ABSTRACT BACKGROUND: Managing cervical intraepithelial neoplasia grade 2 (CIN2) is challenging, considering the CIN2 regression rate, perinatal risks associated with excisional procedures, and insufficient well-established risk factors to predict progression. OBJECTIVES: To determine the ability of p16INK4a and Ki-67 staining in biopsies diagnosed with CIN2 to identify patients with higher-grade lesions (CIN3 or carcinoma). DESIGN AND SETTING: Cross-sectional study conducted at a referral center for treating uterine cervical lesions. METHODS: In 79 women, we analyzed the correlation of p16INK4a and Ki-67 expression in CIN2 biopsies with the presence of a higher-grade lesions, as determined via histopathology in surgical specimens from treated women or via two colposcopies and two cytological tests during follow-up for untreated women with at least a 6-month interval. The expression of these two biomarkers was verified by at least two independent pathologists and quantified using digital algorithms. RESULTS: Thirteen (16.8%) women with CIN2 biopsy exhibited higher-grade lesions on the surgical excision specimen or during follow-up. p16INK4a expression positively and negatively predicted the presence of higher-grade lesions in 17.19% and 86.67% patients, respectively. Ki-67 expression positively and negatively predicted the presence of higher-grade lesions in 40% and 88.24% patients, respectively. CONCLUSIONS: Negative p16INK4a and Ki67 immunohistochemical staining can assure absence of a higher-grade lesion in more than 85% of patients with CIN2 biopsies and can be used to prevent overtreatment of these patients. Positive IHC staining for p16INK4a and Ki-67 did not predict CIN3 in patients with CIN2 biopsies.

Abstract This study aimed to estimate the cost of implementing a center for assisted human reproduction in a public reference hospital in Rio de Janeiro. The cost analysis was carried out from the perspective of the SUS provider of assistance. The eligible population was men and women diagnosed with the most frequent causes of infertility. The cost items included in primary care and medium complexity were consultations and examinations and in high complexity were equipment, human resources and supplies. Costs were identified and quantified through consultation with assisted reproduction clinics, specialists and literature. They have been valued through public databases. Data analysis was performed using an analytical decision model that included costs of assisted reproduction and effectiveness procedures. The cost per procedure in high complexity was R$ 18,829 for in vitro fertilization with intracytoplasmic sperm injection and R$ 5,649 for artificial insemination. The initial investment required to operate the high complexity center for 480 cycles was R$ 15,903,361 in the first year, which included structuring the physical environment. Estimating the investment required for the incorporation and maintenance of services in SUS is essential for the management of available financial resources.

Resumo O objetivo do estudo foi estimar o custo da implantação de um centro de reprodução humana em um hospital público de referência nacional localizado no Rio de Janeiro. A população elegível foi a de homens e mulheres que possuem diagnóstico das causas mais frequentes de infertilidade. Os itens de custos incluídos foram consultas, exames, equipamentos, recursos humanos e insumos. Os custos foram identificados e quantificados a partir de consulta a clínicas de reprodução assistida, especialistas e literatura. Foram valorados através de bases públicas. A análise dos dados foi realizada através de um modelo de decisão analítico. A perspectiva do estudo foi do SUS provedor. O custo por procedimento na alta complexidade foi de R$ 18.829 para a fertilização in vitro com injeção intracitoplasmática de espermatozoide e de R$ 5.649 para a inseminação artificial. O investimento inicial necessário para funcionamento do centro de alta complexidade para a realização de 480 ciclos foi de R$ 15.903.361 no primeiro ano, o qual incluiu a estruturação do ambiente físico. A estimativa do investimento necessário para a incorporação e manutenção dos serviços no SUS é indispensável para a gestão financeira.

Abstract This study aimed to estimate the cost of implementing a center for assisted human reproduction in a public reference hospital in Rio de Janeiro. The cost analysis was carried out from the perspective of the SUS provider of assistance. The eligible population was men and women diagnosed with the most frequent causes of infertility. The cost items included in primary care and medium complexity were consultations and examinations and in high complexity were equipment, human resources and supplies. Costs were identified and quantified through consultation with assisted reproduction clinics, specialists and literature. They have been valued through public databases. Data analysis was performed using an analytical decision model that included costs of assisted reproduction and effectiveness procedures. The cost per procedure in high complexity was R$ 18,829 for in vitro fertilization with intracytoplasmic sperm injection and R$ 5,649 for artificial insemination. The initial investment required to operate the high complexity center for 480 cycles was R$ 15,903,361 in the first year, which included structuring the physical environment. Estimating the investment required for the incorporation and maintenance of services in SUS is essential for the management of available financial resources.

