Neoplasia intraepitelial escamosa cervical: abordagem por estimativas de risco / Cervical squamous intraepithelial neoplasia: risk estimation approach

As neoplasias intraepiteliais cervicais representam a fase pré-tumoral da neoplasia invasiva do colo uterino; são identificadas por citologia e testes de DNA-HPV e conduzidas por intervenções ambulatoriais. A perspectiva de estimativas de risco, para abordagem de tais lesões, constitui uma verdadeira mudança de paradigma, tendo em vista que as recomendações serão baseadas em riscos, não em resultados.(AU)

Cervical intraepithelial neoplasms represent the pre-tumor phase of invasive cervical cancer; identified by cytology, HPV-DNA testing and conducted by outpatient interventions. The perspective of risk estimates, to address such injuries, constitutes a true paradigm shift, considering that recomendations will be based on risks, not results.(AU)

Histerectomia radical após parto cesáreo por adenocarcinoma de colo uterino: relato de caso / Radical hysterectomy after c-section in cervical adenocarcinoma: a case report

Mundialmente, o câncer de colo uterino ocupa o quarto lugar das neoplasias em mulheres, porém, nos países em desenvolvimento, as taxas de incidência superam de forma impactante os casos de países desenvolvidos. Apesar de ser um evento incomum durante a gestação, é cada vez mais observado, o que talvez possa ser atribuído às gestações programadas em idades mais avançadas. O caso descrito refere-se a uma paciente de 32 anos de idade, diagnosticada no terceiro trimestre da gestação com adenocarcinoma de origem endocervical com estadiamento anatomopatológico final (FIGO 2018) 1B2. Ela foi submetida à abordagem cirúrgica como tratamento inicial. Foi adotada como conduta a resolução da gestação, com boa vitalidade fetal, ao final da 34ª semana, após corticoterapia para maturação pulmonar fetal. Foi realizado parto cesariano seguido de histerectomia radical tipo C1 na classificação de Querleu e Morrow associado a linfadenectomia pélvica, no mesmo ato operatório.(AU)

Worldwide, cervical cancer ranks fourth in female cancers, but when assessing data from developing countries, incidence rates are significantly higher than in developed countries. Although it is an uncommon event during pregnancy, it is increasingly observed, which may perhaps be justified due to pregnancies postponed at older ages. The case described relates to a 32-year-old woman diagnosed in the third trimester of pregnancy with endocervical adenocarcinoma, whose final anatomopathological staging (FIGO 2018) was IB2. The same was submitted to the surgical approach as an initial treatment. It was adopted as a conduct, the resolution of pregnancy, with good fetal viability, at the end of the 34th week, after corticosteroid therapy for fetal lung maturation. The patient underwent cesarean section followed by radical type C1 hysterectomy in the classification of Querleu and Morrow associated with pelvic lymphadenectomy in the same surgery.(AU)

Correlation of ER with Bcl-2 in cervical cancer and pre-cancerous lesion / 中国肿瘤临床

Objective:This study aimed to investigate the relationship between estrogen receptor (ER) and Bcl-2 in cervical can-cer and precancerous lesions. Methods:ER and Bcl-2 were evaluated by immunohistochemistry in 20 non-tumor tissues, 30 low-grade cervical intraepithelial neoplasias, 70 high-grade cervical intraepithelial neoplasias, and 80 cervical cancers. Results:The positive rate of ER was 75%in non-tumor tissues;this rate decreased with disease severity (χ2=24.266, P<0.01). The overexpression of ER protein was remarkably lower in cervical intraepithelial neoplasias (CIN) Ⅱ-Ⅲ and carcinomas than in non-tumorous cervices. Differences were not significant between CINⅠand non-tumorous cervices (χ2=0.751, P=0.386). Furthermore, ER expression was not correlated with histological type and tumor grade. The positive rate of Bcl-2 was 75.38%in squamous cell carcinoma. This rate increased with dis-ease severity (χ2=27.715, P<0.01). The Bcl-2 protein overexpression was remarkably higher in CINⅠ, CINⅡ-Ⅲ, and carcinomas than in non-tumorous cervices. Bcl-2 expression was also not correlated with histological type (P=0.500);by comparison, Bcl-2 expression was correlated with tumor pathological grade (χ2=4.862, P=0.027). The co-expression of ER and Bcl-2 was 38.57%and 15.38%in CINⅡ-Ⅲand squamous cell carcinoma, respectively;the differences between these two values were significant (χ2=9.108, P=0.003). A cor-relation between ER and Bcl-2 was observed in CINⅡ-Ⅲ(r=0.506, P<0.01);no correlation was observed between other groups. Con-clusion: ER expression was inversely correlated with Bcl-2 in cervical cancer progression. The co-expression of these markers may have an important function in the course of high-grade cervical intraepithelial neoplasia.

Respuesta inmune celular en pacientes con lesiones benignas y malignas del cuello uterino / Cellular immune response in patients presenting with benign and malignant lesions of cervix

Objetivo: estudiar parámetros inmunológicos en pacientes con lesiones intraepiteliales (NIC) y carcinoma in situ del cuello uterino en el Instituto Nacional de Oncología y Radiobiología durante el año 2009. Métodos: se realizó un estudio en 20 pacientes donde se determinaron las características inmunofenotípicas de los linfocitos de sangre periférica mediante citometría de flujo y la capacidad funcional frente a diversos mitógenos utilizando el método de síntesis de DNA. El análisis de correlación entre variables inmunológicas y epidemiológicas se realizó mediante el cálculo del coeficiente de correlación de Pearson. Para las pruebas estadísticas se utilizó el paquete estadístico SPSS (versión 11.5). Resultados: la subpoblación de los linfocitos Tc CD8+, mostró valores superiores estadísticamente significativos (p=0,004) solo para las pacientes con NIC I. En todas las pacientes, independientemente del estadio de la enfermedad y del mitógeno utilizado, los índices de estimulación (IE) resultaron inferiores a los valores del grupo control. Conclusión: las alteraciones en el sistema inmune en las pacientes con patología de cuello están asociadas al progreso de la enfermedad y las células T son fundamentales en el control de la progresión de las lesiones

Objective: To study the immunologic parameters in patients presenting with intraepithelial lesions (IEL) and carcinoma in situ of cervix in the National Institute of Oncology and Radiotherapy over 2009. Methods: A study was conducted in 20 patients to determine the immuno-phenotypical of lymphocytes in peripheral blood by flow-cytometry and the functional ability in face of diverse mitogen using the AND synthesis method. The correlation analysis among the immunologic and epidemiologic variables was carried out by an estimation of Pearson's correlation coefficient. For the statistic test the SPSS statistical package was used (version 11.5). Results: The subgroup of Tc + CD8 lymphocytes showed higher values statistically significant ( p= 0.004) only for patients presenting with IEL. In all patients, independently of disease stage and of the mitogen used, the stimulation rates (SR) were lower than the values of controls. Conclusions: The alterations in the immune system in patients with cervix pathology are associated with the progress of lesions

Prevalência dos genótipos do papilomavírus humano: comparação entre três métodos de detecção em pacientes de Pernambuco, Brasil / Prevalence of human papillomavirus genotypes: comparison between three detection methods in patients of Pernambuco, Brazil

OBJETIVO: comparar três métodos para detecção do HPV e determinar a prevalência dos genótipos encontrados. MÉTODOS: um total de 120 amostras de raspagem da região cervical de mulheres portadoras de neoplasia intraepitelial cervical foram analisadas pela reação em cadeia da polimerase convencional, usando os sistemas de primers MY09/11, GP05+/06+ e pela Nested-PCR. As amostras foram submetidas à extração de DNA e, logo após, amplificadas com os primers GH20 e PC04 (β-globina) para verificação da qualidade do DNA obtido e pela reação em cadeia da polimerase convencional e Nested-PCR. Os fragmentos amplificados foram visualizados em gel de agarose a 1,2 por cento, corados com Blue Green Loading Dye I. As amostras positivas foram sequenciadas usando o sequenciador automático de DNA "MegaBACE 1000". Para análise estatística foram utilizados os teste do Χ2 e o de Fisher com nível de significância de 5 por cento. RESULTADOS: quinze amostras não se amplificaram para os primers de β-globina, sendo eliminadas do estudo. Das amostras restantes, 40 por cento (42/105) foram positivas para os primers MY09/11, 98 por cento (103/105) para os primers GP05+/06+ e 92 por cento (97/105) para Nested-PCR. Considerado as técnicas MY09/11 e GP05+/06+, foi possível observar 100 por cento de amostras positivas para o HPV. Neste estudo, a prevalência dos genótipos foi de 58, 23, 5, 4 e 3 por cento para HPVs 16, 18, 31, 33 e 56, respectivamente. Os HPV 67 e 83 apresentaram 2 por cento e os HPV 6, 11, 58 e candHPV85, 1 por cento cada. A prevalência dos genótipos neste estudo está de acordo com o reportado em todo o mundo (IC95 por cento=0,4657-0,8976). CONCLUSÕES: para obter resultados mais confiáveis, é necessário o uso de mais que um sistema de primers para detecção do HPV. Acredita-se que as três técnicas estudadas são importantes e adequadas para o diagnóstico clínico do HPV quando apropriadamente combinadas.

