Regulation of cell cycles is of key importance in human papillomavirus (HPV)-associated cervical carcinogenesis

The rapid progress in molecular biology has allowed the identification of the genes involved in different functions of normal cells and has also improved our understanding of the mechanisms of human carcinogenesis. The human papillomavirus (HPV) is a small double-stranded DNA tumor virus and its genes can manipulate cell cycle control to promote viral persistence and replication. The E6 and E7 proteins of high-risk HPV bind to cell cycle regulatory proteins and interfere with both G1/S and G2/M cell cycle checkpoints much more effectively than the low-risk HPV. The difference between the ability of low and high-risk HPV types to induce immortalization and transformation may well lie in their abilities to interact with the various cell cycle components, resulting in the loss of multiple cell cycle checkpoints, which are important in host genome fidelity, thus potentially resulting in accumulation of genetic abnormalities. Cervical cancer is one of the leading malignancies in women worldwide, with substantial morbidity and mortality. According to current concepts, HPV is recognized as the single most important causal agent in the pathogenesis of this cancer. HPV infection clearly precedes the development of malignancy, while being regularly associated with cervical cancer precursor lesions (all grades of squamous intraepithelial lesions). HPV-infected low-grade squamous intraepithelial lesion (SIL) has three possible outcomes: a) it may regress; b) it can persist; or c) it can make a clinical progression to in situ or invasive carcinoma. It has been well established by prospective cohort studies that the spontaneous regression rate increases in parallel with follow-up duration. In contrast, the clinical progression of lesions usually takes place quite rapidly, i.e. during the first two years from diagnosis. The mechanisms responsible for this divergent clinical behavior of HPV-associated squamous intraepithelial lesions are largely unknown, but currently under intense study in different laboratories worldwide

Knowledge, attitudes, and practices related to the Pap smear among women with cervical cancer

Despite screening programs, Brazil has a high cervical cancer mortality rate. The objective of this cross-sectional study was to analyze knowledge, attitudes, and practices related to the Pap smear and to understand why women fail to submit to this screening test. A structured questionnaire was used to interview 138 women: 90 with high grade intraepithelial neoplasia and 48 with invasive cervical cancer. Inadequate practices were more frequent among women with invasive cancer. In terms of difficulties in obtaining medical care, more than 80% of women reported lack of motivation, 60% reported that physicians failed to conduct a complete physical examination, and some 50% reported that physicians' schedules were busy. Having a Pap smear usually depended on a physician's request and the woman being symptomatic. Women over than 56 years old showed more frequent inadequate knowledge, attitudes and practices. However, those with more schooling were more knowledgeable of the Pap smear procedure. Age and less schooling could be barriers against women participating in screening programs, but socioeconomic problems must also be considered for improving practices related to the Pap smear.O câncer de colo uterino apresenta alta mortalidade no Brasil, apesar dos programas para rastreamento. O objetivo deste estudo, de corte transversal, foi analisar conhecimento, atitude e prática do exame de Papanicolaou e entender a não adesão das mulheres a este exame. Foram entrevistadas 138 mulheres: noventa com neoplasia intra-epitelial de alto grau e 48 com câncer invasivo de colo uterino. As mulheres com câncer invasivo tiveram prática mais inadequada do exame. No entanto, independente do diagnóstico, mais de 80% delas referiram desmotivação/vergonha, 60% relataram que os médicos não examinavam e, cerca de 50% apontaram o tempo de espera para a consulta e a demora no agendamento como dificuldades para serem atendidas. Em geral, a prática do exame dependeu da iniciativa do médico e a periodicidade da coleta foi determinada pela procura de consulta devido a sintomas. As mulheres com 56 anos ou mais mostraram maior inadequação no conhecimento, na atitude e na prática. No entanto, aquelas com maior escolaridade conheciam melhor o exame. A maior idade e a menor escolaridade podem estar associados a não adesão das mulheres ao exame, porém as dificuldades sociais e econômicas para conseguir atendimento em saúde precisam ser consideradas para aumentar a prática do exame.90991

Prevalence of codon 72 P53 polymorphism in Brazilian women with cervix cancer

The p53 codon 72 polymorphism seems to be associated with HPV-carcinogenesis, although controversial data have been reported. A series of Brazilian women with cervix carcinomas were analyzed. Ninety-nine (67%) of 148 women were found to be homozygous (arg/arg) for the arginine polymorphism, and 49 (33%) were heterozygous (arg/pro). This polymorphism may be an important determinant of the risk for cervix cancer, but does not seem to be sufficient for carcinogenesis.49649

Prevalence of codon 72 P53 polymorphism in Brazilian women with cervix cancer

The p53 codon 72 polymorphism seems to be associated with HPV-carcinogenesis, although controversial data have been reported. A series of Brazilian women with cervix carcinomas were analyzed. Ninety-nine (67%) of 148 women were found to be homozygous (arg/arg) for the arginine polymorphism, and 49 (33%) were heterozygous (arg/pro). This polymorphism may be an important determinant of the risk for cervix cancer, but does not seem to be sufficient for carcinogenesis.Hospital Maternidade Leonor Mendes de Barros Oncologia GinecológicaUniversidade Federal de São Paulo (UNIFESP) Laboratório de Ginecologia MolecularUniversidade Estadual de Campinas Faculdade de Medicina Oncologia GinecológicaUniversidade de São Paulo Departamento de Medicina Social Faculdade de Medicina de Ribeirão PretoIstituto Superiore di Sanità Laboratory of Epidemiology and Biostatistics Cytopathology UnitUNIFESP, Laboratório de Ginecologia MolecularSciEL

O uso de dados epidemiológicos como base para o desenvolvimento de um currículo médico

CONTEXT AND OBJECTIVE: Epidemiology may help educators to face the challenge of establishing content guidelines for the curricula in medical schools. The aim was to develop learning objectives for a medical curriculum from an epidemiology database. DESIGN AND SETTING: Descriptive study assessing morbidity and mortality data, conducted in a private university in São Paulo. METHODS: An epidemiology database was used, with mortality and morbidity recorded as summaries of deaths and the World Health Organization's Disability-Adjusted Life Year (DALY). The scoring took into consideration probabilities for mortality and morbidity. RESULTS: The scoring presented a classification of health conditions to be used by a curriculum design committee, taking into consideration its highest and lowest quartiles, which corresponded respectively to the highest and lowest impact on morbidity and mortality. Data from three countries were used for international comparison and showed distinct results. The resulting scores indicated topics to be developed through educational taxonomy. CONCLUSION: The frequencies of the health conditions and their statistical treatment made it possible to identify topics that should be fully developed within medical education. The classification also suggested limits between topics that should be developed in depth, including knowledge and development of skills and attitudes, regarding topics that can be concisely presented at the level of knowledge

Expressão proteica de P53 e C-MYC como marcadores no prognostico do carcinoma de colo uterino

Orientadores: Luiz Carlos Zeferino, Glauce Aparecida PintoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasDoutorad