Submitted by Carvalho Dias João Paulo (joao.dias@famerp.br) on 2018-04-04T14:21:17Z No. of bitstreams: 1 leandrofreitascolturato_dissert.pdf: 2059005 bytes, checksum: 00cf44fb001e34750da28245f55440a6 (MD5) / Made available in DSpace on 2018-04-04T14:21:17Z (GMT). No. of bitstreams: 1 leandrofreitascolturato_dissert.pdf: 2059005 bytes, checksum: 00cf44fb001e34750da28245f55440a6 (MD5) Previous issue date: 2016-06-20 / Introduction: Ten to 15% of cervical cancer patients have had tumor recurrence in early stage (FIGO IB1 - IIA). They have presented negative lymph nodes to hematoxylin-eosin (HE) staining technique. Objectives: In patients with cervical cancer in stage IB1 - IIA (FIGO): 1) to assess the prevalence of pelvic lymph node micrometastasis (MI) through the immunoreactivity of antibody anti pan - cytokeratin AE1/AE3 in lymph node tissue and its correlation with tumor recurrence and overall survival; 2) to describe, in the primary tumor of patients with recurrence tumor and/or lymph node micrometastasis, the immunohistochemical expression (IHC) of the lymphatic endothelial marker D2-40 and their correlation with histopathologic findings by conventional hematoxylin-eosin staining. Material and Method: We studied 83 medical records of patients admitted at Centro de Referência da Saúde da Mulher do Estado de São Paulo (Hospital Pérola Byington) in clinical stages IB1, IB2, and IIA. They were submitted exclusively to primary surgical treatment with hysterectomy Querleu C1 and had no lymph node metastases in the presence of Hematoxylin-Eosin. We collected data from the patients’ medical records. We studied variables, such as sociodemographic, reproductive, and histopathological characteristics, as well as the therapeutic follow-up of these patients. The histological sections of the tumors were reviewed systematically. Each lymph node was analyzed by IHC with AE1/AE3 antibody with six histological sections of three micrometers thick. The patients were divided into groups with recurrence (GCR) and without recurrence (GSR). The patients were also separated according to the presence or absence of lymph node micrometastasis or isolated tumor cells. Qualitative and quantitative variables between groups were compared using chi-square test and parametric Student's t-test. Results: Fifteen patients (18.07%) have had recurrence. At a significance level of 5%, there was significant difference between the GCR and GSR and the variables: pregnancies, size of the major axis of the tumor (cm), lymph node micrometastasis, clinical stage IB2 or IIA, and the mean number of negative lymph nodes. The direct analysis with lymph node micrometastasis or isolated tumor cells showed a significant difference among the variables clinical stage IB2 or IIA, and a stromal invasion depth greater than 2/3. Conclusions: The presence of lymph node micrometastasis is an important risk factor to tumor recurrence. These patients should be considered eligible for radiochemotherapy adjuvant treatment. / Introdução: Dez a 15% das pacientes com câncer do colo do útero em estádio clínico inicial (FIGO IB1 – IIA), com linfonodos negativos à técnica de Hematoxilina-eosina (HE), apresentam recidiva tumoral. Objetivos: Em pacientes com câncer de colo do útero nos estádios IB1 – IIA (FIGO): 1) Avaliar a prevalência de micrometástase (MI) linfonodal pélvica por meio da imunoexpressão do anticorpo anti-pan – citoqueratina AE1/AE3 no tecido linfonodal e sua correlação com recidiva tumoral e sobrevida global; 2) Descrever, no tumor primário de pacientes com recidiva tumoral e/ou MI linfonodal, a expressão imuno-histoquímica (IHQ) do marcador endotelial linfático D2-40 e sua concordância com achados histopatológicos convencionais, por meio da coloração HE. Material e Método: Estudaram-se 83 prontuários de pacientes admitidas no Centro de Referência da Saúde da Mulher do Estado de São Paulo – Hospital Pérola Byington nos estádios clínicos IB1, IB2 e IIA, submetidas ao tratamento cirúrgico primário com histerectomia Querleu C1 exclusivamente e que apresentavam ausência de metástases linfonodais à HE. A coleta de dados foi realizada nos prontuários e realizou-se levantamento das características sociodemográficas, reprodutivas, histopatológicas, terapêuticas e de seguimento dessas pacientes. Os cortes histológicos dos tumores foram revisados de forma sistemática e cada linfonodo analisado por IHQ com anticorpo AE1/AE3, com seis cortes histológicos de três micrometros de espessura. As pacientes foram divididas em grupos com recidiva (GCR) e sem recidiva do tumor (GSR). Foram também divididas de acordo com a variável presença ou ausência de MI linfonodal ou células tumorais isoladas. Para comparar os grupos em relação às variáveis qualitativas e quantitativas foi utilizado o teste Qui-quadrado e o teste paramétrico t de Student, respectivamente. Resultados: Quinze pacientes (18,07%) apresentaram recidiva tumoral. Com significância de 5%, houve diferença significante entre os GCR e GSR e as variáveis: gestações, tamanho do maior eixo do tumor (cm), MI linfonodal, estadiamento clínico IB2 ou IIA e número médio de linfonodos negativos. Na análise direta, com MI linfonodal ou CTI, houve diferença significante com as variáveis estadiamento clínico IB2 ou IIA e profundidade de invasão estromal maior do que 2/3. Conclusões: A presença de MI linfonodal é fator de risco importante para recidiva tumoral. Essas pacientes devem ser consideradas elegíveis para tratamento radioquimioterápico adjuvante.

