recommandation. Cette thèse propose des données et des outils originaux pour l’évaluation et l’optimisation de l’impact de la vaccination HPV en France. Pour les aspects quantitatifs, une modélisation de la transmission de l’infection à HPV appuyée sur des données détaillées décrivant les partenariats sexuels dans la population générale est nécessaire. L’exploration du lien potentiel entre la participation au dépistage du CCU des femmes précaires et leur choix d’administrer le vaccin HPV à leurs filles, l’appréciation de l’acceptabilité de la vaccination à partir des réseaux sociaux, et l’évaluation médico-économique de la pertinence de l’extension de la vaccination aux hommes, sont déterminants pour parfaire le ciblage des populations à atteindre.Méthodes : Nous avons développé une plateforme de modélisation destinée à l'étude des contacts sexuels et de la dynamique de transmission des infections par les HPV à partir des données de l’enquête Contexte de la Sexualité en France. Grâce à des modèles de mélange de lois, nous avons identifié des classes latentes d’activité sexuelle, permettant de définir des profils à risque d’infections sexuellement transmissibles. Ensuite, nous avons interrogé les femmes consultant au sein du Centre de Prévention et d’Éducation pour la Santé de Lille, ayant au moins une fille éligible à la vaccination HPV, sur leurs attitudes vis-à-vis du dépistage du CCU et de la vaccination. Puis, nous avons analysé les opinions exprimées par les internautes sur le forum en ligne d’un site d’information en santé, concernant la sécurité, l’efficacité et la perception du vaccin HPV. Enfin, nous avons réalisé une revue systématique des études médico-économiques relatives à l’extension de la vaccination HPV aux hommes.Résultats : Les simulations sur la plateforme de modélisation ont permis de reproduire les données de prévalence des infections à HPV mais les résultats restent sensibles aux hypothèses sur les comportements sexuels qui présentent des incohérences entre les hommes et les femmes. Cinq classes latentes d’activité sexuelle ont été identifiées pour les hommes ainsi que pour les femmes. Le cluster correspondant au niveau d’activité sexuelle le plus élevé représente 3,3% chez les femmes et 4,8% chez les hommes. Par ailleurs, le statut vaccinal des filles ne diffère pas selon le profil de dépistage de leur mère. L’argument majoritairement rapporté par les mères pour justifier la non-vaccination de leurs filles concerne le manque d’information, surtout parmi celles qui ne se dépistent pas. De plus, les opinions négatives, exprimées sur le forum de discussion en ligne, sont passées de 28,6 % des avis exprimés en 2006 à 42,2 % en 2013. Les arguments avancés par les « anti-vaccinaux » concernent la sécurité du vaccin et la perception de la vaccination. Enfin, les modèles médico-économiques montrent que l’extension de la vaccination aux hommes est très rarement une stratégie coût-efficace. Néanmoins, la vaccination ciblée des homosexuels masculins semble être la stratégie optimale du point de vue éthique et médico-économique.Discussion : La plateforme de modélisation des contacts sexuels constitue le socle de l’évaluation de l’impact de la vaccination HPV. La surveillance des forums de discussion en ligne permet le monitoring de l’acceptabilité de la vaccination et le ciblage des actions d’information. L’optimisation de couverture vaccinale nécessite la mise en place d’un programme organisé de vaccination des jeunes filles. À défaut d’une implémentation en milieu scolaire, les centres de prévention offrent une alternative intéressante. / Introduction: Since 2007, prophylactic vaccination against human papillomavirus (HPV) has been recommended in addition to cervical screening in French women. However, given the low vaccine coverage in France, the epidemiological impact of the vaccination is debated, as well as the choice of the target population and the means to ensure compliance with the recommendation. This doctoral thesis provides original data and tools for the evaluation and the improvement of the impact of HPV vaccination in France. For quantitative aspects, modelling HPV transmission based on the best data describing sexual partnerships in the general population is essential. The investigation of potential links between participation to cervical screening of deprived women and their choice of vaccinating their daughters, the appraisal of vaccine acceptability through social media and the cost-effectiveness evaluation of the relevance of extending the HPV vaccination program to include males are key elements to improve the focus on targeted populations.Methods: We developed a modelling platform to study the dynamics of HPV transmission, using data from Social Context of Sexuality, the latest national French sexual behavior study. Using finite mixture models, we identified latent classes of sexual activity to define profiles of partner acquisition with age, likely to have different risks of sexually transmitted infections. Then, we asked women attending the Centre for Preventive Medicine and Health Education of Lille, who had at least a daughter eligible for HPV vaccination, about their attitudes towards cervical screening and HPV vaccination. Next, we explored sentiments about HPV vaccine safety, efficacy and perceptions, spontaneously expressed by web users on the online discussion forum of a French-speaking health information website. Finally, we performed a systematic review of the cost-effectiveness studies about extending HPV vaccination to include males.Results: Simulations from the modelling platform reproduced HPV infection prevalence observed in France. Nevertheless, results were sensitive to assumptions about sexual behavior, with discrepancies