Thesis--University of Oklahoma. / Bibliography: leaf 87.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A pesquisa objetivou analisar os fatores de risco para a descontinuidade na detecÃÃo precoce do cÃncer de colo uterino. Trata-se de um estudo retrospectivo, documental, quantitativo, desenvolvido no Centro de Parto Natural LÃgia Barros Costa. Do total de 3357, foram analisados 2878 prontuÃrios de mulheres atendidas no setor de prevenÃÃo ginecolÃgica, desde o inÃcio do seu funcionamento atà dezembro de 2011, apÃs aplicaÃÃo dos critÃrios de inclusÃo, quais sejam: ter iniciado atividade sexual e ter realizado a coleta citolÃgica. Os dados foram coletados de marÃo a setembro de 2013. O instrumento foi validado por trÃs juÃzes e consistiu em um formulÃrio estruturado composto por variÃveis de identificaÃÃo, histÃrico geral, ginecolÃgico, sexual e obstÃtrico da paciente e a avaliaÃÃo da continuidade do cuidado em detecÃÃo precoce do cÃncer de colo uterino, avaliada pela periodicidade adequada e retorno para busca do laudo citopatolÃgico. Verificou-se as associaÃÃes entre a descontinuidade e as variÃveis independentes por meio dos seguintes testes: qui-quadrado e anÃlise de regressÃo logÃstica. A idade das mulheres variou de 12 a 91 anos, com uma mediana de 33 anos. A maioria das mulheres 1343 (53,8%) possuÃa apenas o ensino fundamental, 1426 (56,5%) eram casadas ou conviviam em uniÃo estÃvel, 130 (63,1%) trabalhavam fora de casa, e 1651 (57,4%) residiam no mesmo bairro da instituiÃÃo. A infecÃÃo pelo HPV foi a DST mais frequente, acometendo 184 (77%) das mulheres. Do total, 1623 (56,4%) mulheres apresentavam alguma queixa que motivou a consulta. Em relaÃÃo aos mÃtodos contraceptivos, observou-se que 942 (35%) mulheres utilizavam contraceptivo hormonal (oral e/ou injetÃvel), 722 (26,9%) utilizavam o preservativo, 383 (14,2%) eram laqueadas e 525 (19,5%) nÃo utilizavam nenhum mÃtodo. A maioria das mulheres analisadas apresentou descontinuidade na detecÃÃo precoce do CCU, 2516 (87,4%), com 669 (23,2%) que nÃo receberam o laudo do Ãltimo exame e a quase totalidade da amostra, 2460 (96,6%) apresentou periodicidade inadequada na realizaÃÃo do teste. O estudo evidenciou os seguintes fatores de risco para a descontinuidade na detecÃÃo precoce do CCU: morar no bairro comum à instituiÃÃo (p=0,024), nÃo morar com companheiro (p=0,013), nÃo ter diagnÃstico de hipertensÃo arterial (p=0,038), baixo nÃmero de consultas para coleta citolÃgica (p=0,000), apresentar queixa no exame (p=0,035), nÃo estar em amenorrÃia (p=0,005) ou menopausa (p=0,021), nÃo utilizar preservativo (p=0,009), apresentar dispareunia (p=0,027) e ter iniciado a vida sexual atà os 20 anos de idade (p=0,039). Conclui-se que a prevalÃncia de descontinuidade na detecÃÃo precoce do CCU à alta na populaÃÃo estudada. A identificaÃÃo dos fatores de risco pode direcionar aÃÃes de educaÃÃo em saÃde com vistas a promover o conhecimento dessa populaÃÃo, visando maior adesÃo à realizaÃÃo do exame na periodicidade correta e a busca do laudo citopatolÃgico.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Estudo desenvolvido com o objetivo de testar os efeitos das intervenÃÃes comportamentais e educativas por telefone no comparecimento das mulheres à consulta de retorno para receber o resultado do exame colpocitolÃgico. Este à um estudo experimental randomizado controlado, realizado a partir de trÃs grupos: educativo (intervenÃÃo educativa via telefone), comportamental (lembrete telefÃnico) e comparaÃÃo (usual â cartÃo de marcaÃÃo). Os dados foram coletados de janeiro a agosto de 2014, no Centro de Desenvolvimento Familiar (CEDEFAM), situado no bairro Planalto Pici, Fortaleza, CearÃ. A amostra totalizou 510 mulheres, conforme os seguintes critÃrios de inclusÃo: ter iniciado atividade sexual, realizar o exame de prevenÃÃo do cÃncer do colo uterino no perÃodo da coleta de dados e possuir telefone mÃvel ou fixo. O instrumento aplicado referente ao inquÃrito CAP (Conhecimento, Atitude e PrÃtica) havia sido validado anteriormente em outro estudo experimental. Para padronizar a intervenÃÃo educativa elaborou-se um roteiro segundo os preceitos da entrevista motivacional. Os dados foram analisados com o auxÃlio do programa estatÃstico Statistical Package for the Social Sciences (SPSS), versÃo 20.0. As informaÃÃes referentes ao conhecimento deixaram evidente que, embora, 96,9% jà tivessem ouvido falar sobre a prevenÃÃo do cÃncer do colo uterino, somente 33,7% demonstraram conhecimento adequado. Na avaliaÃÃo da atitude 40,8% foram classificadas com atitude adequada, enquanto a prÃtica revelou 72,2% de adequabilidade. Das 510 mulheres estudadas, 429 (84,1%) retornaram para buscar o resultado do exame, o que totalizou uma taxa geral de nÃo retorno de 15,9%. Entre as 429 participantes, 64,1% compareceram na data aprazada e os grupos educativo e comportamental foram os mais assÃduos. As mulheres que receberam uma dessas duas intervenÃÃes apresentaram 7,3% de nÃo retorno e 6,2 (IC 95%: 3,7-10,5) vezes mais chances de comparecer ao serviÃo em relaÃÃo ao grupo comparaÃÃo. A anÃlise individual das intervenÃÃes provou que ambas sÃo eficazes, jà que a comportamental aumentou a chance da mulher comparecer ao serviÃo em 7,1 vezes (IC 95%: 3,6-14,2) e a educativa, em 5, 5 (IC 95%: 2,9-10,4). As taxas de nÃo retorno foram, respectivamente, 6,5% e 8,2%, contra 33,1% no grupo comparaÃÃo. Portanto, as intervenÃÃes comportamentais e educativas por telefone configuram estratÃgias de base populacional eficazes para o retorno e, assim, o sucesso no rastreamento e seguimento das lesÃes precursoras do cÃncer cÃrvico-uterino. / Study developed to test the effects of behavioral and educational interventions by phone in women on receiving the results of Pap test. It is, therefore, a randomized controlled experimental study conducted on three groups: education (educational intervention by telephone), behavioral (telephone reminder) and comparison (usual â reminder chart). Data were collected from January to August 2014 in the Family Development Center (CEDEFAM), located in the Planalto Pici neighborhood, Fortaleza, CearÃ. The sample included 510 women, according to the following inclusion criteria: already having initiation of sexual activity, take the examination for the prevention of cervical cancer in the data collection period and have a mobile phone or landline. The KAP survey instrument applied has been validated in a previous experimental study. In order to standardize the educational intervention, a guide based by motivational interviewing was formulated. Data were analyzed with the Statistical Package for Social Sciences (SPSS), version 20.0. Information about the knowledge showed that, although 96,9% had heard about the prevention of cervical cancer, only 33,7% demonstrated adequate knowledge. In assessing the attitude, 40,8% were classified as appropriate and 72,2% had an adequate practice. Of the 510 women studied, 429 (84,1%) returned to check the test results, which amounted to a general rate of no return of 15,9%. Among the 429 participants, 64, 1% attended at the due date, and the educational and behavioral groups was the most frequent. Women who received one of the two interventions showed 7,3% of no return and 6,2 (CI 95%: 3,7-10,5) times more likely to attend the service compared to the comparison group. Individual analysis of interventions proved that both are effective, because the behavioral increased the chance of women attending the service at 7,1 (CI 95%: 3,6-14,2) times and the educational at 5,5 (CI 95%: 2,9-10,4). Non-return rates were, respectively, 6,5% and 8,2%, compared to 33,1% in the comparison group. Therefore, behavioral and educational interventions by phone can be configured as effective population-based strategies for the return, being thus successful in the screening and follow up of cervical cancer precursor lesions.