INTRODUÇÃO: Pouco se sabe sobre parâmetros ultrassonográficos transvaginais possíveis de serem avaliados durante a gestação além do comprimento do colo uterino. A escassa literatura sugere que o volume calculado através da ultrassonografia tridimensional, a quantificação de sinal power Doppler em todo o órgão e o Doppler das artérias uterinas possam sofrer alterações de acordo com o comprimento cervical, e até mesmo anteceder seu encurtamento no processo que leva ao parto. OBJETIVOS: agregar novos parâmetros bi e tridimensionais ultrassonográficos à avaliação do colo uterino em gestações únicas. MÉTODO: Estudo transversal desenvolvido com dados de 2014 a janeiro de 2018 do projeto PROPE, no qual foi realizada ultrassonografia transvaginal em pacientes entre 20 e 23 semanas e 6 dias de gestação. Foram compilados e submetidos à análise secundária os dados de 162 gestantes com comprimento do colo uterino >= 25 mm (grupo Controle), 68 gestantes com comprimento do colo >= 15 mm e < 25 mm (grupo Colo Curto) e 18 gestantes com comprimento do colo < 15 mm (grupo Colo Muito Curto). Foram analisadas as características demográficas e antecedentes obstétricos das gestantes, e foram comparados entre os grupos os parâmetros cervicais de comprimento, volume e vascularização, além do Doppler de artérias uterinas bilateralmente. RESULTADOS: O comprimento médio (± DP) dos colos uterinos de cada grupo foi 35,28 ± 5,12 mm para o grupo Controle, 20,51 ± 2,47 mm para o grupo Colo Curto, e 10,72 ± 2,51 mm para o grupo Colo Muito Curto. Houve diferença entre os grupos quanto à idade materna, cor (etnia) e idade gestacional de inclusão. Quanto aos antecedentes obstétricos, houve associação somente entre a presença de colo curto na gestação atual e pelo menos um parto prematuro anterior em gestantes não nulíparas (p = 0,021). Em relação aos parâmetros ultrassonográficos, verificou-se correlação linear positiva moderada entre volume e comprimento do colo (coeficiente de Pearson=0.587, valor p < 0.0001). Os grupos Controle, Colo Curto e Colo Muito Curto foram estatisticamente diferentes em relação às médias (± DP) de volume (46,38 ± 13,60 cm vs. 32,15 ± 13,14 cm vs. 22,08 ± 11,10 cm, respectivamente)(p <= 0,001), e em relação às médias (± DP) de índice de fluxo (IF) (39,81 ± 6,42 cm vs. 38,73 ± 4,99 cm vs. 36,02 ± 5,34 cm, respectivamente) (p = 0,027), em que a diferença estatística ocorre entre os grupos Controle e Colo Muito Curto. Porém, na presença da informação do volume, após regressão linear, a associação entre os grupos e IF deixa de ser significativa. Também não houve relação entre os grupos estudados e o Doppler de artérias uterinas. CONCLUSÃO: Existe correlação linear positiva entre o volume e o comprimento do colo uterino. Na ausência de informações sobre o volume, comprimento cervical e índices de vascularização não se correlacionam. O comprimento cervical também não está relacionado a alterações no Doppler de artérias uterinas. Apesar das limitações de uma amostra pequena e escassez de dados comparativos na literatura, este estudo foi realizado com uma amostra homogênea da população e abre caminho para maiores pesquisas sobre o assunto / INTRODUCTION: Little is known about transvaginal ultrasound parameters other than cervical length that can be assessed during gestation. The literature suggests that changes in volume on three-dimensional ultrasound, quantification of power Doppler signal in the entire organ, and Doppler sonography of uterine arteries may be related to cervical length, and even precede its shortening during spontaneous delivery. OBJECTIVES: To include new two- and three-dimensional ultrasonographic parameters for evaluation of the uterine cervix in single pregnancies. METHODS: A crosssectional study of data from Project PROPE on transvaginal ultrasonography performed in patients between 20 and 23 weeks and 6 days of gestation from May 2014 to January 2018 was conducted. Secondary analysis of data from 162 pregnant women with uterine cervical length >= 25 mm (Control group), 68 pregnant women with cervical length >= 15 mm and < 25 mm (Short Cervix group), and 18 pregnant women with cervical length < 15 mm (Very Short Cervix group) was performed. The demographic characteristics and obstetric history of the pregnant women were analyzed, and the cervical length, volume, and vascularization were compared between the groups. In addition, Doppler velocimetry of the uterine arteries was performed bilaterally. RESULTS: The mean cervical length (± SD) was 35.28 ± 5.12 mm for the Control group, 20.51 ± 2.47 mm for the Short Cervix group, and 10.72 ± 2, 51 mm for the Very Short Cervix group. The groups differed in maternal age, ethnicity, and gestational age. When analyzing the obstetric history of only non-nulliparous patients we observed a significant association between the presence of a short cervix in the current pregnancy and at least one previous preterm birth (p = 0.021). With regard to the ultrasonographic parameters, we observed a moderate positive linear correlation between the volume and length of the cervix (Pearson coefficient = 0.587, p < 0.0001). The Control, Short Cervix, and Very Short Cervix groups showed differences in the mean (± SD) volume (46.38 ± 13.60 cm vs. 32.15 ± 13.14 cm vs. 22.08 ± 11.10 cm, respectively) (p <= 0.001) and mean (± SD) flow index (FI) parameter of cervical vascularization (39.81 ± 6.42 cm vs. 38.73 ± 4.99 cm vs. 36.02 ± 5.34 cm, respectively) (p = 0.027), and the difference between the Control and Very Short Cervix groups was statistically significant. However, after linear regression, in the presence of volume information, we found no association between the groups and FI. CONCLUSION: Cervical length and volume are positively correlated. When information about the volume is not provided, there\'s no association between cervical length and vascularization. Uterine artery Doppler is not related to cervical length. Despite the limitations of a small sample size and less comparative data in the literature, this study was performed with a homogeneous sample population and paves the way toward further research on the subject

