'Missing adenocarcinomas': are they a real problem in cervical cancer screening in Brazil?

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Tissue Microarrays For Testing Basal Biomarkers In Familial Breast Cancer Cases.

The proteins p63, p-cadherin and CK5 are consistently expressed by the basal and myoepithelial cells of the breast, although their expression in sporadic and familial breast cancer cases has yet to be fully defined. The aim here was to study the basal immunoprofile of a breast cancer case series using tissue microarray technology. This was a cross-sectional study at Universidade Estadual de Campinas, Brazil, and the Institute of Pathology and Molecular Immunology, Porto, Portugal. Immunohistochemistry using the antibodies p63, CK5 and p-cadherin, and also estrogen receptor (ER) and Human Epidermal Receptor Growth Factor 2 (HER2), was per-formed on 168 samples from a breast cancer case series. The criteria for identifying women at high risk were based on those of the Breast Cancer Linkage Consortium. Familial tumors were more frequently positive for the p-cadherin (p = 0.0004), p63 (p < 0.0001) and CK5 (p < 0.0001) than was sporadic cancer. Moreover, familial tumors had coexpression of the basal biomarkers CK5+/ p63+, grouped two by two (OR = 34.34), while absence of coexpression (OR = 0.13) was associated with the sporadic cancer phenotype. Familial breast cancer was found to be associated with basal biomarkers, using tissue microarray technology. Therefore, characterization of the familial breast cancer phenotype will improve the understanding of breast carcinogenesis.125226-3

Prognostic assessment of breast carcinoma submitted to neoadjuvant chemotherapy with pathological non-complete response

Breast cancer with pathological non-complete response (non-pCR) after neoadjuvant chemotherapy (NAC) has a worse prognosis. Despite Neo-Bioscore has been validated as an independent prognostic model for breast cancer submitted to NAC, non-pCR carcinoma was not assessed in this setting.MethodsThis is a retrospective trial that included women with localized breast cancer who underwent NAC and had non-pCR carcinoma in surgical specimen between 01/01/2013 to 12/31/2015 with a three-year follow-up. Survival analysis was performed by Kaplan-Meier estimator and hazard ratio (HR) set by log-rank test for the primary and secondary endpoints, respectively Disease-Free Survival (DFS) and Overall Survival (OS). According to Neo-Bioscore, the proposed prognostic model named Clustered Neo-Bioscore was classified into low (0-3), low-intermediate (4-5), high-intermediate (6) and high (7) risk. The prognostic accuracy for recurrence risk was assessed by time-dependent receiver operating characteristic (time-ROC) methodology. Multivariate Cox regression assessed the menopausal status, histological grade, Ki-67, estrogen receptor, HER2, tumor subtype, pathological and clinical stages. Confidence interval at 95% (CI95%) and statistical significance at set 2-sided p-value less than 0.05 were adopted.ResultsAmong the 310 women enrolled, 267 patients (86.2%) had non-pCR carcinoma presenting size T3/T4 (63.3%), node-positive axilla (74.9%), stage III (62.9%), Ki-6720% (71.9%) and non-luminal A (78.3%). Non-pCR carcinoma presented worse DFS-3y (HR=3.88, CI95%=1.18-11.95) but not OS-3y (HR=2.73, CI95%=0.66-11.40). Clustered Neo-Bioscore discerned the recurrence risk for non-pCR carcinoma: low (DFS-3y=0.86; baseline), low-intermediate (DFS-3y=0.70; HR=2.61), high-intermediate (DFS-3y=0.13, HR=14.05), and high (DFS-3y=not achieved; HR=22.19). The prognostic accuracy was similar between Clustered Neo-Bioscore and Neo-Bioscore (0.76 vs 0.78, p>0.05). Triple-negative subtype (HR=3.6, CI95%=1.19-10.92) and pathological stages II (HR=5.35, CI95%=1.19-24.01) and III (HR=6.56, CI95%=1.29-33.32) were prognoses for low-intermediate risk, whereas pathological stage III (HR=13.0, CI95%=1.60-106.10) was prognosis for low risk.ConclusionsClustered Neo-Bioscore represents a novel prognostic model of non-pCR carcinoma undergoing NAC with a more simplified and appropriate score pattern in the assessment of prognostic factors1

The Impact Of A Community Intervention To Improve Cervical Cancer Screening Uptake In The Amazon Region Of Brazil.