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-09-19T12:24:49Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação - Giwellington Albuquerque - AVALIAÇÃO IMUNOHISTOQUÍMICA DA ONCOPROTEÍNA E6, P16INK4a.pdf: 2878324 bytes, checksum: 0e191e85139b55d89a691fa2d3d6418f (MD5) / Made available in DSpace on 2016-09-19T12:24:49Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação - Giwellington Albuquerque - AVALIAÇÃO IMUNOHISTOQUÍMICA DA ONCOPROTEÍNA E6, P16INK4a.pdf: 2878324 bytes, checksum: 0e191e85139b55d89a691fa2d3d6418f (MD5) Previous issue date: 2016-02-16 / CAPES / O Câncer de colo uterino é o quarto mais comum em mulheres no mundo. Sabe-se que a carcinogênese cervical precede da infecção e persistência do Papilomavírus humano (HPV), o qual tem a capacidade de se integrar ao genoma do hospedeiro introduzindo os genes E6 e E7. O produto desses genes, as oncoproteínas E6 e E7 perturbam o ciclo celular promovendo superexpressão da proteína p16INK4a e as metaloproteinases de matriz (MMP), que são moléculas capazes de promover a progressão das lesões cervicais uterinas. Nesse intuito, o presente estudo avaliou a expressão da oncoproteína E6, p16INK4a, metaloproteinase de matriz 3 (MMP-3) e inibidor tissular de metaloproteínase 2 (TIMP-2) nos diferentes graus de lesões e câncer cervical, associando com a presença do HPV e seus genótipos. Foram utilizadas 86 amostras de escovado cervical e de fragmentos de biopsias de mulheres que foram diagnosticadas citologicamente com lesões cervicais intraepiteliais e invasivas. Todas as amostras foram genotipadas e submetidas a técnica de imunohistoquímica para a identificação da oncoproteína E6-HPV16/18, p16INK4a, MMP-3 e TIMP-2. O perfil genotípico identificou o HPV16 (44,4%) como o mais prevalente, seguido por HPV31 (30,3%), HPV58 (15,1%), HPV18 (6,1%) e HPV33 (4,1%). A reação imunohistoquímica para E6 se mostrou mais intensa nos casos de invasão, assim como p16INK4a. Entretanto MMP-3 e o TIMP-2 se mostraram mais reativos em lesões pré-malignas. Portanto, este estudo mostra maior prevalência do HPV-16 em mulheres atendidas no Hospital das Clínicas – UFPE e sugere que a oncoproteína E6 e a proteína p16INK4a são biomarcadores úteis para aumentar a precisão do diagnóstico precoce de câncer de colo do útero. Contudo, em lesões pré-malignas os biomarcadores clinicamente úteis seriam MMP-3 e TIMP-2. / Cervical cancer is the fourth most common in women worldwide. Cervical carcinogenesis is known to precede the infection and persistence of human papillomavirus (HPV), which has the ability to integrate into the host genome by introducing the E6 and E7 genes. The product of these genes, E6 and E7 oncoproteins disrupt the cell cycle promoting overexpression of p16INK4a protein and matrix metalloproteinases, molecules which are able to promote the progression of cervical uterine injury. To that end, the present study aimed to evaluate the expression of the oncoprotein E6, p16INK4a, matrix metalloproteinase 3 and the tissue inhibitor of metalloproteinase 2 in varying degrees of injuries and cervical cancer, associated with the presence of HPV and its genotypes. 86 cervical brush samples were used and biopsies fragments of women who were diagnosed cytologically with intraepithelial cervical lesions and invasive. All samples were genotyped and subjected to immunohistochemistry to identify the oncoprotein E6, HPV16 / 18, p16INK4a, MMP-3 and TIMP-2. The genotype profile identified HPV16 (44.4%) was the most prevalent, followed by HPV31 (30.3%), HPV58 (15.1%), HPV18 (6.1%) and HPV33 (4.1%). The immunohistochemical reaction for E6 was more reactive in the case of invasion, as well as p16INK4a. However MMP-3 and TIMP-2 were more reactive in premalignant lesions. Therefore, this study showed a higher prevalence of HPV-16 in women treated at the Hospital - UFPE and suggests that the E6 oncoprotein and p16INK4a protein biomarkers are useful to improve the accuracy of early diagnosis of cervical cancer. However, in premalignant lesions would be clinically useful biomarkers MMP-3 and TIMP-2.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O cÃncer de colo uterino (CCU), segunda causa de morte por neoplasias em mulheres, caracteriza-se por possuir fatores de risco relacionados a hÃbitos e estilos de vida que poderiam ser minimizados e/ou eliminados atravÃs de aÃÃes de promoÃÃo da saÃde. Para tanto, realizou-se o presente estudo com os objetivos de avaliar as aÃÃes de promoÃÃo da saÃde desenvolvidas por enfermeiras do Programa de SaÃde da FamÃlia (PSF) no controle do CCU, identificar fatores de risco para CCU e verificar associaÃÃo entre a promoÃÃo de informaÃÃes sobre os fatores de risco e o conhecimento das usuÃrias sobre esses fatores. Tratou-se de estudo avaliativo realizado no municÃpio de SÃo GonÃalo do Amarante - CE, com 11 enfermeiras e 390 usuÃrias que compareceram a unidade de saÃde para realizaÃÃo do exame de Papanicolaou no perÃodo de maio a agosto de 2007. Os dados foram coletados por meio de entrevista, observaÃÃo indireta da coleta citolÃgica e registros fotogrÃficos e documentais das aÃÃes de promoÃÃo da saÃde. Foram utilizados trÃs instrumentos: um questionÃrio voltado ao levantamento do perfil profissional das enfermeiras; e dois formulÃrios, um abordando as cinco estratÃgias de promoÃÃo da saÃde e outro voltado à vulnerabilidade das clientes. Os dois primeiros foram aplicados Ãs enfermeiras e o Ãltimo Ãs usuÃrias. O formulÃrio aplicado Ãs enfermeiras teve como base o instrumento de AvaliaÃÃo para a Melhoria da Qualidade da EstratÃgia de SaÃde da FamÃlia (AMQ) adotada pelo MinistÃrio da SaÃde. Os dados estatÃsticos foram analisados atravÃs do sistema SPSS 13.0 e discutidos segundo a literatura pertinente. Verificou-se a realizaÃÃo de aÃÃes de promoÃÃo da saÃde principalmente relacionadas Ãs estratÃgias de promoÃÃo de ambientes favorÃveis à saÃde, desenvolvimento de habilidades pessoais e polÃticas pÃblicas saudÃveis, em detrimento das estratÃgias de participaÃÃo comunitÃria e reorientaÃÃo dos serviÃos de saÃde. Observou-se a participaÃÃo multiprofissional nas aÃÃes promotoras de saÃde e a diversidade de tÃcnicas e recursos utilizados nas atividades educativas. Os fatores de riscos para CCU mais presentes na populaÃÃo feminina estavam relacionados Ãs condiÃÃes socioculturais, econÃmicas e à saÃde sexual e reprodutiva. A maioria das usuÃrias (61,28%) referiu conhecer, no mÃnimo, um fator de risco para CCU. Os fatores de risco mais conhecidos foram: pluralidade de parceiros, higiene Ãntima inadequada, desuso de condom e infecÃÃes genitais de repetiÃÃo. A enfermeira foi reconhecida como a principal fonte de informaÃÃo, pelas clientes. As mudanÃas, mais citadas, ocasionadas pelo conhecimento dos fatores de risco foram: realizaÃÃo periÃdica do exame de Papanicolaou, monogamia e uso de condom. Verificou-se associaÃÃo estatisticamente relevante entre as aÃÃes educativas desenvolvidas pelas enfermeiras no controle do CCU e o conhecimento das usuÃrias sobre os fatores de risco. Portanto, o estudo demonstrou a atuaÃÃo das enfermeiras como as principais agentes promotoras de saÃde. Contudo, ainda existe a necessidade de envolver a comunidade e os demais setores da sociedade na discussÃo e enfrentamento dos problemas de saÃde, o que justificaria estudos nessa Ãrea.