OBJECTIVES To determine if health care workers are aware of the HPV vaccine and its availability, uptake of the vaccine and prescribing practices and reasons for non – uptake of the vaccine . METHODS Health care providers working in the private sector, in the Ethekweni health district in Kwazulu Natal, were interviewed. Health care workers included: 100 general practitioners, 50 gynaecologists, 50 paediatricians, 50 medical staff and 50 nursing staff. A questionnaire was designed for purpose of this study. Visits were be made to health care providers. All heath care providers who were willing to participate were interviewed. STATISTICS Comparisons of awareness among subgroups of health care providers was analysed using Chi-square tests. If significant, pairwise comparisons were made using a Bonferroni adjustment for multiple comparisons. Associations between awareness and other factors, such as demographic, uptake and beliefs were tested using a chi square test. Analysis was done by Stata v11 (StataCorp, 2009) i RESULTS Three hundred health care workers were interviewed - 50 gynecologists (16.7%), 52 pediatricians (17.3%), 99 general practitioners (33%), 49 other medical doctors (16.3%) and 50 (16.7%) nurses. Two hundred and sixty seven health care workers (89%) were aware of the HPV vaccine and one hundred and eighty eight health care workers (70.4%) informed patients of the availability of the HPV vaccine. Most (77.9%) practitioners have only prescribed the vaccine less than ten times. Gardasil® was prescribed by 46%, Cervarix® by 6.5% and prescription of either vaccine of health care workers was 50.2%. Practitioners were generally unaware that Gardasil® could be prescribed to males (62.9%). CONCLUSION Health care workers were aware of the HPV vaccine and prescribed the vaccine on request. However even though practitioners were aware of the vaccine, most have prescribed the vaccine less than ten times since licensing in 2008. Knowledge with regards to the licensed use of the HPV vaccines is deficient. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2012.

Background According to the Programme for Appropriate Technology in Health (PATH), global statistics show that nearly half a million new cases of invasive cervical cancer are diagnosed each year. More than a quarter million women die of this disease annually, with the highest incidence and mortality rates being in developing countries. In South Africa a woman's risk of developing cervical cancer is one in 26. Each year 6 700 women develop cervical cancer while 3 700 die from the disease annually. The overall aim of this research was to determine the patterns of health seeking behaviour of women being treated for cervical cancer. The specific objectives were to: Describe the health service utilization characteristics of patients being treated for cervical cancer. Describe the need factors associated with decision to seek care. Describe the enabling factors associated with decision to seek care. Describe the predisposing factor associated with the decision to seek care. Analysis of factors associated with health seeking behavior in women treated for cervical cancer. Methods An observational study with a descriptive and analytic component was undertaken. The study was conducted in the Oncology Department of Grey‟s Hospital, which is a referral hospital located in Pietermaritzburg from the Umgungundlovu, Umzinyathi, Zululand, Uthukela and Amajuba Health District which has a population of 995 303. All patients treated for cervical cancer within the study period, who provided informed consent for their participation in the study, were enrolled. The total number included in the study was 109. Descriptive statistics were used to explore frequencies emanating from the data. Pearson Chi square tests were used to explore the relationship between two categorical variables and the p-value was used to decide how much evidence there was against the null hypothesis. Odds ratio was also used as a measure of risk to compare whether the probability of a variable is the same for the outcome variables. Regression was performed on the variables that were found to be statistically significant to the outcome variables in the bivariate analyses. Results The variables that most influenced health seeking behaviour and that still remained statistically associated with the outcome variables under the multivariate analysis were found to be age, marital status, employment status, social support for medical treatment, educational level, knowledge of Pap smear screening and recognition of cervical cancer. Conclusion The study achieved its aim of determining the patterns of health seeking behavior of women being treated for cervical cancer at Grey‟s Hospital. It also identified that proper implementation of HPV vaccination and cervical screening programme can be an entry point to address the incidence and presentation of cancer at advance stages, as well the treatment of precancerous lesions of the cervix in the women of reproductive age. An awareness campaign, support for women to undergo screening program and availability of health centers is also recommended. All recommendations need to be considered by the department of health and appropriate authorities in South Africa to minimize the widespread of cervical cancer. / M. Med. Sc. University of KwaZulu-Natal, Durban 2012.

Thesis (Ph. D.)--Ohio State University, 2003. / Title from PDF t.p. (viewed on May 7, 2006). Includes bibliographical references (p. 297-304).

Orientador: Aarão Mendes Pinto-Neto / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T03:36:10Z (GMT). No. of bitstreams: 1 Vaz_AnaFrancisca_D.pdf: 1602661 bytes, checksum: 0dbc9ea54c85593a5a17af092c3b8961 (MD5) Previous issue date: 2011 / Resumo: Objetivos: Investigar a frequência de eventos adversos antes e após a radioterapia, a proporção de mulheres sexualmente ativas, avaliar a qualidade de vida (QV) e identificar seus preditores em uma coorte de mulheres com câncer ginecológico. Métodos: Estudo de coorte prospectivo com 107 mulheres com câncer ginecológico (colo do útero ou endométrio), idade (21 a 75) anos, tratadas com radioterapia, 89 (teleterapia e braquiterapia) 10 (braquiterapia) 8 (teleterapia) no Hospital da Mulher Prof. Dr. José Aristodemo Pinotti CAISM/UNICAMP. A QV foi avaliada através do questionário da Organização Mundial da Saúde - (WHOQOL-breve), antes da radioterapia (T0), 4 meses (T1), 1ano (T2) e 3 anos (T3) após o tratamento. Os eventos adversos após a radioterapia foram graduados de acordo com a escala Common Terminology Criteria Adverse Event (CTCAE) v 3.0. Os escores de QV foram avaliados através do teste de Wilcoxon pareado e os seus preditores identificados por meio de regressão linear. Utilizou-se o teste de McNemar para avaliar as diferenças entre as frequências de sintomas sexuais e da menopausa, e da proporção de mulheres sexualmente ativas após a radioterapia em relação à avaliação inicial. Resultados: A mediana da idade das participantes antes da radioterapia foi 60 anos. O domínio meio ambiente e a saúde geral eram os mais comprometidos antes da radioterapia. Dor (49,5%) e sangramento vaginal (36,9%) foram as queixas mais frequentes. Anemia (p<0,01) e náusea e/ou vômito (p=0,01) interferiram negativamente no domínio físico; dor no domínio físico (p<0,01), QV global (p=0,02) e saúde geral (p=0,01), e história de cirurgia positivamente na saúde geral (p<0,01). Três anos após a radioterapia observou-se uma redução da frequência de secura vaginal (26,7% em T0 vs 8,3% em T3; p<0,005), aumento da proporção de mulheres sexualmente ativas (21,5% em T0 vs 44,2% em T3; p=0,005) em relação à avaliação inicial, e aumento significativo dos escores de QV para o domínio psicológico, saúde geral e QV global. Dor associou-se negativamente com os domínios físico, psicológico e relacionamento social (p<0,05); dispareunia com os domínios físico e relacionamento social (p<0,05); diminuição do interesse sexual com o domínio psicológico (p<0,01) e maior renda positivamente com o domínio psicológico e saúde geral (p<0,05). Conclusão: O domínio meio ambiente e a questão relacionada à saúde eram os mais prejudicados antes da radioterapia. Os sintomas do câncer foram os fatores de maior interferência na QV. Três anos após a radioterapia verificou-se melhora da QV e aumento significativo do número de mulheres sexualmente ativas em relação à avaliação prévia. A presença de dor, dispareunia e diminuição do interesse sexual interferiram negativamente na QV / Abstract: Objectives: To investigate the frequency of adverse events before and after radiotherapy, the proportion of sexually active women, evaluate quality of life (QOL) and identify their predictors in a cohort of women with gynecologic cancer. Methods: A prospective cohort study of 107 women with gynecologic cancer (cervical or endometrial), aged (21 to 75) years, treated with radiotherapy, 89 (teletherapy and brachytherapy) 10 (brachytherapy) 8 (teletherapy) in the Prof. Dr. José Aristodemo Pinotti Women?s Hospital-CAISM/UNICAMP. QOL was assessed by the World Health Organization- (WHOQOL-BREF) questionnaire, before radiotherapy (T0), 4 months (T1),1year (T2) and 3 years (T3) after treatment. The adverse events following radiotherapy were scored according to the Common Terminology Criteria Adverse Event (CTCAE) scale, v 3.0. QOL scores were assessed by the paired Wilcoxon test and their predictors were identified by linear regression analysis. The McNemar test was used to assess the differences between the frequencies of sexual symptoms and menopause, as well as the proportion of sexually active women after radiotherapy compared to baseline evaluation. Results: The median age of the participants before radiotherapy was 60 years. The environmental domain and general health were the most impaired before radiotherapy. Pain (49.5%) and vaginal bleeding (36.9%) were the most frequent complaints encountered. Anemia (p<0.01), nausea and/or vomiting (p=0.01) negatively interfered with the physical domain. Pain negatively interfered with the physical domain (p<0.01), global QOL (p=0.02) and general health (p=0.01). A history of surgery positively interfered with general health (p<0.01). Three