between men and women. Five latent classes of sexual activity were identified in men and in women. The cluster describing the highest level of sexual behavior represents 3.3% in women and 4.8% in men. Besides, daughters’ vaccination profile did not differ with their mothers’ profile of participation to cervical screening. The main reason for not vaccinating their daughters reported by mothers was lack of information, especially for those non-compliant with cervical screening recommendations. Moreover, negative sentiments, reported by the health website forum, evolved from 28.6% of total opinions in 2006 to 42.2% in 2013. The arguments expressed by “anti-vaccine” postings involved most often vaccine safety and negative vaccine perceptions. Finally, cost-effectiveness analyses show that extending the HPV vaccination program to include males is rarely found to be a cost-effective strategy. Nevertheless, the targeted vaccination of men having sex with men seems to be the best strategy from ethical and cost-effectiveness points of view.Discussion: The modelling platform of sexual contacts represents the basis of the evaluation of HPV vaccination impact. The surveillance of online forums enables the monitoring of vaccine acceptability and hence the targeting of preventive messages. Improving the HPV vaccine coverage requires offering girls and young women an organized vaccination program. In the lack of a school-based vaccination program, Centres for Preventive Medicine and Health Education offer an interesting alternative.

The first aim of the research was to determine the applicability of certain variables from the Health Belief Model (HBM), the Theory of Reasoned Action (TRA), the risk dimensions from the Psychometric Paradigm, the Common-Sense Model of Illness Representations and the Locus of Control to Italian women’s beliefs and behaviours in relation to screening mammography. These models have predominantly been derived and evaluated with English-speaking persons. The study used quantitative and qualitative methods to enable explanation of research-driven and participant-driven issues. The second aim was to include Italian women in health behaviour research and to contrast the Italian sample with the Anglo-Australian sample to determine if differences exist in relation to their beliefs. In Australia many studies in health behaviour research do not include women whose first language is not English. The third aim was to evaluate the Anti-Cancer Council of Victoria’s (ACCV) Community Language Program (CLP) by: (a) identifying the strengths and weaknesses of the program as seen by the participants; and (b) assessing the impact of the program on women’s knowledge and beliefs about breast cancer, early detection of breast cancer, self-reported and intended breast screening behaviours. The CLP is an information service that uses women’s first language to convey information to women whose first language is not English. The CLP was designed to increase knowledge about breast and cervical cancer. The research used a pre-test-intervention-post-test design with 174 Italian-born and 138 Anglo-Australian women aged 40 years and over. Interviews for the Italian sample were conducted in Italian. The intervention was an information session that related to breast health and screening mammography. Demographic variables were collected in the Pre-Test only. Qualitative open-ended questions that related specifically to the information session were collected in the Post-Test phase of the study. Direct logistic regression was used with the participants’ beliefs and behaviours to identify the relevant variables for language (Italian speaking and English-speaking), attendance to an information session, mammography screening and breast self-examination (BSE) behaviour. Pre- and Post-Test comparisons were conducted using chi-square tests for the non-parametric data and paired sample t-tests for the parametric data. Differences were found between the Italian and Anglo-Australian women in relation to their beliefs about breast cancer screening. The Italian women were: (1) more likely to state that medical experts understood the causes of breast cancer; (2) more likely to feel that they had less control over their personal risk of getting breast cancer; (3) more likely to be upset and frightened by thinking about breast cancer; (4) less likely to perceive breast cancer as serious; (4) more likely to only do what their doctor told them to do; and (5) less likely to agree that there were times when a person has cancer and they don’t know it. A pattern emerged for the Italian and Anglo-Australian women from the logistic regression analyses. The Italian women were much more likely to comply with medical authority and advice. The Anglo-Australian women were more likely to feel that they had some control over their health. Specifically, the risk variable ‘dread’ was more applicable to the Italian women’s behaviour and internal locus of control variable was more relevant to the Anglo-Australian women. The qualitative responses also differed for the two samples. The Italian women’s comments were more general, less specific, and more limited than that of the Anglo-Australian women. The Italian women talked about learning how to do BSE whereas the Anglo-Australian women said that attending the session had reminded them to do BSE more regularly. The key findings and contributions of the present research were numerous. The focus on one cultural group ensured comprehensive analyses, as did the inclusion of an adequate sample size to enable the use of multivariate statistics. Separating the Italian and Anglo-Australian samples in the analyses provided theoretical implications that would have been overlooked