PURPOSE: to compare three methods for the detection of HPV infection and to determine the prevalence of the genotypes found. METHODS: a total of 120 cervical scrape samples from patients with cervical intraepithelial neoplasia were analyzed by the conventional polymerase chain reaction using the MY09/11 and GP05+/06+ primers, and by the Nested polymerase chain reaction. The samples were subjected to DNA amplification with the GH20 and PC04 primers (β-globin) to verify DNA quality and also by polymerase chain reaction and Nested polymerase chain reaction. The amplicons were visualized in 1.2 percent agarose gel stained with Blue Green Loading Dye I. Positive samples also were sequenced using the automatic DNA sequencer "MegaBACE 1000". The Χ2 and Fisher tests were used for statistical analysis with the level of significance set at 5 percent. RESULTS: fifteen samples were eliminated from the study because they failed to amplify the β-globin gene. Of the remaining samples, 40 percent (42/105) were positive using primers MY09/11, 98 percent (103/105) using primers GP05+/06+, and 92 percent (97/105) using Nested-PCR. With the MY09/11 and GP05+/06+ techniques, it was possible to obtain 100 percent HPV-positive samples. In this study, the prevalence of the genotypes found was 57, 23, 5, 4 and 3 percent for HPV genotypes 16, 18, 31, 33 and 56, respectively. HPVs 67 and 83 were present in 2 percent, and genotypes 6, 11, 58 and candHPV85 were present in 1 percent each. The prevalence of the more common genotypes (HPV 16 and 18) in this study agrees with that reported worldwide (IC95 percent=0.4657-0.8976). CONCLUSIONS: to obtain more reliable results, it is necessary the use of more than one primer system to detect HPV infections. We believe that the three techniques studied are important and suitable for the clinical diagnosis of HPV, when they are appropriately combined.

Determinantes de la regresión de lesiones cervicales de bajo grado en una cohorte de mujeres colombianas / Determinants of LSIL regression in women from a colombian cohort

Objective: To analyze the role of Human Papillomavirus (HPV) and other risk factors in the regression of cervical lesions in women from the Bogotá Cohort. Methods: 200 HPV positive women with abnormal cytology were included for regression analysis. The time of lesion regression was modeled using methods for interval censored survival time data. Median duration of total follow-up was 9 years. Results: 80 (40%) women were diagnosed with Atypical Squamous Cells of Undetermined Significance (ASCUS) or Atypical Glandular Cells of Undetermined Significance (AGUS) while 120 (60%) were diagnosed with Low Grade Squamous Intra-epithelial Lesions (LSIL). Globally, 40% of the lesions were still present at first year of follow up, while 1.5% was still present at 5 year check-up. The multivariate model showed similar regression rates for lesions in women with ASCUS/AGUS and women with LSIL (HR= 0.82, 95% CI 0.59-1.12). Women infected with HR HPV types and those with mixed infections had lower regression rates for lesions than did women infected with LR types (HR=0.526, 95% CI 0.33-0.84, for HR types and HR=0.378, 95% CI 0.20-0.69, for mixed infections). Furthermore, women over 30 years had a higher lesion regression rate than did women under 30 years (HR= 1.53, 95% CI 1.03-2.27). The study showed that the median time for lesion regression was 9 months while the median time for HPV clearance was 12 months. Conclusions: In the studied population, the type of infection and the age of the women are critical factors for the regression of cervical lesions.

Objetivo: Analizar el papel del virus del papiloma humano (VPH) y otros factores en la regresión de lesiones del cuello del útero en mujeres de la cohorte de Bogotá, Colombia. Métodos: El tiempo medio de seguimiento fue nueve años. Se incluyeron 200 mujeres VPH positivas con citología anormal. El tiempo de regresión de lesión fue modelado mediante análisis de supervivencia censurando por intervalos. Resultados: 80 mujeres (40%) tuvieron células escamosas atípicas de significado indeterminado (ASCUS) o células glandulares atípicas de significado indeterminado (AGUS) y 120 (60%) tuvieron lesiones escamosas intraepiteliales de bajo grado (LEI-BG). El 40% de las lesiones estaban presentes en el primer año de seguimiento, mientras que el 1,5% aún estaba a los cinco años. Se observaron tasas similares de regresión para ASCUS/AGUS y LEI-BG (HR=0,82, IC 95% 0,59-1,12). Mujeres infectadas con VPH de alto riesgo y aquéllas con infecciones mixtas tuvieron tasas inferiores de regresión de las lesiones que las mujeres con VPH de bajo riesgo (HR=0,526, IC 95% 0,33-0,84, para los VPH de alto riesgo, y HR=0,378, IC 95% 0,20-0,69, para las infecciones mixtas). Las mujeres mayores de 30 años tuvieron una mayor tasa de regresión de lesiones que las menores de 30 (HR= 1,53, IC 95% 1,03-2,27). El tiempo medio de regresión de las lesiones fue 9 meses, y el tiempo medio para la eliminación del VPH fue 12 meses. Conclusiones: En la población estudiada, el tipo de infección y la edad de las mujeres son factores críticos para la regresión de lesiones cervicales.