years after radiotherapy, there was a decrease in the frequency of vaginal dryness (26.7% in T0 vs 8.3% in T3; p<0.005), an increase in the proportion of sexually active women (21.5% in T0 vs 44.2% in T3; p=0.005) in comparison to baseline assessment, and a significant increase in QOL scores for the psychological domain, general health and global QOL. Pain was negatively associated with the physical, psychological and social relationship domains (p<0.05). Dyspareunia was negatively associated with the physical and social relationship domains (p<0.05). Decreased sexual interest was negatively associated with the psychological domain (p<0.01). A higher income was positively associated with the psychological domain and general health (p<0.05). Conclusion: The environmental domain and the question related to general health were the most compromised before radiotherapy. Cancer symptoms were the factors that most interfered with QOL. Three years after radiotherapy, there was an improvement in QOL and a significant increase in the number of sexually active women compared to prior evaluation. Pain, dyspareunia and decreased sexual interest negatively interfered with QOL / Doutorado / Fisiopatologia Ginecológica / Doutor em Ciências da Saúde

Orientadores: Sophie Françoise Mauricette Derchain, Cecilia Maria Roteli Martins / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-05T07:54:01Z (GMT). No. of bitstreams: 1 Gontijo_RenataClementino_D.pdf: 141945 bytes, checksum: 2c58c2feab74004e7047e409bad433a0 (MD5) Previous issue date: 2005 / Resumo: Introdução: Mulheres com resultado de citologia negativa e sem infecção pelo papilomavírus humano (HPV) têm teoricamente um risco quase nulo de terem uma lesão intra-epitelial escamosa cervical de alto grau ou câncer invasor. Porém, muitas mulheres com citologia negativa e colo uterino morfologicamente normal são infectadas pelo HPV, e o significado clínico desta infecção em relação ao risco de vir a apresentar anormalidades citológicas ou histológicas futuras ainda não está totalmente esclarecido. Objetivo: Investigar a incidência em 24 meses de alterações citológicas e histológicas cervicais segundo a detecção do HPV, em mulheres com citologia inicial normal, incluídas na coorte Latin American Screening study (LAMS). Material e métodos: Um grupo de 365 mulheres com resultado de citologia normal e resultado de Captura Híbrida II (CH II) para HPV de alto risco oncogênico positivo e negativo, foram seguidas por 24 meses em Campinas e São Paulo. Todas as mulheres responderam a um questionário referente aos fatores sociodemográficos e reprodutivos, e foram submetidas à coleta de material para citologia oncológica e CH II. As mulheres com pelo menos um exame positivo e uma amostra aleatória de 10% de mulheres com ambos os testes negativos foram convocadas para colposcopia com biópsia, se necessário, e seguimento semestral com citologia e colposcopia. Foram comparadas as mulheres com infecção pelo HPV com aquelas não infectadas, segundo as características sociodemográficas e reprodutivas, utilizando-se o cálculo do risco relativo (RR) e a análise de regressão logística em stepwise com intervalo de confiança (IC) de 95%. Foram calculados também a taxa de incidência e o RR com IC de 95% de desenvolver anormalidades citológicas ou histológicas durante o seguimento. Tomou-se como padrão-ouro a colposcopia. Quando a colposcopia foi normal ou quando a biópsia apresentou cervicite, as mulheres foram consideradas como diagnóstico negativo. As mulheres cuja biópsia foi compatível com neoplasia intra-epitelial cervical (NIC) grau 1 ou mais foram consideradas como diagnóstico positivo. Resultados: A incidência de lesões de baixo e alto graus na citologia foi maior entre as mulheres com resultado de CH II positivo, tanto aos 12 quanto aos 24 meses de seguimento. Até 12 meses de seguimento, mulheres com CH II de rastreamento positivo apresentaram um RR significativamente maior de lesões de baixo (1,4; IC 95% 1,1-1,7) e alto (1,5; IC 95% 1,4-1,7) graus na citologia. O RR para lesão de alto grau aumentou para 1,7 (IC 95% 1,5-1,9) naquelas acompanhadas por 24 meses. Em relação aos resultados histológicos, a incidência de NIC 1, 2 e 3 também foi maior entre as mulheres com resultado de CH II positivo, tanto aos 12 quanto aos 24 meses de seguimento. As mulheres com CH II positivo apresentaram um RR de 1,5 (IC 95% 1,4-1,6) para NIC 2 e 3 durante o seguimento até 12 meses e este RR aumentou para 1,7 (IC 95% 1,5-1,9) naquelas seguidas até 24 meses. Conclusão: O teste para detecção do HPV associado à citologia pode selecionar entre as mulheres com citologia normal aquelas com maior risco de lesão cervical subseqüente / Abstract: Introduction: Women with normal baseline cytology and non-infected by Human papillomavirus (HPV) have, in theory, no risk to develop a high-grade cervical