In the northern region of Brazil, cervical cancer is the most important cause of cancer-related deaths among women. There is considerable likelihood, however, that official incidence and mortality figures are greatly underestimated. The aim of this study was to estimate the repercussions from improvement in cervical cancer screening programs on the incidence of pre-invasive and invasive cervical lesions in a municipality in this region. This was a quasi-experimental study that assessed process dimensions relevant to the program objectives. The study comprised a sample of 2,226 women seen at primary healthcare units in Cruzeiro do Sul, a small city in the Brazilian Amazon region, from April 2003 to July 2004. Women were recruited through local radio advertisements and by oral communication from the investigators. The women answered a structured questionnaire and underwent pelvic examination, which included Papanicolaou (Pap) smears and naked-eye inspection of the cervix after applying diluted acetic acid. Women with positive Pap smears or abnormal gynecological examination were referred for colposcopy and possible biopsy, diathermic large loop excision of the transformation zone or conization. The results obtained were compared with historical official data retrieved from the Brazilian Ministry of Health's database. Intervention resulted in a 40% increase in positive Pap smears and detection of cancer was nine times higher than had been observed in routine screening. Detection of pre-invasive and invasive cervical lesions in the intervention group was remarkably higher than among women seen during routine screening.12542-

Why does the prevalence of cytopathological results of cervical cancer screening can vary significantly between two regions of Brazil?

PURPOSE:To analyze the prevalence of cervical cytopathological results for the screening of cervical cancer with regard to women's age and time since the last examination in Macei&#243; and Rio de Janeiro, Brazil, among those assisted by the Brazilian Unified Health System.METHODS: Cervical cytopathological results available in the Information System of Cervical Cancer Screening for the year 2011 were analyzed, corresponding to 206,550 for Rio de Janeiro and 45,243 for Macei&#243;.RESULTS: In Rio de Janeiro, examination at one and two year intervals predominated, while in Macei&#243; examination at one and three year intervals had a higher predominance. Women who underwent cervical smear screening in Macei&#243; were older than those in Rio de Janeiro. The prevalence of invasive squamous cell carcinoma was similar for the two cities, but all the other results presented a higher prevalence in Rio de Janeiro: ASCUS (PR=5.32; 95%CI 4.66-6.07); ASCH (PR=4.27; 95%CI 3.15-5.78); atypical glandular cells (PR=10.02; 95%CI 5.66-17.76); low-grade squamous intraepithelial lesions (PR=6.10; 95%CI 5.27-7.07); high-grade squamous intraepithelial lesions (PR=8.90; 95%CI 6.50-12.18) and adenocarcinoma (PR=3.00; 95%CI 1.21-7.44). The rate of unsatisfactory cervical samples was two times higher in Macei&#243; and that of rejected samples for analysis was five times higher in Macei&#243; when compared to Rio de Janeiro.CONCLUSIONS: The prevalence rates of altered cervical cytopathological results was significantly higher in Rio de Janeiro than in Macei&#243;. There is no objective information that may justify this difference. One hypothesis is that there may be a difference in the diagnostic performance of the cervical cancer screening, which could be related to the quality of the Pap smear. Thus, these findings suggest that it would be necessary to perform this evaluation at national level, with emphasis on the performance of cervical cancer screening in order to improve the effectiveness of cervical cancer control.OBJETIVO:Analisar a prevalência dos resultados citopatológicos empregados para o rastreamento do câncer do colo do útero em relação à faixa etária da mulher e ao tempo de realização do último exame, no Rio de Janeiro e Maceió, pelo Sistema Único de Saúde.MÉTODOS:Foram analisadas as informações do Sistema de Informação do Câncer do Colo do Útero referentes aos resultados dos exames citopatológicos realizados em 2011, que totalizaram 206.550 para Rio de Janeiro e 45.243 para Maceió.RESULTADOS: No Rio de Janeiro, predominaram exames citopatológicos realizados com intervalo de um e dois anos e, em Maceió, controles com intervalo de um e três anos. As mulheres atendidas no Maceió eram mais velhas do que aquelas do Rio de Janeiro. A prevalência do resultado citopatológico carcinoma escamoso invasor foi semelhante entre os municípios, porém todos os demais resultados apresentaram prevalência superior no Rio de Janeiro: atipias de significado indeterminado em células escamosas (RP=5,32; IC95% 4,66-6,07); atipias de significado indeterminado não podendo excluir lesão de alto grau (RP=4,27; IC95% 3,15-5,78); células glandulares atípicas (RP=10,02; IC95% 5,66-17,76); lesão intraepitelial escamosa de baixo grau (RP=6,10; IC95% 5,27;-7,07); lesão intraepitelial escamosa de alto grau (RP=8,90; IC95% 6,50-12,18) e adenocarcinoma (RP=3,00; IC95% 1,21-7,44). A taxa de amostras insatisfatórias para a análise foi duas vezes maior e de lâminas rejeitadas foi cinco vezes maior em Maceió, quando comparado ao Rio de Janeiro.CONCLUSÕES:As taxas de prevalência de resultados citopatológicos foram significativamente superiores no Rio de Janeiro do que em Maceió, e não há informações objetivas que possam justificar tal diferença. Uma hipótese é que haveria diferença no desempenho diagnóstico do exame citopatológico, o que poderia estar relacionada à qualidade do exame. Assim, tais achados sugerem que seria necessário avaliar este cenário no âmbito nacional, com ênfase no desempenho do exame citopatológico, visando melhorar a efetividade do controle do câncer de colo do útero.19219