Orientadores: Luiz Carlos Zeferino, Silvia Helena Rabelo dos Santos / Texto em português e inglês / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T17:34:21Z (GMT). No. of bitstreams: 1 Burger_MarianaGenaro_M.pdf: 2615876 bytes, checksum: 488a52bb185fe37468bb4b59d9eb01b6 (MD5) Previous issue date: 2014 / Resumo: O papel da proteína SOD2 na carcinogênese e progressão tumoral, particularmente no carcinoma de células escamosas do colo uterino, continua a ser o objeto de incerteza e controvérsia. Assim, este estudo teve como objetivo avaliar a variabilidade na expressão da proteína SOD2 em cortes histológicos de epitélio cervical. Este estudo transversal incluiu 277 mulheres com indicação de procedimento conização ou excisão da zona de transformação devido a suspeita de NIC 2 ou lesão mais grave. A expressão SOD2 foi avaliada por ensaios de imunoistoquímicos realizados com base na porcentagem de células coradas em áreas representativas do diagnóstico histopatológico. A expressão positiva, independentemente da intensidade foi positivamente associada com o diagnóstico de NIC2/ NIC3 (OR = 2,64; 1,57-4,60) e carcinoma (OR = 14,32; 4,08-50,26). Tomando expressão SOD2 como referência para casos de NIC2/ NIC3, observou-se que a expressão positiva, independentemente da intensidade foi positivamente associada com um diagnóstico de carcinoma (OR = 5,33; 1,56-18,25). Observou-se que a expressão intensa SOD2 foi positivamente associada com o diagnóstico de NIC2/ NIC3 (OR = 7,31; 1,68-31,86) e carcinoma (OR = 36,63; 7,76-172,85). Quando a expressão de SOD2 foi tomada como referência para casos NIC2/ NIC3, observou-se que a expressão intensa foi positivamente associada com um diagnóstico de carcinoma (OR = 5,01; 2,24-11,20). Expressão SOD2 é observada com maior frequência e mais intensa em NIC2/ NIC3 e carcinoma espinocelular do que em tecido normal / NIC 1 . Além disso, a expressão SOD2 também é mais frequente e intensa em carcinomas do que em NIC2/ NIC3. Embora NIC2/ NIC3 e carcinomas invasivos iniciais são lesões contíguas na carcinogênese cervical, a expressão SOD2 pode diferenciá-los / Abstract: The role of SOD2 protein in carcinogenesis and tumor progression, particularly in squamous cell carcinoma of the uterine cervix, remains the object of uncertainty and controversy. Therefore this study aimed to evaluate the variability in SOD2 protein expression in histological specimens from cervical epithelium. This study cross-sectional study included 277 women with indication of conization procedure or transformation zone excision due to suspicion of CIN 2 or more severe lesion. The SOD2 expression was assessed by performed immunohistochemical assays based on the percentage of stained cells in representative areas of the histopathological diagnosis. Positive expression regardless of intensity was positively associated with a diagnosis of CIN2/CIN3 (OR=2.64; 1.57- 4.60) and carcinoma (OR=14.32; 4.08-50.26). Taking SOD2 expression as a reference for cases of CIN2/CIN3, it was observed that a positive expression, regardless of intensity was positively associated with a diagnosis of carcinoma (OR=5.33; 1.56-18.25). It was observed that intense SOD2 expression was positively associated with a diagnosis of CIN2/CIN3 (OR=7.31; 1.68-31.86) and carcinoma (OR=36.63; 7.76-172.85). When SOD2 expression was taken as a reference for CIN2/CIN3 cases, it was observed that intense expression was positively associated with a diagnosis of carcinoma (OR=5.01; 2.24-11.20). SOD2 expression is most frequently observed and more intense in CIN2/CIN3 and squamous carcinoma than in normal tissue/CIN 1. In addition, SOD2 expression is also more frequently observed and intense in carcinoma than in CIN2/CIN3. Although CIN 2/CIN 3 and early invasive carcinomas are contiguous lesions in cervical carcinogenesis, SOD2 expression can differentiate them / Mestrado / Oncologia Ginecológica e Mamária / Mestra em Ciências da Saúde

Orientadores: Luiz Carlos Zeferino, Silvia Helena Rabelo dos Santos / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T17:52:24Z (GMT). No. of bitstreams: 1 D'Ottaviano_MariaGabrielaLoffredo_D.pdf: 1516066 bytes, checksum: 6d0ec9bd4a1234053c224b579db92914 (MD5) Previous issue date: 2012 / Resumo: A infecção pelo HPV é considerada fator etiológico da neoplasia do colo do útero e a integração do HPV DNA ao DNA da célula hospedeira são apontados como passo importante na carcinogênese do epitélio. O melhor conhecimento da infecção do vário tipo de HPV e o status físico do HPV 16 nas NIC 2 pode colaborar na identificação das lesões que teriam maior risco de progredir para NIC 3 e, portanto, deveriam ser consideradas como lesões precursoras do câncer do colo uterino. O objetivo desta série de casos foi descrever a presença dos diferentes tipos de HPV e a integração do HPV DNA 16 em mulheres com diagnóstico histológico de NIC 2 acompanhadas por 12 meses. Trinta e sete mulheres com citologia inicial, resultado de lesão de baixo grau e atípicas de células escamosas de significado indeterminado e NIC 2, confirmado por biópsia, foram seguidas por 12 meses com citologia, colposcopia, tipagem de HPV e determinação do status físico do HPV DNA 16 a cada três meses. A evolução clínica da NIC 2 foi classificada como regressão em 49% (18\37) dos casos, persistência em 22% (8\37) e progressão em 29% (11\37). A infecção por múltiplos tipos de HPV foi observada em 41% (15\37) dos casos na admissão e durante o seguimento 54% (20\37) dos casos apresentaram infecção por novos tipos de HPV. O HPV 16 foi considerado como possível causa em 67% (10\15) dos casos que persistiram ou progrediram e em 10% (1\10) dos que regrediram (p=0,01). Entre as 20 mulheres que apresentaram HPV 16 na admissão, a forma integrada foi detectada em 25% dos casos e a forma episomal em 75% dos casos. Não foram observados casos de progressão para NIC 3 sem integração do HPV DNA 16 em algum momento do seguimento. Entretanto, foram observados casos de integração do HPV DNA 16 e regressão da NIC 2. Concluindo, a infecção por múltiplos tipos de HPV é frequente nas mulheres com diagnóstico histológico de NIC 2, assim como a infecção por outros tipos de HPV durante o seguimento de 12 meses. As NIC 2 associadas à detecção do HPV 16 persistem ou progridem com maior frequência. As NIC 2 que progrediram para NIC 3 apresentaram o HPV DNA 16 na forma integrada na admissão ou em algum momento do seguimento / Abstract: Human papillomavirus (HPV) persistent infection is considered a necessary cause for the development of cervical cancer and HPV DNA integration considered an important step in the progression of persistent high risk HPV infection to invasive cancer.The knowledge of HPV infection and the HPV DNA 16 physical status in women with cervical intraepithelial neoplasia grade 2 (CIN 2) can better characterize the biological behavior of the lesion. This case series aimed to describe the HPV types and HPV DNA 16 physical status in women with CIN 2 biopsy proven followed for 12 months and clinical outcome. Thirty seven women with CIN 2 biopsy proven, cervical referral smear showing low-grade squamous intraepithelial lesions or atypical squamous cells of undetermined significance and with HPV type, were followed up 12 months with cervical smear, colposcopy, HPV type and HVP DNA 16 every three months. At the end of twelve months follow-up, the CIN 2 regression rate was 49% (18/37), persistence as CIN1 or CIN 2 was 22% (8/37), and progression to CIN 3 was 29% (11/37). Multiple HPV types were observed at admission in 41% (15/37) of cases. During follow-up, 54% (20/37) of the women showed one or more new HPV type detected. HPV 16 was considered possibly causal type in 67% (10/15) of the cases that persisted or progressed and in 10% (1/10) that regressed (p=0.01). Among the twenty women with HPV DNA 16, at admission, 25% showed integrated HPV DNA 16 and 75% episomal form. There were no cases of CIN 2 progression to CIN 3 without HPV DNA 16 integration, but there were cases of HPV DNA 16 integration and CIN 2 regression. Concluding, multiple HPV infections were frequently detected among women with CIN 2 at admission and during the follow up. The CIN 2 associated with HPV 16 was more likely to persist or to progress to CIN 3. The HPV DNA 16 integration is associated with CIN 2 persistence and progression to CIN 3 / Doutorado / Oncologia Ginecológica e Mamária / Doutora em Ciências da Saúde

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-04-15T13:55:03Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Lianne versão final.pdf: 1813010 bytes, checksum: 7347cf54c764e95be94ff262dc30ccb5 (MD5) / Made available in DSpace on 2016-04-15T13:55:03Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Lianne versão final.pdf: 1813010 bytes, checksum: 7347cf54c764e95be94ff262dc30ccb5 (MD5) Previous issue date: 2015-08-11 / CAPEs / O câncer do colo uterino é o quarto tipo de câncer mais comum entre as mulheres mundialmente, e o sétimo no geral. No Brasil, esta neoplasia é a terceira mais frequente no gênero feminino, com mais de 15 mil casos novos a cada ano. A infecção persistente pelo papilomavírus humano dos tipos de alto risco oncogênico está associada ao câncer cervical, porém uma pequena percentagem de mulheres infectadas por estes vírus desenvolve lesões pré-malignas que podem evoluir à invasão. Portanto, outros cofatores são necessários para a persistência viral que, após 2 anos sem intervenção, leva à expressão desregulada e concomitante das oncoproteínas transformantes E6 e E7. As enzimas degradadoras de matriz extracelular conhecidas como metaloproteinases da matriz tem sido extensamente estudadas devido ao seu papel na invasão, metástase, angiogênese e recidiva tumoral. Nas lesões cervicais, um aumento na expressão das metaloproteinases foi identificado, porém, seu papel na progressão das lesões pré-invasivas e sua interação com a infecção pelo papilomavírus ainda não está bem esclarecida. Neste intuito, o presente estudo visou avaliar, através de técnica imuno-histoquímica, a associação dos níveis de expressão das metaloproteinases da matriz 2 e 9 com os graus de lesões cervicais. Para isso, foram utilizadas amostras de biopsias parafinadas, diagnosticadas e arquivadas entre 2011 e 2015 no Laboratório de Anatomia Patológica do Hospital das Clínicas de Recife, Pernambuco, Brasil, incluindo 115 biopsias de lesões cervicais, obtidas por conização, bem como 14 casos de tecidos cervicais sem lesão. Os resultados obtidos neste trabalho demonstraram um aumento da expressão das metaloproteinases 2 e 9 nos casos de invasão em relação a condições pré-malignas, tanto no citoplasma quanto no núcleo de células epiteliais escamosas, sendo a intensidade da expressão nuclear das metaloproteinases estudadas mais significativa nas células cancerosas. Também foi observada diminuição da expressão das metaloproteinases 2 e 9 no citoplasma das células glandulares adjacentes na presença do carcinoma escamoso invasor, quando comparadas ao controle. Mais estudos precisam ser realizados para avaliar o valor prognóstico das metaloproteinases 2 e 9 nas condições pré-malignas e malignas do colo uterino. / The cervical cancer is the fourth most common cancer among women worldwide, and seventh overall. In Brazil, this cancer is the third most common in women, with more than 15,000 new cases each year. Persistent infection with human papillomavirus types of high oncogenic risk is associated with cervical cancer, but a small percentage of women infected by these viruses develop precancerous lesions that may progress to invasion. Therefore, other cofactors are required for viral persistence which, after 2 years without intervention, leads to unregulated and concomitant expression of transformants E6 and E7 oncoproteins. The extracellular matrix degrading enzymes known as matrix metalloproteinases has been extensively studied because of its role in invasion, metastasis, angiogenesis and tumor recurrence. In cervical lesions, an increase in the expression of metalloproteinases was identified, however, its role in the progression of pre-invasive lesions and their interaction with the papillomavirus infection is not well understood. To this end, the present study evaluated, through immunohistochemical technique, the association of the expression levels of matrix metalloproteinases 2 and 9 with grades of cervical lesions. For this, we used paraffined biopsy samples, diagnosed and filed between 2011 and 2015 at the Pathology Laboratory of the Hospital das Clínicas of Recife, Pernambuco, Brazil, including 115 biopsies of cervical lesions, obtained by conization, and 14 cases of tissues without cervical injury. The results of this study demonstrated an increased expression of metalloproteinases 2 and 9 in invasion compared to pre-malignant conditions, in both cytoplasm and nucleus of squamous epithelial cells, and a more significant intensity of the nuclear expression of metalloproteinases studied in cancer cells. It was also observed decreased expression of metalloproteinases 2 and 9 in the cytoplasm of adjacent glandular cells in the presence of invasive squamous cell carcinoma, when compared to control. More studies are needed to assess the prognostic value of metalloproteinases 2 and 9 in premalignant and malignant conditions of the cervix.

