European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010. They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.Fil: Arrossi, Silvina. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: von Karsa, Lawrence. International Agency for Research on Cancer; FranciaFil: Patrick, J.. NHS Cancer Screening Programmes Sheffield; Reino Unido. University of Oxford; Reino UnidoFil: Segnan, N.. International Agency for Research on Cancer; Francia. AO Città della Salute e della Scienza di Torino; ItaliaFil: Atkin, W.. Imperial College London; Reino UnidoFil: Halloran, S.. University of Surrey; Reino UnidoFil: Saito, H.. National Cancer Centre; JapónFil: Sauvaget, C.. International Agency for Research on Cancer; FranciaFil: Scharpantgen, A.. Ministry of Health; LuxemburgoFil: Schmiegel, W.. Ruhr-Universität Bochum; AlemaniaFil: Senore, C.. AO Città della Salute e della Scienza di Torino; ItaliaFil: Siddiqi, M.. Cancer Foundation of India; IndiaFil: Sighoko, D.. University of Chicago; Estados Unidos. Formerly International Agency for Research on Cancer; FranciaFil: Smith, R.. American Cancer Society; Estados UnidosFil: Smith S.. University Hospitals Coventry & Warwickshire NHS Trust; Reino UnidoFil: Suchanek, S.. Charles University; República ChecaFil: Suonio, E.. International Agency for Research on Cancer; FranciaFil: Tong, W.. Chinese Academy of Sciences; República de ChinaFil: Törnberg, S.. Stockholm Gotland Regional Cancer Centre. Department of Cancer Screening; SueciaFil: Van Cutsem, E.. Katholikie Universiteit Leuven; BélgicaFil: Vignatelli, L.. Agenzia Sanitaria e Sociale Regionale; ItaliaFil: Villain, P.. University of Oxford; Reino UnidoFil: Voti, L.. Formerly International Agency for Research on Cancer; Francia. University of Miami; Estados UnidosFil: Watanabe, H.. Niigata University; JapónFil: Watson, J.. University of Oxford; Reino UnidoFil: Winawer, S.. Memorial Sloan–Kettering Cancer Center; Estados UnidosFil: Young, G.. Flinders University. Gastrointestinal Services; AustraliaFil: Zaksas, V.. State Patient Fund; LituaniaFil: Zappa, M.. Cancer Prevention and Research Institute; ItaliaFil: Valori, R.. NHS Endoscopy; Reino Unid

Factors Associated with Colposcopy-Histopathology Confirmed Cervical Intraepithelial Neoplasia among HIV-Infected Women from Rio De Janeiro, Brazil

Introduction: Despite the availability of preventive strategies (screening tests and vaccines), cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV) and thus development of cervical squamous intraepithelial neoplasia (CIN). Methods:Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ). At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+diagnosis. Results:The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28–41 years). The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+was 6.0%. Factors associated with CIN2+diagnosis in the multivariate model were age,years compared to$35 years (aPR = 3.22 95CD4 T-cell count,350 cells/mm3 when compared to$350 cells/mm3 (aPR = 6.03 95%CI 1.50–24.3) and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR = 2.68 95%CI 0.99–7.24). Discussion:Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical cancer mortality in this group of wome

Correção da magnitude da mortalidade por câncer do colo do útero no Brasil, 1996-2005

