Hormonal contraceptives and the length of their use are not independent risk factors for high-risk HPV infections or high-grade CIN.

AIMS: To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study. METHODS: A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+. RESULTS: HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions. CONCLUSIONS: No evidence was found for an association between the use of HOC with an increased risk for HR-HPV infection or high-grade CIN in this cohort.

Can living in the surroundings of a petrochemical complex be a risk factor for autoimmune thyroid disease?

BACKGROUND: Based on a suspicion raised by a health professional and due to a subsequent legal request, a cross-sectional study was made with a comparison group to investigate a possible excess of Hashimoto's thyroiditis-HT and antibodies-ATA in the surroundings of a Petrochemical Complex. METHODS: People of both sexes aged over 20 years were investigated in a random sample of residents in the area surrounding the Petrochemical Complex. Controls were investigated in an area with steel industries. In the areas searched, participants were chosen randomly and stratified a priori by sex and age group. As a result, 90.5% of the expected sample was obtained, totaling 1533 individuals. HT and ATA prevalences were compared by the chi-square test. Logistic regression was used to control the possible confounding factors for HT and ATA. RESULTS: Both TH (9.3%) and ATA (17.6%) prevalences were higher in the Petrochemical Complex area than in the control area (3.9% and 10.3%, respectively). After controlling the possible confounding factors, the POR for living in the surroundings of the Complex and presenting HT was 2.39 (CI95%: 1.42-4.03). According to the ATA criterion, the POR for living in the surroundings of the Complex was 1.78 (CI95%: 1.23-2.60). CONCLUSIONS: The authors have found higher prevalence and risk of developing thyroiditis and anti-thyroid antibodies among residents of areas surrounding the Petrochemical Complex and think these findings need to be further studied in similar areas.

Increased risk of oncogenic human papillomavirus infections and incident high-grade cervical intraepithelial neoplasia among smokers: experience from the Latin American screening study.

BACKGROUND: The purpose of this study was to assess the effect of smoking on the prevalence and incidence of high-risk human papillomavirus (hr-HPV) infection and cervical intraepithelial neoplasia (CIN) in a large sample of Latin American women. METHODS: The study examines baseline data on over 12,000 women included in the Latin American Screening Study (Brazil and Argentina), and over 1000 women followed-up for a period of 36 months. Three groups were formed: never smokers, current, and past smokers. The prevalence of hr-HPV infection and CIN were compared between the study groups. In the prospective analysis, women were controlled at 6-month intervals to assess the cumulative risk of incident hr-HPV infection, smear abnormalities, and CIN. RESULTS: A higher prevalence (21.7%) of hr-HPV infection was found among current smokers as compared to never smokers (16.5%) or past smokers (13.5%). Being current smoker was significantly (P <0.01) associated with hr-HPV detection (OR = 1.6; 95% CI = 1.2-2.1). Being a current smoker was a significant predictor of incident hr-HPV during the follow-up [Hazards ratio (HR) = 1.4; 95% CI 1.0-1.9]. For incident CIN2+, being a past smoker (HR = 3.6; 95% CI 1.6-9.8) or current smoker (HR = 3.6; 95% CI 1.5-8.6) were the significant independent predictors. Current and past smokers had a significantly increased risk of incident CIN2+ (P <0.01). CONCLUSIONS: Smoking increases the risk of contracting hr-HPV infection and modifies the effect of a persistent hr-HPV infection by further increasing the risk of developing CIN2+. It seems that this effect modification persists over several years after smoking cessation.

Interlaboratory quality control in gynecologic cytopathology using the novel CONQUISTADOR software. Interobserver reproducibility in the Latin American screening study.

OBJECTIVE: The recently developed software (CONQUISTADOR), capable of computing all intralaboratory and interlaboratory quality control (QC) indicators, was used to evaluate the diagnostic agreement among 4 cytology laboratories participating in the LAMS Study. STUDY DESIGN: The study was an interlaboratory exchange of specially designed 5 slide sets, each comprising 20 (conventional cytology) slides. At the first step, 80 slides (with "clear-cut" cases) were divided into four sets (A, B, C, D) of 20 specimens, each including inadequate and negative cases as well as in different proportions of all diagnostic TBS 2001 categories. In the second round, a fifth set (E) of 20 slides ("difficult cases") was designed, with all diagnostic categories, ASC and AGC included. Common measures of reproducibility (kappa and weighted kappa), accuracy (SE, SP, PPV, NPV) and 3 indices of diagnostic variability were calculated for sets A-D and set E, separately. RESULTS: For the 5 slide sets together, the weighted kappa was 0.8 (95% CI 0.76-0.85), which is the lower limit of the "almost perfect" ranking of kappa statistics, indicating an excellent interlaboratory agreement. The interlaboratory reproducibility was lower only for the difficult set (E). Similarly, the sensitivity for set E (70.0%) was lower than that (92.1%) for sets A-D. The diagnostic variability indices were not substantially different between the difficult (set E) and clearcut (sets A-D) cases. CONCLUSION: High interlaboratory reproducibility was obtained for sets A-D ("clear-cut" cases), while more interlaboratory variation was evident in the difficult samples. The new CONQUISTADOR software is a valuable tool in calculating the indicators needed in this intralaboratory and interlaboratory.