Orientadores: Aarão Mendes Pinto-Neto, Luiz Francisco Cintra Baccaro / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-28T02:15:08Z (GMT). No. of bitstreams: 1 Grion_ReginaCelia_M.pdf: 1187288 bytes, checksum: 0b2958f9fcacbd79b79fe0ddbbea538b (MD5) Previous issue date: 2015 / Resumo: Introdução: O câncer cervical é a terceira neoplasia mais frequente em mulheres brasileiras e a radioterapia pélvica é uma das principais modalidades terapêuticas disponíveis. Com a diminuição da mortalidade associada à doença, a avaliação da qualidade de vida e da função sexual ganha cada vez mais importância. Vários estudos descrevem estes aspectos após o tratamento do tumor, porém, há poucos relatos sobre os fatores que influenciam a qualidade de vida e a função sexual antes do início do tratamento radioterápico. Os objetivos do presente estudo foram avaliar os fatores associados à função sexual e à qualidade de vida em mulheres com câncer do colo uterino antes do início da radioterapia. Métodos: estudo de corte-transversal com 80 mulheres portadoras de câncer do colo do útero, com idade de 18 a 75 anos, encaminhadas para tratamento radioterápico no Hospital da Mulher Prof. Dr. José Aristodemo Pinotti (CAISM-UNICAMP) de janeiro/2013 a março/2014. As variáveis dependentes foram a função sexual, avaliada através do Índice de Função Sexual Feminino (IFSF), e a qualidade de vida, avaliada através da versão abreviada do questionário da Organização Mundial da Saúde (WHOQOL-bref). As variáveis independentes foram os dados sociodemográficos, os hábitos de saúde e as características da neoplasia. A análise estatística foi realizada através dos testes T de Student, Mann-Whitney, ANOVA e regressão linear múltipla. Resultados: A média etária foi de 48,1 anos, 57,5% das mulheres se encontravam na pré-menopausa e 55% apresentavam estadio clínico IIIB. A maioria das mulheres (62%) relatou ter parceiro sexual e 30% se encontravam sexualmente ativas nos três meses prévios à radioterapia. Os principais sintomas durante as relações sexuais foram sangramento (41,7%), falta de prazer (33,3%), dispareunia (25%) e secura vaginal (16,7%). A avaliação pelo IFSF mostrou que as 18 mulheres que se encontravam sexualmente ativas no último mês, apresentavam disfunção sexual significativa (escore total = 25,6). Ter realizado cirurgia antes da radioterapia se associou negativamente com os domínios satisfação (p = 0,02) e excitação (p = 0,01) do IFSF. Mulheres com sangramento vaginal durante a relação sexual tiveram menores escores nos domínios orgasmo (p = 0,04) e satisfação (p = 0,03). Apresentar qualquer sintoma adverso durante a relação sexual se associou negativamente com o domínio dor (p = 0,02). Falta de prazer às relações se associou negativamente com o domínio orgasmo (p = 0,04) e fumar se associou positivamente com o escore total do IFSF (p = 0,04). Estadio clínico avançado, uso de medicação crônica e não ter realizado cirurgia correlacionaram-se negativamente com a qualidade de vida. Ter maior renda familiar, maior nível de escolaridade e não fumar correlacionaram-se positivamente com a qualidade de vida. Conclusão: um terço das mulheres com câncer de colo do útero mantinham relações sexuais três meses antes da radioterapia, porém apresentavam disfunção sexual significativa. Fatores relacionados à doença e ao seu tratamento foram os principais responsáveis pela deterioração da função sexual. A qualidade de vida sofre influência não apenas dos fatores relacionados à neoplasia, mas também de hábitos de vida, presença de comorbidades e características sociodemográficas como baixa renda familiar e escolaridade / Abstract: Introduction: cancer of the cervix is the third most common gynecological tumor in Brazilian women and pelvic radiotherapy is one its major therapeutic methods. With the decreasing mortality associated with the disease, evaluation of quality of life and sexual function is becoming increasingly important. Several studies describe these aspects after the tumor treatment, however, there are few reports about the factors influencing quality of life and sexual function before the start of radiotherapy. The objectives of this study were to evaluate the factors associated with sexual function and quality of life in women with cervical cancer before the start of radiotherapy. Methods: a cross-sectional study was conducted with 80 women with cervical cancer, aged 18-75 years, referred for radiotherapy at the Women's Hospital Prof. Dr. José Aristodemo Pinotti (CAISM-UNICAMP), from January 2013 to March 2014. The outcome variables were sexual function, assessed using the Female Sexual Function Index (FSFI), and quality of life, assessed using the abbreviated version of the World Health Organization (WHOQOL-BREF) questionnaire. The independent variables were sociodemographic data, health related habits and the characteristics of the neoplasm. Statistical analysis was carried out using Student's T test, Mann-Whitney test, ANOVA and multiple linear regression. Results: The mean age was 48.1 years, 57.5% were premenopausal and 55% had clinical stage IIIB. Thirty percent had been sexually active in the three months prior to their interviews. The majority of women (62%) reported having sexual partner and 30% had been sexually active in the three months prior to their interviews. The main adverse events during sexual intercourse were bleeding (41.7%), lack of pleasure (33.3%), dyspareunia (25%), and vaginal dryness (16.7%). The 18 women who had been sexually active in the previous month showed significant sexual dysfunction (total mean FSFI score = 25.6). Having undergone surgery before radiotherapy was negatively associated with arousal (p = 0.01) and satisfaction (p = 0.02) domains. Women with vaginal bleeding during intercourse had significantly lower scores in the orgasm (p = 0.04) and satisfaction (p = 0.03) domains. Women with any adverse symptoms during intercourse had lower scores in the pain domain (p = 0.02). Lack of pleasure during intercourse was negatively associated with the orgasm domain (p = 0.04) whereas smoking was positively associated with total FSFI score (p = 0.04). Advanced clinical stage, using any chronic medication and not having undergone surgery for cancer were negatively correlated with QOL. Higher family income, a longer duration of schooling and no smoking were positive correlated with QOL. Conclusion: one third of women with cervical cancer were sexually active three months prior to their interviews, but have concomitant significant sexual dysfunction. Factors related to the disease and its treatment were mainly responsible for the deterioration in sexual function. Quality of life is influenced not only by factors related to cancer, but also by lifestyle habits, comorbidities and sociodemographic characteristics such as low family income and schooling / Mestrado / Fisiopatologia Ginecológica / Mestra em Ciências da Saúde

研究背景： / 2009年起，中國政府發起並資助了一項覆蓋全國31個省221個鄉村、針對100萬名農村婦女的細胞學及肉眼觀察宮頸癌篩查試點項目。國家及地方政府需要對可行的篩查策略進行衛生經濟學評估，為下一步擴大規模的篩查提供政策依據。 / 研究目標： / 應用人群特異性Markov模型，對巴氏塗片及肉眼觀察的宮頸癌篩查策略進行成本效果及成本效用兩方面的衛生經濟學評估，進而為中國農村婦女宮頸癌篩查政策的制定提供依據。 / 研究方法： / 本論文工作建立了Markov人群動態擬合模型，該模型能夠整合與中國農村宮頸癌流行情況相吻合的成本及健康狀況的數據，進而用於擬合20年內35-59歲中國農村婦女在有/無篩查幹預下的成本、效用和效果。本文分析的八個備選篩查策略包括：採用醋酸染色肉眼觀察（VIA）或傳統細胞學（巴氏塗片）分別進行10年，5年，3年及1年一次的篩查。 / 本文從社會學角度出發，成本數據涵蓋篩查、診斷及治療過程中產生的直接及間接成本。模型在結構上綜合了已被廣泛認可的宮頸癌自然發展史模型，以及宮頸癌及其癌前病變（CIN）在中國農村進行篩查和治療的標準臨床路徑。模型輸入參數盡可能地使用了能夠反映中國農村婦女人群特異性的數據。通過對比國家報告數據與模型預測結果，本文從全死因死亡率、宮頸癌死亡率及宮頸癌發病率三個方面驗證了模型的可信度。 / 模型的結局變量包括：累計成本、累計生命年(LYs)、累計質量調整生命年(QALYs)、預期宮頸癌死亡率及發病率降低百分比(%)、CIN 相對風險、宮頸浸潤癌相對風險，增量成本效用比(ICUR, 表述為每挽救一個質量調整生命年消耗的成本)及增量成本效果比(ICER, 表述為每挽救一個生命年消耗的成本)等。與無篩查幹預相比，我們界定ICUR及ICER小於三倍人均國內生產總值（76,824元，2009年)的優勢策略為‘具有成本效益’的選擇，並將其中ICUR和ICER最低的策略，定義為‘最具成本效益’的策略，將具有最大健康效益的策略（挽救最多質量調整生命年或生命年的策略），定義為‘最有效’的策略。同時，我們對可能影響決策的不確定因素進行了敏感性分析。 / 結果： / 與無篩查幹預相比，肉眼觀察及巴氏塗片篩查均能夠減少宮頸癌患病例數，進而顯示出一定的健康效益。較短的篩查間隔具有更高的健康效益。模型預測在不同的篩查策略幹預下，宮頸癌死亡率和發病率分別有望降低6.67-31.95%和5.12-24.71%，預期CIN發病相對風險為0.89-0.98，預期宮頸癌發病相對風險為0.73-0.95。篩查幹預對健康的保護作用在本研究中得到了證實。 / 成本效用分析顯示，10年一次的肉眼觀察策略最具成本效益，其次為5年一次、3年一次、1年一次的肉眼觀察篩查策略及1年一次的巴氏塗片篩查策略。與無篩查幹預相比，如上策略每挽救一個質量調整生命年消耗的成本為11,921至26,069元（1,892-4,138美元，2012年）。同時成本效果分析也顯示，10年一次的肉眼觀察策略最具成本效益，其次為5年一次的肉眼觀察策略及5年一次的巴氏塗片篩查策略。同樣與無篩查幹預相比，如上策略每挽救一個生命年消耗的成本為37,211至68,226元（5,906-18,830美元，2012年）。 / 對於某一既定策略，相應的ICUR和ICER受當地經濟狀況相關因素的影響最大，這些因素包括治療成本、篩查成本和成本貼現率。從檢測技術水平上看，肉眼觀察對分析結果的影響小於巴氏塗片，原因是前者敏感度範圍較小。篩查覆蓋率、初篩陽性隨訪率、診斷陽性治療率也都與相應的ICUR和ICER呈負相關性。敏感性分析結果顯示本文中模型對於健康結局的預測，及相關的衛生經濟學分析，受自然史模型中HPV感染和CIN之間轉移概率的不確定性的影響最大。HPV感染與CIN間的進展和逆轉概率是該項模型研究的核心參數。 / 結論： / 本文中成本效用和成本效果分析均顯示，相較於傳統的細胞學篩查策略，採用間隔時間較長（10年或5年）的肉眼觀察篩查策略，對一般發病地區的35-59歲的農村婦女來說，是更具‘成本效益’的選擇。對於宮頸癌高發地區，其篩查頻率可以提高到1年一次。1年一次的巴氏塗片篩查策略，是最有效的篩查策略，可以挽救最多的生命。但採用該策略時，應在財政預算允許的前提下，確保篩查技術和項目完成的質量。 / 篩查項目的高覆蓋率，對篩查陽性患者良好的隨訪和診治，初篩檢測技術平均水平以上的表現，以及較低的篩查和治療成本是確保篩查項目具備成本效益優勢的核心因素。本文完成的成本效用及成本效果分析，能夠為公共衛生決策提供重要的輔助作用。 / Background: / A Chinese government-sponsored cytology/visual inspection pilot cervical cancer screening program covered 10 million rural women in 221 counties of 31 provinces was initiated in 2009. Both the local and national governments in China need health economic evaluations of feasible strategies so as to make better policies for the next-step enlarging screening. / Objectives: / To perform health economic evaluations of Pap smear and visual inspection cervical cancer screening strategies using population-specific Markov modeling cost-utility (CUA) and cost-effectiveness (CEA) analyses, in order to assist screening policy making for women in rural China. / Methods: / Markov simulation models were developed to synthesize the evidence on costs and health outcomes related to cervical cancer epidemiology in rural China, and applied to predict the long-term utility, effectiveness and costs for hypothetical cohorts of 35-59 years old rural Chinese women, with or without the presence of screening over 20 years. The eight alternative screening strategies assessed were visual inspection with acetic acid (VIA) or traditional cytology (Pap smear) each with ten-year, five-year, three-year and one year screening intervals. / The study was conducted from the societal perspective, thus both directed and non-direct costs related to screening, diagnosis and treatment interventions were considered. The model structures incorporated with the well-accepted the natural history model of cervical cancer and the standard clinical pathway of screening and treatment interventions for precancerous lesions (CIN) and cervical cancer in real practice in rural China. Population-specific data were used as much as possible to be the model inputs. The model estimates were validated by comparison of our predictions of all-cause mortality, cervical cancer mortality and cervical cancer incidence with the national reported data. / Outcome variables included cumulative cost, life years (LYs), quality-adjusted life years (QALYs), predicted reduction(%) in cervical cancer mortality and incidence, relative risk of CIN, relative risk of cervical cancer, incremental cost-utility ratio (ICUR, presented as cost per QALY saved) and incremental cost-effectiveness ratio (ICER, presented as cost per life year saved). Compared with no screening, not-dominated strategies with ICUR and ICER less than three times China’s GDP per capita (76,824 CNY, 2009) were considered to be ‘cost-effective’ options. Among the identified ‘cost-effective’ options, the strategy with lowest ICUR or ICER was defined as the most cost-effective strategy, and the strategy with the highest health benefit (largest QALY saved or life year saved) was defined as the most effective strategy. Sensitivity analyses were conducted to test the effect of uncertainties on decision making. / Results: / All of the VIA and Pap smear screening strategies of showed certain benefits due to the decreased number of women developing cervical cancer, when compared with no screening. A trend for shorter screening interval to have greater benefit was also found. Cervical cancer mortality and incidence were expected to be reduced by 6.67-31.95% and 5.12-24.71% with different screening strategies. And the predicted relative risks of CIN and invasive cervical cancer of 0.89-0.98 and 0.73-0.95, respectively, also demonstrated the protective effect of screenings. / Modeling cost-utility analysis identified ten years VIA screening as the most cost-effective strategy followed by VIA screening with five-, three- and one year interval and Pap smear screening with a one year interval. Compared with no screening, the incremental costs per QALY saved of these strategies ranged from 11,921 to 26,069 Yuan (1,892-4,138 US dollars, 2012). In the meanwhile, modeling cost-effectiveness analysis also identified ten-years VIA screening as the most cost-effective strategy followed by VIA screening with five-year intervals and Pap smear screening with five-year intervals. Compared with no screening, the incremental costs per life year saved of these strategies ranged from 37,211 to 68,226 Yuan (5,906-18,830 US dollars, 2012). / Both ICUR and ICER of a selelected strategy were greatest influnced by factors related to variations in local economies , including treatment cost, screening cost and discounting rate of the cost. The influence of primary test performance of VIA was rather less than that of Pap smear due to the narrower ranges of the VIA sensitivities. Screening coverage, follow-up rate and treatment rate were also negatively associated with ICUR and ICER. Health outcome predictions and health economic analyses were mostly influenced by the uncertainties in HPV infection and CIN transitions in the natural history. Progression and regression probabilities between HPV infection and CIN were considered to be the key parameters of the simulation models. / Conclusions: / Baseline CUA and CEA results suggested that in comparison with traditional cytology screening strategies, organized VIA screening with long intervals (ten or five years) were more cost-effective options than for 35-59 years old women in normal incidence areas of rural China. The VIA screening interval can be shorten to one year in high incidence areas. Pap smear strategy with one year interval can be utilized as the most effective strategy with most lives saved when budget allows and the performances of program and test are ensured. / High coverage of the screening program, good management of screening positives, average or above performance of primary test, and lower screening and treatment costs are key elements for a cost-effective screening program. Cost-utility and cost-effectiveness analyses, such as the one conducted in this thesis study, can be considered important adjuncts to policy decision-making about public health objectives. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Li, Xue. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 388-401). / Abstracts also in Chinese; appendixes includes Chinese. / Abstract of thesis --- p.i / 中文摘要 --- p.v / ACKNOWLEDGEMENTS --- p.viii / TABLE OF CONTENTS --- p.1 / LIST OF TABLES --- p.8 / LIST OF FIGURES --- p.11 / ABBREVIATIONS --- p.12 / Chapter CHAPTER 1 --- INTRODUCTION --- p.14 / Chapter 1.1 --- Epidemiological patterns and disease burden of cervical cancer --- p.14 / Chapter 1.1.1 --- Cervical cancer incidence and mortality worldwide --- p.14 / Chapter 1.1.2 --- Risk factors for cervical cancer --- p.15 / Chapter 1.1.2.1 --- Human Papillomavirus (HPV) --- p.15 / Chapter 1.1.2.2 --- Parity --- p.16 / Chapter 1.1.2.3 --- Smoking --- p.16 / Chapter 1.1.2.4 --- Human Immunodeficiency Virus (HIV) --- p.17 / Chapter 1.1.2.5 --- Contraception --- p.17 / Chapter 1.1.2.6 --- Sexual behavior, nutrition and other factors --- p.18 / Chapter 1.1.3 --- Disease burden of cervical cancer in China --- p.18 / Chapter 1.1.3.1 --- Epidemiology of Cervical Cancer in China --- p.18 / Chapter 1.1.3.2 --- Cervical cancer in different geographic areas of China --- p.20 / Chapter 1.2 --- The need for cost-effectiveness analysis of cervical screening strategies in China --- p.21 / Chapter 1.2.1 --- Cervical cancer prevention in China --- p.21 / Chapter 1.2.2 --- Why do we need a modeling cost-effectiveness analysis? --- p.23 / Chapter 1.3 --- Natural history of cervical cancer --- p.25 / Chapter 1.3.1 --- Terminology --- p.25 / Chapter 1.3.2 --- Natural history of cervical cancer --- p.27 / Chapter 1.4 --- Secondary prevention strategies of cervical cancer --- p.29 / Chapter 1.4.1 --- Screening tests --- p.29 / Chapter 1.4.1.1 --- Cervical cytology --- p.29 / Chapter 1.4.1.2 --- Visual Inspection --- p.32 / Chapter 1.4.1.3 --- HPV testing --- p.36 / Chapter 1.4.2 --- Summary of different screening strategies all over the world --- p.37 / Chapter CHAPTER 2 --- LITERATURE REVIEW --- p.40 / Chapter 2.1 --- Background --- p.40 / Chapter 2.2 --- Objectives of the literature review --- p.41 / Chapter 2.3 --- Search strategies and results --- p.41 / Chapter 2.3.1 --- Search strategies --- p.41 / Chapter 2.3.2 --- Inclusion and exclusion criteria --- p.42 / Chapter 2.4 --- Literature results summary --- p.44 / Chapter 2.4.1 --- Methodology, target population and analytical perspective --- p.44 / Chapter 2.4.2 --- Screening test and program performance --- p.47 / Chapter 2.4.3 --- Cost and utility estimation --- p.49 / Chapter 2.4.4 --- Model parameter sources and validation --- p.53 / Chapter 2.4.5 --- Alternatives and identified cost-effective strategies --- p.58 / Chapter 2.5 --- Conclusions --- p.63 / Chapter CHAPTER 3 --- OBJECTIVES --- p.64 / Chapter 3.1 --- General Objectives --- p.64 / Chapter 3.2 --- Alternative cervical cancer screening strategies in this study --- p.64 / Chapter 3.3 --- Decision rules for recommended cost-effective options --- p.65 / Chapter 3.4 --- Analytical perspective and time horizon --- p.65 / Chapter 3.5 --- Objectives --- p.66 / Chapter 3.6 --- Analytical scenario in this study --- p.66 / Chapter 3.6.1 --- Patterns of cervical screening program delivery in rural China --- p.67 / Chapter 3.6.2 --- Demographic profile of the simulated hypothetical cohort --- p.67 / Chapter 3.6.3 --- Summary of model assumptions --- p.68 / Chapter 3.6.3.1 --- Assumptions related to screening performance and clinical practice --- p.68 / Chapter 3.6.3.2 --- Assumptions related to epidemiological characteristics of cervical cancer --- p.68 / Chapter 3.6.3.3 --- Assumptions related to economic evaluation --- p.69 / Chapter CHAPTER 4 --- METHODOLOGY --- p.70 / Chapter 4.1 --- Alternative strategies in this study --- p.70 / Chapter 4.2 --- Markov Model Developments and Applications --- p.72 / Chapter 4.2.1 --- General introduction of Markov Transition Model --- p.72 / Chapter 4.2.2 --- Structure of Markov models --- p.76 / Chapter 4.2.2.1 --- Natural history model of cervical cancer --- p.76 / Chapter 4.2.2.2 --- Structure of Pap smear and Visual Inspection screening models --- p.82 / Chapter 4.2.2.3 --- Structure of precancerous lesion and invasive cancer treatment models --- p.83 / Chapter 4.2.2.4 --- Interaction of the models --- p.85 / Chapter 4.2.3 --- Demographic profile of the hypothetical cohort --- p.86 / Chapter 4.2.4 --- Probabilities --- p.88 / Chapter 4.2.4.1 --- Identification and converting between rate and probability --- p.89 / Chapter 4.2.4.2 --- Initial probabilities --- p.90 / Chapter 4.2.4.3 --- Transition probabilities --- p.91 / Chapter 4.2.5 --- Screening, diagnosis and treatment characteristics --- p.101 / Chapter 4.2.5.1 --- Screening program characteristics --- p.101 / Chapter 4.2.5.2 --- Diagnosis test performance --- p.104 / Chapter 4.2.5.3 --- Precancerous lesions treatment characteristics --- p.104 / Chapter 4.2.5.4 --- Invasive cancer and treatment characteristics --- p.106 / Chapter 4.2.6 --- Model validation --- p.111 / Chapter 4.3 --- Cost data collection --- p.112 / Chapter 4.3.1 --- Perspective of study --- p.112 / Chapter 4.3.2 --- Selection of study sites --- p.113 / Chapter 4.3.3 --- Screening cost data collection --- p.113 / Chapter 4.3.4 --- Treatment cost data collection --- p.115 / Chapter 4.4 --- Cost-utility analysis and cost-effectiveness analysis --- p.117 / Chapter 4.4.1 --- General introduction of these two analyses --- p.117 / Chapter 4.4.2 --- Utility Estimates --- p.118 / Chapter 4.4.3 --- Screening utility and effectiveness evaluation --- p.120 / Chapter 4.4.4 --- Cost-effectiveness and cost-utility analysis method --- p.122 / Chapter 4.5 --- Time horizon and discounting rate --- p.125 / Chapter 4.6 --- Summary of modeling assumptions --- p.126 / Chapter 4.6.1 --- Assumptions related to screening performance and clinical practice --- p.126 / Chapter 4.6.2 --- Assumptions related to epidemiological characteristics of cervical cancer --- p.127 / Chapter 4.6.3 --- Assumptions related to economic evaluation --- p.128 / Chapter 