OBJETIVO: Desenvolver uma metodologia para correção da magnitude dos óbitos por câncer do colo do útero no Brasil. MÉTODOS: Os dados sobre os 9.607.177 óbitos foram obtidos do Sistema de Informação sobre Mortalidade, para o período de 1996 a 2005. Para a correção do sub-registro, foram utilizados os fatores de expansão gerados pelo Projeto Carga Global de Doença no Brasil - 1998. Para correção das categorias de diagnósticos desconhecidos, incompletos ou mal definidos de óbitos, foi aplicada redistribuição proporcional. Os dados ausentes de idade foram corrigidos por imputação. As correções foram aplicadas por Unidade Federativa e os resultados apresentados para o Brasil, região e áreas geográficas (capital, demais municípios das regiões metropolitanas e interior) por meio do percentual de variabilidade da magnitude das taxas, antes e após a correção dos óbitos. O comportamento das correções foi analisado por modelo de regressão linear multivariada com termos de interação entre região do País e área geográfica. RESULTADOS: As taxas corrigidas de mortalidade por câncer do colo do útero no Brasil mostraram um acréscimo de 103,4%, variando de 35% para as capitais da região Sul a 339% para o interior da região Nordeste. A redistribuição dos óbitos por câncer de útero sem especificação de localização anatômica promoveu os maiores acréscimos na magnitude das taxas. Os percentuais de correção, segundo ano de ocorrência do óbito, mostraram tendência estacionária no Brasil. CONCLUSÕES: Os resultados permitem concluir que a metodologia proposta foi adequada para corrigir a magnitude das taxas de mortalidade por câncer do colo do útero no País, mostrando que a mortalidade por esse câncer é ainda maior do que o observado nos informes oficiais.OBJETIVO: Desarrollar una metodología para corrección de la magnitud de los óbitos por cáncer de colon uterino en Brasil. MÉTODOS: Los datos sobre los 9.607.177 óbitos fueron obtenidos del Sistema de Información sobre Mortalidad de Brasil, para el período de 1996 a 2005. Para la corrección del sub-registro, fueron utilizados los factores de expansión generados por el Proyecto Carga Global de Enfermedad en Brasil-1998. Para la corrección de las categorías de diagnósticos desconocidos, incompletos o mal definidos de óbitos, fue aplicada la metodología de redistribución proporcional. Los datos ausentes de edad fueron corregidos por imputación. Las correcciones fueron aplicadas por Unidad Federativa y los resultados son presentados para Brasil, región y áreas geográficas (capital, demás municipios de las regiones metropolitanas e interior) por medio del porcentaje de variabilidad de la magnitud de las tasas, antes y después de la corrección de los óbitos. El comportamiento de las correcciones fue analizado por modelo de regresión linear multivariada con términos de interacción entre región del país y área geográfica. RESULTADOS: Las tasas corregidas de mortalidad por cáncer de colon uterino en Brasil mostraron un aumento de 103,4%, variando de 35% para las capitales de la región Sur a 339% para el interior de la región Noreste. La redistribución de los óbitos por cáncer uterino sin especificación de localización anatómica promovió los mayores aumentos en la magnitud de las tasas. Los porcentajes de corrección, según año de ocurrencia de óbito, mostraron tendencia estacionaria en Brasil. CONCLUSIONES: Los resultados permiten concluir que la metodología propuesta fue adecuada para corregir la magnitud de las tasas de mortalidad por cáncer de colon uterino en Brasil, muestreando que la mortalidad por ese cáncer es aún mayor a lo observado en los informes oficiales.OBJECTIVE: To develop a methodology for correction of reported cervical cancer deaths in Brazil. METHODS: Data on 9,607,177 cancer deaths were obtained from the Brazilian National Mortality Database for the period between 1996 and 2005. For correction of underreporting of deaths, factors generated by the Global Burden of Disease Study in Brazil-1998 were used. Proportional distribution was used in order to correct the categories of unknown, incomplete or ill-defined death diagnosis. The corrections were applied to each Brazilian state and the results were presented for Brazil nationwide, macroregions, and geographical areas (capital, other cities of metropolitan areas and interior cities) as percent variability of cervical mortality rates before and after correction. Corrections were analyzed by multivariate linear regression with interaction terms between macroregion and geographical area. RESULTS: After correction, cervical cancer mortality rates showed an increment of 103% nationwide, ranging between 35% (Southern region capitals) and 339% (Northeastern region interior cities). The reallocation of cervical cancer deaths not otherwise specified resulted in greater mortality rate increments. The percent correction by year of death revealed steady trends nationwide. CONCLUSIONS: The study results showed that the proposed methodology was appropriate for the correction of cervical cancer mortality rates in Brazil. It evidenced that cervical cancer mortality is even higher than that reported

Prevalence of high-risk human papillomavirus types in Mexican women with cervical intraepithelial neoplasia and invasive carcinoma