Performance characteristics of Pap test, VIA, VILI, HR-HPV testing, cervicography, and colposcopy in diagnosis of significant cervical pathology.

We sought to evaluate the performance of diagnostic tools to establish an affordable setting for early detection of cervical cancer in developing countries. We compared the performance of different screening tests and their feasibility in a cohort of over 12,000 women: conventional Pap smear, liquid-based cytology, visual inspection with acetic acid (VIA), visual inspection with Iodine solution (VILI), cervicography, screening colposcopy, and high-risk human papillomavirus (HPV) testing (HR-HPV) collected by physician and by self-sampling. HR-HPV assay collected by the physician has the highest sensitivity (80 %), but high unnecessary referrals to colposcopy (15.1 %). HR-HPV test in self-sampling had a markedly lower (57.1 %) sensitivity. VIA, VILI, and cervicography had a poor sensitivity (47.4, 55, and 28.6 %, respectively). Colposcopy presented with sensitivity of 100 % in detecting CIN2+, but the lowest specificity (66.9 %). Co-testing with VIA and VILI Pap test increased the sensitivity of stand-alone Pap test from 71.6 to 87.1 % and 71.6 to 95 %, respectively, but with high number of unnecessary colposcopies. Co-testing with HR-HPV importantly increased the sensitivity of Pap test (to 86 %), but with high number of unnecessary colposcopies (17.5 %). Molecular tests adjunct to Pap test seems a realistic option to improve the detection of high-grade lesions in population-based screening programs.

Cinética celular em lesöes pré-invasivas e invasivas do epitélio escamoso cervical: estudo morfológico e imunoistoquímico / Cellular kinetics in preinvasive and invasive lesions of cervical squamous epithelium: morphologic and immunohistochemical study

Avaliar quantitativamente a apoptose (morte celular programada) e a taxa de proliferaçäo celular no espectro das lesöes neoplásicas do colo uterino. Materiais e Métodos: Analisamos 81 biópsias cervicais previamente diagnosticadas na Divisäo de Patologia do Instituto Adolfo Lutz segundo a classificaçäo da OMS como sendo: neoplasia intraepitelial cervical de grau 1 NIC 1=20,NIC2=19,NIC3=23 e carcinoma de células escamosas (CCE)=19. Foi utilizado o método imunoistoquímico para detecçäo das células em proliferaçäo (MIB-1) e o método de TUNEL para a apoptose. As células foram contadas através de fotomicrografia digital, sendo que o número variou de 83 a 2975 média=1515,62) para MIB-1 e 315 a 3565 para apoptose (média=1273,24). Resultados: Houve um aumento progressivo nas taxas de proliferaçäo (por cento) com a severidade da lesäo (NIC 1=22,7;NIC 2=34,5;NIC 3=38,3;CCE=52,6P<0,0001). O mesmo foi obtido com as taxas de apoptose (por cento) (NIC 1=0,30;NIC 2=0,55;NIC 3=0,70;CCE=1,19p<0,0001) e o índice de renovaçäo celular (por cento) (NIC 1=23,0;NIC 2=35,0;NIC 3=39,0;CCE=53,8p<0,0001). Surpreendentemente a razäo das taxas proliferaçäo/ apoptose näo mostrou aumento progressivo (NIC 1=75,6;NIC 2=62,7;NIC 3=54,7; CCE=44,2). Conclusäo: Observamos aumento paralelo tanto nas taxas de proliferaçäo como nas de apoptose com o grau das lesöes cervicais. As taxas crescentes de apoptose possivelmente representam a persistência de alguns mecanismos compensatórios de regulaçäo da populaçäo celular

To assess proliferative and apoptotic rates in squamous lesions of the uterine cervix. Materialand Methods: 81 cervical biopsies were classified as cervical intraepithelial neoplasia grade 1 CIN1 = 20,CIN2 = 19, CIN3 = 23 and squamous cell carcinoma (SCC) = 19, according to WHO classification. Histologicalsections were submitted to MIB-1 immunostaining by streptavidin-peroxidase amplification. In situ end-labeling of DNA strand breaks by TUNEL method was used to enhance the detection of apoptosis. Allcells representative of the pertinent lesion were counted in each sample in digital hotomicrographs andthe results were expressed as positive cells %. The groups were compared using a one-way analysis ofvariance (ANOVA). Statistical significance was defined as a P< 0.05. Results: There was progressiveincrease of proliferation rate (%) with the severity of lesion CIN 1 = 22.7; CIN 2 = 34.5; CIN 3 = 38.3; SCC =52.6 p<0.0001). The same was obtained with apoptotic rate (%) (CIN 1 = 0.30; CIN 2 = 0.55; CIN 3 = 0.70;SCC = 1.19 p<0.0001), and turnover rate (%) (CIN 1 = 23.0; CIN 2 = 35.0; CIN 3 = 39.0; SCC = 53.8 p<0.0001).Surprisingly, the ratio of proliferation/apoptotic rate did not show a progressive increase (CIN 1 = 75.6;CIN 2 = 62.7; CIN 3 = 54.7; SCC = 44.2). Conclusions: There is an increase in both proliferation andapoptosis with increasing atypical in cervical lesions. Increase in apoptotic rate possibly representspersistence of some compensatory regulation mechanisms of cell population

Avaliaçäo da celularidade citológica em preparados de base líquida / Cellularity evaluation in liquid-based cytology preparations

O método de citologia em base líquida parece apresentar uma série de vantagens em relação ao convencional: melhor disposição celular, facilitando a interpretação; redução do número de hemácias,exsudato inflamatório e muco, preparação de lâminas adicionais do mesmo caso sem ter que se convocara paciente; utilização de material residual para testes moleculares para identificação de HPV e outros microrganismos .O método de base líquida, pelas vantagens mencionadas, detecta maior número delesões, além de menor índice de amostras inadequadas ou limitadas por alguma razão. O presente trabalhoteve como objetivo avaliar os achados citológicos obtidos com duas metodologias diferentes de preparo de citologia em base líquida, o novo sistema DNA - CITOLIQ (DIGENE-Brasil) e o sistema Autocyte(TRIPATH, USA), e correlacioná-los com os achados de citologia convencional obtidos da rotina do Setor de Citologia Oncótica do Instituto Adolfo Lutz. Foram estudadas 509 amostras consecutivas pelosistema DNA - CITOLIQ e 398 amostras pelo sistema Autocyte, de mulheres atendidas no HospitalLeonor Mendes de Barros no ano de 2002, participantes voluntárias do projeto INCODEV ICA4-CT-2001-(10013). Das 509 citologias preparadas pelo método DNA - CITOLIQ (DIGENE-Brasil), 0,6% foraminsatisfatórios; 89,3% negativos; 2,0% lesões de baixo grau; 0,8% lesões de alto grau; 0,2% carcinoma e7,1% ASCUS / AGUS. Apresentou ainda 89% de amostras satisfatórias, 10,0% satisfatórias mas limitada spor ausência de JEC e 0,4% limitadas por outras causas. Pelo método Autocyte, em 398 casos, 0,5% foraminsatisfatórios; 88,2% negativos; 3,0% ASCUS / AGUS; 6,8% lesões de baixo grau e 1,5% lesões de alto grau. Apresentou 84% de amostras satisfatórias, 15,25% satisfatórias mas limitados por ausência de JECe 0,25% satisfatórias mas limitados por outras causas. Foram examinadas 33.313 citologias colhidas pelo método convencional em 2001, onde 5,0% foram insatisfatórios; 92,6% negativos; 1,3% lesões de baixo grau; 0,3% lesões de alto grau e 0,05% de carcinoma invasivo; 0,7 ASCUS / AGUS. Em relação à qualidade da amostra, apenas 22,7% dos casos apresentaram células da JEC. Conclui-se que ambos métodos decitologia em base líquida apresentaram performances semelhantes quanto à qualidade das amostras, comenos casos insatisfatórios que o convencional. Observamos ainda, para ambos métodos, aumento significativo na sensibilidade para detecção de lesões intraepiteliais, sobretudo as de baixo grau, quando comparadas ao método convencional. (AU)