4.7 --- Sensitivity analysis --- p.128 / Chapter 4.8 --- Ethical approval --- p.129 / Chapter CHAPTER 5 --- RESULTS --- p.130 / Chapter 5.1 --- Model validation --- p.130 / Chapter 5.2 --- Cost analysis results --- p.134 / Chapter 5.2.1 --- Screening costs results --- p.134 / Chapter 5.2.2 --- Treatment cost results --- p.136 / Chapter 5.2.3 --- The proportional costs breakdown for different screening strategies --- p.139 / Chapter 5.3 --- Utility estimation results --- p.141 / Chapter 5.4 --- Cost-utility analysis results --- p.144 / Chapter 5.4.1 --- Baseline analysis --- p.144 / Chapter 5.4.2 --- Influence of screening program performance --- p.148 / Chapter 5.4.2.1 --- Coverage of the screening program --- p.148 / Chapter 5.4.2.2 --- Follow up rate and treatment rate of positives --- p.155 / Chapter 5.4.3 --- Influence of screening test performance --- p.159 / Chapter 5.4.4 --- Influence of costs --- p.165 / Chapter 5.4.4.1 --- Influence of screening costs --- p.165 / Chapter 5.4.4.2 --- Influence of treatment costs --- p.168 / Chapter 5.4.5 --- Influence of discounting --- p.171 / Chapter 5.4.6 --- Summary of factors and their influences on the baseline CUA results --- p.174 / Chapter 5.5 --- Cost-Effectiveness analysis results --- p.180 / Chapter 5.5.1 --- Baseline analysis --- p.180 / Chapter 5.5.1.1 --- Life year saved --- p.181 / Chapter 5.5.1.2 --- Cervical cancer mortality reduction --- p.185 / Chapter 5.5.1.3 --- Cervical cancer incidence reduction --- p.187 / Chapter 5.5.1.4 --- Relative risk of CIN and cervical cancer --- p.189 / Chapter 5.5.1.5 --- Effectiveness summary of alternative screening strategies on the hypothetical 100,000 rural Chinese women --- p.191 / Chapter 5.5.2 --- Factors that influence the CEA results --- p.195 / Chapter 5.5.2.1 --- Best scenario analysis --- p.196 / Chapter 5.5.2.2 --- Worst scenario analysis --- p.201 / Chapter 5.5.2.3 --- Summary of the possible ranges of costs and effectiveness in different scenarios --- p.206 / Chapter 5.6 --- Sensitivity analysis --- p.209 / Chapter 5.6.1 --- Sensitivity analysis of Cost-Utility analysis results --- p.209 / Chapter 5.6.1.1 --- Tornado analysis --- p.209 / Chapter 5.6.1.2 --- One-way sensitivity analysis --- p.213 / Chapter 5.6.2 --- Sensitivity analysis of Cost-Effectiveness analysis results --- p.220 / Chapter 5.6.2.1 --- Tornado analysis --- p.220 / Chapter 5.6.2.2 --- One-way sensitivity --- p.224 / Chapter 5.6.3 --- Summary of sensitivity results --- p.236 / Chapter CHAPTER 6 --- SUMMARY, DISSICUSSION AND CONCLUSIONS --- p.240 / Chapter 6.1 --- Summary of Markov model development and validation --- p.240 / Chapter 6.1.1 --- Category and source summary of input parameters --- p.240 / Chapter 6.1.2 --- Model validation --- p.244 / Chapter 6.2 --- Summary of modeling results --- p.245 / Chapter 6.2.1 --- Summary of Cost-Utility Analysis --- p.245 / Chapter 6.2.1.2 --- Baseline analysis findings --- p.245 / Chapter 6.2.1.2 --- Influential factors on the cost-effective manner of alternative strategies --- p.246 / Chapter 6.2.2 --- Summary of Cost-Effectiveness Analysis --- p.250 / Chapter 6.2.2.1 --- Baseline analysis findings --- p.251 / Chapter 6.2.2.2 --- Possible ranges for cost and effectiveness of alternative strategies under different scenarios --- p.253 / Chapter 6.2.3 --- Summary of CUA and CEA findings --- p.257 / Chapter 6.2.4 --- Summary of sensitivity analysis --- p.259 / Chapter 6.2.4.1 --- Important variables on health outcome predictions --- p.259 / Chapter 6.2.4.2 --- Sensitive variables to the baseline CUA and CEA recommendations --- p.260 / Chapter 6.2.4.3 --- Overview of the sensitivity analysis --- p.263 / Chapter 6.3 --- Discussion --- p.264 / Chapter 6.3.1 --- Alternative strategies of cervical cancer screening in rural China --- p.264 / Chapter 6.3.1.1 --- Target ages --- p.265 / Chapter 6.3.1.2 --- Screening intervals --- p.266 / Chapter 6.3.1.3 --- Feasible primary screening tests --- p.267 / Chapter 6.3.1.4 --- Service delivering patterns --- p.269 / Chapter 6.3.1.5 --- Time horizon of this thesis study --- p.270 / Chapter 6.3.2 --- Transition probability estimation --- p.271 / Chapter 6.3.3 --- Screening and treatment cost estimation --- p.276 / Chapter 6.3.3.1 --- Representativeness of the selected counties --- p.276 / Chapter 6.3.3.2 --- Screening costs of VIA and Pap smear --- p.277 / Chapter 6.3.3.3 --- Treatment costs --- p.279 / Chapter 6.3.4 --- Utility estimation --- p.280 / Chapter 6.3.4.1 --- Instrument selection --- p.280 / Chapter 6.3.4.2 --- Utility estimation between studies --- p.281 / Chapter 6.3.5 --- Baseline cost-utility and cost-effectiveness analyses --- p.283 / Chapter 6.3.6 --- Sensitivity Analysis --- p.284 / Chapter 6.3.7 --- Strengths and limitations --- p.286 / Chapter 6.3.7.1 --- Limitations --- p.286 / Chapter 6.3.7.2 --- Strengths --- p.288 / Chapter 6.4 --- Policy implications --- p.289 / Chapter 6.4.1 --- How to manage a cost-effective cervical cancer screening program? --- p.289 / Chapter 6.4.2 --- How can VIA screening be adopted? --- p.290 / Chapter 6.4.3 --- How can Pap smear screening be adopted? --- p.291 / Chapter 6.4.4 --- Framework for policy decision making --- p.292 / Chapter 6.5 --- Conclusions --- p.295 / Chapter APPENDIX --- p.300 / Chapter Appendix 1-1 --- The 2001 Bethesda System* --- p.300 / Chapter Appendix 1-2 --- The FIGO Staging for cervical cancers* --- p.301 / Chapter Appendix 1-3 --- Cervical Cancer Screening Program in different countries --- p.302 / Chapter Appendix 4-1 --- WHO World Standardized Population Distribution (%) --- p.305 / Chapter Appendix 4-2 --- Summary of transition probabilities literature review --- p.306 / Chapter Appendix 4-3 --- Price Indices from 1978 to 2010 --- p.326 / Chapter Appendix 4-4 --- Screening Cost Questionnaire --- p.327 / Chapter Appendix 4-5 --- Programmatic Cost Survey Questionnaire --- p.339 / Chapter Appendix 4-6 --- Treatment Cost Survey Questionnaire --- p.342 / Chapter Appendix 4-7 --- EQ-5D Algorism (UK) --- p.344 / Chapter Appendix 4-8 --- Chinese Version of EQ5D----HQOL score questionnaire --- p.345 / Chapter Appendix 5-1 --- Calibrated variables and its final settings --- p.348 / Chapter Appendix 5-2 --- Cervical cancer new cases and deaths all over the world in 2008 --- p.349 / Chapter Appendix 5-3 --- Data distribution of CIN2-3 and cervical cancer treatment costs --- p.350 / Chapter Appendix 5-4 --- Relative risk of CIN and cervical cancer by age groups of alternative screening strategies --- p.361 / Chapter Appendix 5-5 --- Influence of discounting rate of life years on the CEA results --- p.363 / Chapter Appendix 5-6 --- Tornado analysis results based on the effect on QALYs predictions --- p.367 / Chapter Appendix 5-7 --- Tornado analysis results based on the effect on life-year predictions --- p.372 / Chapter Appendix 6-1 --- Summary of Markov Model Inputs and Sources --- p.377 / REFERENCE --- p.388