<p>Abstract</p> <p>Background</p> <p>Prevalence of high risk (HR) human papillomavirus (HPV) types in the states of San Luis Potosí (SLP) and Guanajuato (Gto), Mexico, was determined by restriction fragment length-polymorphism (RFLP) analysis on the E6 ~250 bp (E6-250) HR-HPV products amplified from cervical scrapings of 442 women with cervical intraepithelial neoplasia and invasive carcinoma (280 from SLP and 192 from Gto). Fresh cervical scrapings for HPV detection and typing were obtained from all of them and cytological and/or histological diagnoses were performed on 383.</p> <p>Results</p> <p>Low grade intraepithelial squamous lesions (LSIL) were diagnosed in 280 cases (73.1%), high grade intraepithelial squamous lesions (HSIL) in 64 cases (16.7%) and invasive carcinoma in 39 cases (10.2%). In the 437 cervical scrapings containing amplifiable DNA, only four (0.9%) were not infected by HPV, whereas 402 (92.0%) were infected HR-HPV and 31 (7.1%) by low-risk HPV. RFLP analysis of the amplifiable samples identified infections by one HR-HPV type in 71.4%, by two types in 25.9% and by three types in 2.7%. The overall prevalence of HR-HPV types was, in descending order: 16 (53.4%) > 31 (15.6%) > 18 (8.9%) > 35 (5.6) > 52 (5.4%) > 33 (1.2%) > 58 (0.7%) = unidentified types (0.7%); in double infections (type 58 absent in Gto) it was 16 (88.5%) > 31 (57.7%) > 35 (19.2%) > 18 (16.3%) = 52 (16.3%) > 33 (2.8%) = 58 (2.8%) > unidentified types (1.0%); in triple infections (types 33 and 58 absent in both states) it was 16 (100.0%) > 35 (54.5%) > 31 (45.5%) = 52 (45.5%) > 18 (27.3%). Overall frequency of cervical lesions was LSIL (73.1%) > HSIL (16.7%) > invasive cancer (10.2%). The ratio of single to multiple infections was inversely proportional to the severity of the lesions: 2.46 for LSIL, 2.37 for HSIL and 2.15 for invasive cancer. The frequency of HR-HPV types in HSIL and invasive cancer lesions was 16 (55.0%) > 31 (18.6%) > 35 (7.9%) > 52 (7.1%) > 18 (4.3%) > unidentified types (3.6%) > 33 (2.9%) > 58 (0.7%).</p> <p>Conclusion</p> <p>Ninety percent of the women included in this study were infected by HR-HPV, with a prevalence 1.14 higher in Gto. All seven HR-HPV types identifiable with the PCR-RFLP method used circulate in SLP and Gto, and were diagnosed in 99.3% of the cases. Seventy-one percent of HR-HPV infections were due to a single type, 25.9% were double and 2.7% were triple. Overall frequency of lesions was LSIL (73.1%) > HSIL (16.7%) > invasive cancer (10.2%), and the ratio of single to multiple infections was inversely proportional to severity of the lesions: 2.46 for LSIL, 2.37 for HSIL and 2.15 for invasive cancer. The frequency of HR-HPV types found in HSIL and invasive cancer was 16 (55.0%) > 31 (18.6%) > 35 (7.9%) > 52 (7.1%) > 18 (4.3%) > unidentified types (3.6%) > 33 (2.9%) > 58 (0.7%). Since the three predominant types (16, 31 and 18) cause 77.9% of the HR-HPV infections and immunization against type 16 prevents type 31 infections, in this region the efficacy of the prophylactic vaccine against types 16 and 18 would be close to 80%.</p

Global Gene Expression Profiling Of Human Pleural Mesotheliomas: Identification of Matrix Metalloproteinase 14 (MMP-14) as Potential Tumour Target

BACKGROUND:The goal of our study was to molecularly dissect mesothelioma tumour pathways by mean of microarray technologies in order to identify new tumour biomarkers that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets. METHODOLOGY:We performed Affymetrix HGU133A plus 2.0 microarray analysis, containing probes for about 39,000 human transcripts, comparing 9 human pleural mesotheliomas with 4 normal pleural specimens. Stringent statistical feature selection detected a set of differentially expressed genes that have been further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes, never associated before to mesotheliom that could be involved in tumour progression. Notable is the identification of MMP-14, a member of matrix metalloproteinase family. In a cohort of 70 mesothelioma patients, we found by a multivariate Cox regression analysis, that the only parameter influencing overall survival was expression of MMP14. The calculated relative risk of death in MM patients with low MMP14 expression was significantly lower than patients with high MMp14 expression (P = 0.002). CONCLUSIONS:Based on the results provided, this molecule could be viewed as a new and effective therapeutic target to test for the cure of mesothelioma