Liquid-based cytology (LBC) presents several advantages when compared to theconventional smears, such as clean background, residual material for additional cytological preparationsor even for molecular tests to infectious agents identification, mainly HPV. Besides these advantages,LBC detects more lesions than the conventional smears, and also reduce the number of unsatisfactorysamples and false negative cases. The goal of this work was to evaluate the cytologic findings of twodifferent LBC methodologies, DNACITOLIQ ® (DIGENE-Brasil) and Autocyte system (Tripath, USA)concerning the adequacy of the samples and diagnosis performance, and compare these results to thosereported by conventional smears daily routine analyzed at Adolfo Lutz Institute. A total of 509 samples ofDNA- CITOLIQ ® and 398 Autocyte consecutive cases from women examined at Leonor Mendes deBarros Hospital in 2002 (INCODEV ICA-CT-2001-10013 project) were analyzed. From DNACITOLIQ®cases 0.6% were unsatisfactory, 89.3% were negative, 7,1% ASCUS/ AGUS, 2.0% LSIL, 0.8% HSIL and0.2% squamous carcinoma. Regarding adequacy parameters 89% were satisfactory, 10.0% were limited byabsence of glandular cells and 0.4 limited by other reasons. Autocyte system diagnosis were: 0.5%unsatisfactory, 88.2% negative, 3.0% ASCUS/AGUS, 6.8% LSIL and 1.5% HSIL. Conventional smearscomprised 33,313 samples where 5.0% were unsatisfactory, 92.6% were negative, 0.7% ASCUS/ AGUS,1.3% LSIL, 0.3% HSIL and 0.05% squamous carcinoma. Satisfactory samples with glandular cellsrepresentation account 22.7%. Both methods of liquid-based cytology have presented similar performancesregarning the adequacy of the samples, presenting lesser inadequate cases than the conventional. Wehave also observed that both methods have showed better sensitivity than the conventional to identifyintraepithelial lesions, mainly the low grade. (AU)

O impacto do diagnóstico citológico de atipias indeterminadas no sistema público de saúde / The impact of cytological diagnosis of undetermined atypias in public health system

Introdução: as alterações citológicas, de significado indeterminado representam uma importante limitação diagnóstica nos programas de escrutíneo de lesões cérvico-vaginais. A introdução de métodos biomoleculares, como o sistema de captura híbrida para detecção de HPV de alto risco contribui para a otimização da conduta clínica dessas pacientes, indicando colposcopia com precisão. Objetivo: avaliar o significado de lesões de significado indeterminado com relação à infecção pelo HPV, com o uso do teste de DNA para HPV com o método da captura de híbridos II. Métodos: foram estudadas amostras de 236 casos consecutivos examinados no laboratório da DIGENE-BRASIL, de pacientes com diagnóstico citológico prévio de ASCUS. As amostras foram submetidas ao teste de captura híbrida para identificação de DNA-HPV dc alto e baixo riscos. Resultados: dos 236 casos analisados, 183 (77,5 por cento) foram negativos para o teste de captura híbrida, seis (2,6 por cento) foram positivos para HPV de baixo risco e 47 (19,9 por cento) foram positivos para HPV de alto risco. Conclusão: as amostras positivas para HPV de baixo risco representam uma pequena e não-considerável minoria de casos, provavelmente, transientes. Cerca de 20 por cento dos casos foram positivos para HPV de alto risco e deverão ser encaminhados à colposcopia e biópsia, se necessário. Esses casos representam um grande potencial de progressão para lesões cervicais

Programa de controle de qualidade em citologia ginecológica do Instituto Adolfo Lutz: estratégias e análise crítica dos resultados de sua implantaçäo-piloto / Program of quality control in gynecological cytology at Instituto Adolfo Lutz: strategies and critical analysis of results its implantation-pilot

O Programa de Controle de Qualidade em Citologia Ginecológica do Instituto Adolfo Lutz foi criado para oferecer garantia ao bom funcionamento do Sistema de Detecçäo e Prevençäo do Câncer Ginecológico do SUDS/SP. Este trabalho apresenta as estratégias do Programa em nível intralaboratorial e análise dos resultados de sua implantaçäo-piloto. A metodologia de seleçäo de casos de maior risco de neoplasias para uma revisäo dirigida, a classificaçäo e o sistema de aferiçäo das discrepâncias de interpretaçöes säo contribuiçöes desta experiência, sendo que, dos 32.018 casos estudados prospectivamente, 492 preencheram critérios de seleçäo para revisäo. destes, 45 tiveram interpretaçäo inicial em graus inferiores ao da conclusäo diagnóstica, sempre com discrepâncias pequenas, nenhum dos quais classificável como "falso-negativo". Em 51 casos, a interpretaçäo inicial foi em graus superiores aos da conclusäo, registrando-se apenas três casos, classificáveis como "falso-positivo". A partir destes dados iniciais, o Programa deverá ser ampliado para os demais laboratórios da rede do SUDS/SP, incluindo-se controle interno e externo, sob supervisäo do Instituto Adolfo Lutz