intraepithelial lesion or cancer. However, many women with normal cytology and with morphologically normal uterine cervix are HPV infected, and, the clinical significance of this infection regarding to the risk of devoloping cytological or histological abnormalities in the future are not totally clear yet. Purpose: To investigate the incidence of cytological and histological cervical lesions in a 24 months follow-up, according to HPV detection among women with baseline normal cytology result, in a subgroup of women included in the Latin American Screening study (LAMS). Study design: A group of 365 women with normal Pap smear whatever the Hybrid Capture (HC) II test result were followed for 24 months at Campinas e São Paulo (Brazil). They answered a questionnaire regarding sociodemographic and reproductive factors and were submitted to a clinical exam, including Pap smear and HC II. Women with at least one positive result and a 10% random sample of women with both tests negative were referred to colposcopy and followed with cytology and colposcopy in a six-month interval. Women with positive and negative HPV test were compared regarding sociodemographic and reproductive factors using relative risk (RR) and stepwise logistic regression analysis calculated with 95% confidence interval (CI). Also the incidence rate and RR of developing any cytological or histological abnormality during the follow-up were calculated within 95% confidence limits. Colposcopy was considered as the gold standard. When colposcopy result was normal or biopsy result was cervicitis it was considered as negative diagnosis. Women with histologic diagnosis of cervical intraepithelial neoplasia (CIN) 1 or higher were considered as positive diagnosis. Results: Incidence of low and high-grade cytological lesion was higher in women with positive HPV testing than in women with negative HPV testing after 12 and 24 months of follow-up. In up to 12 months of follow-up, women with baseline positive HPV test had a significantly higher proportion of low-grade (1.4; 95% CI 1.1-1.7) and high -grade (1.5; 95%CI 1.4-1.7) cytological lesion. The RR for high-grade lesion increased to 1.7 (95%CI 1.5-1.9) for those followed-up in up to 24 months. For histological outcomes, the incidence of CIN 1, 2 or 3 was also higher in women with positive HPV testing than in women with negative HPV testing after 12 and 24 months of follow-up. Women with positive HPV test had a higher RR of CIN 2 and 3 (1.5; 95%CI 1.4-1.6) during the follow-up in up to 12 months and the RR increased to 1.7 (95%CI 1.5-1.9) for those followed-up in up to 24 months. Conclusions: HPV test is useful in addition to cytology to select from women with normal cytology those who are at highest risk for underlying cervical lesion / Doutorado / Tocoginecologia / Doutor em Tocoginecologia

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Objetivos: comparar a mensuraÃÃo ultra-sonogrÃfica transvaginal do colo uterino e o Ãndice de Bishop, na prediÃÃo do parto vaginal apÃs induÃÃo do trabalho de parto com misoprostol 25mcg, assim como, determinar os principais fatores relacionados à evoluÃÃo para parto vaginal. Sujeitos e MÃtodos: realizou-se estudo de validaÃÃo de tÃcnica diagnÃstica na Maternidade-Escola Assis Chateaubriand da Universidade Federal do CearÃ, com 126 gestantes com indicaÃÃo para induÃÃo do trabalho de parto que foram avaliadas pelo Ãndice de Bishop e ultra-sonografia transvaginal para mensuraÃÃo cervical. As pacientes foram submetidas à ultra-sonografia obstÃtrica transabdominal, para avaliaÃÃo da estÃtica e peso fetais e Ãndice de lÃquido amniÃtico, e à cardiotocografia basal para avaliaÃÃo da vitalidade fetal. Procedeu-se à induÃÃo do trabalho de parto com misoprostol vaginal e sublingual, um dos comprimidos contendo 25mcg da droga e o outro apenas placebo. Os comprimidos foram administrados a cada seis horas, em um numero mÃximo de oito. A anÃlise estatÃstica foi realizada com o programa SPSS 10.0 (SPSS Co, Chicago, IL, USA), utilizando-se distribuiÃÃo de frequÃncias, mÃdias, desvios-padrÃo e medianas; assim como, anÃlise univariada e construÃÃo de curvas ROC, correlacionando Ãndice de Bishop e parto vaginal, e medida ultra-sonogrÃfica do colo uterino e parto vaginal. Em anÃlise multivariada foram pesquisadas outras variÃveis relacionadas ao parto vaginal. Resultados: atravÃs de curva ROC correlacionando a mensuraÃÃo do colo uterino por ultra-sonografia transvaginal e a evoluÃÃo para o parto vaginal, evidenciou-se uma Ãrea sob a curva de 0,513 com p=0,801. Outra curva ROC, analisando a relaÃÃo da avaliaÃÃo cervical pelo Ãndice de Bishop com o parto vaginal, demonstrou Ãrea sob a curva de 0,617 com p=0,025. AtravÃs de anÃlise de regressÃo logÃstica mÃltipla, evidenciou-se paridade &#8805; 1, escore de Bishop &#8805; 4 e presenÃa de lÃquido amniÃtico claro como associados à evoluÃÃo para o parto vaginal. ConclusÃes: a medida ultra-sonogrÃfica transvaginal do colo uterino nÃo foi boa preditora da evoluÃÃo para parto vaginal em pacientes com trabalho de parto induzido com misoprostol. O Ãndice de Bishop foi melhor preditor para parto vaginal nestas circunstÃncias. Os fatores preditivos mais importantes para parto vaginal, apÃs induÃÃo com misoprostol, foram paridade &#8805; 1, Ãndice de Bishop &#8805; 4 e presenÃa de lÃquido amniÃtico claro