[why Does The Prevalence Of Cytopathological Results Of Cervical Cancer Screening Can Vary Significantly Between Two Regions Of Brazil?].

To analyze the prevalence of cervical cytopathological results for the screening of cervical cancer with regard to women's age and time since the last examination in Maceió and Rio de Janeiro, Brazil, among those assisted by the Brazilian Unified Health System. Cervical cytopathological results available in the Information System of Cervical Cancer Screening for the year 2011 were analyzed, corresponding to 206,550 for Rio de Janeiro and 45,243 for Maceió. In Rio de Janeiro, examination at one and two year intervals predominated, while in Maceió examination at one and three year intervals had a higher predominance. Women who underwent cervical smear screening in Maceió were older than those in Rio de Janeiro. The prevalence of invasive squamous cell carcinoma was similar for the two cities, but all the other results presented a higher prevalence in Rio de Janeiro: ASCUS (PR=5.32; 95%CI 4.66-6.07); ASCH (PR=4.27; 95%CI 3.15-5.78); atypical glandular cells (PR=10.02; 95%CI 5.66-17.76); low-grade squamous intraepithelial lesions (PR=6.10; 95%CI 5.27-7.07); high-grade squamous intraepithelial lesions (PR=8.90; 95%CI 6.50-12.18) and adenocarcinoma (PR=3.00; 95%CI 1.21-7.44). The rate of unsatisfactory cervical samples was two times higher in Maceió and that of rejected samples for analysis was five times higher in Maceió when compared to Rio de Janeiro. The prevalence rates of altered cervical cytopathological results was significantly higher in Rio de Janeiro than in Maceió. There is no objective information that may justify this difference. One hypothesis is that there may be a difference in the diagnostic performance of the cervical cancer screening, which could be related to the quality of the Pap smear. Thus, these findings suggest that it would be necessary to perform this evaluation at national level, with emphasis on the performance of cervical cancer screening in order to improve the effectiveness of cervical cancer control.36192-

Duration of Intraepithelial Neoplasia and Invasive Carcinoma of the Cervix in Relation to Age at Diagnosis

Purpose: to estimate the duration of cervical neoplasia from human pappilomavirus (HPV) infection to advanced invasive carcinoma, using as paremeter the mean age of the women at diagnosis. Methods: this cross-sectional study included 1,177 women with HPV infection, 1,561 with cervical intraepithelial neoplasia (CIN) and 773 with invasive carcinoma. Results: the mean ages of CIN 1 and CIN 2 on diagnosis were not statistically different. The mean duration of CIN 2 was 2.2 years. The mean duration of CIN 3 was 10.3 years, with 4.1 years as severe dysplasia and 6.2 years as carcinoma in situ (CIS). The mean duration of high grade squamous intraepithelial lesions was 12.5 years. The duration means of invasive carcinoma stages Ia, Ib and II were 3.0, 2.7 and 3.7 years, respectively. Conclusions: according to the results, CIN 1 and CIN 2 may arise directly from HPV infection and most of these lesions are transient. CIS presented the longest duration and the mean asymptomatic period of cervical neoplasia is 18.2 years. These results were discussed considering the present knowledge of the natural history of cervical carcinoma and other studies on duration of this neoplasia.Objetivo: estimar a duração e o tempo de evolução da neoplasia do colo uterino, a partir da infecção por papilomavírus humano (HPV) até as formas invasoras avançadas, tomando como parâmetro a idade média ao diagnóstico. Método: estudo observacional-transversal que incluiu 1.177 mulheres com infecção por HPV, 1.561 com neoplasia intra-epitelial cervical (NIV) e 773 com carcinoma invasor. Resultados: não houve diferença estatisticamente significante entre as médias de idade ao diagnóstico da NIC 1 e NIC 2. A duração da NIC 2 foi 2,2 anos e da NIC 3 foi 10,3 anos, sendo 4,1 anos como displasia grave e 6,2 anos como carcinoma in situ (CIS). A duração da lesão intra-epitelial escamosa de alto grau foi 12,5 anos e do carcinoma invasor estádio Ia, Ib e II foram, respectivamente, 3,0, 2,7 e 3,7 anos. Conclusões: de acordo com os resultados deste estudo, as NIC 1 e NIC 2 originam-se diretamente da infecção por HPV e a maioria das NIC 2 seria uma lesão transiente. A lesão de maior duração é o CIS e o tempo médio do período subclínico da neoplasia do colo uterino é de 18,2 anos. Estes resultados são discutidos em função do conhecimento mais atual da história natural do carcinoma do colo uterino e de outros estudos que estimaram a duração desta neoplasia.56556

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

Idade Precoce De Início Da Atividade Sexual Está Associada A Elevada Prevalência De Lesão Intraepitelial Escamosa De Alto Grau

To evaluate the association of age at first sexual intercourse with the results of the cervicovaginal cytology. Study Design Observational analytical study about the prevalence of altered cervicovaginal cytology results in women aged between 18 and 34 years from a densely populated area in Brazil, during 10 years. The patients were stratified into 2 categories according to their age at first sexual intercourse (13-16 years and 17-24 years). Results From the total of 2,505,154 exams, 898,921 tests were in accordance with the inclusion criteria. Considering women with 4 years or less from the first sexual intercourse as a reference, those with 5 to 9 years and 10 years or more showed a higher prevalence of high-grade squamous intraepithelial lesions (HSILs). Women with an earlier onset of sexual intercourse (13-16 years) showed higher prevalence ratios for atypical squamous cells (ASC), low-grade squamous intraepithelial lesion (LSIL) and HSIL. The prevalence ratio for HSIL adjusted by age at diagnosis and by age at first sexual intercourse was higher only for women with an earlier onset of sexual intercourse. Conclusions The age of first sexual intercourse could be a variable that might qualify the selection among young women who are really at a higher risk for HSIL.3928085FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOAvaliar a associação entre idade de início da atividade sexual e os resultados de citologia cervico-vaginal. Métodos Estudo observacional sobre a prevalência dos resultados de citologia cervico-vaginal alterados em mulheres com idade entre 18 e 34 anos na região de Campinas – SP, Brasil, durante 10 anos. As pacientes foram estratificadas em dois grupos de acordo com a idade de início da atividade sexual (13 a 16 anos e 17 a 24 anos). Resultados Do total de 2.505.154 exames, 898.921 preencheram os critérios de inclusão. Considerando mulheres com tempo desde a primeira relação sexual menor ou igual a 4 anos como grupo de referência, mulheres com intervalos de 5 a 9 anos e 10 anos ou mais entre a data do exame e a primeira relação sexual mostraram maior prevalência de lesão intraepitelial escamosa de alto grau (LIEAG). Mulheres com início da atividade sexual mais precoce (13–16 anos) mostraram altas prevalências de atipia de células escamosas, lesão intraepitelial escamosa de baixo grau e LIEAG. A razão de prevalência de LIEAG ajustada pela idade na data do exame e pela idade do início da atividade sexual foi maior somente para mulheres que apresentaram início mais precoce da atividade sexual. Conclusão A idade de início da atividade sexual pode ser uma possível variável de seleção das mulheres com maior risco de LIEA

Estimating the public health impact of a national guideline on cervical cancer screening: an audit study of a program in Campinas, Brazil

A Brazilian guideline on cervical cancer screening was released in 2011. The objective was to verify changes in screening indicators around this period. Methods An audit study which sample was all screening tests performed by the public health system of Campinas city from 2010 to 2016. Variables were absolute tests numbers, excess tests, intervals and results, by age. For trend analysis was used Cochran-Armitage x 2 and linear regression. Results Were carried out 62,925 tests in 2010 and 43,523 tests in 2016, a tendency at a reduction (P = 0.001). Excess tests were higher than 50% over the years, with a tendency at a reduction (P < 0.001). Tests performed on women under 25 ranged from 20.2 to 15.4% in the period (P < 0.001), while in the 25-64 years age-group, it ranged from 75.1 to 80.2% (P < 0.001). In 2010 the most frequent interval was annual (47.5%) and in 2016 biennial (34.7%). There was a tendency at a reduction in the proportion of tests performed at the first time and those with an annual interval (P < 0.001), and also a tendency at an increase in tests with intervals equal to or greater than biannual (P < 0.001). We observed a tendency at a reduction in LSIL and HSIL-CIN2 results (P = 0.04 and P = 0.001, respectively), and a tendency at an increase in HSIL-CIN3 result (P = 0.02). Conclusion The proportion of cervical cancer screening tests performed out of the recommendation showed a significant reduction in the period. This indicates a tendency to align cervical cancer screening in Campinas with the standards recommended19CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQSem informaçã