if the two groups were combined. The use of both qualitative and quantitative data capitalised on the strengths of both techniques. The inclusion of an Anglo-Australian group highlighted key theoretical findings, differences between the two groups and unique contributions made by both samples during the collection of the qualitative data. The use of a pre-test-intervention-post-test design emphasised the reticence of the Italian sample to participate and talk about breast cancer and confirmed and validated the consistency of the responses across the two interviews for both samples. The inclusion of non-cued responses allowed the researcher to identify the key salient issues relevant to the two groups. The limitations of the present research were the lack of many women who were not screening and reliance on self-report responses, although few differences were observed between the Pre- and Post-Test comparisons. The theoretical contribution of the HBM and the TRA variables was minimal in relation to screening mammography or attendance at the CLP. The applicability of these health behaviour theories may be less relevant for women today as they clearly knew the benefits of and the seriousness of breast cancer screening. The present research identified the applicability of the risk variables to the Italian women and the relevance of the locus of control variables to the Anglo-Australian women. Thus, clear cultural differences occurred between the two groups. The inclusion of the illness representations was advantageous as the responses highlighted ideas and personal theories salient to the women not identified by the HBM. The use of the illness representations and the qualitative responses further confirmed the relevance of the risk variables to the Italian women and the locus of control variables to the Anglo-Australian women. Attendance at the CLP did not influence the women to attend for mammography screening. Behavioural changes did not occur between the Pre- and Post-Test interviews. Small incremental changes as defined by the TTM and the stages of change may have occurred. Key practical implications for the CLP were identified. Improving the recruitment methods to gain a higher proportion of women who do not screen is imperative for the CLP promoters. The majority of the Italian and Anglo-Australian women who attended the information sessions were women who screen. The fact that Italian women do not like talking or thinking about cancer presents a challenge to promoters of the CLP. The key theoretical finding that Italian women dread breast cancer but comply with their doctor provides clear strategies to improve attendance at mammography screening. In addition, the inclusion of lay health advisors may be one way of increasing attendance to the CLP by including Italian women already attending screening and likely to have attended a CLP session. The present research identified the key finding that improving Anglo-Australian attendance at an information session is related to debunking the myth surrounding familial risk of breast cancer and encouraging the Anglo-Australian women to take more control of their health. Improving attendance for Italian women is related to reducing the fear and dread of breast cancer and building on the compliance pattern with medical authority. Therefore, providing an information session in the target language is insufficient to attract non-screeners to the session and then to screen for breast cancer. Suggestions for future research in relation to screening mammography were to include variables from more than one theory or model, namely the risk, locus of control and illness representations. The inclusion of non-cued responses to identify salient beliefs is advantageous. In addition, it is imperative to describe the profile of the cultural sample in detail, include detailed descriptions of the translation process and be aware of the tendency of Italian women to acquiesce with medical authority.

<p>2-Methoxyestradiol (2-ME), a metabolite of 17β-estradiol, is a potent antitumor and antiangiogenesis agent in vitro and in vivo. This study aimed to investigate the effects of 2-ME on human cervical and endometrial cancers in vitro and in vivo. Human cervical cancer HeLaS3 cells, endometrial cancer HEC-1-A and RL-95-2 cells, and severe combined immune deficient (SCID) mice were used. On cervical cancer HeLaS3 cells, 2-ME inhibited the cell growth which is accompanied by apoptosis via iNOS pathway and by G₂/M cell cycle arrest. 2-ME had slight effects on normal cervical epithelial cells. In vivo on SCID mice, 2-ME (75 mg/kg p.o.) inhibited the growth of human cervical carcinoma by 34% (p < 0.05) and showed slight side effects to liver and spleen. On human endometrial cancer cells (HEC-1-A and RL-95-2 cells), 2-ME inhibited the growth by blocking cell cycle progress in S- and G₂/M-phase in both cell types, and by inducing apoptosis in HEC-1-A cells and by causing necrosis in RL-95-2 cells. 2-ME had no effects on normal endometrial cells. The apoptotic effect, in HEC-1-A cells, was prevented by iNOS-inhibitor 1400W and eliminated by Caspase-inhibitor Z-VAD-FMK. The necrosis, on RL-95-2 cells, was due to a severe disruption of the mitochondrial membrane potential. Unfortunately, 2-ME had no significant effects on endometrial cancer xenografts. It showed slight toxicity to liver, spleen and proliferative effect on uterus. In conclusion, 2-ME inhibits the growth of human cervical and endometrial cancer cells in vitro. However, a weaker anti-tumor effect was observed in our animal model and 2-ME was slightly toxic to liver and spleen. Considering the proliferative effect on uterus, 2-ME might not be a suitable therapeutic agent in gynecological tumors.</p>