Resumo O objetivo do estudo foi estimar o custo da implantação de um centro de reprodução humana em um hospital público de referência nacional localizado no Rio de Janeiro. A população elegível foi a de homens e mulheres que possuem diagnóstico das causas mais frequentes de infertilidade. Os itens de custos incluídos foram consultas, exames, equipamentos, recursos humanos e insumos. Os custos foram identificados e quantificados a partir de consulta a clínicas de reprodução assistida, especialistas e literatura. Foram valorados através de bases públicas. A análise dos dados foi realizada através de um modelo de decisão analítico. A perspectiva do estudo foi do SUS provedor. O custo por procedimento na alta complexidade foi de R$ 18.829 para a fertilização in vitro com injeção intracitoplasmática de espermatozoide e de R$ 5.649 para a inseminação artificial. O investimento inicial necessário para funcionamento do centro de alta complexidade para a realização de 480 ciclos foi de R$ 15.903.361 no primeiro ano, o qual incluiu a estruturação do ambiente físico. A estimativa do investimento necessário para a incorporação e manutenção dos serviços no SUS é indispensável para a gestão financeira.

This article tries to understand the intersections and differences of narratives among health professionals, users of a highly complex institution within the Unified Health System (SUS) and mothers of children with complex health conditions; also reflects on actions that can contribute to a better communication among these two actors and the formulation of guiding policies for this dialogical exchange in a more effective and efficient way. Focus groups and semi-structured interviews were carried out, totaling 36 participants, including doctors, nurses, social workers, managers, cleaning professionals, front desks and users/mothers of children under treatment at this institution in Rio de Janeiro, during a six-month period. The results were treated from a qualitative-quantitative perspective using the MAXQDA® software, which supported the identification of synergies and antagonisms among the collected narratives, pointing to three main categories of narratives: communication flow between actors; the perception about the institution, including care aspects; and feelings about health, illness and death. As perspectives, we believe the results can be inspiring when reflecting on Social Determinants in Health and SUS.

This articlenbsp;triesnbsp;to understand the intersections and differencesnbsp;of narratives amongnbsp;health professionals,nbsp;users of anbsp;highly complex institution within the Unified Health Systemnbsp;(SUS)nbsp;andnbsp;mothers of children with complex health conditions; alsonbsp;reflectsnbsp;on actions that can contribute to a better communicationnbsp;amongnbsp;these two actors and the formulation of guiding policies for this dialogical exchange in a more effective and efficient way. Focus groups and semi-structured interviews were carried out, totaling 36 participants, including doctors, nurses, social workers, managers, cleaning professionals,nbsp;front desksnbsp;and users/mothersnbsp;of children undernbsp;treatment at this institution in Rio de Janeiro,nbsp;during a six-month period. The results were treated from a qualitative-quantitative perspective using the MAXQDA® software, whichnbsp;supported the identification ofnbsp;synergies and antagonisms among the collected narratives, pointing to three main categories of narratives: communicationnbsp;flownbsp;between actors;nbsp;thenbsp;perceptionnbsp;aboutnbsp;the institution, includingnbsp;care aspects; and feelings about health, illness and death. As perspectives, we believe the results can be inspiring when reflecting on Social Determinants in Health and SUS.

ABSTRACT BACKGROUND: Cervical cancer screening in Brazil is done using Pap smears. Women who are most likely to have a preinvasive lesion or cervical cancer are immediately referred for colposcopy. OBJECTIVE: The aim of this study was to evaluate the diagnostic performance of endocervical cytological tests in diagnosing preinvasive cervical lesions in women with initial high-grade squamous intraepithelial lesions (HSIL), or atypical squamous cells in which high-grade lesions could not be ruled out (ASC-H), or atypical glandular cells (AGC), and whose colposcopy did not show any abnormalities, with no fully visible transformation zone (types 2 and 3). DESIGN AND SETTING: Retrospective observational study conducted in Rio de Janeiro, Brazil. METHODS: Data from women who came to the cervical pathology outpatient clinic between January 2012 and April 2017 were analyzed. The results from endocervical cytological tests were compared with the final diagnosis, which was obtained through examination of a surgical specimen or, among women who did not undergo an excisional procedure, after cytological and colposcopic follow-up for two years. RESULTS: We included 78 women. The sensitivity of endocervical cytological tests was 72.7%; specificity 98.5%; positive and negative predictive values 88.9% and 95.6%, respectively; and positive and negative likelihood ratios 48.7 and 0.28. CONCLUSION: Endocervical cytological tests are simple, inexpensive and noninvasive, and form a reliable method for determining management among patients with HSIL, ASC-H and AGC cytological findings and negative colposcopic findings without visualization of the squamocolumnar junction.