Identificaçäo de micronúcleos (MN) em células de colo uterino de pacientes assintomáticas: correlaçäo dos métodos de Papanicolaou e Feulgen-fast-grenn / Identification of micronuclei (MN) in uterine cervix cells of asymptomatic patients: correlation between Papanicolaou and Feulgen-fast-green methods

Foram estudados esfregaços cervicovaginais corados pelo Papanicolaou de mulheres assintomáticas submetidas a exame ginecológico de rotina, com o objetivo de se identificar micronúcleos nesse material e correlacionar os achados com os de esfregaços das mesmas pacientes corados pelo método de Feulgen-Fast-green. Os resultados demonstraram que o método de Papapicolaou, embora com sensibilidade menor que a de Feulgen-Fast-green na detecçäo de micronúcleos, mostrou-se útil para estudos retrospectivos de séries previamente coradas, sobretudo as que apresentam lesöes epiteliais correlacionadas com condiçöes mutagênicas

Identificaçäo diferencial do Mobiluncus sp nas vaginoses bacteriana atraves do diagnostico morfologico e sua importancia na rede de Saude Publica / The value of Mobiluncus sp in the Public Health

Foram selecionados 1.180 amostras de esfregacos cervicovaginais,provenientes de varias Unidades de Saude do Estado de Sao Paulo,corados pelo metodo de Papaniculau,com achados previos de Flora e Gardnerella vaginalis,para deteccao de Mobiluncus sp,em esfregacos negativos para malignidade.Das amostras diagnosticadas inicialmente como Gardnerella vaginalis ou Flora mista,a revisao foram detectados 10,8 por cento de Mobilluncus sp,distribuidos da seguinte forma:7,1 por cento so Mobiluncus sp e 92,9 por cdento associados a outros agentes infecciosos,tais como:Gardnerella vaginalis,Flora mista,Trichomonas vaginalis,Candida sp e Papilimavirus Humano.Concluiu-se que o metodo de Papaniculau e util na deteccao do Mobilluncus sp e sua introducao na rotina diagnostica em laboratorios de saude publica viabilizara a eventual necessidade de diferenciacao no tratamento das vaginoses bacterianas.

Fatores interferentes na correlaçåo cito-histológica em papilomavírus (HPV) / Sample collection factors related to cyto-histologic discrepancies in papilomavirus detection

Cuidados com a colheita, critérios morfológicos, procedimentos técnicos e fases da infecçåo såo fatores fundamentais na integraçåo cito-histológica em Papilomavirus (HPV). Partindo de 22 biópsias cervicais, com infecçåo por HPV, segundo os critérios histológicos definidos por MEISELS e col., revimos as citologias correspondentes seguindo os critérios citológicos de Meisels e os de Schneider. Hibridaçåo "in situ" com sondas biotiniladas para HPV 6, 11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52 e 56 e ampliaçåo pelo sistema avidina-biotina-peroxidase foi feita em novos cortes das biópsias. A revisåo da citologia revelou 16 casos com alteraçöes por HPV, dos quais 15 com representaçåo endocervical, que nåo foi detectada nos 6 restantes casos negativos. 18 casos (81,8 por cento) foram positivos para DNA-HPV, tendo 2 dos negativos áreas descoladas durante a reaçåo. Todos os casos foram fixados em excesso (m=18,5 dias nos negativos e 11,6 nos positivos). Este trabalho reafirma a importância da revisåo das amostras citológicas dos casos biopsiados, ressaltando a queståo da amostragem como causa dos falsos negativos. A hibridizaçåo mostrou-se útil mesmo em biópsias de rotina, mas a fixaçåo parece interferir com a reatividade do DNA viral

Low and high-risk HPV types detected with hybrid capture II - HC2 - in liquid-based cytology - DNA Citoliq System: experience from the LAMS - Latin American Screening study

Avalia a performance do meio UCM - Universal Collecting Médium - do novo sistema DNACITOLIQ - Digene-Brasil - para citologia de base líquida e ensaios biomoleculares em uma população geral submetida a ratreio de rotina para lesões de colo uterino associadas ao HPV de baixo e alto riscos

Rastreamento de cåncer de colo uterino em São Paulo: resultados parciais em 3.000 mulheres / Cervical cancer screening in São Paulo: preliminary results for 3.000 women

Foram examinadas 3.000 mulheres entre fevereiro de 2002 e março de 2003 para prevençao de cancer do colo uterino