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

Thesis (M.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. / Source: Masters Abstracts International, Volume: 46-05, page: 2671. Advisers: Stephanie L. Mc Fall; Maria E. Fernandez. Includes bibliographical references.

Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 1999. / Bibliography: leaves 118-138.

Made available in DSpace on 2015-07-22T20:49:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-10-28 / Em 2002, o Estado de Mato Grosso aderiu à segunda fase de intensificação Programa Nacional de Controle do Câncer do Colo do Útero (PNCCU) como medida de enfrentamento das altas taxas da doença e de morte por neoplasia cervical. Com o objetivo de analisar os principais resultados do PNCCU, foi feito um estudo em duas partes. A primeira parte teve como objetivo levantar o perfil da doença e a cobertura do exame rastreamento pelo PNCCU no Estado. Os objetivos da segunda parte foram: analisar o seguimento clínico da população rastreada, analisar as diferentes características evolutivas da doença associadas aos fatores sócio-demográficos e clínicos, bem como analisar o risco de óbito e a taxa de sobrevida estratificada pelas variáveis sócio-demográficas e clínicas das mulheres que apresentaram carcinoma invasivo. Na primeira parte, foi utilizado estudo do tipo transversal e na segunda parte, foi realizado um estudo de coorte. O período do estudo compreendeu de 2002 a 2007 e abrangeu todos os municípios do Estado de Mato Grosso. A população estudada na primeira fase do estudo correspondeu todas as mulheres que fizeram o exame de rastreamento no ano de 2002. Na segunda parte do estudo, a população correspondeu a uma amostra aleatória representativa das mulheres que apresentaram alterações citológicas na primeira fase do estudo, totalizando 323 mulheres. A fonte de dados utilizada foi o sistema de informação oficial de saúde, dentre eles o SISCOLO, SIM, APAC, além de dados oficiais da Secretaria Estadual de Saúde/MT (SES/MT), dados disponíveis no site do INCA e do DATASUS e prontuários clínicos. Para análise estatística dos dados foram utilizadas técnicas descritivas e inferenciais. Na parte descritiva foram utilizados tabelas, gráficos e medidas de posição e de dispersão. Para avaliar a o risco de adoecer por carcinoma cervical invasor foi utilizado regressão logística univariada e multivariada. Para analisar a taxa de sobrevida global foi utilizado o estimador de Kaplan-Meier e para analisar os fatores prognósticos, foi utilizado o modelo de riscos proporcionais de Cox. Dentre os principais resultados, destaca-se que no período estudado, Mato Grosso apresentou taxas de incidência elevadas, acima da média nacional. Os dados do seguimento clínico mostraram os diferentes desfechos, dentre eles, destaca-se que: entre as 323 mulheres, 18 (6,2%) foram a óbito tendo o câncer do colo do útero como causa básica da morte. Foi analisado o risco de a doença evoluir para o carcinoma invasor, segundo as variáveis sócio-demográficas e clínicas, sendo que as variáveis: faixa etária, estado civil, tabagismo, menarca e município foram as que apresentaram forte associação com a doença na fase invasora. Já na análise de sobrevivência, a taxa de sobrevida global em 60 meses, estimada pelo método de Kaplan-Meier, foi de 66,7%. No modelo final de risco proporcional de Cox, as variáveis com maior risco de óbito foi o estágio avançado da doença e a raça/cor. Estes dados levam a concluir que a doença no Estado de Mato Grosso tem uma determinação social muito grande, considerando a dificuldade de acesso aos serviços de saúde da população desfavorecida pelas condições raciais, sócio-econômicas, e chegam aos serviços com a doença em fase adiantada, quando a chance de sobrevivência é muito pequena. Conclui-se que para o efetivo combate a doença são necessárias políticas governamentais, como o PNCCU, que garantam a universalidade da assistência, principalmente da população desfavorecida socialmente. / In 2002, the State joined the second phase of intensification of the National Program for the Control of Cervical Cancer (PNCCU) as a measure to deal with the high rates of the disease and of death by cervical neoplasia. With the aim of analyzing the main PNCCU results, a two-stage study was carried out. The first phase aimed at presenting the disease profile and the coverage of the screening exam by the PNCCU in the State. The aims of the second phase were to analyze the clinical follow-up of the population that was screened, analyze the different evolutionary characteristics of the disease associated to socio-demographic and clinic factors, as well as analyze the factors associated to death risk and the stratified survival rate by the socio-demographic and clinical variables of women that presented invasive carcinoma. In the first part, the cross-sectional study was used and a cohort study was used in the second phase. The period of study was from 2002 to 2007 and comprised all the municipalities of the State of Mato Grosso. The population studied in the first phase of the study was all the women who had undergone the screening test in 2002. The population used in the second phase of the study was a representative random sample of those that presented cytological alterations in the first phase of the study, a total of 323 women. The source of data used was the official health information system, among them the SISCOLO, SIM, APAC, and also the official data of the State Health Department/MT (SES/MT), data available in the INCA and DATASUS sites and medical records. For the statistical analysis of the data, descriptive and inferential techniques were used. In the descriptive part, tables, graphics and position and dispersion measures were used. In order to evaluate the risk of being sick due to invasive cervical carcinoma, the univariate and multivariate logistic regression analysis was used. The Kaplan-Meier estimator was used to analyze the survival rate and to analyze the prognostic factors, the Cox proportional hazards model was used. Among the main results it is highlighted that in 2002, Mato Grosso presented high incidence rates, above the national average. The data of the clinical follow up showed the different clinical outcomes, among the 323 women, 18 (6,2%) died having as the basic cause of death the cervical cancer. The risk of the disease developing into the invasive carcinoma was analyzed according to the socio-demographic and clinical variables, and the variables: age group, marital status, smoking history, menopause and municipality were those that presented a strong association with the disease in the invasive phase. However, in the survival analysis, the global survival rate in 60 months, estimated by the Kaplan-Meier method, was of 66,7%. In the final Cox proportional hazards model, the variables with higher death risk was the advanced stage of the disease and the race/color. These data lead to a conclusion that the disease in the State of Mato Grosso has a very large social determination, considering the difficulties in the access to the health services by the population affected by racial, socio-economic conditions that arrive in the health services with the disease in an advanced stage, when the survival probability is very small. The conclusion is that for the effective fight against the disease governmental policies such as the PNCCU are necessary, and that the universality of the assistance be guaranteed, mainly to the socially disadvantaged population. / TEDE / BV UNIFESP: Teses e dissertações

A infecção por papilomavirus é a principal causa de desenvolvimento de neoplasias intraepiteliais cervicais (NIC) e câncer do colo do útero (CCU). Estudos epidemiológicos têm demonstrado que a persistência do genoma viral encontra-se associado a variantes moleculares específicas de papilomavirus humano (HPV) de alto risco. As moléculas HLA de classe II têm um importante papel na resposta imune. Associações entre HLA e CCU ou infecção por HPV tem sido demonstrado em diferentes populações. O nosso objetivo foi verificar se a variabilidade de HLA-DRB1 e DQB1 estavam associada ao CCU e NIC III em mulheres de Belém, uma população formada pelos 3 principais grupos étnicos humanos e uma área de alto risco para o CCU no Norte do Brasil. Foi investigada a existência de diferenças na distribuição de alelos HLA entre mulheres com CCU e NIC III portadoras de diferentes variantes de HPV-16 e mulheres citologicamente normais. Os genes HLA DQB1 e DRB1 foram tipados pelo método de PCR-SSO em 95 casos e 287 controles de mulheres com citologia normal atendidas em um centro de prevenção do colo do útero na mesma cidade. As variantes de HPV-16 foram tipadas por sequenciamento de um fragmento da região controladora do genoma viral (LCR). O polimorfismo na posição 350 do gene E6 foi tipado baseado em um protocolo de hibridização em pontos, para identificar a alteração na posição 350T→G. A magnitude das associações foi estimada por odds ratio (OR) e os respectivos intervalos de confiança (IC), ajustados para potenciais fatores de confusão. Uma associação positiva foi observada entre CCU e os haplótipos DRB1* 150 l-DQB1*0602, DRB1*04-DQB1*0301 e DRB1*1602-DQB1*0301. Ao contrário, DRB1*01-DQB1*0501 mostrou um efeito protetor. Os alelos DRB1*0804, DQB1*0402 apresentaram efeito protetor contra positividade por HPV. O alelo DQB1*0502 e o grupo DRB1*15 foram positivamente associados. Os nossos resultados mostram que as associações positivas de DRB1*1501 e DRB1*1602 podem ser atribuídas a variantes asiático-americanas quando comparado a variantes européias. O risco conferido a DRB1*1501 foi encontrado associado tanto a variantes E6350G quanto a variantes E6350T, entretanto, o maior efeito foi devido às variantes E6250T. A associação positiva de DRB1*1602 foi significativa somente no grupo de mulheres positivas para E6350G. Estes resultados estão de acordo com a composição étnica da população estudada bem como um maior potencial oncogênico de certas variantes. Nossos dados sugerem que a contribuição dos alelos HLA na susceptibilidade genética ao CCU difere de acordo com a distribuição das variantes de HPV em uma dada região geográfica ou grupo étnico. / Papillomavirus infection is the major cause for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) in humano Epidemiological studies have demonstrated that persistence of the viral genome and development of cervical cancer are associated with specific molecular variants of high-risk human Papillomavirus (HPV). Human leukocyte antigen (HLA) molecules play a role in immune response and associations between HLA and IeC or HPV infections have been reported in several populations. We aimed to verify if HLA-DRB1 and DQB1 variability is related to ICC and CIN III in women from Belem, a population formed by the three main human ethnic groups and a high-risk area for this disease in Northem Brazil. We also investigated if there are differences in the HLA class II alleles distribution between women with ICC and CIN III that harbor different HPV-16 variants and women without cancer. HLA DRB1 and DQB1 were typed by PCR-SSO based methods in 95 ICC cases and 287 controls consisting of normal cytology from women attending cervical cancer screening programs in the same city. HPV-16 variants were typed by sequencing a PCR-amplified fragment of long control region (LCR) of the viral genome. The E6350 polymorphism was typed on the basis of a dot blot protocol targeting a specific nucleotide alteration in the position 350T→G of the E6 gene. The magnitude of associations was estimated by odds ratio (OR) and the respective 95% confidence interval (CI), adjusted for potential confounder factors. A positive association was found between ICC cases and DRB1*150 l-DQB1*0602, DRB1*04-DQB1*0301 and DRB1*1602-DQB1*0301 haplotypes. Conversely, DRB1*01-DQB1*05 showed a protective effect. DRB1*0804, DQB1*0402 showed negative association against HPV infection. DQB1*0502 and DRB1*15 were positively associated with HPV infection. Our study showed that positive association of DRB1*1501 and DRB1*1602 alleles may be attributed to AsianAmerican then European variants. Furthermore, the DRB1*1501 was found associated with both women carrying E6350G or E350T, however, a higher effect was observed for E6350T variants carriers. The positive association of DRB1*1602 was significant for women harboring E6350G then E6350T variants. These data are in agreement with ethnical component of the studied population as well as a higher oncogenic potential of certain HPV variants. Our results also suggest that the contribution of HLA class II alieles to the genetic susceptibility to ICC differs depending on the HPV-16 variants distribution in a given geographic and ethnic group.

Introdução: O câncer do colo do útero é uma das neoplasias malignas mais frequentes, particularmente nos países em desenvolvimento e, sobretudo nos grupos com maior vulnerabilidade social. As estimativas de incidência e mortalidade tendem para a redução, porém em ritmo lento. Vários são os fatores de risco identificados, no entanto, apresenta um dos mais altos potenciais de prevenção e cura. A estratégia utilizada para a detecção precoce é o exame de Papanicolaou. Inquéritos de base populacional representam oportunidades únicas para a obtenção de informações que possibilitam avanço no conhecimento das condições de vida e saúde da população e para a formulação e avaliação de políticas sociais de saúde. Objetivo: Analisar a realização do exame de Papanicolaou segundo variáveis socioeconômicas, demográficas, de estilo de vida, estado de saúde e o uso de serviços de saúde das mulheres com 20 anos ou mais de idade, residentes no município de São Paulo, Brasil. Métodos: Estudo transversal de base populacional, com dados obtidos através do Inquérito de Saúde no Município de São Paulo ISA Capital, 2008, em amostra composta por 1.236 mulheres com 20 anos ou mais. Considerou-se a prevalência do exame realizado nos últimos 3 anos que antecederam à entrevista. Para as análises estatísticas foi utilizado o módulo survey do programa Stata 10.0. O modelo de regressão de Poisson foi aplicado para verificar associações mais precisas da realização do exame com as variáveis estudadas. A confidencialidade foi garantida. Resultados: As associações estatisticamente significantes encontradas foram: idade (20 a 29 anos), ser casada ou ter companheiros, escolaridade (12 anos), tabagismo (exfumantes), mulheres que possuíam exame clínico das mamas e plano de saúde. O Sistema Único de Saúde foi responsável por 39,2 por cento dos exames de Papanicolaou realizados. O motivo referido para a não realização do exame mais frequente foi não era necessário/sou saudável. Discussão: Ao considerar a realização do exame conforme recomendada pelo Ministério da Saúde, seria esperada cobertura de Papanicolaou superior à observada. Em termos de condições socioeconômicas, as associações com renda e atividade remunerada não permaneceram no modelo final, sugerindo equidade social na realização do exame. Entretanto, os serviços de saúde devem criar estratégias que ampliem o acesso às populações mais vulneráveis proporcionando maior conhecimento e envolvimento da população na incorporação das práticas preventivas do câncer do colo do útero, oferecendo um atendimento de maior qualidade a todas as mulheres, sobretudo, as SUS dependentes. Considerações Finais: Para o êxito do programa de rastreamento, deve-se priorizar a capacitação dos profissionais de saúde, a qualidade dos exames, a garantia do seguimento e tratamento dos casos e o estabelecimento de intervenções mais humanizadas e equitativas na utilização dos serviços de saúde do SUS / Introduction: Cervical cancer is one of the most frequent malignancies, particularly in developing countries and especially in groups with higher social vulnerability. Estimates of incidence and mortality tend to decrease but at a slow pace. Several risk factors are identifies, however, shows one of the highest potential for prevent and cure. The strategy used for early detection is the Pap smear. Population-based surveys represent unique opportunities to obtain information to enable an advance in knowledge of living conditions and population health and for the formulation and evaluation of welfare policies. Objective: To analyze the performance of Pap smears according to socioeconomic variables, demographic, lifestyle, health status and use of health services for women aged 20 or older, residing in São Paulo, Brazil. Methods: Cross-sectional population-based data obtained from the Survey of Health in São Paulo - ISA Capital, 2008, in a sample of 1,236 women aged 20 years or more. We considered the prevalence of the examination in the last three years prior to the interview. For statistical analysis we used the survey module in Stata 10.0. The Poisson regression model was applied to assess associations more precise examination carried out with the variables. Confidentiality was guaranteed. Results: Statistically significant associations were found: age (20 to 29 years old), be married or have partners, education ( 12 years), smoking (former smokers), women who had a clinical breast exam and health plan. The Unified National Health System was responsible for 39,2 per cent of the reported Pap smears. The most frequent reported reason for not undergoing the test was \"not necessary / I\'m healthy.\" Discussion: When considering the test as recommended by the Ministry of Health, Pap smear coverage would be expected higher than that observed. In terms of socioeconomic conditions, the association with income and remunerated activity did not remain in the final model, suggesting an social equity in the exam. However, health services should develop strategies to increase access to vulnerable populations by providing greater knowledge and involvement of the population in the incorporation of preventive practices of cancer of the cervix, providing a higher quality care to all women, mainly the SUS dependent. Final considerations: For the success of the screening program, one should prioritize the training of health professionals, the quality of examinations, ensuring the monitoring and treatment of cases, and the establishment of more humane and equitable interventions at use of SUS´s health services

Cheung, Tak Hong. / "July 2011." / Thesis (M.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 166-199). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.

INTRODUÇÃO: O câncer do colo uterino é a terceira neoplasia maligna que mais afeta as mulheres brasileiras e, quando não detectada precocemente, apresenta prognóstico reservado. O câncer do colo uterino é consequência da infecção pelo Papilomavírus humano (HPV). Pouco é conhecido sobre a influência dos genótipos do HPV na apresentação clínica e o seu impacto na taxa de sobrevida no câncer do colo uterino. Os objetivos do estudo foram identificar os genótipos de HPV no tecido tumoral da população atendida no Instituto do Câncer do Estado de São Paulo e associar os genótipos de HPV aos fatores de risco conhecidos para o câncer do colo uterino. MÉTODOS: Foram incluídas mulheres com diagnóstico de câncer do colo uterino atendidas no Instituto do Câncer do Estado de São Paulo (ICESP) entre maio de 2008 e junho de 2012. A análise do material tumoral parafinado confirmou histologicamente o diagnóstico de câncer do colo uterino. O DNA tumoral foi extraído de três fragmentos de 10?m de espessura do bloco de parafina de carcinoma do colo uterino e submetido ao ensaio clínico Onclarity (sistema automatizado da BD Viper LT) para detecção e genotipagem do HPV. Idade ao diagnóstico, estadiamento clínico, tipo histológico e tempo de sobrevida foram obtidos a partir de registros do prontuário até dezembro de 2015. RESULTADOS: Foram analisadas 414 pacientes. As frequências dos genótipos estudados foram HPV16 (54%) HPV18(9%), HPV33-­58 (6%), HPV45 (5%), HPV31 (3%), HPV39-­68-­ 35 (3%), HPV59-­56-­66(3%), HPV52 (2%) e HPVnegativo (14%). A idade da população estudada variou de 17 a 87 anos, com média etária de 50,8 (DP=13,8 anos). Os tipos histológicos foram carcinoma de células escamosas (75%), adenocarcinoma (21%) e outros tipos histológicos (4%). Conforme o estadiamento clínico adotado pela FIGO (2009), 35% foi classificado como 1A1, 1A2 e 1B1, 17% como 1B2 e 2A e 48% como 2B a 4B. O genótipo do HPV apresentou distribuição diferente quanto à idade ao diagnóstico, tipo histológico e estadiamento. A mediana do tempo de sobrevida global desta coorte de pacientes com câncer do colo uterino foi de 37 meses [12-­53 meses]. A sobrevida global acumulada em 5 anos após o diagnóstico de câncer do colo uterino foi de 55%. Ocorreram 119 (38%) óbitos no período e 133 (42%) recidivas subdivididas em três grupos: local (12%), regional (30%) e à distância (58%). Curvas de sobrevida de Kaplan-­Meier e estatística de Log-­rank demonstraram que os genótipos de HPV 16 e 18 (59%) não se relacionaram a um pior prognóstico em comparação com outros genótipos de HPV (41%) (P=0,17). Idade ao diagnóstico, estadiamento clínico, tipo histológico, invasão vascular, metástase linfonodal, tamanho do tumor e os genótipos HPV16, HPV18 e HPVoutros foram analisados individualmente em um modelo de regressão de Cox. O genótipo do HPV se associou a pior taxa de sobrevida global apenas quando detectado mais de um HPV no material tumoral analisado. CONCLUSÃO: Apesar das diferentes distribuições dos os genótipos do HPV quanto à idade ao diagnóstico, tipo histológico e estadiamento, o genótipo do HPV não se mostrou como fator prognóstico independente no câncer do colo uterino / INTRODUCTION: Uterine cervical cancer is the third most common malignant neoplasm affecting Brazilian women. Prognosis is poor when diagnosis is delayed. Cervical cancer is a consequence of human papillomavirus (HPV) infection. Little is known about the influence of HPV genotypes in Brazil and its impact on cancer survival rate The purpose of the present study were to identify HPV genotypes of tumoral tissue from the affected population and to examine the association between HPV genotype and traditional cervical cancer risk factors. METHODS: Women diagnosed with cervical cancer at the Cancer Institute of the State of São Paulo (ICESP) between May 2008 and June 2012 were included in the study. Tumor specimens were reviewed to confirm the diagnosis of cervical cancer. Tumor DNA was extracted from three 10?m-­thick paraffin block fragments of each subject. HPV genotype was detected using the Onclarity system (BD Viper LT automated system). Age at diagnosis, clinical staging, histological type and survival time were obtained from the hospital electronic data records until December 2015. RESULTS: 414 patients were analyzed. The HPV genotypes studied were HPV16 (54%) HPV18 (9%), HPV33-­58 (6%), HPV45 (5%), HPV31 (3%), HPV39-­68-­35 (3%), HPV59-­56-­ 66(3%), HPV52 (2%) and HPVnegative (14%). The age of the study population ranged from 17 to 87 years, mean age= 50.8 (SD=13.8 years). Histological types were classified as squamous cell carcinoma (75%), adenocarcinoma (21%) and other histological types (4%). According to the 2009 FIGO clinical staging, 35% were classified as 1A1, 1A2 and 1B1, 1B2 and 17% as 2A and 48% as 2B the 4B. HPV genotypes showed different distributions regarding age, histologic tumor types and clinical staging. The median overall survival time was 37 months [12-­53 months]. The cumulative overall survival at 5 years after diagnosis of cervical cancer was 55%. There were 119 (38%) deaths during the study period and 133 (42%) recurrences subdivided into three groups: local (12%), regional (30%) and distant (58%). Kaplan-­Meier survival curves and Log-­rank statistics showed that HPV 16/18 (59%) did not influence prognosis compared to other HPV subtypes (41%) (P=0.17). Age at diagnosis, clinical stage, histological type, vascular invasion, lymph node metastasis, tumor size and HPV16 genotypes, HPV18 and HPVothers were individually analyzed in a Cox regression model. HPV genotype was associated with poorer overall survival rate only when multiple HPV infection was detected in the tumoral specimen. CONCLUSION: Although HPV genotype showed different distribution regarding age at diagnosis, histological type and clinical staging, HPV genotype was not an independent prognostic factor of cervical cancer in the study population