Estimaram-se parâmetros para planejamento e programação da oferta de procedimentos para rastreamento, investigação diagnóstica e tratamento de lesões precursoras do câncer do colo do útero e, com base nessas estimativas, avaliou-se a adequação da produção nacional dos procedimentos realizados pelo Sistema Único de Saúde (SUS) em 2017. As estimativas foram calculadas utilizando como referencial as condutas preconizadas nas diretrizes nacionais para o rastreamento. Os dados referentes aos exames de rastreamento foram obtidos no Sistema de Informação do Câncer do Colo do Útero, e os dados de seguimento, em prontuários médicos de uma unidade de referência em patologia cervical. A produção nacional dos procedimentos foi obtida a partir de dados dos Sistemas de Informações Ambulatoriais e Hospitalares do SUS. Para cada cem mil mulheres na faixa etária alvo do rastreamento (25-64 anos), estimou-se a necessidade anual de 44.134 exames citopatológicos, 1.886 colposcopias, 275 biópsias, 236 excisões tipo 1 e 2 ambulatoriais, 236 excisões tipo 2 e 3 hospitalares e 39 encaminhamentos para alta complexidade para realização de cirurgia, quimioterapia e/ou radioterapia. Aplicando-se os parâmetros estimados ao número de mulheres rastreadas no Brasil em 2017, identificou-se déficit de todos os procedimentos para o seguimento adequado das mulheres com alterações, variando de 7% nas colposcopias a 74% nas excisões tipo 3. Os resultados apontam necessidade de ampliar e qualificar a oferta de procedimentos da linha de cuidado do câncer do colo do útero. Os parâmetros estimados poderão subsidiar gestores na programação e implementação de programas de rastreamento organizado.

The study estimated parameters for planning and programming the supply of procedures for screening, diagnostic workup, and treatment of precursor lesions of uterine cervical cancer. These estimates were used as the basis for assessing the adequacy of Brazil’s production of procedures performed by the Brazilian Unified National Health System (SUS) in 2017. Estimates were calculated using as the reference the recommended management in the national screening guidelines. Data on screening tests were obtained from the Information System on Uterine Cervical Cancer and the follow-up data from patient charts in a referral center for cervical pathology. Brazil’s production of procedures was obtained from data in the Outpatient and Hospital Information Systems of the SUS. For every one hundred thousand women in the target age bracket for screening (25 to 64 years) there was an estimated annual need for 44,134 cytopathology tests, 1,886 colposcopies, 275 biopsies, 236 type 1 and 2 outpatient exicision procedures, 236 type 2 and 3 hospital exicision procedures, and 39 high-complexity referrals for surgery, chemotherapy, and/or radiotherapy. Applying the estimated parameters to the number of women screened in Brazil in 2017, a deficit was identified in all the procedures for adequate follow-up of the women with altered test results, varying from 7% in colposcopies to 74% in type 3 excisions. The results point to the need to expand and upgrade the supply of line of care procedures for cervical cancer. The estimated parameters can support policymakers in programming and implementing organized screening programs.

Se estimaron parámetros para la planificación y programación de la oferta de procedimientos, con el fin de detectar, realizar investigación diagnóstica y tratar lesiones precursoras del cáncer de cuello uterino. En base a las mismas, se evaluó la adecuación del protocolo nacional de procedimientos realizados por el Sistema Único de Salud (SUS) en 2017. Las estimaciones se calcularon utilizando como marco de referencia los procedimientos recomendados en las directrices nacionales para la detección de este tipo de cáncer. Los datos referentes a los exámenes de detección se obtuvieron en el Sistema de Información del Cáncer de Cuello de Útero, y los datos de seguimiento en registros médicos de una unidad de referencia en patología cervical. La producción nacional de los procedimientos se obtuvo a partir de datos de los sistemas de información ambulatoria y hospitalaria del SUS. De cada cien mil mujeres, en la franja de edad objetivo de la detección (25 a 64 años), se estimó una necesidad anual de 44.134 exámenes citopatológicos, 1.886 colposcopias, 275 biopsias, 236 escisiones tipo 1 y 2 ambulatorias, 236 escisiones tipo 2 y 3 hospitalarias y 39 derivaciones hacia centros hospitalarios de alta complejidad para la realización de cirugías, quimioterapia y/o radioterapia. Aplicando los parámetros estimados al número de mujeres a quienes se les realizó el examen en Brasil durante 2017, se identificó un déficit de todos los procedimientos para un seguimiento adecuado de las mujeres con alteraciones, variando de un 7% en las colposcopias, a un 74% en las escisiones tipo 3. Los resultados apuntan la necesidad de ampliar y dotar la oferta de procedimientos en la línea de cuidados del cáncer de cuello uterino. Los parámetros estimados podrán ayudar a los gestores en la programación e implementación de programas organizados de detección.

Estimaram-se parâmetros para planejamento e programação da oferta de procedimentos para rastreamento, investigação diagnóstica e tratamento de lesões precursoras do câncer do colo do útero e, com base nessas estimativas, avaliou-se a adequação da produção nacional dos procedimentos realizados pelo Sistema Único de Saúde (SUS) em 2017. As estimativas foram calculadas utilizando como referencial as condutas preconizadas nas diretrizes nacionais para o rastreamento. Os dados referentes aos exames de rastreamento foram obtidos no Sistema de Informação do Câncer do Colo do Útero, e os dados de seguimento, em prontuários médicos de uma unidade de referência em patologia cervical. A produção nacional dos procedimentos foi obtida a partir de dados dos Sistemas de Informações Ambulatoriais e Hospitalares do SUS. Para cada cem mil mulheres na faixa etária alvo do rastreamento (25-64 anos), estimou-se a necessidade anual de 44.134 exames citopatológicos, 1.886 colposcopias, 275 biópsias, 236 excisões tipo 1 e 2 ambulatoriais, 236 excisões tipo 2 e 3 hospitalares e 39 encaminhamentos para alta complexidade para realização de cirurgia, quimioterapia e/ou radioterapia. Aplicando-se os parâmetros estimados ao número de mulheres rastreadas no Brasil em 2017, identificou-se déficit de todos os procedimentos para o seguimento adequado das mulheres com alterações, variando de 7% nas colposcopias a 74% nas excisões tipo 3. Os resultados apontam necessidade de ampliar e qualificar a oferta de procedimentos da linha de cuidado do câncer do colo do útero. Os parâmetros estimados poderão subsidiar gestores na programação e implementação de programas de rastreamento organizado.

The study estimated parameters for planning and programming the supply of procedures for screening, diagnostic workup, and treatment of precursor lesions of uterine cervical cancer. These estimates were used as the basis for assessing the adequacy of Brazil’s production of procedures performed by the Brazilian Unified National Health System (SUS) in 2017. Estimates were calculated using as the reference the recommended management in the national screening guidelines. Data on screening tests were obtained from the Information System on Uterine Cervical Cancer and the follow-up data from patient charts in a referral center for cervical pathology. Brazil’s production of procedures was obtained from data in the Outpatient and Hospital Information Systems of the SUS. For every one hundred thousand women in the target age bracket for screening (25 to 64 years) there was an estimated annual need for 44,134 cytopathology tests, 1,886 colposcopies, 275 biopsies, 236 type 1 and 2 outpatient exicision procedures, 236 type 2 and 3 hospital exicision procedures, and 39 high-complexity referrals for surgery, chemotherapy, and/or radiotherapy. Applying the estimated parameters to the number of women screened in Brazil in 2017, a deficit was identified in all the procedures for adequate follow-up of the women with altered test results, varying from 7% in colposcopies to 74% in type 3 excisions. The results point to the need to expand and upgrade the supply of line of care procedures for cervical cancer. The estimated parameters can support policymakers in programming and implementing organized screening programs.

Se estimaron parámetros para la planificación y programación de la oferta de procedimientos, con el fin de detectar, realizar investigación diagnóstica y tratar lesiones precursoras del cáncer de cuello uterino. En base a las mismas, se evaluó la adecuación del protocolo nacional de procedimientos realizados por el Sistema Único de Salud (SUS) en 2017. Las estimaciones se calcularon utilizando como marco de referencia los procedimientos recomendados en las directrices nacionales para la detección de este tipo de cáncer. Los datos referentes a los exámenes de detección se obtuvieron en el Sistema de Información del Cáncer de Cuello de Útero, y los datos de seguimiento en registros médicos de una unidad de referencia en patología cervical. La producción nacional de los procedimientos se obtuvo a partir de datos de los sistemas de información ambulatoria y hospitalaria del SUS. De cada cien mil mujeres, en la franja de edad objetivo de la detección (25 a 64 años), se estimó una necesidad anual de 44.134 exámenes citopatológicos, 1.886 colposcopias, 275 biopsias, 236 escisiones tipo 1 y 2 ambulatorias, 236 escisiones tipo 2 y 3 hospitalarias y 39 derivaciones hacia centros hospitalarios de alta complejidad para la realización de cirugías, quimioterapia y/o radioterapia. Aplicando los parámetros estimados al número de mujeres a quienes se les realizó el examen en Brasil durante 2017, se identificó un déficit de todos los procedimientos para un seguimiento adecuado de las mujeres con alteraciones, variando de un 7% en las colposcopias, a un 74% en las escisiones tipo 3. Los resultados apuntan la necesidad de ampliar y dotar la oferta de procedimientos en la línea de cuidados del cáncer de cuello uterino. Los parámetros estimados podrán ayudar a los gestores en la programación e implementación de programas organizados de detección.

Resumo O uso de diretrizes clínicas baseadas em evidências visa assegurar as melhores práticas na área de cuidado à saúde. O uso de testes de ácido desoxirribonucleico de papilomavírus humano (DNA-HPV) vem crescendo e se disseminando sem que existam recomendações de uso no cenário brasileiro.Emnomeda Associação Brasileira de Patologia doTrato Genital Inferior e Colposcopia (ABPTGIC), grupos de revisores pesquisaram evidências e formularamrecomendações para o uso dos testes de DNA-HPV no rastreamento do câncer do colo do útero, no seguimento de mulheres com atipias citológicas, e após tratamento de neoplasia intraepitelial cervical (NIC). O produto desse processo foi debatido e foi buscado consenso entre participantes. Os testes de DNA-HPV são recomendados num cenário de rastreamento organizado para identificação de mulheres portadoras de lesões precursoras ou câncer assintomático com mais de 30 anos e podem ser realizados a cada 5 anos. Também têm valor após a citologia mostrando células escamosas atípicas de significado indeterminado (ASC-US) ou lesão intraepitelial escamosa de baixo grau (LSIL) como teste de triagempara colposcopia, na investigação de outras alterações citológicas quando não são observados achados anormais à colposcopia, buscando excluir doença, ou, ainda, no seguimento após tratamento das neoplasias intraepiteliais de alto grau, para exclusão de doença residual.

Abstract Evidence-based clinical guidelines ensure best practice protocols are available in health care. There is a widespread use of human papillomavirus deoxyribonucleic acid (HPVDNA) tests in Brazil, regardless of the lack of official guidelines. On behalf of the Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym), a team of reviewers searched for published evidence and developed a set of recommendations for the use of HPV-DNA tests in cervical cancer screening in Brazil. The product of this process was debated and consensus was sought by the participants. One concern of the authors was the inclusion of these tests in the assessment of women with cytologic atypia and women treated for cervical intraepithelial neoplasia (CIN). Testing for HPV is recommended in an organized screening scenario to identify women with precursor lesions or asymptomatic cervical cancer older than 30 years of age, and it can be performed every 5 years. It also has value after the cytology showing atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSILs) as a triage test for colposcopy, in the investigation of other cytological alterations when no abnormal findings are observed at colposcopy, seeking to exclude disease, or, further, after treatment of high-grade cervical intraepithelial neoplasia, to rule out residual disease.

ABSTRACT Introduction: Cervical cancer remains an important burden for HIV-infected women in the era of combination antiretroviral therapy. Recommendations for cervical screening in these women diverge and may include high-risk HPV (HRHPV) testing. We aimed to evaluate the clinical usefulness of a single HRHPV testing for cervical screening of HIV-infected women. Methods: 723 HIV-infected women from a Brazilian prospective cohort were included between 1996 and 2012. Inclusion criteria were: normal cervical cytology at baseline and having a HRHPV-test at baseline. We calculated incidence rates of any squamous intraepithelial lesion (SIL) and high grade SIL+ (HSIL+) and negative predictive values (NPV) within 12 and 36 months. Hazard Ratios were obtained using Cox proportional hazards regression models. Results: Incidence rate for both outcomes was low (9.9 cases per 100 PY [95% CI 8.8–11.0] for any SIL and 1.3 cases per 100 PY [95% IC 0.9–1.8] for HSIL+). Women with a HRHPV positive status at baseline had 1.7-fold (95% CI 1.3–2.2) and 3.2-fold (95% CI 1.5–7.1) increased risk of presenting any SIL and HSIL+, respectively, during follow-up. Negative-HRHPV test presented high NPV for both periods and outcomes (any SIL: 92.4% [95% CI 89.7–94.6] for 12 months and 80.9% [95% CI 77.2–84.3] for 36 months; and HSIL+: 99.8% [95% CI 98.9–100.0] for 12 months and 99.0 [95% CI 97.6–99.7] for 36 months). Conclusions: Incidence of any and high grade cytological abnormality was significantly higher among HIV-infected women with positive-HRHPV test. A single negative-HRHPV test helped reassure follow-up free of cytological abnormalities through three years of follow-up in HIV-infected women with negative cytology.

INTRODUÇÃO: A proteína p16 tem sido estudada como um biomarcador potencialmente específico de lesões cervicais precursoras e como uma forma de diferenciar as lesões parecidas com Neoplasia intra-epitelial cervical (NIC). Contudo existem várias controvérsias sobre a utilização de p16 como um biomarcador prognóstico e como uma ferramenta para o diagnóstico de câncer cervical e de lesões pré-câncer. O objetivo deste estudo foi a revisão de dados científicos por pares de bases, relacionados com a utilização da p16 e suas controvérsias. MÉTODOS: O estudo foi projetado como uma revisão da literatura das publicações do Medline/PubMed que avaliam o significado clínico, diagnóstico ou prognóstico do p16 em lesões de NIC e no câncer cervical no período de janeiro de 2009 a junho de 2017. RESULTADOS: o uso do p16 como um marcador prognóstico ainda não é confiável, apesar de que a p16 poderia ser uma ferramenta útil para o diagnóstico em lesões de NIC com morfologia indeterminada. Além disso, a p16 parece ser um marcador específico de infecção por HPV de alto risco oncogênico. CONCLUSÃO: A presente revisão mostra a potencial utilidade da proteína p16, bem como os inconvenientes para uso clínico-patológico e diagnóstico no câncer cervical. Contudo são necessários mais estudos para fundamentar o papel da p16 em conjunto com os outros biomarcadores mais sensíveis e específicos para diagnosticar NIC e prever a sua progressão.

INTRODUCTION: Protein p16 has been extensively studied as a potential biomarker for precursor lesions to distinguish cervical Intraepithelial neoplasia (CIN) from their mimics. However, the use of p16 as prognostic biomarker for diagnosis of cervical cancer and precancer is controversial. This study focuses on the assessment of peer-reviewed scientific data related to the use of p16 to predict disease severity and its controversies. METHODS: We reviewed publications in MEDLINE/PubMed assessing the clinical, diagnostic and prognostic significance of p16 in CIN and cervical cancer; we included publications from 2009 to June 2017. RESULTS: The use of p16 as a prognostic marker is still unreliable, although it could be a useful tool for diagnosis of Cervical Intraepithelial Neoplasia lesions with undetermined morphology. Moreover, p16 appears to be a specific marker of high-risk oncogenic HPV infection. CONCLUSION: This review shows the potential utility and drawbacks of p16 for clinical practice and the diagnosis of cervical cancer. Further studies are required to substantiate the role of p16 in conjunction with other more sensitive and specific biomarkers for diagnosing CIN and predicting its progression.

OBJETIVO: verificar o valor da citologia convencional no diagnóstico de lesões macroscópicas do canal anal e descrever as limitações das amostras obtidas.MÉTODO: avaliamos 395 exames citológicos convencionais obtidos por escovado do canal anal de pacientes predominantemente do sexo masculino, soropositivos para HIV, e comparamos com a presença de lesões macroscópicas do canal anal constatadas ao exame proctológico.RESULTADO: o percentual de amostras adequadas foi de 91,6%, e os elementos celulares representativos da zona de transformação anal foram observados em 63,5% das amostras. Encontramos sensibilidade de 80% e 31% na presença ou ausência desta celularidade, respectivamente.CONCLUSÃO: O estudo demonstra a possibilidade de utilização da citologia anal convencional no rastreio de lesões macroscópicas do canal anal em pacientes ambulatoriais.

OBJECTIVES: To verify the value of conventional cytology for the diagnosis of macroscopic lesions of the anal canal and to describe the limitations of the samples.METHOD: We evaluated 395 conventional cytology samples obtained by brushing the anal canal of patients (predominantly male, HIV-positive) and compared them to the presence of macroscopic lesions of the anal canal observed under anorectal examination.RESULTS: Of the total, 91.6% of samples were classified as adequate. Cellular elements representative of the anal transformation zone were observed in 63.5% of samples. Sensitivity in the presence or absence of cellularity was 80% and 31%, respectively.CONCLUSION: The study demonstrates the feasibility of using conventional anal cytology in outpatients.

CONTEXTO E OBJETIVOS: Mulheres infectadas pelo vírus da imunodeficiência humana (HIV) apresentam maior incidência, prevalência, persistência e recorrência após tratamentos de lesões pré-invasivas do colo uterino (NIC II ou III). O objetivo foi verificar o risco de recorrência de NIC II/III em mulheres infectadas pelo HIV (HIV+) e não infectadas (HIV-) em uma coorte tratada pela exérese eletrocirúrgica da zona de transformação do colo uterino (EZT). TIPO DE ESTUDO E LOCAL: Estudo de tipo coorte realizado no Instituto Fernandes Figueira/Fundação Oswaldo Cruz (IFF/Fiocruz). MÉTODOS: 60 HIV+ e 209 HIV- foram incluídas em uma coorte após terem sido submetidas à EZT para tratamento de NIC II/III. Foi considerado como recorrência o diagnóstico histopatológico de NIC II/III. Foram estudadas as seguintes variáveis possivelmente confundidoras: idade no tratamento e ao final do seguimento, grau histológico da doença intra-epitelial tratada, comprometimento de margens, adequação da colposcopia no seguimento, contagem de linfócitos CD4+, carga viral de HIV e tipo de terapia antiretroviral. RESULTADOS: Dentre as 60 mulheres HIV+, 6 apresentaram doença recorrente durante o seguimento. De 209 HIV-, 7 apresentaram uma nova lesão precursora. O risco relativo de recorrência de doença nas HIV+ foi de 4,21 (IC 95% 1,42-12,43). Uma curva de Kaplan-Meyer mostra que o risco de recorrência é significativamente maior em mulheres HIV+ (teste de log-rank: P = 0,0111). CONCLUSÃO: Mulheres HIV+ em nossa coorte apresentaram risco de recorrência pelo menos 42% maior do que mulheres HIV-. Essas pacientes devem fazer parte de um protocolo de rastreio e acompanhamento rigoroso para identificação e tratamento adequado das lesões precursoras do câncer de colo uterino.

CONTEXT AND OBJECTIVE: Human immunodeficiency virus (HIV)-infected women have higher incidence, prevalence, persistence and recurrence of pre-invasive cervical lesions (CIN II or III). The aim here was to investigate the risk of recurrence of CIN II/III among HIV-infected women (HIV+) and uninfected women in a cohort treated by means of large-loop excision of the transformation zone (LLETZ). DESIGN AND SETTING: Cohort study conducted at Instituto Fernandes Figueira/Fundação Oswaldo Cruz (IFF/Fiocruz). METHODS: 60 HIV+ and 209 HIV-negative patients were included in a cohort for follow-up after undergoing LLETZ to treat CIN II/III. A histopathological diagnosis of CIN II/III during the follow-up was taken to constitute recurrence. The following possible confounding variables were assessed: age at treatment and at end of follow-up; histological grade of intraepithelial disease treated; surgical margin involvement; adequacy of colposcopy during the follow-up; CD4+ lymphocyte count; HIV viral load; and type of antiretroviral therapy. RESULTS: Among the 60 HIV+ women, six showed recurrent disease during the follow-up. However, among the 209 HIV-negative women, seven showed a new precursor lesion. The relative risk of disease recurrence in the HIV+ women was 4.21 (95% CI = 1.42 to 12.43). The Kaplan-Meyer curve showed that the risk of recurrence was significantly higher among HIV+ women (log-rank test: P = 0.0111). CONCLUSION: The HIV+ women in our cohort presented a risk of CIN II/III recurrence at least 42% higher than among the HIV-negative women. These patients should form part of a rigorous screening and follow-up protocol for identification and appropriate treatment of cervical cancer precursor lesions.

Although several studies have evaluated the role of p16INK4a as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16INK4a in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16INK4a as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16INK4a was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16INK4a expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16INK4a in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16INK4a under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16INK4a expression in CIN 2-3.

CONTEXTO E OBJETIVO: As lesões precursoras do câncer de colo uterino, mesmo se tratadas adequadamente, têm risco de persistirem ou recidivarem. O objetivo foi quantificar o risco de persistência da lesão intraepitelial escamosa de alto grau (HSIL) em um e dois anos após tratamento excisional eletrocirúrgico do colo uterino com margens comprometidas. TIPO DE ESTUDO E LOCAL: Revisão sistemática da literatura e metanálise no Instituto Fernandes Figueira. METÓDO: Metanálise de estudos publicados entre janeiro de 1989 e julho de 2009 identificados em Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, Isis Web of Science e Sigle. Os artigos eram selecionados se fossem estudos tipo coorte sobre tratamento excisional eletrocirúrgico de HSIL com acompanhamento mínimo de um ano e tivessem como desfecho histopatológico a persistência de HSIL com pequeno risco de viés. RESULTADOS: Foram identificados 7.066 artigos e mais 21 nas listas de referências desses artigos. Após aplicação de critérios de seleção e de exclusão, somente quatro artigos ofereciam dados passíveis de extração. O risco de persistência da HSIL em um ano foi 11.36 vezes maior nas pacientes com margens comprometidas (intervalo de confiança, IC 95%: 5.529-23.379; P < 0,0001) e, em dois anos, chegou a quatro vezes, embora sem significância estatística (IC 95% 0.996-16.164). CONCLUSÃO: Esta metanálise confirma a importância de margem comprometida como indicador de tratamento incompleto no primeiro ano e ressalta a necessidade de uma adequada escolha da técnica eletrocirúrgica em função da localização e extensão da doença e um acompanhamento adequado dessas pacientes.

CONTEXT AND OBJECTIVE: Even if precursor lesions of cervical cancer are properly treated, there is a risk of persistence or recurrence. The aim here was to quantify the risks of persistence of high-grade intraepithelial squamous lesions, one and two years after cervical electrosurgical excisional treatment with positive margins. DESIGN AND SETTING: Systematic review of the literature and meta-analysis at Instituto Fernandes Figueira. METHODS: This meta-analysis was on studies published between January 1989 and July 2009 that were identified in Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, ISI Web of Science and Sigle. Articles were selected if they were cohort studies on electrosurgical excisional treatment of high-grade squamous intraepithelial lesions with a minimum follow-up of one year, a histopathological outcome of persistence of these lesions and a small risk of bias. RESULTS: The search identified 7,066 articles and another 21 in the reference lists of these papers. After applying the selection and exclusion criteria, only four articles were found to have extractable data. The risk of persistence of high-grade intraepithelial lesions after one year was 11.36 times greater (95% confidence interval, CI: 5.529-23.379, P < 0.0001) in patients with positive margins and after two years, was four times greater (95% CI: 0.996-16.164), although without statistical significance. CONCLUSION: This meta-analysis confirms the importance of positive margins as an indicator of incomplete treatment after the first year of follow-up and highlights the need for appropriately chosen electrosurgical techniques based on disease location and extent, with close surveillance of these patients.

CONTEXTO E OBJETIVO: O desempenho do teste de DNA-HPV (ácido desoxirribonucleico-papilomavírus humano) oncogênico estratificado por idade para triagem de lesão intraepitelial escamosa de baixo grau (LSIL) demanda investigação. O objetivo do estudo foi avaliar e comparar o desempenho, para detecção de neoplasia intraepitelial cervical (NIC3), do teste de DNA-HPV oncogênico e da citologia de repetição estratificados por idade (ponto de corte 35 anos), para triagem de LSIL. TIPO DE ESTUDO E LOCAL: Revisão sistemática da literatura. Foram identificados estudos em nove bases de dados eletrônicas e listas de referências dos artigos recuperados. MÉTODOS: Critérios de elegibilidade: citologia inicial LSIL, realização do teste de DNA-HPV oncogênico e da citologia de repetição e detecção de NIC3. A diretriz QUADAS (Quality Assessment of Diagnostic Accuracy Studies) foi utilizada para avaliação da qualidade. As informações foram sintetizadas qualitativamente. RESULTADOS: Dentre 7.776 estudos, 284 eram pertinentes ao tema e três atenderam aos critérios de elegibilidade. A prevalência de NIC3 apresentou variação entre 6% e 12%. A taxa de positividade do teste de DNA-HPV apresentou variação entre 64% e 83%; a sensibilidade para NIC3 apresentou variação entre 95,2% e 100%; a especificidade estava disponível em dois estudos (27% e 52%). A sensibilidade da citologia de repetição (ponto de corte ASCUS - células escamosas atípicas de significado indeterminado) estava disponível em dois estudos (33% e 90,8%); a especificidade estava disponível em um estudo (53%). CONCLUSÕES: Não existem, atualmente, evidências científicas disponíveis para comprovar que, em mulheres com 35 anos ou mais e citologia LSIL, a triagem colposcópica com teste de DNA-HPV oncogênico apresenta melhor desempenho para detecção de NIC3 do que a repetição citológica.

CONTEXT AND OBJECTIVE: The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL) requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years) of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3), in order to triage for LSIL. DESIGN AND SETTING: Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved. METHODS: The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) guidelines were used for quality assessment. Qualitative information synthesis was performed. RESULTS: Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6% to 12%. The HPV-DNA positivity rate ranged from 64% to 83%; sensitivity for CIN3 detection ranged from 95.2% to 100%; and specificity was available in two studies (27% and 52%). The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS), was available in two studies (33% and 90.8%); and specificity was available in one study (53%). CONCLUSIONS: Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.