RESUMEN
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.
RESUMEN
Early stages of cervical cancer in young women need conservative treatments. Electrosurgical therapies (LLETZ, LEEP, SWETZ, NETZ) have been recommended for these women. However, there are recommendations to perform a second excision when the specimen margins are not free of disease. This can lead to some important complications. This article aims to verify the frequency of residual invasive or microinvasive disease after the excisional procedure in women with IA1CC. Data on women with IA1CC diagnosed between 1990 and 2022, were retrieved from medical records. Post-treatment disease was detected during a second surgical procedure or postoperative follow-up. Among the 69 included women, three (4.3 percent; CI95 percent 0-9.2) had residual microinvasive lesions, while none showed invasive disease during a second procedure or follow-up. Only the age of 37 years or more was significantly related to the presence of preinvasive or microinvasive residual lesions. Nearly 80 percent of the women who underwent a second procedure showed no residual lesions. The absence of invasive disease in a second procedure or during the follow-up of these women and the large proportion of women with no residual lesion questions the need for a new surgical procedure even when the surgical margins of the initial specimen are involved.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Femenino , Humanos , Adulto , Neoplasias del Cuello Uterino/cirugía , Conización/métodos , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Histerectomía , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Carcinoma , Displasia del Cuello del Útero , Embarazo , Humanos , Femenino , Masculino , Antígeno Ki-67 , Estudios Transversales , BiopsiaRESUMEN
BACKGROUND: Screening of anal cancer is rarely available or performed in Brazil. This study analyzes the diagnostic performance of conventional cytology (CC) in the prevention of anal cancer in a coloproctology and gynecology outpatient clinics in a public hospital in Rio de Janeiro, Brazil. METHODS: From 2005 to 2017, 1066 conventional cytological samples were collected. We analyze the causes of unsatisfactory samples (11.3%) and compare the cytological diagnoses of 83 samples from persons living with HIV and persons not living with HIV and in specific situations, using as the gold standard high-resolution anoscopy or histopathology in cases biopsied within 6 months after cytology. RESULTS: The sensitivity of cytology with diagnosis of ASC-US for detection of anal intraepithelial neoplasia of any grade was 85%, specificity was 41%, positive and negative predictive values were 64% and 75%, respectively, and positive and negative likelihood ratios were 1.46 and 0.35, respectively. CONCLUSION: Conventional cytology available in resource-limited settings is a simple, noninvasive, low-cost method that proved feasible for outpatient screening of precursor lesions of the anal canal.
Asunto(s)
Neoplasias del Ano , Carcinoma in Situ , Infecciones por VIH , Infecciones por Papillomavirus , Humanos , Virus del Papiloma Humano , Brasil/epidemiología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/patología , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/epidemiología , Carcinoma in Situ/patología , Canal Anal/patología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/patología , PapillomaviridaeRESUMEN
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.
RESUMEN
BACKGROUND: According to the Brazilian Guidelines on Cervical Cancer Screening, women with cytopathologic diagnosis of high-grade intraepithelial lesion, abnormal colposcopic findings, fully visible squamocolumnar junction and age 25 years or older should be treated at the first visit ("see and treat-S&T"). The main limitation to this approach is the risk of overtreatment, identified by histology without preinvasive lesion. The objectives of this study were to identify the overtreatment rate in women undergoing S&T in cervical cancer prevention at a referral center with extensive experience with the method and to detect possible factors associated with this rate. METHODS: This was a cross-sectional study that analyzed records from a database with 616 women submitted to S&T from 1996 to 2017. Negative histology was defined as the following histopathologic results: human papillomavirus without cervical intraepithelial neoplasia (CIN), inflammatory, low-grade squamous intraepithelial lesion, and CIN 1. RESULTS: Of the 616 women, there were 52 (8.44%, 95%CI 6.25-10.64%) with a histopathologic report without preinvasive cervical lesion. No statistical association was found between this outcome and age or a significant downward trend over time. CONCLUSION: The overtreatment rate in this study can be considered low and consistent with the acceptable rates reported in the literature, reinforcing the prevailing Brazilian guideline, in which the benefits of immediate treatment outweigh the risk of losses following biopsy.
Asunto(s)
Colposcopía , Neoplasias del Cuello Uterino , Adulto , Brasil/epidemiología , Colposcopía/métodos , Estudios Transversales , Detección Precoz del Cáncer , Femenino , Humanos , Embarazo , Derivación y Consulta , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapia , Frotis VaginalRESUMEN
The interplay between cervical cancer (CC) and immune cells, mainly intratumoral lymphocytes, has a pivotal role in carcinogenesis. In this context, we evaluated the distribution of CD45RA+ and CD45RO+ cells as well as CCR6+ and CCL20+ cells in intraepithelial (IE) and marginal stroma (MS) areas from cervical intraepithelial neoplasia (CIN) I-III, and CC as 'immunoscore' for HPV-induced CC outcome. We observed increased CD45RA+ and CD45RO+ cells distribution in IE and MS areas in the CC group compared to CIN groups and healthy volunteers. Interestingly, there is a remarkable reduction of CCL20+ expressing cells distribution according to lesion severity. The CC group had a significant decrease in CCL20+ and CCR6+-expressing cells distribution in both IE and MS areas compared to all groups. Using the 'immunoscore' model, we observed an increased number of women presenting high CD45RA+/CD45RO+ and low CCL20+/CCR6+ 'immunoscore' in the CC group. Our results suggested a pattern in cervical inflammatory process with increasing CD45RA+/CD45RO+, and decreasing CCL20+/CCR6+ expression in accordance with CIN severity. Taken together, these markers could be evaluated as 'immunoscore' predictors to CC response. A more comprehensive analysis of longitudinal studies should be conducted to associate CD45RA+/CD45RO+ and CCL20+/CCR6+ 'immunoscore' to CC progression and validate its value as a prognosis method.
Asunto(s)
Alphapapillomavirus/patogenicidad , Antígenos Comunes de Leucocito/inmunología , Infecciones por Papillomavirus/inmunología , Neoplasias del Cuello Uterino/inmunología , Adulto , Estudios de Casos y Controles , Quimiocina CCL20 , Femenino , Humanos , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Pronóstico , Receptores CCR6 , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virologíaRESUMEN
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.
Asunto(s)
Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Brasil , Colposcopía , Detección Precoz del Cáncer , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Frotis VaginalRESUMEN
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.
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.
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.
Asunto(s)
Tamizaje Masivo/métodos , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Biopsia , Brasil , Colposcopía , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Persona de Mediana Edad , Programas Nacionales de Salud , Neoplasias del Cuello Uterino/prevención & control , Salud de la MujerRESUMEN
TNF-α is involved in HPV infection control by triggering cell signaling through binding in specific receptors TNFR1 and TNFR2. Genetic polymorphisms in these receptors may influence TNF-α signaling. Herein, we investigated TNFR1 rs767455 and rs2234649 single nucleotide polymorphisms, and TNFR1 protein expression in cervical squamous intraepithelial lesions (SIL) to identify their role in cervical pre-malignant development. SIL patients (n = 179) and healthy volunteers (n = 227) were enrolled for TNFR1 genotyping analysis by PCR-RFLP in blood samples and TNFR1 protein expression in cervical tissue by immunohistochemistry. No statistical differences regard genotypes and allelic frequencies for both polymorphisms were observed. Cervical TNFR1-expressing cells were rare in epithelium and basal layer regardless the groups. However, a progressive increase in infiltrating cells was observed in the stromal area, mainly in high SIL (HSIL) group compared to low SIL (LSIL, p < 0.001) and control (p < 0.001) groups. TNFR1-expressing cells frequency was higher in TNFR1 rs767455AG/GG (p < 0.001), and in rs2234649AA (p < 0.001) genotypes carries in HSIL subgroup. These data indicated that TNFR1-expression is abrogated in cervical epithelium, where HPV-induced pre-malignant lesion occurs, increasing its frequency in inflammatory cells in stroma, and is genetically controlled by TNFR1 rs767455AG/GG and rs234649AA genotypes. These biomarkers may be useful to identify cervical precancerous lesions progression.
RESUMEN
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.
Asunto(s)
Humanos , Femenino , Adulto , Persona de Mediana Edad , Neoplasias del Cuello Uterino/diagnóstico , Tamizaje Masivo/métodos , Biopsia , Brasil , Neoplasias del Cuello Uterino/prevención & control , Salud de la Mujer , Colposcopía , Detección Precoz del Cáncer/métodos , Programas Nacionales de SaludRESUMEN
Evidence-based clinical guidelines ensure best practice protocols are available in health care. There is a widespread use of human papillomavirus deoxyribonucleic acid (HPV-DNA) 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.
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. Em nome da Associação Brasileira de Patologia do Trato Genital Inferior e Colposcopia (ABPTGIC), grupos de revisores pesquisaram evidências e formularam recomendações 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 triagem para 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.
Asunto(s)
Detección Precoz del Cáncer/métodos , Pruebas de ADN del Papillomavirus Humano/normas , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Brasil , Femenino , HumanosRESUMEN
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.
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.
Asunto(s)
Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Infecciones por Papillomavirus/diagnóstico , Pruebas de ADN del Papillomavirus Humano/normas , Detección Precoz del Cáncer/métodosRESUMEN
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.
Asunto(s)
Humanos , Femenino , Adulto , Infecciones por VIH/complicaciones , Tamizaje Masivo/métodos , Medición de Riesgo/métodos , Infecciones por Papillomavirus/complicaciones , Lesiones Intraepiteliales Escamosas de Cuello Uterino/diagnóstico , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Valores de Referencia , Factores de Tiempo , Modelos de Riesgos Proporcionales , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores de Riesgo , Recuento de Linfocito CD4 , Carga Viral , Diagnóstico Precoz , Lesiones Intraepiteliales Escamosas de Cuello Uterino/patologíaRESUMEN
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.
Asunto(s)
Infecciones por VIH/complicaciones , Tamizaje Masivo/métodos , Infecciones por Papillomavirus/complicaciones , Medición de Riesgo/métodos , Lesiones Intraepiteliales Escamosas de Cuello Uterino/diagnóstico , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Adulto , Brasil , Recuento de Linfocito CD4 , Diagnóstico Precoz , Femenino , Humanos , Análisis Multivariante , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Valores de Referencia , Reproducibilidad de los Resultados , Factores de Riesgo , Lesiones Intraepiteliales Escamosas de Cuello Uterino/patología , Factores de Tiempo , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Carga ViralRESUMEN
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.
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.
Asunto(s)
Humanos , Biomarcadores de Tumor , Neoplasias del Cuello Uterino/diagnóstico , Displasia del Cuello del Útero , Infecciones por PapillomavirusRESUMEN
The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing. CDKN1A 31A allele presents a genetic pattern of protection for the development of high-grade cervical lesions (CC vs CA genotype: OR = 0.60; 95 % CI = 0.38-0.95; p = 0.029; CA+AA vs CC genotype: OR = 0.60; 95 % CI = 0.39-0.93; p = 0.021). Allele distributions of the CDKN1A 70C>T polymorphism were also different between the two study groups, with the CDKN1A 70T allele being less prevalent among cases. Moreover, the double heterozygote genotype combination 31CA-70CT decreases the chance of developing high-grade squamous intraepithelial lesion (HSIL) and cancer (OR = 0.55; 95 % CI = 0.32-0.93; p = 0.034) by 50 %, representing a protective factor against the development of more severe cervical lesions.
Asunto(s)
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleótido Simple , Lesiones Intraepiteliales Escamosas de Cuello Uterino/genética , Displasia del Cuello del Útero/genética , Neoplasias del Cuello Uterino/genética , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adenocarcinoma/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Estudios de Casos y Controles , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/fisiología , Etnicidad/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Persona de Mediana Edad , Proteínas de Neoplasias/fisiología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Prevalencia , Lesiones Intraepiteliales Escamosas de Cuello Uterino/epidemiología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/patología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virologíaRESUMEN
OBJECTIVES: HIV-infected women are at increased risk of human papillomavirus (HPV) infection. Time trends in annual prevalences of cervical high-risk human papillomavirus (HR-HPV) genotypes among a non-vaccinated, HIV-infected female cohort in urban Brazil were assessed for the period 2006-2012. METHODS: Cervical specimens were collected for HPV genotyping yearly between January 2006 and December 2012 in a cross-sectional analysis of participants aged ≥18 years enrolled in the Women's HIV Cohort at Fiocruz in Rio de Janeiro, Brazil. Age-adjusted generalized estimating equation models with an exchangeable matrix were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for annual HPV positivity (reference year: 2006). RESULTS: Among the 590 participants, the median age across all study years ranged from 35.5 to 40.0 years. The prevalence of any HR-HPV was ≥53% every year; prevalences of HR-HPV 16, 58, 59, and 68 were ≥24% in at least 1 year. The odds of HPV 16 and 68 decreased in 2012. HPV 58 prevalence followed a U-shape, beginning and ending at >20%. HPV 59 prevalence followed a linear trend, with increased odds in 2012 (OR 16.0, 95% CI 3.8-67.3; Bonferroni-adjusted p-value <0.01). CONCLUSIONS: The prevalences of HR-HPV 58, 59, and 68 were high in this cohort. Given current HR-HPV vaccine coverage and availability, further investigations are needed to optimize vaccine recommendations for this population.
Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Adulto , Brasil/epidemiología , Estudios de Cohortes , Estudios Transversales , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Papillomaviridae/genética , Prevalencia , Factores de Riesgo , Factores de Tiempo , Población UrbanaRESUMEN
BACKGROUND: Cervical cancer is the third most common cancer in Brazil and has a high potential for prevention and cure. The prevalence of invasive and preinvasive disease in women with cytological diagnosis of high-grade lesion - cannot exclude microinvasion (HSIL-micro) is not known. METHODS: This cross-sectional study used a cytology lab database to identify women with HSIL-micro and HSIL referred to two colposcopic units from June 2006 to December 2012. For each woman with HSIL-micro, four women with cytologic diagnosis of HSIL who met the inclusion criteria were identified. Data were obtained from review of medical records. RESULTS: Forty-seven patients with report of HSIL-micro and 188 patients with report of HSIL were included. The final diagnoses revealed a frequency of preinvasive lesions of 31.9 % (15/47) and 59.6 % (112/188) in patients with HSIL-micro and HSIL, respectively, while the frequency of invasive disease was 63.8 % (30/47) and 11.7 % (22/188), respectively. The HSIL-micro group showed prevalence of preinvasive or invasive disease 6.5 times greater (95 % CI = 1.6-5.7) and, for invasive disease, 2.4 times greater (95 % CI = 1.7-3.6) than the HSIL group. CONCLUSION: Higher risk of preinvasive and invasive lesions in women with cytologic diagnosis of HSIL-micro reinforces recommendations for immediate investigation.
Asunto(s)
Neoplasias del Cuello Uterino/diagnóstico , Adulto , Brasil/epidemiología , Biología Celular , Colposcopía/estadística & datos numéricos , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Prevalencia , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Frotis Vaginal/estadística & datos numéricosRESUMEN
The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings.