Why Are Women With Cervical Cancer Not Being Diagnosed in Preinvasive Phase? An Analysis of Risk Factors Using a Hierarchical Model

Objective: To assess the risk factors for delayed diagnosis of uterine cervical lesions. Materials and Methods: This is a case-control study that recruited 178 women at 2 Brazilian hospitals. The cases (n = 74) were composed of women with a late diagnosis of a lesion in the uterine cervix (invasive carcinoma in any stage). The controls (n = 104) were composed of women with cervical lesions diagnosed early on (low-or high-grade intraepithelial lesions). The analysis was performed by means of logistic regression model using a hierarchical model. The socioeconomic and demographic variables were included at level I (distal). Level II (intermediate) included the personal and family antecedents and knowledge about the Papanicolaou test and human papillomavirus. Level III (proximal) encompassed the variables relating to individuals' care for their own health, gynecologic symptoms, and variables relating to access to the health care system. Results: The risk factors for late diagnosis of uterine cervical lesions were age older than 40 years (odds ratio [OR] = 10.4; 95% confidence interval [CI], 2.3-48.4), not knowing the difference between the Papanicolaou test and gynecological pelvic examinations (OR, = 2.5; 95% CI, 1.3-4.9), not thinking that the Papanicolaou test was important (odds ratio [OR], 4.2; 95% CI, 1.3-13.4), and abnormal vaginal bleeding (OR, 15.0; 95% CI, 6.5-35.0). Previous treatment for sexually transmissible disease was a protective factor (OR, 0.3; 95% CI, 0.1-0.8) for delayed diagnosis. Conclusions: Deficiencies in cervical cancer prevention programs in developing countries are not simply a matter of better provision and coverage of Papanicolaou tests. The misconception about the Papanicolaou test is a serious educational problem, as demonstrated by the present study.

Expression of BAG-1 and PARP-1 in Precursor Lesions and Invasive Cervical Cancer Associated with Human Papillomavirus (HPV)

Cervical cancer remains persistently the second most common malignancies among women worldwide, responsible for 500,000 new cases annually. Only in Brazil, the estimate is for 18,430 new cases in 2011. Several types of molecular markers have been studied in carcinogenesis including proteins associated with apoptosis such as BAG-1 and PARP-1. This study aims to demonstrate the expression of BAG-1 and PARP-1 in patients with low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs) and invasive squamous cell carcinomas (SCCs) of the uterine cervix and to verify a possible association with HPV infection. Fifty samples of LSILs, 50 samples of HSILs and 50 samples of invasive SCCs of the uterine cervix were analyzed by immunohistochemistry for BAG-1 and PARP-1 expression. PCR was performed to detect and type HPV DNA. BAG-1 expression levels were significantly different between LSILs and HSILs (p = 0,014) and between LSILs and SCCs (p = 0,014). In regards to PARP-1 expression, we found significant differences between the expression levels in HSILs and SCCs (p = 0,022). No association was found between BAG-1 expression and the presence of HPV. However, a significant association was found between PARP-1 expression and HPV positivity in the HSILs group (p = 0,021). In conclusion our research suggests that BAG-1 expression could contribute to the differentiation between LSIL and HSIL/SCC whereas PARP-1 could be useful to the differentiation between HSIL HPV-related and SCC. Further studies are needed to clarify the molecular aspects of the relationship between PARP-1 expression and HPV infection, with potential applications for cervical cancer prediction.

Human papillomavirus genotypes distribution in 175 invasive cervical cancer cases from Brazil

Abstract Background Invasive cervical cancer is the second most common malignant tumor affecting Brazilian women. Knowledge on Human Papillomavirus (HPV) genotypes in invasive cervical cancer cases is crucial to guide the introduction and further evaluate the impact of new preventive strategies based on HPV. We aimed to provide updated comprehensive data about the HPV types’ distribution in patients with invasive cervical cancer. Methods Fresh tumor tissue samples of histologically confirmed invasive cervical cancer were collected from 175 women attending two cancer reference hospitals from São Paulo State: ICESP and Hospital de Câncer de Barretos. HPV detection and genotyping were performed by the Linear Array HPV Genotyping Test (Roche Molecular Diagnostics, Pleasanton,USA). Results 170 out of 172 valid samples (99%) were HPV DNA positive. The most frequent types were HPV16 (77.6%), HPV18 (12.3%), HPV31 (8.8%), HPV33 (7.1%) and HPV35 (5.9%). Most infections (75%) were caused by individual HPV types. Women with adenocarcinoma were not younger than those with squamous cell carcinoma, as well, as women infected with HPV33 were older than those infected by other HPV types. Some differences between results obtained in the two hospitals were observed: higher overall prevalence of HPV16, absence of single infection by HPV31 and HPV45 was verified in HC-Barretos in comparison to ICESP patients. Conclusions To our knowledge, this is one of the largest studies made with fresh tumor tissues of invasive cervical cancer cases in Brazil. This study depicted a distinct HPV genotype distribution between two centers that may reflect the local epidemiology of HPV transmission among these populations. Due to the impact of these findings on cervical cancer preventive strategies, extension of this investigation to routine screening populations is warranted.

Awareness and knowledge of HPV, cervical cancer, and vaccines in young women after first delivery in São Paulo, Brazil - a cross-sectional study

Abstract Background The success of HPV vaccination programs will require awareness regarding HPV associated diseases and the benefits of HPV vaccination for the general population. The aim of this study was to assess the level of awareness and knowledge of human papillomavirus (HPV) infection, cervical cancer prevention, vaccines, and factors associated with HPV awareness among young women after birth of the first child. Methods This analysis is part of a cross-sectional study carried out at Hospital Maternidade Leonor Mendes de Barros, a large public maternity hospital in Sao Paulo. Primiparous women (15-24 years) who gave birth in that maternity hospital were included. A questionnaire that included questions concerning knowledge of HPV, cervical cancer, and vaccines was applied. To estimate the association of HPV awareness with selected factors, prevalence ratios (PR) were estimated using a generalized linear model (GLM). Results Three hundred and one primiparous women were included; 37% of them reported that they "had ever heard about HPV", but only 19% and 7%, respectively, knew that HPV is a sexually transmitted infection (STI) and that it can cause cervical cancer. Seventy-four percent of interviewees mentioned the preventive character of vaccines and all participants affirmed that they would accept HPV vaccination after delivery. In the multivariate analysis, only increasing age (P for trend = 0.021) and previous STI (P < 0.001) were factors independently associated with HPV awareness ("had ever heard about HPV"). Conclusions This survey indicated that knowledge about the association between HPV and cervical cancer among primiparous young women is low. Therefore, these young low-income primiparous women could benefit greatly from educational interventions to encourage primary and secondary cervical cancer prevention programs.

The influence of human papillomavirus type and HIV status on the lymphomononuclear cell profile in patients with cervical intraepithelial lesions of different severity

Abstract Background Immunological alterations are implicated in the increased prevalence of high-grade squamous intraepithelial lesions (HG-SIL) and persistent human papillomavirus (HPV) infection. This study evaluated the expression of CD4, CD8, CD25 (IL-2Rα) and CD28 antigens from SIL biopsies, stratified by HIV status and HPV-type. Biopsies specimens from 82 (35 HIV+) women with a normal cervix, low-grade (LG-SIL) or high-grade lesions (HG-SIL) were studied. CD molecule expression was evaluated by immunohistochemistry and HPV detection/typing performed using PCR techniques. Results CD4 stromal staining was increased in patients with HPV18. Women with HPV16 infection showed decreased: a) CD8 and CD25 stromal staining, b) CD25 staining in LG-SIL epithelium and in HG-SIL stroma. In HIV- women samples, CD28 epithelial staining and CD8 stromal staining surrounding metaplastic epithelium were less intense and even absent, as compared to HIV+ women. Both epithelial and stromal CD8 staining was more intense in the HG-SIL/HIV+ group than in the HG-SIL/HIV- group. Positive correlations were observed between CD4/CD25, CD4/CD28 and CD25/CD28 in the stroma and CD25/CD28 in the epithelium. Conclusion HIV status and HPV-type may influence the lymphomononuclear cell profile present in the spectrum of cervical lesions. The knowledge of the infiltrating cell profile in cervical tumours may help the development of specific anti-tumoural strategies.

Grau de dilatação cervical e solicitação da analgesia regional por parturientes com membranas corioamnióticas íntegras e rotas

JUSTIFICATIVA E OBJETIVOS: Durante o processo de parturição, diversos fatores alteram a intensidade da dor, tais como a paridade, a rotura de membranas corioamnióticas, a dilatação cervical, bem como influências culturais e ambientais. Assim, os objetivos deste estudo foram verificar o número de requisições de analgesia regional e o grau de dilatação cervical no momento da solicitação da analgesia pelas parturientes com membranas corioamnióticas íntegras e aquelas com corioamniorrexe. MÉTODO: Trata-se de um estudo descritivo e retrospectivo, com análise de 208 prontuários de parturientes primigestas, 129 com membranas corioamnióticas íntegras e 79 com corioamniorrexe, assistidas no Centro da Saúde da Mulher de Ribeirão Preto, SP, no período de novembro de 2008 a maio de 2009. Para análise estatística dos dados foram utilizados os testes de Mann-Whitney e o Qui-quadrado, com nível de significância p < 0,05 e intervalo de confiança de 95%. RESULTADOS: Foi solicitada analgesia regional por 87,9% das parturientes selecionadas para esta pesquisa. A média da dilatação cervical para as pacientes com membranas íntegras foi de 6,26 ± 1,67 cm e para aquelas com corioamniorrexe foi com dilatação de 6,11 ± 1,75 cm, não havendo diferença significativa entre esses dois grupos de parturientes (p = 0,12). Em relação ao tipo de analgesia, houve predomínio do duplo bloqueio, sem diferenças significativas entre os dois grupos avaliados (p = 0,84). CONCLUSÃO: A maioria das parturientes deste estudo solicitou analgesia regional tipo duplo bloqueio com em média 6 cm, de acordo com a dilatação cervical, não havendo diferença entre primigestas com membranas corioamnióticas rotas e íntegras.

Avaliação das técnicas cirúrgicas para tratamento da mielorradiculopatia espondilótica cervical

OBJETIVO: Avaliar a eficácia do tratamento cirúrgico da mielorradiculopatia espondilótica cervical na produção de melhora neurológica pós-operatória, aferida em pontos pela escala da JOA e taxa de recuperação e as complicações do tratamento. MÉTODOS: Análise dos prontuários e os exames de imagem de 200 indivíduos submetidos a tratamento cirúrgico da mielorradiculopatia cervical no HC-FMUSP, no período de janeiro de 1993 a janeiro de 2007. A avaliação clínica foi quantificada pela escala da JOA, com média de segmento de 06 anos e 08 meses. RESULTADOS: Evidenciou-se melhora neurológica pós-operatória nas vias anterior e posterior, exceto nas laminectomias sem fusão, onde houve piora neurológica tardia. A via anterior mostrou um significante maior índice de complicações, relacionados a déficit de fusão intervertebral, deslocamento de enxerto, síndrome de disco adjacente, disfonia, disfagia, o mau posicionamento de enxerto e placas, lesão de raiz nervosa e significativo maior índice de re-intervenção cirúrgica. Na via posterior maior ocorrência de instabilidade em cifose pós-operatória na laminectomia, não sendo observada na laminoplastia, esta última com índices semelhantes aos encontrados na via anterior. Não houve melhora da dor axial nas laminoplastias e houve piora nas laminectomias, enquanto que nas discectomias e corpectomias houve significativa melhora do sintoma. CONCLUSÃO: As vias anterior e posterior foram eficazes em produzir melhora neurológica, exceto as laminectomias sem fusão. A via anterior produziu mais complicações, mas trata melhor a dor.

Fatores prognósticos associados ao tratamento cirúrgico da mielorradiculopatia espondilótica cervical

OBJETIVO: Identificar os fatores clínicos dos indivíduos, fatores sociais, ambientais e dos exames de imagem que se correlacionam ao resultado final de melhora neurológica em pacientes submetidos ao tratamento cirúrgico da mielopatia espondilótica cervical. MÉTODOS: A avaliação clínica foi quantificada pela escala deficitária da JOA. Analisamos 200 casos de mielorradiculopatia cervical, operados no HC-FMUSP, no período de janeiro de 1993 a janeiro de 2007. A média de segmento foi de 06 anos e 08 meses. A análise radiológica foi baseada nos critérios de instabilidade de White e scala de Kellgren. RESULTADOS: Em 80% houve melhora, 14% estabilização e em 6% piora do quadro neurológico. A piora neurológica não foi associada com nenhum fator clínico, ambiental ou de imagem. A melhora neurológica foi diretamente proporcional a menor idade na cirurgia, ausência de co-morbidade, sinal de Hoffman, atrofia muscular, hipersinal medular na RNM, menor período de evolução pré-operatório, melhor status neurológico pré-operatório e inversamente proporcional ao diâmetro AP do canal medular e multiplicidade de compressões. Identificou-se associação com o tabagismo. Mais de 70 anos, evolução superior a 24 meses, atrofia muscular, pontuação JOA igual ou inferior a sete pontos e diâmetro AP do canal inferior ou igual a seis mm não foram associado à melhora.

Influence of cervical preflaring on determination of apical file size in the palatal roots of maxillary molars

PURPOSE: The aim of this study was to investigate the influence of cervical preflaring in determining the initial apical file (IAF) in the palatal roots of maxillary molars, and to determine the morphologic shape of the canal 1 mm short of the apex. METHODS: After preparing standard access cavities the group 1 received the IAF without cervical preflaring (WCP). In groups 2 to 5, preflaring was performed with Gates-Glidden (GG), Anatomic Endodontics Technology (AET), GT Rotary Files (GT) and LA Axxes (LA), respectively. Each canal was sized using manual K-files, starting with size 08 files, and making passive movements until the WL was reached. File sizes were increased until a binding sensation was felt at the WL. The IAF area and the area of the root canal were measured to verify the percentage occupied by the IAF inside the canal in each sample by SEM. The morphologic shape of the root canal was classified as circular, oval or flattened. Statistical analysis was performed by ANOVA/Tukey test (P < 0.05). RESULTS: The decreasing percentages occupied by the IAF inside the canal were: LA>GT=AET>GG>WCP. The morphologic shape was predominantly oval. CONCLUSION: The type of cervical preflaring used interferes in the determination of IAF.

Predicción del parto pretérmino mediante la medición ecográfica de la longitud cervical

Programa de Patología Quirúrgica, Reproducción Humana,Factores Psicológicos y el Proceso de Enfermar

Papel de MVP en la reparación del ADN, la progresión tumoral y la hipoxia en carcinoma cervical: impacto pronóstico

Programa de doctorado: Cáncer: biología y clínica.