Association of the E-cadherin gene polymorphism with cervical intraepithelial neoplasm and cervical cancer in Korean population / 대한산부인과학회지

OBJECTIVE: The aim of this study was to explore the association between E-cadherin promoter -160C>A polymorphism and the risk of cervical cancer and cervical intraepithelial neoplasm (CIN) in a Korean population. METHODS: We investigate 107 patients with histopathologically confirmed cervical cancer, 119 patients with histopathologically confirmed CIN and 112 control group women who were surgically proven to have normal cervices. The genetic distribution of E-cadherin promoter -160C>A polymorphism were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) of PCR products. RESULTS: We found no overall association between each individual E-cadherin promoter -160C>A genotype and the risk of cervical cancer and CIN. In the cervical cancer group, the allele frequency of C was 83.6%, in the control group 83.5%, showing no significant difference (p=0.941). Similarly, in the CIN group, the allele frequency of C was 81.9%, in the control group 83.5%, showing no significant difference (p=0.645). A subgroup analysis of the clinical parameters in CC, CA, AA genotype also showed no significant difference suggesting the lack of an association between E-cadherin promoter -160C>A polymorphism and cervix cancer stages (p=0.413), then its polymorphism and HPV infection (p=0.634). CONCLUSION: our results show that Korean women with specific polymorphism in E-cadherin promoter -160C>A are neither more susceptible to develop the cervical cancer or CIN nor more valuable for the cancer progression.

Correlation of adenoassociated virus type 2 and high-risk human papillomavirus type 16 and 18 infection in the cervix of Korean women / 대한산부인과학회지

OBJECTIVE: Previous studies were showed that adenoassocited virus (AAV) infection was had negative effects on human papillomavirus (HPV) infection and that the cervical cancer cell growth is inhibited by AAV infection. We detected of AAV 2 and high-risk HPV infection and researched correlation with AAV 2 and HPV in cervical cell. METHODS: Cell of normal cervix (49 persons), infected HPV cervix (45 persons), cervical intraepithelial neoplasm (CIN) I (31 persons), II (20 persons), III (35 persons), and invasive cancer (30 persons) were investigated by PCR using AAV-2 and HPV type 16 and 18 specific primers. RESULTS: AAV 2 was detected in 8 out of 49 normal cervix (16.3%), 2 out of 45 infected HPV cervix (4.4%), 3 out of 31 CIN I (9.7%), 4 out of 20 CIN II (20%), 8 out of 35 CIN III (22.8%), and 3 out of 30 invasive cervical cancer cases (30%). However, HPV 16 was detected in 5 out of 49 normal cervix (10.2%), 20 out of 45 infected HPV cervix (44.4%), 13 out of 31 CIN I (42%), 11 out of 20 CIN II (55%), 19 out of 35 CIN III (54.3%), and 21 out of 30 invasive cervical cancer cases (70%). HPV 18 was detected in 6 out of 49 normal cervix (12.2%), 18 out of 45 infected HPV cervix (40%), 16 out of 31 CIN I (51.6%), 10 out of 20 CIN II (50%), 22 out of 35 CIN III (62.8%), and 13 out of 30 invasive cervical cancer cases (43.3%). CONCLUSION: AAV 2 was detected in normal and infected HPV cervix, CIN (I, II, III) and invasive cervical cancer. As compared to normal, CIN I and CIN II, suggesting significant correlation between AAV 2 and HPV type 16. Further, researches continue to be done relationship to AAV 2 and HPV infection in cervix.

Papanicolaou smear in cervical intraepithelial neoplasm and invasive cancer / 대한산부인과학회잡지

OBJECTIVES: To investigate whether the aspects of Pap smear affect cervical abnormality in our country. METHODS: We compared the sensitivity of Pap smear of 241 cases of pathologic proven CIN & invasive cancer, compared to that of 655 cases with normal cervical biopsy, and reviewed the history of the test of 138 cases, retrospectively. RESULTS: The sensitivity of the test was 89.6%, 92.7% in CIN & invasive cancer group, respectively, with 96.9% specificity. Among 241 cases, 138 cases were examined for the frequency of test during the 3 years with the result of 2.42, 2.17/3yr in CIN and invasive cancer. And distribution of the test was not different between the two groups. The mean intervals of last two Pap smear before diagnosing final pathology in CIN and cancer were 12.1, 13.7 months, respectively, with no statistical significance (p>0.05). CONCLUSION: We concluded that in our country the aspects of Pap smear such as frequency and interval do not influence the result of cervical abnormality, so recommend the annual Pap test as a screening.