INTRODUÇÃO: A lesão intraepitelial cervical de alto grau causada pelo HPV, precursora do câncer cervical, é facilmente diagnosticada e seu tratamento pode ser realizado de maneira ambulatorial, sem muitas complicações. Mesmo assim, o seguimento das pacientes tratadas deve ser feito de maneira criteriosa e sistemática para que a recorrência ou persistência da doença não passe despercebida. Conseguir identificar o grupo de pacientes com maior probabilidade de recorrência ou persistência da doença facilitaria sobremaneira esse seguimento, diminuindo o ônus econômico e psicológico que o seguimento generalizado produz. O objetivo deste trabalho é identificar marcadores que possam indicar o grupo de pacientes com maior possibilidade de recorrência da lesão intraepitelial cervical de alto grau. MÉTODOS: Neste estudo 114 mulheres com diagnóstico de lesão intraepitelial cervical de alto grau foram submetidas à conização cervical por cirurgia de alta frequência (CAF) no Setor de Patologia do Trato Genital Inferior (PTGI) da Divisão da Clínica Ginecológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) no período entre março de 2006 e maio de 2009. O seguimento foi realizado a cada seis meses durante o período de 24 meses. No seguimento foi coletada a citologia cervical, captura híbrida para HPV e realizada a colposcopia. Foram avaliados os testes de captura híbrida para HPV coletadas durante o seguimento, imuno-histoquímicos para oncoproteína viral E6 e proteína p16 na peça cirúrgica como possíveis marcadores de recorrência. RESULTADOS: A avaliação anatomopatológica da peça cirúrgica diagnosticou 85 (74,6%) casos de lesão intraepitelial cervical de alto grau e 29 (25,4%) casos de lesão intraepitelial de baixo grau. Nessas peças, 45 (39,5%) apresentaram expressão positiva para oncoproteína E6 e 69 (60,5%) apresentaram expressão negativa para E6; 74 (64,9%) apresentaram expressão positiva para p16 e 40 (35,1%) apresentaram expressão negativa para p16. A oncoproteína E6 não se associou com a apresentação mais grave da doença. Já a proteína p16 esteve positiva em 68 (80%) casos diagnosticados como lesão intraepitelial de alto grau e negativa em 23 (79,3%) casos com diagnóstico anatomopatológico de lesão intraepitelial de baixo grau ou cervicite crônica. A CH coletada no primeiro retorno apresentou sensibilidade de 83,3%, especificidade de 87,8%, VPP de 50% e VPN de 97,3%. Comparando a CH coletada no primeiro retorno com a citologia coletada após os 24 meses de seguimento, a CH apresentou sensibilidade de 75%, especificidade de 83,1%, VPP de 20% e VPN de 98,3%. CONCLUSÕES: A expressão das oncoproteína E6 e proteína p16 na peça cirúrgica não demonstraram ter valor para predizer recorrência no seguimento de pacientes tratadas por lesão intraepitelial cervical de alto grau, mesmo a p16 estando associada à presença de lesões mais graves. A CH pode ser usada como um teste preditivo de recorrência durante o seguimento de pacientes tratadas por lesão intraepitelial de alto grau. O VPN do teste é bastante alto e seu resultado negativo, seis meses após o tratamento indica uma taxa baixíssima de recorrência da doença / INTRODUCTION: The high grade cervical intraepithelial lesion caused by HPV, a pre-malignant condition, is easily diagnosed and its treatment can be done in outpatients without many complications. Nevertheless the patients follow-up must be done in a very systematic way to avoid any recurrence or persistence of the disease. To be able to identify the group of patients with higher rate of recurrence or persistence of the disease would make this follow-up much easier and decrease the economic and psychological burden of stressed outcome. The goal of our study is to identify markers that could indicate the group of patients more likely to recur. METHODS: In this study, 114 women diagnosed with high grade cervical intraepithelial lesion were treated with LLETZ at the Discipline of Gynecology, Faculty of Medicine, São Paulo University from March 2006 and May 2009. The follow-up visits after the treatment included Pap smear, HPV DNA test and colposcopy and occurred every 6 months for 24 months. The markers evaluated were the HPV DNA test collected during the follow-up and immunohistochemical tests performed on the surgical specimen: E6 oncoprotein and protein p16. RESULTS: We found 85 cases (74,6%) of HSIL and 29 cases (25,4%) of LSIL in the surgical specimen obtained with the LLETZ. The E6 oncoprotein was expressed in 45 (39,5%) and not expressed in 69 (60,5%) of the specimen; 74 (64,9%) expressed p16 and 40 (35,1%) didnt express p16. The E6 oncoprotein was not associated with severe presentation of the disease. The protein p16 was positive in 68 (80%) cases of diagnosed HSIL and negative in 23 (79,3%) cases with diagnosed LSIL or chronic cervicitis. The HPV DNA test collected at the first follow-up consult at 6 months presented a sensitivity of 83,3% specificity of 87,8%, positive predictive value (PPV) of 50% and negative predictive value (NPV) of 97,3%. Comparing the HPV DNA test collected at the first follow-up visit and the cervical cytology collected at the fourth and last follow-up visit at 24 months, the HPV DNA test presented a sensitivity of 75%, specificity of 83,1%, PPV of 20% and NPV of 98,3%. CONCLUSIONS: The E6 oncoprotein and protein p16 expression on the surgical specimen were not able to predict recurrence of the disease during the follow-up of the patients. The HPV DNA test can be used as a marker of the recurrence on the follow-up of patients treated for HSIL with LLETZ. The HPV DNA test negative result at the 6 month follow-up visit represents an extremely low recurrence rate

Human papillomavirus (HPV) is a double-stranded DNA virus, typically infecting mucosal or cutaneous epithelial keratinocytes. Today, more than 118 different HPV types have been formally described. Sexual transmission of mucosal HPVs is very common and generally asymptomatic, but HPV infection can be associated with benign lesions such as condylomata acuminata or, in rare cases, with malignant lesions such as cervical cancer. Two prophylactic vaccines are currently available in Europe, protecting against HPV-16 and HPV-18 (Cervarix&63720;) or against HPV-6, HPV-11, HPV-16 and HPV-18 (Gardasil&63720;). In order to assess the impact of the vaccination program, it is mandatory to obtain geographically widespread date on the baseline HPV prevalence and type distribution in cervical samples from women, presenting or not, normal or abnormal cytologic or histologic results. We undertook an epidemiological study in the Capital Region of Brussels to determine the HPV prevalence and type-distribution in 1526 cervical samples of women presenting a cytology within normal limits (WINL), atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intra-epithelial lesions (LSIL), high-grade squamous intra-epithelial lesions (HSIL) or invasive cervical cancer (ICC). The HPV prevalence was 10.8% (95%CI: 8.8-12.8) for NILM, 34.5% (95%CI: 28.3-40.8) for ASC-US, 54.0% (95%CI: 47.4-60.6) for LSIL and 100% for HSIL and ICC. With an HPV-16 and HPV-18 prevalence of 63.3% (95%CI: 44.1-67.7) and 73.5% (95%CI: 63.0-84.0) in mono-infected HSIL and ICC, respectively, HPV 16/18 L1 VLP vaccines would be expected to significantly reduce the management and treatment of women suffering from HSIL and ICC in the Capital Region of Brussels. We also detected HPV-30, HPV-53, HPV-66 and HPV-68 in mono-infected HSIL and ICC samples, possibly providing arguments for the reconsideration of the carcinogenicity of these types. <p>Vertical transmission of HPV was also previously reported, but in most cases one could not exclude a placental contamination by HPV positive cells from an infected birth canal. In order to confirm that the placenta can be infected with HPV, we analysed residual cells from 35 transabdominally obtained placental samples from pregnant women undergoing chorionic villous sampling for screening of suspected foetal abnormalities and found that two samples were positive for HPV-16 and HPV-62, respectively. The clinical importance of these results remains to be elucidated, but the previously observed association between placental HPV infection and pregnancy loss might gain further in importance. HPV gene regulation in placental trophoblastic cells has not been studied so far. We studied the HPV-16 early gene expression regulation in transiently transfected monolayer cultured trophoblastic cells with an HPV-16 long control region (LCR) driven reporter plasmid. We observed important differences in constitutive HPV-16 LCR activities between trophoblastic cell lines and could identify progesterone as an important inducer of HPV-16 early gene expression. Steroid hormones are induced during pregnancy and could therefore lead to an enhanced expression of the E5, E6 and E7 proteins upon placental HPV infection. Since these proteins were previously shown to affect trophoblast adhesion, survival, migration and invasion, their enhanced expression might eventually contribute to pregnancy loss. We furthermore found that the transcription of episomally maintained HPV-16 is not regulated by E2 or E1, but by E5, E6 and/or E7. <p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished