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1.
Rev. bras. ginecol. obstet ; 42(6): 340-348, June 2020. tab, graf
Article in English | LILACS | ID: biblio-1137843

ABSTRACT

Abstract Objective To evaluate the performance of the hybrid capture 2 (HC2) high-risk papillomavirus (hrHPV) assay and cytological test in women with previous abnormalities, to detect cervical intraepithelial neoplasia grade 2 or worse (≥ CIN 2). Methods A cytological test and HC2 (Qiagen, Gaithersburg, Maryland, EUA) for hrHPV were conducted in 359 liquid-based (Sure Path, Becton Dickinson, TriPath Imaging, Burlington, NC, USA) samples collected from women from the Vale do Ribeira Region, during July 2013 and September 2015 with previous cytology classified as atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC-H), and atypical glandular cells (AGC). The histopathological examination was conducted in 179 women. The performance evaluations were calculated using the "exact" Clopper-Pearson 95% confidence interval (CI) test by MEDCALC (Medcalc Software Ltd, Ostend, Belgium). Results The ≥ CIN 2 frequency was 11.7% (21/179). The HC2 for hrHPV and repeat cytology to detect ≥ CIN 2 obtained, respectively, a sensitivity of 90.5% (95% CI = 69.6-98.8) and 90.5%, (95%CI = 69.6-98.8), a specificity of 65.8% (95% CI = 57.9-73.2) and 43.7% (95%CI = 35.8-51.8), a positive predictive value of 26.0% (95% CI = 21.4-31.3) and 17.6%, (95%CI = 14.9-20.6), and a negative predictive value of 98.1% (95%CI = 93.3-99.5) and 97.2% (95% CI = 90.1-99.2). Conclusion Hybrid capture 2 for hrHPV improves the performance of the detection of ≥ CIN 2, without compromising sensitivity, and provides a greater safety margin to return to the triennial screening of women undergoing follow-up due to previous abnormalities, without underlying ≥ CIN 2.


Resumo Objetivo Avaliar o desempenho da captura híbrida 2 (CH2) para papilomavírus humano de alto risco (HPVar) e repetição do exame citopatológico em mulheres com anormalidades em citologia anterior, para detectar neoplasia intraepitelial cervical grau 2 ou pior (≥ NIC 2). Métodos Foi realizado exame citopatológico e CH2 para HPVar (Qiagen, Gaithersburg, Maryland, EUA) em 359 amostras em meio líquido (Sure Path, Becton Dickinson, TriPath Imaging, Burlington, NC, USA) coletadas de mulheres da região do Vale do Ribeira, durante julho de 2013 e setembro de 2015 com citologia anterior classificada como células escamosas atípicas de significado indeterminado (ASC-US), lesão intraepitelial de baixo grau (LSIL), células escamosas atípicas, não podendo excluir lesão de alto grau (ASC-H) e células glandulares atípicas (AGC). O exame histopatológico foi realizado em 179 mulheres. As avaliações de desempenho foram calculadas usando o teste de intervalo de confiança (IC) "exato" de Clopper-Pearson de 95% pelo software MEDCALC (Medcalc Software Ltd, Ostend, Bélgica). Resultados A frequência de≥ NIC 2 foi 11,7% (21/179). A CH2 para o HPVar e a citologia de repetição para a detecção ≥ NIC 2 obteve, respectivamente, sensibilidade de 90.5% (IC 95% = 69,6-98,8) e 90,5% (IC 95% = 69,6-98,8), especificidade de 65,8% (IC 95% = 57,9-73,2) e 43,7%, (IC 95% = 35,8-51,8), valor preditivo positivo de 26,0% (IC 95% = 21,4-31,3) e 17,6%, (IC95% = 14,9-20,6), e valor preditivo negativo de 98,1% (IC 95% = 93,3-99,5) e 97,2%, (IC 95% = 90,1-99,2). Conclusão No geral, a CH2 para HPVar aprimora o desempenho para detecção de ≥ NIC 2, sem comprometer a sensibilidade e proporciona maior margem de segurança do retorno ao rastreio trienal de mulheres com anormalidades citológicas prévias, sem≥ NIC 2 subjacente.


Subject(s)
Humans , Female , Adolescent , Adult , Aged , Young Adult , Papillomaviridae/isolation & purification , Vaginal Smears , Uterine Cervical Neoplasms/diagnosis , Triage , Cervical Intraepithelial Neoplasia/diagnosis , Papillomavirus Infections/diagnosis , Atypical Squamous Cells of the Cervix/pathology , Brazil , Uterine Cervical Neoplasms/pathology , Cross-Sectional Studies , Sensitivity and Specificity , Cervical Intraepithelial Neoplasia/pathology , Papillomavirus Infections/pathology , Middle Aged
2.
Rev. bras. ginecol. obstet ; 42(3): 140-145, Mar. 2020. tab
Article in English | LILACS | ID: biblio-1098862

ABSTRACT

Abstract Objective To describe the referral for colposcopy in a Hospital in Brazil and the relative frequency of patients who benefited from it, considering the correct indications for the examination and its final diagnoses. Methods A retrospective study was performed in the colposcopy service database of the Hospital Universitário de Taubaté, Taubaté, state of São Paulo, Brazil. The frequency validated in the analysis of the medical records of women referred for clinical indication or cytological alteration, attended from March 2015 to March 2017. The population selected and analyzed included 256 results that were correlated to the cytological, clinical data and the result of the colposcopy. Results Of the women referred, 45% presented out of the age of screening according to the guidelines of cervical cancer screening, 8.6% being adolescents and young adults < 25 years old, and 36.4% of the patients being ≥ 65 years old. A total of 50% of the patients had no indication of colposcopy, that is, normal cytologies, benign changes, ectopia, cervicitis, atypical squamous cells of indeterminate significance (ASC-US) and low-grade intraepithelial lesion (LSIL) without persistence and normal clinical appearance. A total of 39.84% who underwent colposcopy had high-grade lesion or cancer results, thus benefiting from the adequate referral. Conclusion Most (60.16%) of the patients referred to the colposcopy service did not benefit from the referral for results without changes, such as negative colposcopies, histologies with no cervical intraepithelial neoplasm (CIN) or only CIN 1, or were out of the age for screening. These findings therefore demonstrate a significant number of unnecessary and inadequate referrals.


Resumo Objetivo Descrever os encaminhamentos para colposcopia em um hospital no Brasil e a frequência relativa dos pacientes que foram beneficiados, considerando as indicações corretas para o exame e seus diagnósticos finais. Métodos Foi realizado um estudo retrospectivo no banco de dados do serviço de colposcopia do Hospital Universitário de Taubaté, Taubaté, SP, Brasil. A frequência validou em análise de prontuários de mulheres encaminhadas por indicação clínica ou alteração citológica, atendidas no período de março de 2015 a março de 2017. A população selecionada e analisada incluiu 256 resultados que estavam correlacionadas aos dados citológicos, clínicos e com o resultado da colposcopia. Resultados Das mulheres encaminhadas, 45% apresentaram-se fora da idade de rastreamento conforme as diretrizes de rastreio de câncer de colo uterino, sendo que 8,6% eram adolescentes e adultas jovens < 25 anos de idade e 36,4% das pacientes tinham idade ≥ 65 anos. Um total de 50% das pacientes não possuía indicação de colposcopia, ou seja, citologias normais, de alterações benignas, ectopia, cervicite, células escamosas atípicas de significado indeterminado (ASC-US) e lesão intraepitelial escamosa de baixo grau (LSIL) sem persistência e aspecto clínico normal. Um total de 39,84% das pacientes que realizaram a colposcopia tiveram resultados de lesão de alto grau ou câncer e, dessa forma, se beneficiaram com o encaminhamento adequado. Conclusão A maioria (60,16%) das pacientes encaminhadas para o serviço de colposcopia não se beneficiou com o encaminhamento, por resultados sem alterações como colposcopias negativas, histologias com ausência de neoplasia intraepitelial cervical (NIC) ou apenas NIC 1, ou estavam fora da idade de rastreamento. Esses achados demonstram, portanto, significativo número de encaminhamentos desnecessários e inadequados.


Subject(s)
Humans , Female , Adolescent , Adult , Aged , Aged, 80 and over , Young Adult , Referral and Consultation/statistics & numerical data , Uterine Cervical Neoplasms/pathology , Cervical Intraepithelial Neoplasia/pathology , Colposcopy/statistics & numerical data , Brazil , Women's Health Services , Medical Records , Retrospective Studies , Age Factors , Hospitals , Middle Aged
3.
Rev. saúde pública (Online) ; 54: 27, 2020. tab, graf
Article in English | LILACS | ID: biblio-1094408

ABSTRACT

ABSTRACT OBJECTIVES To determine the efficacy and safety of the use of cryotherapy, cold knife or thermocoagulation compared to Loop Electrosurgical Excision Procedure (LEEP) for the treatment of cervical intraepithelial neoplasia. METHODS Systematic review with meta-analysis of randomized controlled trials in women with cervical intraepithelial neoplasia undergoing treatment with cryotherapy, cold knife, or thermo-coagulation compared with LEEP, to estimate its efficacy and safety. The search was conducted on MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus, until September 2018. RESULTS The total of 72 studies were identified, of which only 8 studies met the inclusion criteria. The treatment of CIN with cold knife decreases the risk of residual disease compared with LEEP (RR, 0.54, 95%CI, 0.30-0.96, p = 0.04). The management of premalignant lesions with cryotherapy, compared with LEEP, increases the risk of disease recurrence by 86% (RR, 1.86, 95%CI, 1.16-2.97, p = 0.01), increases the risk of infections (RR, 1.17, 95%CI, 1.08-1.28, p < 0.001) and reduces the risk of minor bleeding by 51% (RR, 0.49, 95%CI) %, 0.40-0.59, p ≤ 0.001). CONCLUSIONS The treatment of premalignant lesions of cervical cancer with cold knife reduces the risk of residual disease. Nevertheless, cryotherapy reduces the risk of minor bleeding in the 24 hours after treatment and increases the risk of recurrence of disease and infections.


RESUMEN OBJETIVOS Evaluar la eficacia y seguridad del uso de crioterapia, cono frio o termo-coagulación en comparación con el procedimiento de escisión electroquirúrgica en asa (LEEP) para el manejo de neoplasias intraepiteliales cervicales. MÉTODOS Revisión sistemática de ensayos controlados aleatorizados en mujeres con neoplasia intraepitelial cervical en tratamiento con crioterapia, cono frio, o termo coagulación y LEEP, para estimar su eficacia y seguridad. La búsqueda se realizó en MEDLINE/PUBMED, Registro Cochrane Central de Ensayos Controlados (CENTRAL) y Scopus, hasta setiembre de 2018. RESULTADOS Se identificaron 72 estudios, ocho cumplieron los criterios de inclusión. Cono frio disminuyó el riesgo de enfermedad residual en comparación con LEEP (RR 0,54; IC del 95%, 0,30-0,96, p = 0,04). Crioterapia en comparación con LEEP incrementó el riesgo de recurrencia de enfermedad en un 86,0% (RR 1,86; IC del 95%, 1,16-2,97, p = 0,01) con un tiempo de seguimiento de seis a 24 meses, y de infecciones (RR, 1,17; IC del 95%, 1,08-1,28, p < 0,001); pero redujo el riesgo de sangrado menor en un 51,0% (RR 0,49; IC del 95%, 0,40-0,59, p ≤ 0,001). CONCLUSIONES Cono frio reduce el riesgo de enfermedad residual. Sin embargo, la crioterapia reduce el riesgo de sangrado menor en las 24 horas posteriores al tratamiento e incrementa el riesgo de recurrencia de enfermedad y de infecciones.


Subject(s)
Humans , Female , Uterine Cervical Neoplasms/surgery , Cryotherapy/methods , Cervical Intraepithelial Neoplasia/surgery , Conization/methods , Electrocoagulation/methods , Postoperative Complications , Uterine Cervical Neoplasms/pathology , Risk , Risk Factors , Cervical Intraepithelial Neoplasia/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/pathology
4.
Biomédica (Bogotá) ; 39(1): 65-74, ene.-mar. 2019. tab, graf
Article in English | LILACS | ID: biblio-1001390

ABSTRACT

Abstract Introduction: Direct visual inspection for cervical cancer screening remains controversial, whereas colposcopy-biopsy is considered the gold standard for diagnosis of preneoplastic cervical lesions. Objectives: To determine the rates of cervical intraepithelial neoplasia grade 2 or more and of false positives for colposcopy and direct visual inspection. Materials and methods: Women aged 25-59 underwent direct visual inspection with acetic acid (VIA), Lugol's iodine (VIA-VILI), and colposcopy. Punch biopsies were obtained for all positive tests. Using histology as the gold standard, detection and false positive rates were compared for VIA, VIA-VILI, and colposcopy (two thresholds). Sensitivity and false positive ratios with the corresponding 95% confidence intervals were estimated. Results: We included 5,011 women in the analysis and we obtained 602 biopsies. Positivity rates for colposcopy high-grade and low-grade diagnosis were 1.6% and 10.8%. Positivity rates for VIA and VIA-VILI were 7.4% and 9.9%. VIA showed a significantly lower detection rate than colposcopy with low-grade diagnosis as the threshold(SR=0.72; 95% CI0.57-0.91), and significantly lower false positive rate (FPR=0.70; 95% CI 0.65-0.76). No differences between VIA-VILI and colposcopy low-grade threshold were observed. VIA and VIA-VILI showed significantly higher detection and false positive rates than colposcopy high-grade threshold. Sensitivity rates for visual inspection decreased with age and false positive rates increased. For all age groups, false positive rates for VIA and VIA-VILI were significantly higher than colposcopy. Conclusions: Detection rates for VIA-VILI similar to colposcopy low-grade threshold representa chance to reduce cervical cancer mortality through see-and-treat approaches among women with limited access to health care. Lower detection rates suggest reviewing high-grade colposcopy findings as the threshold for biopsy incertain settings.


Resumen Introducción. La inspección visual directa para la tamización del cáncer cervical sigue siendo controversial, mientras que la colposcopia y la biopsia siguen considerándose como métodos de referencia para diagnosticar lesiones cervicales precancerosas. Objetivo. Determinar las tasas de detección de neoplasia intraepitelial cervical de grado 2 y de los falsos positivos en la colposcopia y la inspección visual directa. Materiales y métodos. Se seleccionaron mujeres de 25 a 59 años sometidas a citología convencional, inspección visual directa con ácido acético y disolución de Lugol y colposcopia. Se practicó biopsia en todas las pruebas positivas. Utilizando la histología como el medio de verificación de referencia, se compararon las tasas de detección y de falsos positivos de cada prueba. Se estimaron las razones de sensibilidad y de falsos positivos con los correspondientes intervalos de confianza. Resultados. Se incluyeron 5.011 mujeres. Las colposcopias positivas de alto y bajo grado correspondieron a 1,6 y 10,8 %, respectivamente. La inspección visual directa con ácido acético y solución yodada de Lugol fue positiva en 7,4 y 9,9 %, respectivamente. La inspección visual directa con ácido acético tuvo tasas de detección y falsos positivos significativamente menores que la coloscopia con umbral de bajo grado (razón de sensibilidad: 0,72; IC95% 0,57-0,91; razón de falsos positivos: 0,70; CI95% 0,65-0,76); no hubo diferencias entre la inspección visual directa con solución yodada de Lugol y la colposcopia con dicho umbral. Las tasas de detección y de falsos positivos de los dos tipos de inspección visual fueron significativamente más altas que las de la colposcopia con el umbral de alto grado. Las tasas de detección de la inspección visual disminuyeron con la edad y las de falsos positivos aumentaron. Conclusiones: Las tasas de detección similares para la inspección visual directa con ácido acético o con solución yodada de Lugol y la colposcopia con umbral de bajo grado representan una oportunidad para reducir la mortalidad por cáncer de cuello uterino cuando el acceso a los servicios de salud es limitado. Las tasas de detección más bajas para la colposcopia con umbral de alto grado sugieren la necesidad de revisar dicho umbral en ciertos entornos.


Subject(s)
Adult , Female , Humans , Middle Aged , Uterine Cervical Neoplasms/pathology , Cervical Intraepithelial Neoplasia/pathology , Early Detection of Cancer/methods , Biopsy , Colombia , Colposcopy , Acetic Acid , False Positive Reactions , Iodides
5.
Braz. j. med. biol. res ; 52(1): e7517, 2019. tab
Article in English | LILACS | ID: biblio-974267

ABSTRACT

The aim of this study was to explore the value of different combination schemes of liquid-based cytology (LBC) and high-risk human papilloma virus (HPV) test in the screening of high-grade (≥CIN 2) cervical lesions. From 5727 women who had undergone examinations with LBC and high-risk HPV test, 1884 patients with positive results of either or both LBC and HPV test were included in this study and underwent cervical biopsy. Based on the pathological examination results, comparisons of the assessment indicators of all diagnostic tests were made, and the application values of LBC and high-risk HPV test and different combination schemes of the two in the screening of high-grade (≥CIN II) cervical lesions were estimated. Compared with the single test method, the sensitivity and negative predictive value of the combination scheme of LBC+HPV (with one positive result) were increased significantly (98.7% and 99.7%), but the specificity (60.8%) and accuracy rate (65.4%) dropped significantly (P<0.05). The sensitivity of LBC+HPV (with two positive results) was the lowest (80.7%), but the specificity and accuracy rate were the highest (83.5% and 83.1%, P<0.05). Z test showed that differences in the screening efficiency of four schemes were not statistically significant (P>0.05). Both LBC and HPV test were effective methods in the screening of high-grade cervical lesions; combination of the two tests did not improve the screening efficiency, but the scheme of LBC+HPV (with two positive results) significantly increased the sensitivity and negative predictive value, which was of better cost-benefit value.


Subject(s)
Humans , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Precancerous Conditions/pathology , Cervical Intraepithelial Neoplasia/pathology , Papillomavirus Infections/pathology , Liquid Biopsy/methods , Predictive Value of Tests , Sensitivity and Specificity , Papillomavirus Infections/complications , Diagnostic Screening Programs
6.
Rev. chil. obstet. ginecol. (En línea) ; 83(2): 130-138, abr. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-959497

ABSTRACT

RESUMEN Fundamento: La persistencia del virus papiloma posterior a la conización del cuello uterino, se ha considerado un factor de riesgo para la persistencia de lesiones intra epiteliales (LIE) causadas por virus papiloma. Para determinar la asociación entre persistencia de lesión cervical y la presencia del virus papiloma posterior a la conización del cuello uterino, se realizó un estudio observacional prospectivo en un grupo de 123 pacientes portadoras de lesiones intraepiteliales de alto grado (LIEAG) tratadas con conización. Material y métodos: Se siguieron a 123 pacientes portadoras de LIEAG, ingresadas a la Unidad de Patología Cervical entre Abril de 2013 y Abril de 2014, las que fueron seguidas por 2 años hasta Abril de 2016. Se realizó genotipificación antes, y entre 4 a 6 meses posterior a la conización. Los datos se tabularon considerando la edad, paridad, tipo de virus, persistencia de LIE, reconización o requerimiento de histerectomía posterior. Resultados: La mediana de la edad fue de 37 años, el 91% fueron multíparas, y solo el 9% fueron nulíparas. El 56% ingresó por NIE III y el 44% por NIE II. Los virus más frecuentes fueron el 16, 31,58, 52 y 56. La persistencia de virus papiloma se constató en el 37% de las pacientes conizadas. La persistencia de LIE se observó en el 27% de las pacientes que fueron positivas para virus papiloma posterior a la conización, en comparación a sólo el 5% en las que fueron negativas. Del total de pacientes positivas para virus papiloma posterior a la conización, 12 de ellas presentaron persistencia de lesión confirmadas histológicamente por biopsia cervical, 8 pacientes requirieron recono por LIE de alto grado, 2 pacientes fueron a histerectomía y en 2 casos se realizó seguimiento estricto por NIE I. Cuando la tipificación post cono fue negativa solamente 3 pacientes requirieron conización y en sólo una se realizó seguimiento estricto por NIE I. Conclusión: La persistencia del virus papiloma posterior a la conización se asocia a mayor persistencia de LIEAG, mayor frecuencia de reconización o histerectomía posterior.


ABSTRACT Backgroud: The persistence of papilloma virus after conization of the cervix has been considered a risk factor for the persistence of cervical intra epithelial lesion (CIN) caused by papilloma virus. Aim: In order to determine the association between cervical lesion persistence and the presence of papilloma virus after conization, a prospective observational study was performed in a group of 123 patients with intraepithelial lesions treated with conization. Material and methods: We followed 123 patients with high grade CIN who were admitted to the Cervical Pathology Unit, between April 2013 and April 2014; they were followed for 2 years until April 2016. Viral genotyping was done before, and among the 4 to 6 months after the LEEP. Data were tabulated considering age, parity, type of virus, persistence of CIN, reconization or requirement of posterior hysterectomy. Results: The median age was 37 years, 91% were multiparous, and only 9% were nulliparous. 56% had NIE III and 44% NIE II. The most frequent viruses were 16, 31, 58, 52 and 56. The persistence of papillomavirus was present in 37% of patients. The persistence of CIN was observed in 27% of patients who were positive for papilloma virus after conization, compared to only 5% in those who were negative. Of the total number of patients positive for papilloma virus, in 12 of them had intra epitelial lesions were confirmed by cervical biopsy, 8 patients required recone for high grade CIN, 2 patients underwent hysterectomy, and 2 patients underwent follows up strictly by CIN I. When post cone typing was negative only 3 patients required conization and only one was followed strictly by CIN I.


Subject(s)
Humans , Female , Adult , Middle Aged , Young Adult , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Conization , Papillomavirus Infections/pathology , Papillomaviridae/physiology , Biopsy , Uterine Cervical Neoplasms/complications , Prospective Studies , Follow-Up Studies , Cervical Intraepithelial Neoplasia/surgery , Cervical Intraepithelial Neoplasia/pathology , Colposcopy , Cytodiagnosis , Papillomavirus Infections/genetics , Observational Study
8.
Rev. chil. obstet. ginecol. (En línea) ; 82(5): 539-553, Nov. 2017. tab, graf
Article in English | LILACS | ID: biblio-899940

ABSTRACT

OBJETIVOS: En la actualidad, existe una alta tasa de sobre-tratamiento de lesiones precursoras cervicales, la cual, en su causalidad, depende de la inexperiencia del operador que toma las decisiones. El objetivo del presente trabajo fue desarrollar un método estandarizado de ponderación/juicio de variables diagnósticas y tratamiento útiles de ser usadas por especialistas jóvenes a fin de minimizar el riesgo de manejo inadecuado. MATERIALES Y MÉTODOS: Se incluyeron 471 pacientes referidos por citología anormal y tratados mediante asa de LEEP. Se calcularon la sensibilidad, la especificidad, los valores predictivos y las relaciones de probabilidad para el diagnóstico de NIE2+ para cada uno de los métodos de diagnóstico. A cada residente se le enseñó un protocolo estandarizado de tratamiento mediante asa. Una vez identificados los mejores predictores, se construyó una escala de puntaje que ponderaba las variables y se definió mediante curva ROC el major punto de corte para la predicción de NIE2+. Las diferencias entre los grupos se compararon mediante Chi-cuadrado, ANOVA o t-test. Se construyó curva de fallas mediante el método de 1-Kaplan Meier. RESULTADOS: La prevalencia de NIE2+ en esta cohorte fue 66%. La concordancia entre las pruebas diagnósticas fue baja, teniendo la colposcopia el peor valor predictivo positivo y el mayor riesgo de sobre-tratamiento. Para la escala de puntaje se incluyeron la edad, la citología, la colposcopia (estratificación basada en la extensión de compromiso por cuadrantes), la biopsia por mascada y la concordancia entre pruebas diagnósticas. Un puntaje≥ 9 asociado al uso de un protocolo estandarizado, obtuvo tasas de sobre-tratamiento <15%, de recurrencias de NIE2+ <5% a 5 años y una baja tasa de procedimientos sub-óptimos o con complicaciones (<2 %). CONCLUSIONES: El método CONO-UC al combinar un sistema de puntaje integrado (punto de corte) con un protocolo estandarizado de excisión, permite minimizar el riesgo de sobretratamiento o tratamiento inadecuado, por parte de especialistas jóvenes, de lesiones preinvasoras del cuello uterino, reduciendo además el número de procedimientos indicados innecesariamente y manteniendo una alta tasa de éxito terapéutico.


GOALS: Currently, there is a high rate of over-treatment of precursor cervical lesions, which, in their causality, depends on the inexperience of the decision-making operator. The objective of the present study was to develop a standardized method of weighting / judgment of diagnostic variables and treatment useful to be used by young specialists in order to minimize the risk of improper handling. MATERIAL AND METHODS: We included 471 patients referred by abnormal cytology and treated by LEEP. Sensitivity, specificity, predictive values and likelihood ratios for the diagnosis of CIN2+ were calculated for each of the diagnostic methods. Each resident was taught a standardized protocol to carry out a LEEP procedure. Once the best predictors were identified, a scoring scale was constructed that weighted the variables and the best cut-off point for the prediction of CIN2+ was defined by ROC curve. Differences between groups were compared using Chi-square, ANOVA or t-test. Failure curves were built up using the 1-Kaplan Meier method. RESULTS: The prevalence of CIN2+ in this cohort was 66%. The agreement between the diagnostic tests was low, with colposcopy having the worst positive predictive value and the highest risk of over-treatment. Age, cytology, colposcopy (stratification based on the extent of compromise by quadrants), punch biopsy, and agreement between diagnostic tests were included for building the scoring scale. A score ≥ 9 in association with the use of a standardized protocol obtained rates of over-treatment <15%, recurrences of CIN2+ <5% at 5-year follow-up and a low rate of suboptimal procedures or complications (<2%). CONCLUSIONS: The UC-CONE method, by combining an integrated scoring system with a standardized excision protocol, minimizes the risk of over-treatment or inadequate treatment of pre-invasive cervical lesions by young specialists, reducing the number of procedures indicated unnecessarily and maintaining a high rate of therapeutic success.


Subject(s)
Humans , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Cervical Intraepithelial Neoplasia/surgery , Cervical Intraepithelial Neoplasia/pathology , Colposcopy/methods , Electrosurgery/methods , Biopsy , Logistic Models , Cervix Uteri/pathology , Predictive Value of Tests , Retrospective Studies , ROC Curve , Analysis of Variance , Sensitivity and Specificity , Cervical Intraepithelial Neoplasia/diagnosis , Conization , Decision Making
9.
Rev. Col. Bras. Cir ; 44(2): 131-139, Mar.-Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-842657

ABSTRACT

ABSTRACT Objective : to study the association between the histological grading of cervical intraepithelial neoplasia (CIN I, CIN II and CIN III) and the immunohistochemical expression for p16ink4a, hTert and Ki67, as well as to evaluate the relationship of these markers with the risk of recurrence after surgical treatment. Methods : we studied a historical cohort of 94 women with intraepithelial lesions CIN I (low grade), CIN II and CIN III (high grades) submitted to conization or electrosurgical excision of the transformation zone. We evaluated all surgical specimens for immunohistochemical expression of p16ink4a, hTert and Ki67. Results : the mean age was 38.2 years; p16ink4a was absent in most CIN I cases. In patients with CIN II or I/II (association of low and high-grade lesions), we observed p16ink4a ≤10%. In patients with CIN III, we found a higher expression frequency of p16ink4a >50%. In CIN I, the majority had Ki67≤10% and low frequency of Ki67>50%. In the CIN III category, there were fewer patients with Ki67≤10%, and Ki67 was absent in most patients of CIN II and III groups. There was no association between hTert expression and histologic grade. There were no statistically significant differences between the expression of the markers in patients with and without recurrence. Conclusion : there was a statistically significant association of p16ink4a and Ki67 with histological grade. The markers' expression, as for disease recurrence, was not statistically significant in the period evaluated.


RESUMO Objetivo: estudar a associação entre a graduação histológica das neoplasias intraepiteliais cervicais (NIC I, NIC II e NIC III) e a expressão imuno-histoquímica para p16ink4a, hTert e Ki67, assim como, avaliar a relação destes marcadores com o risco de recorrência após tratamento cirúrgico. Métodos: estudo de coorte histórica de 94 mulheres portadoras de lesões intraepiteliais NIC I (baixo grau), NIC II e NIC III (altos graus), submetidas à conização ou à excisão eletrocirúrgica da zona de transformação. Todas as peças cirúrgicas foram avaliadas quanto à expressão imuno-histoquímica para p16ink4a, hTert e Ki67. Resultados: a média de idade das pacientes foi 38,2 anos. Nas pacientes NIC I, a p16ink4a estava ausente na maioria dos casos; nas pacientes NIC II ou I/II (associação de lesões de baixo e alto graus), observou-se frequência de p16ink4a≤10%. Nas pacientes NIC III, observou-se maior frequência de expressão de p16ink4a>50%. Na categoria NIC I, a maioria apresentava Ki67≤10% e baixa frequência de Ki67>50%. Na categoria NIC III houve menor número de pacientes com Ki67≤10%, sendo que a maior parte das pacientes tinha Ki67 ausente nos grupos NIC II e III. Não houve associação entre a expressão do marcador imuno-histoquímico hTert e a graduação histológica. Não houve diferenças estatisticamente significativas entre as expressões dos marcadores em pacientes com e sem recorrência. Conclusão: houve associação estatisticamente significativa apenas de p16ink4a e Ki67 com a graduação histológica. A expressão dos marcadores em relação à recorrência da doença não foi estatisticamente significativa no período avaliado.


Subject(s)
Humans , Female , Adult , Cervical Intraepithelial Neoplasia/metabolism , Telomerase/biosynthesis , Ki-67 Antigen/biosynthesis , Cyclin-Dependent Kinase Inhibitor p16/biosynthesis , Cervical Intraepithelial Neoplasia/pathology , Neoplasm Grading
10.
Rev. bras. ginecol. obstet ; 39(3): 123-127, Mar. 2017. tab
Article in English | LILACS | ID: biblio-843924

ABSTRACT

Abstract Objective Expectant follow-up for biopsy-proven cervical intraepithelial neoplasia (CIN) 1 is the current recommendation for the management of this lesion. Nevertheless, the performance of the biopsy guided by colposcopy might not be optimal. Therefore, this study aimed to calculate the rate of underdiagnoses of more severe lesions in women with CIN 1 diagnosis and to evaluate whether age, lesion extent and biopsy site are factors associated with diagnostic failure. Methods Eighty women with a diagnosis of CIN 1 obtained by colposcopy-guided biopsy were selected for this study. These women were herein submitted to large loop excision of the transformation zone (LLETZ). The prevalence of lesions more severe than CIN 1 was calculated, and the histological diagnoses of the LLETZ specimens were grouped into two categories: "CIN 1 or less" and "CIN 2 or worse." Results The prevalence of lesions diagnosed as CIN 2 or worse in the LLETZ specimens was of 19% (15/80). Three women revealed CIN 3, and 1 woman revealed a sclerosing adenocarcinoma stage I-a, a rare type of malignant neoplasia of low proliferation, which was not detected by either colposcopy or previous biopsy. The underdiagnosis of CIN 2 was not associated with the women's age, lesion extension and biopsy site. Conclusions The standard methods used for the diagnosis of CIN 1 may underestimate the severity of the true lesion and, therefore, women undergoing expectant management must have an adequate follow-up.


Resumo Objetivo O seguimento de mulheres com neoplasia intraepitelial cervical (NIC) 1 comprovada por biópsia é atualmente a recomendação de conduta para esta lesão. Entretanto, o desempenho da biópsia guiada por colposcopia pode falhar. Assim, este estudo teve como objetivo estimar a taxa de subdiagnóstico de lesões mais graves em mulheres comdiagnóstico de NIC 1 e avaliar se a idade, a extensão da lesão e o local da biópsia são fatores associados à falha do diagnóstico. Métodos Foram selecionadas 80 mulheres com diagnóstico de NIC 1 obtido por biópsia dirigida por colposcopia. Estasmulheres foramsubmetidas a excisão da zona de transformação por alça diatérmica (EZTAD). A prevalência de lesões mais graves do que NIC 1 foi calculada, e os diagnósticos histológicos feitos nas amostras obtidas por EZTAD foram agrupados em duas categorias: "NIC 1 ou menos grave" e "NIC 2 ou mais grave". Resultados A prevalência de lesões diagnosticadas como NIC 2 ou mais grave nas amostras de EZTAD foi de 19% (15/80). Três mulheres apresentaram NIC 3, e uma mulher revelou adenocarcinoma esclerosante estágio I-a, um tipo raro de neoplasia maligna de baixa proliferação, que não foi detectado por qualquer exame de colposcopia ou biópsia anterior. O subdiagnóstico de NIC 2 não foi associado à idade, à extensão da lesão ou ao local da biópsia. Conclusão Os métodos de referência utilizados para o diagnóstico da NIC 1 podem subestimar a gravidade da lesão verdadeira e, portanto, as mulheres submetidas a conduta expectante devem ter um seguimento adequado.


Subject(s)
Humans , Female , Adult , Young Adult , Cervical Intraepithelial Neoplasia/pathology , Colposcopy , Uterine Cervical Neoplasms/pathology , Image-Guided Biopsy , Neoplasm Staging
11.
Rev. Col. Bras. Cir ; 43(1): 35-41, Jan.-Feb. 2016. tab, graf
Article in English | LILACS | ID: lil-779023

ABSTRACT

Objective: Io evaluate the expression of p16INK4a and p53 biomarkers in conization specimens from patients with high grade cervical intraepithelial neoplasia (HG-CIN), correlating them with the ability to predict the recurrence. Methods : we conducted a retrospective study of patients with HG-CIN in cervical biopsy treated with conization between January 1999 and January 2006 who had a minimum follow-up of 18 months. The expression of the p16 and p53 was assessed by tissue microarrays and correlated with disease recurrence. For analysis, we used the test of proportions (chi-square), considering value p<0.05, 95% CI and calculations of sensitivity, specificity and accuracy of these immunomarkers in predicting recurrence. Results : the series comprised 83 patients aged between 16 and 86 years (35±11.7), divided into two groups: 30 with HG-CIN recurrence (study group) and 53 without recurrence (control group). Mean age, parity, smoking and conization technique were similar in both groups. The p53 expression was present in 43% of the study group and 57% of the control group, and the p16 was present in 43% of the study group and in 57% of the control group (p>0.05). p53 had a positive predictive value (PPV) of 42% and negative predictive value (NPV) of 73%, sensitivity 70%, specificity of 47% and accuracy of 59%. The p16, PPV 42%, NPV 72%, sensitivity 66%, specificity of 49% and accuracy of 56%. Conclusion : immunohistochemistry expression of p53 and p16 showed low sensitivity and low specificity as predictors of HG-CIN recurrence after conization treatment.


Objetivo : avaliar a expressão dos biomarcadores p16INK4a e p53, nas peças de conização de pacientes com neoplasia intraepitelial cervical de alto grau (NIC-AG), correlacionando com a capacidade de predizer o risco de recorrência. Métodos : estudo retrospectivo de pacientes com NIC-AG em biópsia de colo uterino, tratadas por conização, entre janeiro de 1999 e janeiro de 2006 e seguimento mínimo de 18 meses. A expressão dos biomarcadores p16 e p53 foi avaliada através de técnica de microarranjos teciduais e correlacionada com a recorrência da doença. Para análise utilizou-se o teste das proporções (qui-quadrado), considerando valor p<0,05, IC95% e cálculos de sensibilidade, especificidade e acurácia destes imunomarcadores na predição de recorrência. Resultados : oitenta e três pacientes, idade entre 16 e 86 anos (35±11,7), divididas em dois grupos: 30 com recorrência da NIC-AG (grupo estudo) e 53 sem recorrência (grupo controle). A média de idade, paridade, hábito de fumar e técnica de conização foram semelhantes nos dois grupos. A expressão do p53 esteve presente em 43% do grupo estudo e 57% do grupo controle e para o p16 esteve presente em 43% do grupo estudo e 57% do grupo controle (p>0,05). O p53 apresentou valor preditivo positivo (VPP) de 42% e valor preditivo negativo (VPN) de 73%, sensibilidade de 70%, especificidade de 47% e acurácia de 59%. O p16, VPP de 42% e VPN de 72%, sensibilidade de 66%, especificidade de 49% e acurácia de 56%. Conclusão : a expressão imunoistoquiímica do p53 e do p16 apresentaram baixa sensibilidade e baixa especificidade como marcadores capazes de predizer a recorrência da NIC-AG tratada por conização.


Subject(s)
Humans , Female , Adolescent , Adult , Aged , Aged, 80 and over , Young Adult , Uterine Cervical Neoplasms/chemistry , Tumor Suppressor Protein p53/analysis , Cervical Intraepithelial Neoplasia/chemistry , Cyclin-Dependent Kinase Inhibitor p16/analysis , Neoplasm Recurrence, Local , Immunohistochemistry , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/pathology , Predictive Value of Tests , Retrospective Studies , Cervical Intraepithelial Neoplasia/surgery , Cervical Intraepithelial Neoplasia/pathology , Conization , Middle Aged
12.
Article in English | WPRIM | ID: wpr-216446

ABSTRACT

OBJECTIVE: To identify key factors for predicting positive cone margin and appropriate cone length. METHODS: We retrospectively reviewed the margin status of patients who received conization with high grade cervical intraepithelial neoplasia, along with other factors such as patient age, parity, preoperative cytology, size of disease, type of transformation zone, and cone length from patient records. Cut-off value of cone length was analyzed in women younger than 40 years old because we design conization with minimum length especially for women who wish for future pregnancy. Cut-off value of cone length was defined as length corresponds to estimated probability of positive cone margin equal to 0.1 by logistic regression analysis with variables selected by stepwise methods. RESULTS: Among 300 patients, 75 patients had positive cone margin. Multivariable analysis revealed that squamous cell carcinoma at preoperative cytology (p=0.001), 2 or more quadrant disease (p=0.011), and shorter cone length (p<0.001) were risk factors for positive cone margin. Stepwise methods identified cone length and size of lesion as important variables. With this condition, cut-off value of cone length was estimated as 15 mm in single quadrant disease and 20 mm in 2 or more quadrant disease, respectively. CONCLUSION: We identified the independent risk factors of positive cone margin and identified the cut-off value of cone length to avoid positive cone margin in women younger than 40 years old. Conization should be performed not only according to colposcopic findings including type of transformation zone but size of disease and cone length.


Subject(s)
Adult , Cervical Intraepithelial Neoplasia/pathology , Cervix Uteri/pathology , Conization , Female , Humans , Middle Aged , Retrospective Studies , Uterine Cervical Neoplasms/pathology
13.
Article in English | WPRIM | ID: wpr-21465

ABSTRACT

OBJECTIVE: We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). METHODS: Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. RESULTS: The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001). CONCLUSION: Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.


Subject(s)
Cervical Intraepithelial Neoplasia/pathology , Female , Humans , Neoplasm Recurrence, Local/virology , Neoplasm, Residual , Papillomaviridae/isolation & purification , Papillomavirus Infections/complications , Predictive Value of Tests , Risk Assessment/methods , Sensitivity and Specificity , Uterine Cervical Neoplasms/pathology
14.
Säo Paulo med. j ; 133(6): 480-487, Nov.-Dec. 2015. tab, graf
Article in English | LILACS | ID: lil-770154

ABSTRACT

ABSTRACT CONTEXT AND OBJECTIVE: Worldwide, there is no single strategy for optimal management of patients with ASCUS (atypical squamous cells of undetermined significance) cytology reports. The objective of this study was to determine the kind of clinical management conducted among women with a first ASCUS Pap smear report. DESIGN AND SETTING: Prospective single cohort study at a cervical pathology unit in Santiago, Chile. METHODS: This was an epidemiological, descriptive, observational and quantitative follow-up study on a cohort of women with ASCUS cytological reports. RESULTS: In the screening phase, 92,001 cervical cytological smears were collected in primary healthcare clinics. In the diagnostic phase, all women with a first ASCUS report were selected (n = 446). These women were asked to undergo the Pap test again and it was found that 301 women had normal results, 62 women had abnormal results and 83 did not repeat the test. In the diagnostic confirmation phase, the 62 women with abnormal results underwent colposcopy and, from these results, 58 of them underwent a biopsy. The results from the biopsies showed that 16 women had negative histological reports, 13 had CIN 1 and 29 had CIN 2+. In the treatment phase, the 42 women with lesions underwent a variety of treatments, according to the type of lesion. In the post-treatment phase, cytological and colposcopic monitoring was instituted. CONCLUSION: The clinical management consisted of traditional management of screening, diagnosis, diagnostic confirmation, treatment and post-treatment monitoring.


RESUMO CONTEXTO E OBJETIVO: Mundialmente, não existe estratégia única para o gerenciamento ideal de pacientes com laudos de citologia ASCUS ( atypical squamous cells of undetermined significance ). O objetivo do estudo foi determinar o tipo de gerenciamento clínico realizado em mulheres com o primeiro laudo de Papanicolaou ASCUS. DESENHO E LOCAL: Estudo prospectivo de coorte única em uma unidade de patologia cervical em Santiago, Chile. MÉTODOS: Estudo epidemiológico, descritivo, observacional e quantitativo de seguimento de um grupo de mulheres com laudos de citologia ASCUS. RESULTADOS: Na fase de rastreamento, 92.001 relatórios de citologia cervical foram coletados nos ambulatórios da rede pública de saúde. Na fase de diagnóstico, foi selecionada a totalidade de mulheres com relatórios citológicos de ASCUS (n = 446). Essas mulheres foram submetidas a repetição do exame de Papanicolaou, obtendo-se 301 mulheres com resultados normais, 62 mulheres com resultados anormais e 83 que não repetiram o exame. Na fase de confirmação de diagnóstico, as 62 mulheres com resultados anormais foram submetidas a colposcopia e, considerando-se os resultados obtidos, 58 foram submetidas a biópsia. Os resultados das biópsias mostraram 16 mulheres com laudos histológicos negativos, 13 com NIC 1 e 29 com NIC 2 +. Na fase terapêutica, as 42 mulheres com lesões foram submetidas a diversos tratamentos de acordo com o tipo de lesão. Para a fase pós-tratamento, foi instituído um sistema de monitoramento citocolposcópico. CONCLUSÃO: As condutas clínicas tiveram gestão tradicional de rastreamento, diagnóstico, confirmação diagnóstica, tratamento e acompanhamento pós-tratamento.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Young Adult , Atypical Squamous Cells of the Cervix/pathology , Cervical Intraepithelial Neoplasia/pathology , Cervical Intraepithelial Neoplasia/therapy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy , Chile , Colposcopy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Disease Management , Follow-Up Studies , Neoplasm Staging , Papanicolaou Test , Prospective Studies , Treatment Outcome
15.
Rev. Inst. Nac. Hig ; 46(1/2): 32-42, dic. 2015. ilus, tab
Article in Spanish | LILACS, LIVECS | ID: lil-798271

ABSTRACT

Las infecciones por virus de papiloma humano (VPH) influyen en la expresión de proteínas del ciclo celular y producen alteraciones en el epitelio cervical que promueven el desarrollo de la neoplasia intraepitelial cervical (NIC); los genotipos de VPH se agrupan en VPH de bajo o de alto riesgo oncogénico. Las oncoproteínas virales E6 y E7 de los VPH de alto riesgo (16 y 18), se unen a varios reguladores del ciclo celular, por lo tanto están relacionadas con lesiones de alto grado y cáncer de cuello uterino. El objetivo de este trabajo fue evaluar 36 biopsias de cuello uterino mediante inmunohistoquímica y medir la expresión de los marcadores celulares siguientes: Antígeno Nuclear de Proliferación Celular (PCNA), la proteína de adhesión celular Cadherina E que se inactiva en los momentos iniciales de invasión y metástasis, la expresión de la proteína p16-INK4 que es un inhibidor de las ciclinas que participa en el punto de control G1 del ciclo celular en lesiones de cuello uterino. Los resultados obtenidos indicaron que en todas las muestras evaluadas se obtuvo un incremento en la expresión de P16INK4a (95,86%) y de PCNA (92,27%) en zonas con lesión comparado con zonas sin lesión y una disminución en la expresión de cadherina E (18,94%) en zonas con lesión. En conclusión, el marcador celular p16INK4a (P<0,0033) mostró un mejor comportamiento predictivo de la evolución de las lesiones que PCNA y Cadherina E.


Infections human papillomavirus (HPV) influence the expression of cell cycle proteins and produce changes in the cervical epithelium that promote the development of cervical intraepithelial neoplasia (CIN); HPV genotypes are grouped into HPV low risk or highoncogenic. Viral oncoproteins E6 and E7 of high-risk HPV (16 and 18), bind to various cell cycle regulators, therefore they are related to high-grade lesions and cervical cancer. The aim of this study was to evaluate 36 cervical biopsies by immunohistochemistry and measuring the expression of the following cellular markers: Nuclear Antigen Cell Proliferation (PCNA), the cell adhesion protein E-cadherin is inactivated in the initial moments of invasion and metastasis, p16 expression-INK4 protein is a cyclin inhibitor involved in the G1 checkpoint in the cell cycle cervical lesions. The results showed that in all samples tested increased the expression of p16INK4a (95.86%) and PCNA (92.27%) in lesion areas compared to areas without injury and a decrease in expression was obtained Ecadherin (18.94%) in areas with injury. In conclusion, the p16INK4a cell marker (P <0.0033) showed a better predictive performance of the evolution of lesions PCNA and Ecadherin.


Subject(s)
Humans , Female , Adolescent , Adult , Middle Aged , Immunohistochemistry/methods , Cervical Intraepithelial Neoplasia/pathology , Papillomavirus Infections/transmission , Squamous Intraepithelial Lesions of the Cervix/pathology , Sexually Transmitted Diseases , Public Health
16.
Säo Paulo med. j ; 133(4): 336-342, July-Aug. 2015. tab, graf
Article in English | LILACS | ID: lil-763367

ABSTRACT

CONTEXT AND OBJECTIVE:Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I.DESIGN AND SETTING:Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care.METHODS:We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features.RESULTS:There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression.CONCLUSION:These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions.


CONTEXTO E OBJETIVO:A deficiência na imunidade celular localizada parece contribuir para a patogênese e progressão das neoplasias intraepiteliais cervicais (NIC), no entanto, ainda não está totalmente esclarecido o mecanismo molecular fundamental nesse processo de progressão. A identificação de novos marcadores moleculares de prognóstico e diagnóstico das NIC em estágios precoces pode ajudar a diminuir a quantidade de casos de NIC. Várias novas moléculas com função imunorregulatória foram descobertas nos últimos anos, inclusive o antígeno leucocitário humano G (HLA-G), que, através de interação com os receptores, tem importantes funções tolerogênicas. Diversas linhas de evidência sugerem que as células T-ajudantes produtoras de interleucina-17 (IL-17, células Th17), podem desempenhar um papel na imunidade antitumoral. Porém, recentes relatos implicaram as células Th17 e suas citocinas tanto em processos pro- quanto anti-tumorigênicos. O objetivo do estudo foi avaliar o papel do HLA-G e Th17 na imunopatogênese das NIC I.TIPO DE ESTUDO E LOCAL:Estudo transversal analítico com grupo controle em 58 espécimes cervicais dos arquivos de um hospital universitário público com assistência prestada no nível terciário.MÉTODOS:Avaliamos a expressão de HLA-G e IL-17 por imunoistoquímica no microambiente cervical, associando esses achados com as características clínico-patológicas.RESULTADOS:Houve tendência aumentada da expressão de HLA-G e IL-17 em espécimes que apresentaram NIC I, sugerindo que essas moléculas têm contribuição na progressão cervical.CONCLUSÃO:Estes resultados sugerem que a expressão do HLA-G e da IL-17 pode ser um marcador precoce para avaliar a progressão das lesões cervicais.


Subject(s)
Adult , Female , Humans , Middle Aged , Young Adult , Cervical Intraepithelial Neoplasia/metabolism , Cervix Uteri/metabolism , HLA-G Antigens/metabolism , /metabolism , Uterine Cervical Neoplasms/metabolism , Age Factors , Biopsy , Biomarkers, Tumor/metabolism , Cross-Sectional Studies , Cervical Intraepithelial Neoplasia/pathology , Cervix Uteri/pathology , Coitus/physiology , HLA-G Antigens/analysis , Immunohistochemistry/methods , /analysis , Sexual Partners , Uterine Cervical Neoplasms/pathology
17.
Cad. saúde pública ; 30(9): 1912-1920, 09/2014. tab, graf
Article in English | LILACS | ID: lil-725852

ABSTRACT

The objective of the study was to determine the dynamics of precancerous lesions in women of a cohort treated for cervical intraepithelial neoplasia (CIN) and followed up over the next two years. The conditional probability of failure was calculated using the Kaplan-Meier method, and the raw and adjusted hazard ratios (HR) were determined using Cox regression with a p-value entry of < 0.05. Of the 237 women who were treated, 51.5% were accompanied over 24 months, and treatment failed for 21.9% of those accompanied. Women who had five or more pregnancies (adjusted HR = 3.10, 95%CI: 1.28-7.51) or an initial histological diagnosis of CIN II/III demonstrated an independent risk of treatment failure (adjusted HR = 3.14, 95%CI: 1.20-8.19). Being in a stable relationship was a protective factor against treatment failure (adjusted HR = 0.47, 95%CI: 0.24-0.89). A history of more frequent pregnancies and a histological diagnosis of CIN II/III are directly correlated with risk of CIN treatment failure, whereas being in a stable relationship is inversely correlated with this risk.


O objetivo do estudo foi determinar a dinâmica da lesão intraepitelial cervical (NIC) em mulheres tratadas que foram acompanhadas em uma coorte durante dois anos. Foi calculada a probabilidade condicional de falha usando o método de Kaplan-Meier e foram calculadas as hazard ratios (HR) bruta e ajustada para o risco de falha usando a regressão de Cox com valor de p de entrada < 0,05. Das 237 mulheres que foram tratadas, 51,5% foram acompanhadas por 24 meses e 21,9% delas tiveram falha no tratamento, apresentando recidiva da lesão cervical. Mulheres que tinham mais que cinco gestações (HR = 3,10; IC95%: 1,28-7,51) ou histológico de NIC II/III demonstraram risco independente para falha no tratamento (HR = 3,14; IC95%: 1,20-8,19) e estar em um relacionamento estável mostrou ser um fator de proteção para falha de tratamento (HR = 0,47; IC95%: 0,24-0,89). A história de maior número de gestações e histológico de NIC II/III estão diretamente correlacionados com o risco de falha no tratamento, enquanto que estar em um relacionamento estável é inversamente correlacionado ao risco.


El objetivo del estudio fue determinar la dinámica de las lesiones intraepiteliales de cuello uterino (NIC) en mujeres que fueron tratadas dentro de una cohorte, cuyo seguimiento se realizó durante dos años. Se calculó la probabilidad condicional de error, utilizando el método de Kaplan-Meier y se calcularon los cocientes de riesgo (HR) crudos y ajustados por el riesgo de fracaso mediante la regresión de Cox con el aporte valor p < 0,05. De 237 mujeres que recibieron tratamiento, el 51,5% fueron seguidas durante 24 meses y en el 21,9% fracasó el tratamiento, mostrando la repetición del daño cervical. Las mujeres que tenían más de cinco embarazos (HR = 3,10; IC95%: 1,28-7,51) o NIC histológico II/III mostraron un factor de riesgo independiente para el fracaso del tratamiento (HR = 3,14; IC95%: 1,20-8,19) y estar en una relación estable resultó ser un factor protector para el fracaso del tratamiento (HR: 0,47; IC95%: 0,24-0,89). La historia de embarazos múltiples y con diagnóstico histológico NIC II/III se correlaciona directamente con el riesgo de fracaso del tratamiento, mientras que si está en una relación estable se correlaciona inversamente con la relación riesgo.


Subject(s)
Adult , Female , Humans , Cervical Intraepithelial Neoplasia/therapy , Precancerous Conditions/therapy , Brazil , Cohort Studies , Cervical Intraepithelial Neoplasia/pathology , Precancerous Conditions/pathology , Recurrence , Retrospective Studies , Risk Factors , Socioeconomic Factors , Treatment Failure , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy
18.
Säo Paulo med. j ; 132(1): 15-22, 2014. tab, graf
Article in English | LILACS | ID: lil-699303

ABSTRACT

CONTEXT AND OBJECTIVE: The concept that the presence of atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions (ASC-H) was introduced in the 2001 Bethesda System of cervical cytology classification. This nomenclature defines cervical cancer precursor lesions. The objective of this study was to investigate the colpocytological-histological results from a three-year follow-up conducted on a cohort of women with reports of ASC-H who were attended during 2005-2006 at clinics of the Southern Metropolitan Healthcare Service of Santiago, Chile. DESIGN AND SETTING: Prospective cohort study at primary healthcare clinics in Santiago, Chile. METHODS : Colpocytological-histological follow-up was conducted over a three-year period on 92 women with cytological reports of ASC-H who were attended at primary healthcare clinics during 2005-2006. RESULTS : At the end of the follow-up period, high-grade lesions were evaluated and the following outcomes were observed: seven women presented invasive cancer (7.6%), 49 presented high-grade lesions (53.3%), 26 presented low-grade lesions (28.2%) and 10 presented normal results (10.9%). The "Conditional Probabilities Tree Diagram" was used to show the results from tests and the times of lesion detection. It demonstrated that, after a first report of ASC-H, clinical management needed to be interventionist. CONCLUSION: The follow-up on our cohort of women showed that the majority of uncertain ASC-H diagnoses (82.6%) had abnormal colposcopic results and that during the follow-up using ASC-H smears, two out of every three women developed high-grade lesions. .


CONTEXTO E OBJETIVO: O conceito de que à presença de células escamosas atípicas não se pode excluir lesão intraepitelial de alto grau (ASC-H) foi introduzido pelo Sistema de Bethesda 2001, na classificação de citologia cervical. Esta nomenclatura define lesões precursoras do câncer cervical. O objetivo deste estudo foi investigar os resultados colpo-cito-histológicos de três anos de acompanhamento realizado em uma coorte de mulheres com relatórios de ASC-H que receberam atendimento no período 2005-2006 em clínicas do Serviço Metropolitano de Saúde Sul de Santiago, Chile. TIPO DE ESTUDO E LOCAL: Estudo de coorte prospectivo em unidades básicas de saúde de Santiago, Chile. MÉTODOS: Foi conduzido um acompanhamento colpo-cito-histológico por um período de três anos em 92 mulheres com laudos citológicos de ASC-H, que receberam atendimento nas unidades básicas de saúde de 2005-2006. RESULTADOS: No final do período de acompanhamento, as lesões de alto grau foram avaliadas e os resultados foram observados: sete mulheres apresentaram câncer invasivo (7,6%), 49 apresentaram lesões de alto grau (53,3%), 26 apresentaram lesões de baixo grau (28,2%) e 10 apresentaram resultados normais (10,9%). O "Diagrama de Árvore Condicional de Probabilidades" foi utilizado para mostrar os resultados dos testes e o período de detecção das lesões, demonstrando que, depois de um primeiro relatório de ASC-H, o manejo clínico deve ser intervencionista. CONCLUSÃO: O acompanhamento de nossa coorte de mulheres mostra que a maioria dos diagnósticos incertos de ASC-H (82,6%) tiveram resultado colposcópico anormal e, durante o acompanhamento de esses esfregaços ASC-H, duas de cada três mulheres desenvolvem lesões de alto grau. .


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Young Adult , Cervical Intraepithelial Neoplasia/pathology , Neoplasms, Squamous Cell/pathology , Uterine Cervical Neoplasms/pathology , Chile , Follow-Up Studies , Papanicolaou Test , Predictive Value of Tests , Prospective Studies , Precancerous Conditions/pathology , Risk Factors , Vaginal Smears
19.
Säo Paulo med. j ; 132(2): 92-96, 2014. tab
Article in English | LILACS | ID: lil-705384

ABSTRACT

CONTEXT AND OBJECTIVES: Cervical cancer is an important cause of morbidity and mortality throughout the world. There is some controversy about the factors that may be associated with infection by the human papillomavirus (HPV) that may favor or protect against evolution from a low-grade intraepithelial lesion to a high-grade intraepithelial lesion or invasive neoplasia. The objective here was to evaluate the evolution of low-grade intraepithelial lesions and squamous or glandular lesions of undetermined significance, the associated factors and cytohistological correlations. DESIGN AND SETTING: Retrospective study conducted in a public tertiary-level university hospital. METHODS: Information was obtained by reviewing patient records and/or colposcopy reports. A statistical analysis was performed using logistic regression, calculating the odds ratio and applying chi-square tests. RESULTS: Of the 3390 patients, 409 evolved to high-grade intraepithelial lesions, of which 354 had an initial diagnosis of HPV infection, 27 of squamous atypia of undetermined significance, 22 of low-grade intraepithelial lesions with or without cytological diagnosis of infection by associated HPV and six of glandular cell atypia of undetermined significance. CONCLUSIONS: Lactobacillus sp and bacterial vaginosis on the smears, smoking and immunodepression were factors associated with evolution. A single partner, use of hormonal contraceptives, lower parity, age and a cytological diagnosis of cytolytic vaginosis, T. vaginalis, Candida sp or cocci were factors associated with protection. With regard to cytohistological correlation, there was a 74.08% agreement among patients with high-grade lesions and a biopsy obtained during the same period. .


CONTEXTO E OBJETIVOS: O câncer do colo uterino é importante causa de morbidade e mortalidade no mundo. Existem controvérsias sobre fatores que podem estar associados à infecção por papilomavírus humano (HPV) e favorecer ou proteger contra a evolução de lesão intraepitelial de baixo grau até lesão intraepitelial de alto grau ou neoplasia invasiva. O objetivo aqui foi de avaliar a evolução de lesões intraepiteliais de baixo grau e de significado indeterminado, escamosas ou glandulares, os fatores associados e as correlações citohistológicas. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo realizado em hospital universitário público terciário. MÉTODOS: As informações foram obtidas por meio de revisão de prontuários e/ou fichas de colposcopia. A análise estatística foi realizada por meio de regressão logística, calculando-se o odds ratio e aplicando-se o teste qui-quadrado. RESULTADOS: Das 3.390 pacientes, 409 evoluíram para lesão intraepitelial de alto grau, das quais 354 tinham diagnóstico inicial de infecção por HPV, 27 de atipias escamosas de significado indeterminado, 22 de lesão intraepitelial de baixo grau com ou sem diagnóstico citológico de infecção por HPV associado e 6 de atipias em células glandulares de significado indeterminado. CONCLUSÕES: Lactobacillus sp e vaginose bacteriana nos esfregaços, tabagismo e imunodepressão foram fatores associados com a evolução. Único parceiro, uso de contraceptivo hormonal, baixa paridade, idade e diagnóstico citológico de vaginose citolítica, T. vaginalis, Candida sp ou cocos foram fatores associados a proteção. Com relação à correlação citohistológica, encontramos concordância de 74,08% ...


Subject(s)
Adolescent , Adult , Female , Humans , Middle Aged , Young Adult , Cervical Intraepithelial Neoplasia/pathology , Papillomavirus Infections/pathology , Uterine Cervical Neoplasms/pathology , Biopsy , Colposcopy , Cervical Intraepithelial Neoplasia/etiology , Disease Progression , Neoplasm Grading , Papillomavirus Infections/complications , Retrospective Studies , Risk Factors , Uterine Cervical Neoplasms/etiology , Vagina/microbiology
20.
Rev. Inst. Med. Trop. Säo Paulo ; 55(5): 329-334, Sep-Oct/2013. tab, graf
Article in English | LILACS | ID: lil-685557

ABSTRACT

SUMMARY High-risk human papillomavirus (hr-HPV) infection is necessary but not sufficient for cervical cancer development. Recently, P16INK4A gene silencing through hypermethylation has been proposed as an important cofactor in cervical carcinogenesis due to its tumor suppressor function. We aimed to investigate P16INK4A methylation status in normal and neoplastic epithelia and evaluate an association with HPV infection and genotype. This cross-sectional study was performed with 141 cervical samples from patients attending Hospital Moncorvo Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR and P16INK4A methylation by nested-methylation specific PCR (MSP). HPV frequency was 62.4% (88/141). The most common HPV were HPV16 (37%), HPV18 (16.3%) and HPV33/45(15.2%). An upward trend was observed concerning P16INK4A methylation and lesion degree: normal epithelia (10.7%), low grade lesions (22.9%), high grade (57.1%) and carcinoma (93.1%) (p < 0.0001). A multivariate analysis was performed to evaluate an association between methylation, age, tobacco exposure, HPV infection and genotyping. A correlation was found concerning methylation with HPV infection (p < 0.0001), hr-HPV (p = 0.01), HSIL (p < 0.0007) and malignant lesions (p < 0.0001). Since viral infection and epigenetic alterations are related to cervical carcinoma, we suggest that P16INK4A methylation profile maybe thoroughly investigated as a biomarker to identify patients at risk of cancer. .


RESUMO É reconhecido que infecções por papilomavírus humanos de alto risco (HPV) são causa necessária, mas não suficiente para o desenvolvimento do câncer cervical. Recentemente, estudos de silenciamento gênico apontaram que a hipermetilação do gene p16INK4A é importante co-fator para a carcinogênese cervical, eliminando a função supressora de tumor da proteína p16 em lesões malignas. Entretanto poucos estudos avaliaram a relação da metilação com a progressão da doença. Nosso objetivo foi investigar o padrão de metilação do gene P16INK4A em diferentes graus de lesão cervical e sua associação com a infecção por diferentes tipos de HPV. Nosso estudo de corte transversal avaliou 141 amostras cervicais de pacientes atendidas no Hospital Moncorvo Filho, Rio de Janeiro. A detecção e tipagem do HPV foi realizada pela técnica de reação em cadeia da polimerase (PCR), e a metilação do gene P16INK4A pela PCR-metilação específica em formato nested (MSP). A frequência de HPV foi de 62,4% (88/141). O tipo mais prevalente foi o HPV16 (37%), seguido pelo HPV18 (16,3%) e HPV33/45 (15,2%). Curva ascendente foi observada quanto ao padrão de metilação do gene P16INK4A e o grau da lesão: a metilação foi identificada em somente 10,7% das amostras de epitélio normal, em 22,9% das lesões de baixo grau, em 57,1% das lesões de alto grau e em 93,1% dos carcinomas (p < 0,0001). Foram feitas análises univariada e multivariada a fim de correlacionar metilação, idade, exposição ao tabaco, infecção e genótipo de HPV. Foi encontrada correlação da metilação com a infecção pelo HPV (p < 0,0001), genótipos de alto risco (p = 0,01), ...


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Young Adult , Cervical Intraepithelial Neoplasia/virology , /genetics , DNA Methylation/genetics , Papillomavirus Infections/genetics , Uterine Cervical Neoplasms/virology , Cross-Sectional Studies , Cell Transformation, Neoplastic/genetics , Cervical Intraepithelial Neoplasia/genetics , Cervical Intraepithelial Neoplasia/pathology , DNA, Viral/genetics , Genotype , Polymerase Chain Reaction , Papillomavirus Infections/pathology , Precancerous Conditions/genetics , Severity of Illness Index , Uterine Cervical Neoplasms/pathology
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