Cervical Intraepithelial Neoplasia grade 2 biopsy: Do p16INK4a and Ki-67 biomarkers contribute to the decision to treat? A cross-sectional study

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.

¿Está la virtud en el punto medio? La incertidumbre del CIN2 y el papel del VPH / Is virtue at the midpoint? The uncertainty of CIN2 and the role of HPV

Objetivo: La biopsia guiada por colposcopia (BGC) marca el manejo de la neoplasia intraepitelial cervical. El objetivo de este estudio fue evaluar la concordancia de los resultados entre la BGC y la escisión amplia de la zona de transformación (LLETZ, large loop excision of the transformation zone), y la utilidad del genotipado del virus del papiloma humano (VPH) para seleccionar a las pacientes con riesgo de lesión intraepitelial escamosa de alto grado/neoplasia intraepitelial cervical 3 (HSIL/CIN3). Método: Se compararon los resultados de la BGC y de la LLETZ, siendo esta última el método de referencia. Se evaluó la relación del genotipo del VPH con el diagnóstico final de HSIL/CIN3. Resultados: La precisión de la biopsia comparada con LLETZ fue del 61,4%. La tasa de concordancia fue del 64,4% para CIN1, del 31,4% para CIN2 y del 77,4% para CIN3. La tasa global de sobrediagnóstico fue del 18,68% y la de subdiagnóstico del 19,89%. En mujeres menores de 30 años, la concordancia fue del 62,79% (CIN1 65%, CIN2 39,58% y CIN3 73,08%), la tasa de sobrediagnóstico del 22,67% y la tasa de subdiagnóstico del 15,11%. La infección por VPH16 tuvo una odds ratio de 3,86 para el diagnóstico final de HSIL/CIN3+. Conclusiones: El diagnóstico de CIN2 por BGC parece insuficiente para seleccionar a las pacientes para tratamiento escisional, principalmente en mujeres jóvenes. El hallazgo de VPH16 es un factor de riesgo de HSIL/CIN3+ independientemente del resultado de la biopsia.

Objective: Colposcopy-guided biopsy (CGB) is a basic tool for the management of cervical intraepithelial neoplasia. The aim of this study is to evaluate the concordance of results between CGB and large loop excision of the transformation zone (LLETZ), and the usefulness of human papillomavirus (HPV) genotyping to select patients at risk of H-SIL/CIN3. Method: The results of colposcopy-guided biopsy and LLETZ were compared, with LLETZ being the gold standard. The relationship of HPV genotype to the final diagnosis of CIN3 was assessed. Results: The accuracy of CGB compared to LLETZ was 61.4%. The concordance rate was 64.4% for CIN1, 31.4% for CIN2 and 77.4% for CIN3. The overall overdiagnosis rate was 18.68% and underdiagnosis rate was 19.89%. In women under 30 years of age the concordance rate was 62.79% (CIN1 65%, CIN2 39.58% and CIN3 73.08%), and the rate of overdiagnosis and underdiagnosis was 22.67% and 15.11%, respectively. HPV16 infection had an odds ratio of 3.86 for the final diagnosis of CIN3+ and the result was significant regardless of the biopsy result. Conclusions: The CGB result as CIN2 is inaccurate and seems insufficient to select patients for excisional treatment, mainly in young women. HPV16 infection is a risk factor for CIN3+ regardless of the colposcopy-guided biopsy result.

Effect of Bhandira (Clerodendrum Viscosum) in Cervical Intraepithelial Neoplasia

Cervical Intraepithelial Neoplasia is precursor or pre-invasive lesions of cervical squamous cell cancers. These are classified based on the degree of disruption in epithelial differentiation. Sexually transmitted HPV are the most important risk factor for CIN and Invasive cervical cancers. A pre-post interventional study was conducted in Govt. Ayurveda College Hospital for Women and Children, Poojappura, Thiruvananthapuram, to assess the effect of Bhandira in CIN. Objectives were, to evaluate the effect of Bhandira churna pancake and Bhandira churna yoni pratisarana on CIN, and also to study its effect on HPV infection and associated complaints like discharge per vaginum, vulval itching, burning sensation, lower abdominal pain and dyspareunia. Females of age group 20-50 years with CIN, confirmed by Pap smear and Colposcopy were included. The patients received treatment with Bhandira churna pancake internally and Bhandira churna as Yoni pratisarana for 3 months and follow up was done after 3 months. Outcome variables were changes in Pap smear and Colposcopy findings- regression, persistence or progression and changes in associated symptoms. Data were analyzed by Wilcoxon’s signed rank test and McNemar’s test. The treatment was effective with high statistical significance in making changes in Pap smear and Colposcopy findings (p<0.01) and also in reducing the associated symptoms.

Accuracy of visual inspection, cytology and colposcopy in the diagnosis of high-grade cervical intraepithelial neoplasia / Acurácia da inspeção visual, citologia e colposcopia no diagnóstico da neoplasia intraepitelial cervical de alto grau

Cervical cancer is still one of the leading causes of cancer and mortality in women, especially in low- and middle-income countries. Normally, the prevention of its occurrence is done through efficient screening and treatment programs for high-grade epithelial lesions, which are pre-malignant lesions. Cheaper diagnostic techniques ensure greater access to women, which can prevent a large number of cancer cases worldwide. Objective: The aim of the study was to evaluate the accuracy of visual inspection either with acetic acid or with Lugol's iodine, cervical cytology and colposcopy in the diagnosis of cervical intraepithelial neoplasia 2 and 3. Methods: This is a study of diagnostic accuracy. We evaluated 115 women with high-grade squamous intraepithelial lesion confirmed by biopsy, 54 with cervical intraepithelial neoplasia 2 and 61 with cervical intraepithelial neoplasia 3, from January 2016 to December 2018 at the Lower Genital Tract Pathology and Colposcopy Service of the Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. A comparative analysis of the visual inspection, Pap smear and colposcopy diagnostic methods was performed. Results: The average age was 33.1 years (standard deviation=9.83) for cervical intraepithelial neoplasia 2 cases and 35.2 years (standard deviation=7.97) for cervical intraepithelial neoplasia 3. In the cervical intraepithelial neoplasia 2 group, visual inspection tests were positive for high-grade squamous intraepithelial lesion in 98.1% of the cases with acetic acid and 94.4% with Lugol's iodine. Colposcopy identified a probable high-grade squamous intraepithelial lesion in 94.4% of the cases, while cytology only in 42.6%. In the cervical intraepithelial neoplasia 3 group, the visual inspection tests were positive for high-grade squamous intraepithelial lesion in 91.8% of the cases with acetic acid and 95.1% with Lugol's iodine. Colposcopy identified a probable high-grade squamous intraepithelial lesion in 93.5% of the cases, while cytology in 65.6%. Conclusion: Visual inspection with acetic acid and Lugol's iodine, and colposcopy test were more accurate for the diagnosis of cervical intraepithelial neoplasia 2 and 3 than through cytopathology. (AU)

Introdução: O câncer do colo de útero ainda é uma das principais causas de câncer e mortalidade em mulheres, especialmente em países de baixa e média renda. Normalmente, a prevenção de sua ocorrência é feita por meio de programas eficientes de triagem e tratamento de lesões epiteliais de alto grau, que são as lesões pré-malignas. Técnicas diagnósticas mais baratas garantem maior acesso às mulheres, podendo evitar um grande número de casos de câncer no mundo inteiro. Objetivo: O objetivo deste estudo foi avaliar a acurácia da inspeção visual (com ácido acético e com solução de lugol), da citologia cervical e da colposcopia no diagnóstico de neoplasias intraepiteliais cervicais 2/3. Métodos: Trata-se de um estudo de acurácia diagnóstica. Foram avaliadas 115 mulheres com lesão intraepitelial escamosa de alto grau confirmada por biópsia, 54 com neoplasias intraepiteliais cervicais 2 e 61 com neoplasias intraepiteliais cervicais 3, no período de janeiro de 2016 a dezembro de 2018 no Serviço de Patologia e Colposcopia do Trato Genital Inferior do Hospital de Clínicas de Porto Alegre, em Porto Alegre, Brasil. Foi realizada análise comparativa dos métodos de diagnóstico Inspeção visual com ácido acético, Inspeção visual com Solução de Lugol, colpocitologia oncótica e colposcopia. Resultados: A média de idade foi de 33,11 anos (DP 9,83) para os casos de neoplasias intraepiteliais cervicais 2 e de 35,28 anos (DP 7,97) para neoplasias intraepiteliais cervicais 3. No grupo de neoplasias intraepiteliais cervicais 2, os testes de inspeção visual foram positivos para tratamento de lesões epiteliais de alto grau em 98,1% dos casos com Inspeção visual com ácido acético e em 94,4% daqueles com Inspeção visual com Solução de Lugol. A colposcopia identificou provável tratamento de lesões epiteliais de alto grau em 94,4% dos casos, enquanto a citologia apenas 42,6%. No grupo neoplasias intraepiteliais cervicais 3, os testes de inspeção visual foram positivos para tratamento de lesões epiteliais de alto grau em 91,8% dos casos com Inspeção visual com ácido acético e em 95,1% daqueles com Inspeção visual com Solução de Lugol. A colposcopia identificou provável tratamento de lesões epiteliais de alto grau em 93,5% dos casos, enquanto a citologia em 65,6%. Conclusão: A inspeção visual (com ácido acético e com Solução de Lugol) e a colposcopia foram mais precisas para o diagnóstico de neoplasias intraepiteliais cervicais 2/3 do que a citopatologia. (AU)

Detection of HPV DNA in vaginal samples self-collected by women living with HIV treated through the Brazilian public health system: Prevalence and analysis of risk factors

ABSTRACT Background: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. Methods: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. Results: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037). Conclusions: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.

Tamizaje con citología anal en mujeres con lesiones premalignas del cuello uterino / Anal cytology screening in women with premalignant lesions of the uterine cervix / Rastreamento de citologia anal em mulheres com lesões pré-malignas do colo do útero

Objetivo: nuestro objetivo principal fue evaluar la prevalencia de citología anal patológica en mujeres con antecedentes de neoplasia intraepitelial cervical. Métodos: se trata de un estudio de cohorte transversal desde mayo de 2018 a agosto de 2020 en el Centro Hospitalario Pereira Rossell. Se estudiaron dos cohortes: una de mujeres que tenían diagnóstico de neoplasia intraepitelial cervical y otra de control de mujeres sanas que asistieron al control, con una proporción de 2:1. Se calculó un tamaño muestral total de 205 pacientes, siendo 135 pacientes con NIC con un IC del 95%, suponiendo una prevalencia del 10% de lesiones preneoplásicas anales. El tamaño muestral de la cohorte control fue de 70 pacientes según la relación preestablecida. Resultados: se encontró asociación entre la presencia de lesiones premalignas cervicales y anomalías epiteliales detectadas en la citología anal, con un cociente de prevalencia de 1,77 (IC del 95%: 1,19-2,62) y un odds ratio de 2,69 (1,36-5,30). No se encontraron diferencias significativas en las variables de raza, tipo de relación sexual o tabaquismo. Conclusiones: nuestro estudio concluye que existe una asociación entre la neoplasia intraepitelial cervical relacionada con el VPH y la citología anal patológica.

Objective: the main objective of the study was to assess the prevalence of anal cytology in women with a history of cervical intraepithelial neoplasia. Method: cohort transversal study conducted from May, 2018 until August, 2020 at Pereira Rossell Hospital. Two cohorts were studied, one of which included women with a diagnosis of cervical intraepithelial neoplasia and the other one included healthy women who attended their routine follow up, in a 2:1 ratio. The total size of the sample was 205 patients, 135 of which were patients with cervical intraepithelial neoplasia (confidence interval being 95%), presuming a 10% prevalence of anal pre-neoplasic lesions. The sample size of the control cohort was 70 patients as per the pre-defined ratio. Results: a association was found between the presence of malignant lesions of the cervix and epithelial anomalies detected in the anal cytology, with a prevalence coefficient of 1.77 (CI: 95%: 1,19 - 2,62) and odds ratio of 2,69 (1,36 - 5,30). No significant differences were found between race, type of sexual relationships or smoking variables. Conclusions: our study concludes there is an association between cervical intraepithelial neoplasia related to HPV and pathological anal screening.

Objetivo: Avaliar a prevalência de citologia anal patológica em mulheres com história de neoplasia intraepitelial cervical. Métodos: Trata-se de um estudo de coorte transversal de maio de 2018 a agosto de 2020, no Hospital Pereira Rossell. Foram estudadas duas coortes, uma de mulheres com diagnóstico de neoplasia intraepitelial cervical e outra de controle de mulheres saudáveis que compareceram ao controle na proporção de 2:1. Foi calculada uma amostra total de 205 pacientes, 135 pacientes com NIC com um IC de 95%, assumindo uma prevalência de 10% de lesões pré-neoplásicas anais. O tamanho da amostra da coorte controle foi de 70 pacientes de acordo com a relação pré-estabelecida. Resultados: Foi encontrada associação entre a presença de lesões pré-malignas cervicais e anormalidades epiteliais detectadas na citologia anal, com razão de prevalência de 1,77 (IC 95%: 1,19 - 2,62) e odds ratio 2,69 (1,36-5,30). Não foram encontradas diferenças significativas nas variáveis raça, tipo de relação sexual ou tabagismo. Conclusões: Nossos resultados mostram uma associação entre neoplasia intraepitelial cervical relacionada ao HPV e citologia anal patológica.

The trend and challenge of DNA methylation clinical application in cervical cancer / 中华检验医学杂志

According to the current cervical cancer screening strategy and the World Health Orgnization cervical cancer diagnosis/screening guidelines, gene methylation will be included in the new guidelines in the future. However, the value of detecting DNA methylation at specific sites in the clinical specimens during the cervical cancer treatment remains to be discussed. This article summarised the role of DNA methylation in the development of cervical cancer and discusses the potential clinical application of methylation detection in the management of high-risk human papillomavirus (hrHPV) positive female patients. It is believed that methylation test can not only be used for the preliminary classification of hrHPV positive female patients, but also for the secondary triage of female patients with slight cytological abnormalities to determine the high risk of cervical intraepithelial neoplasia 3(CIN3) or cancer. It can also be used for the withdrawal test of women in the screening program to support the management of CIN.

Impacto de la pandemia COVID-19 en el tiempo entre la detección de lesiones premalignas de cuello de útero y su tratamiento

Introducción: la pandemia por COVID-19 ha afectado la salud de la mujer y en particular a los derechos sexuales y reproductivos. En el contexto de cambios asistenciales por la pandemia COVID 19, podría verse afectado el tamizaje y seguimiento de las lesiones premalignas de los cánceres de cuello de útero (CCU), poniendo en riesgo su diagnóstico oportuno y tratamiento precoz. El objetivo de este estudio es reportar los tiempos transcurridos entre el resultado de screening patológico y el tratamiento de lesiones premalignas de CCU, cotejando con los plazos establecidos por la ordenanza ministerial vigente y comparando los tiempos observados antes y durante la pandemia. Métodos: se realizó un estudio observacional, analítico, de corte transversal, mediante un análisis comparativo antes y después de la pandemia por COVID-19. Se incluyeron usuarias a quienes se les realizó conización quirúrgica en el Centro Hospitalario Pereira Rossell en dos períodos de tiempo: 1 de marzo de 2019 a 29 de febrero de 2020, y 1 de marzo de 2020 a 28 de febrero de 2021. Resultados: la media en días observada desde el PAP hasta la conización fue de 245 para el primer periodo y de 242 para el segundo. El porcentaje de pacientes que cumplen con la ordenanza ministerial en ambos períodos no supera el 5%. Conclusiones: no se evidenció una mayor demora en el seguimiento y tratamiento de estas usuarias durante la pandemia por COVID-19, sin embargo los tiempos observados superan ampliamente los establecidos por Ordenanza Ministerial en los periodos pre pandemia y durante la misma.

Introduction: the COVID-19 pandemic has affected women's health in general, and in particular their sexual and reproductive rights. Within the context of changes in health care services due to the COVID-19 pandemic, the screening and follow up of cervical precancerous lesions could be affected, and in turn, this could prevent timely diagnosis and early treatment. This study aims to report the period of time be-tween pathological findings in screening tests and the treatment of precancerous lesions of cervical cancer, analyze it within the context of deadlines set in the Ministry of Health regulations in force, and compare it to pre-pandemic deadlines and time frames during the COVID-19 pandemic. Method: observational, analytical and transversal study conducted by means of analyzing the situation before and after the COVID-19 pandemic. The study included users who underwent surgical conization at the Pereira Rossell Hospital during two periods of time: Between March 1, 2019 and February 29, 2020 and between March 1, 2020 and February 28, 2021. Results: average number of days from the PAP test until conization was 245 days for the first period and 242 for the second one. The percentage of patients that comply with the Ministerial decree in both periods is lower than 5%. Conclusions: the study found time to treatment in the follow up and management of users did not increase during the COVID-19 pandemic. However, the times ob-served widely exceed the deadlines set in the ministerial decree in both periods, that is before and during the pandemic.

Introdução: a pandemia de COVID-19 afetou a saúde das mulheres e em particular os direitos sexuais e reprodutivos. No contexto das mudanças na saúde devido à pandemia de COVID 19, o rastreamento e o acompanhamento das lesões pré-malignas do câncer de colo de útero (CCU) podem ser afetados, colocando em risco o diagnóstico oportuno e o tratamento precoce. Objetivo: descrever os tempos decorridos entre o resultado do rastreamento patológico e o tratamento das lesões pré-malignas do CCU, comparando-os com os períodos estabelecidos pela atual Portaria Ministerial, e comparar os tempos observados antes e durante a pandemia. Métodos: foi realizado um estudo observacional, analítico e transversal por meio de uma análise comparativa antes e após a pandemia de COVID19. Foram incluídos as usuárias que realizaram a conização cirúrgica no Hospital Pereira Rossell em dois períodos de tempo: 1º de março de 2019 a 29 de fevereiro de 2020 e 1º de março de 2020 a 28 de fevereiro de 2021. Resultados: a média de dias observados do PAP à conização foi de 245 para o primeiro período e 242 para o segundo. O percentual de pacientes que cumprem a Portaria Ministerial em ambos os períodos não ultrapassa 5%. Conclusões: não houve evidência de maior demora no acompanhamento e tratamento desses usuários durante a pandemia por COVID-19, porém os tempos observados superam em muito os estabelecidos por Portaria Ministerial nos períodos pré-pandemia e durante a mesma.

Cervical Intraepithelial Neoplasia: Analyzing the Disease Present Exclusively in the Endocervical Canal / Neoplasia intraepitelial cervical: Analisando a doença presente exclusivamente no canal endocervical

Abstract Objective To evaluate the role of cervical cytology (Pap smear) in the diagnosis of cervical intraepithelial neoplasia 2 or greater (CIN2+), presented exclusively in the endocervical canal, the clinical-epidemiological characteristics of this lesion, the necessary length of canal to be removed to treat, and the rate of invasive lesion hidden in the endocervical canal. Methods Cross-sectional study, by database analysis, of patients with abnormal cytology (high-grade squamous intraepithelial lesion [HSIL]), without visible colposcopy lesion, submitted to loop electrosurgical procedure (LEEP) to evaluate the association of cytology results with the histological product of the conization, to identify the epidemiological characteristics of endocervical lesion and clinical evolution, using a pvalue< 0.05 and 95% CI. Results In 444 cases, the Pap smear sensitivity for CIN2+ diagnosis was 75% (95% CI: 69.8-79.7), specificity was 40% (95% CI: 30.2-49.5), and the prevalence rate of histological lesion was 73% (95% CI: 70.1-78.7). There was a higher prevalence of CIN2+ in women over 42 years old and invasive cancer in those over 56 years old (p<0.001), and it was necessary to remove 2.6 cm in length of the canal to reduce the chance of recurrence (p<0.006). The rate of invasive cancer was 2.7%. Conclusion Cytology was related to a high prevalence to histological lesion (73%) in the diagnosis of CIN2+ in the endocervical disease; older patients presented a higher relationship with histological lesions in the canal disease, and it was necessary to remove an average of 2.6 cm in length of the endocervical canal to avoid the persistence and progression of CIN. The rate of occult neoplasia in the endocervical canal was 2.7%.

Resumo Objetivo Avaliar o papel da citologia oncótica (CO) no diagnóstico da neoplasia intraepitelial cervical 2 ou maior (NIC2+) presente exclusivamente no canal endocervical, as características clínico-epidemiológicas deste tipo de lesão, o comprimento necessário de canal a ser retirado na conização, e a taxa de lesão invasora oculta no canal endocervical. Métodos Estudo transversal, por análise de base de dados, de pacientes comcitologia alterada, sem lesão colposcópica visível, submetidas a conização por cirurgia de alta frequência (CAF), para avaliar a associação dos resultados citológicos com o produto histológico da conização, as características epidemiológicas da lesão endocervical, e evolução clínica, utilizando o valor de p<0.05 e intervalo de confiança (IC) de 95%. Resultados Nos 444 casos analisados, a sensibilidade da CO para o diagnóstico de NIC 2+ foi de 75% (IC 95%: 69.8-79.7), a especificidade foi de 40% (IC 95%: 30.2-49.5), e a taxa de prevalência de lesão histológica foi de 73% (IC 95%: 70.1-78.7). Houve maior prevalência de NIC2+ em pacientes com mais de 42 anos de idade e de neoplasia invasora naquelas commais de 56 anos (p<0.001), e foi necessário a retirada de 2.6 cm de comprimento de canal para diminuir a taxa de recidiva (p<0.006). Foi identificada uma taxa de 2.7% de neoplasia invasora. Conclusão A citologia esteve relacionada a uma alta prevalência de lesão (73%) no diagnóstico das NIC2+ na doença endocervical; quanto maior a idade, maior foi a relação da histologia com a citologia de canal, e se fez necessário retirar uma média de 2.6 cmde comprimento de canal para evitar a persistência e a progressão da NIC. A taxa de neoplasia oculta no canal endocervical foi 2.7%.

When is There no Benefit in Performing a Biopsy in the Suspicion of Intraepithelial Lesions of the Cervix? / Quando não há benefício em realizar biópsia na suspeita de lesões intraepiteliais do colo uterino?

Abstract Objective To evaluate whether colposcopy-directed biopsy is necessary to increase the accuracy of diagnosing cervical intraepithelial lesions in relation to colposcopy. Methods We performed a retrospective, observational study by analyzing medical records obtained fromHospital de Clínicas do Paraná fromFebruary 2008 to February 2018. Patients with results of Pap tests, colposcopy, colposcopy-directed biopsy, and surgical procedures (high-frequency surgery or cold conization) were included. Data such as quadrants involved during colposcopy and age differences were also analyzed. Results A total of 299 women were included. Colposcopy was found to have an accuracy rate of 76.25% (95% confidence interval [CI], 71.4-81.1). Among the highest-grade lesions, the accuracy rate was 80.5% (95% CI, 75.7-85.3). The accuracy rates for biopsy were 79.6% (95% CI, 75-84.2) and 84.6% (95% CI, 80-89.1) for the highest-grade lesions. High-grade lesions were accurately confirmed in 76.9% and 85% of patients with 1 and 2 or more affected quadrants, respectively. For women younger than 40 years, the accuracy rates were 77.6% and 80.8% for colposcopy and biopsy, respectively. For women 40 years or older, the accuracy rates were 72.5% and 76.3% for colposcopy and biopsy, respectively. Conclusion There is no difference between the accuracy of colposcopy and that of biopsy in diagnosing cervical intraepithelial lesions in relation with the result of conization. The patients who received the greatest benefit when biopsy was not performed were those with high-grade lesions at colposcopy, a lesion involving 2 or more quadrants, and those younger than 40 years.

Resumo Objetivo Avaliar se a biópsia colpodirigida é necessária para aumentar a acurácia diagnóstica nas lesões intraepiteliais de colo uterino em relaçãoà colposcopia. Métodos Estudo retrospectivo, observacional, incluindo pacientes submetidas a colposcopia, biópsia colpodirigida, e procedimento cirúrgico (cirurgia de alta frequência ou conização a frio), no período de fevereiro de 2008 a fevereiro de 2018, no Hospital de Clínicas da Universidade Federal do Paraná. Dados como número de quadrantes da lesão presentes na colposcopia, número de fragmentos retirados nas biópsias e diferenças por idade também foram analisados. Resultados Um total de 299 mulheres foram incluídas. Foi encontrada uma acurácia de 76,25% (intervalo de confiança [IC] 95% 71,4-81,1) entre a colposcopia e a conização, sendo 80,5% % (IC 95% 75.7-85.3) nas lesões de maior grau. A acurácia da biópsia foi de 79,6% (IC 95% 75-84,2), sendo 84,6% (IC 95% 80-89,1) nas lesões de maior grau. Pacientes com 1 quadrante acometido tiveram confirmação de 76,9% nas lesões de maior grau, enquanto as com 2 quadrantes acometidos apresentaram o mesmo resultado em 85% dos casos. A acurácia com a biópsia de 1 fragmento foi de 78% e com2 ou mais fragmentos 80%. Paramulheres com menos de 40 anos, a acurácia foi de 77,6% e 80,8% para colposcopia e biópsia, respectivamente. Para mulheres com 40 anos ou mais, a acurácia foi de 72,5% e 76,3% para colposcopia e biópsia, respectivamente. Conclusão Não há diferença entre a acurácia da colposcopia e a da biópsia colpodirigida no diagnóstico de lesões intraepiteliais cervicais em relação ao resultado da conização. As pacientes que tiveram o maior benefício quando a biópsia não foi realizada foram as que apresentaram lesão de alto grau na colposcopia e aquelas com menos de 40 anos, não existindo benefício emrealizar biópsia previamente a conização neste grupo de pacientes.

Limitation of cytology and the impact on reduction of cervical cancer / Limitação da citologia e o impacto na redução do câncer de colo uterino

Introduction: Cervical cancer is the third most common malignant tumor in the female population and the fourth cause of death from cancer in women in Brazil. The squamocolumnar junction and the transformation zone concentrate 90% of pre-invasive and invasive cervical lesions. Objective: To evaluate the prevalence of cytology without cells of the squamocolumnar junction and feasibility of active search. Methods: Cross-sectional study at a university hospital between 2017 and 2018. The prevalence of cytology without squamocolumnar junction cells was calculated. A convenience sample was obtained and mean age and relationship with presence of transformation zone cells were calculated. An active search was performed and cytology collected, with estrogen preparation if indicated. Medical records of the other women were analyzed. Results: Squamocolumnar junction cells were not found in 28.84% of samples. Mean age was 53 years, without association with presence of squamocolumnar junction cells (p=0.409). Seventy-six women returned, 36 of which (47.37%) used estrogen. Level 2 or 3 cervical intraepithelial neoplasia, microinvasive carcinoma or cancer was not identified. A total of 134 medical records were analyzed; only 36 women (26.87%) completed screening. Conclusions: The presence of squamocolumnar junction cells indicates quality of cytology; the use of estrogen in postmenopausal women favors its collection. There were difficulties in active search. An immediate repetition of cytology should be considered.

Introdução: O câncer de colo uterino é o terceiro tumor maligno mais frequente na população feminina e a quarta causa de morte de mulheres por câncer no Brasil. A junção escamo-colunar e a zona de transformação concentram 90% das lesões pré-invasoras e invasoras cervicais. Objetivo: Avaliar prevalência de colpocitologias sem células da junção escamo-colunar e a viabilidade de busca ativa. Métodos: Estudo transversal em hospital universitário entre 2017 e 2018. Calculada prevalência de citologias sem células da junção escamo-colunar. Obtida amostra por conveniência, calculada média de idade e relação com a presença da junção escamo-colunar. Realizada busca ativa e colhidas citologias com preparo estrogênico, se indicado. Analisados os prontuários das demais mulheres. Resultados: A prevalência de ausência de células da junção escamo-colunar foi de 28,84%. A média de idade foi 53 anos, sem associação com presença da junção escamo-colunar (p=0,409). Retornaram 76 mulheres e 36 (47,37%) usaram estrogênio. Não identificamos neoplasia intraepitelial cervical graus 2 ou 3, carcinoma microinvasor e câncer. Analisados 134 prontuários, dos quais apenas 36 mulheres (26,87%) concluíram o rastreio. Conclusões: A presença de células da junção escamo-colunar indica qualidade da coleta, e o uso de estrogênio na pós-menopausa favorece sua obtenção. Houve dificuldade de busca ativa. A repetição imediata da citologia deve ser considerada.

Characteristics of cervical lesions in 1 080 patients with abnormal colposcopic biopsies of TCT and HPV double screening in Shihezi region / 中国医师杂志

Objective:To explore the characteristics of cervical lesions in female patients in the Shihezi region of Xinjiang in the past two years and provide guidance for clinical work and local cervical cancer screening.Methods:The clinicopathological data and characteristics of 1 080 patients with abnormal double screening of human papilloma virus (HPV) and cervical exfoliative cell test (TCT) and vaginal mirror cervical tissue biopsy in the gynecology department of the First Affiliated Hospital of Medical College of Shihezi University from May 2017 to March 2019 were analyzed retrospectively. The influencing factors of cervical lesions were analyzed by logistic regression.Results:(1) Uneducated [odds ratio ( OR)=2.267], irregular vaginal bleeding ( OR=3.275) and number of sexual partners ≥3 ( OR=3.052) were independent risk factors for cervical lesions. (2) Cervical intraepithelial neoplasia (CIN) was detected most frequently in the 30-39 age group (57.54%), and cervical cancer was detected most frequently in the ≥60 age group (14.15%), followed by the 40-49 age group (2.20%). (3) The proportion of HPV positive and the positive rate of high-risk HPV16/18 in the 40-49 age group were the highest, 33.18% and 39.38% respectively. There was no statistically significant difference in HPV viral load between the different age groups ( P>0.05). (4) The detection rates of CIN3 and cervical cancer were higher in the HPV16/18-positive group than in the HPV-positive and TCT≥atypical squamous epithelial cells of undermined significance (ASC-US) group (18.34% vs 11.33%, 4.30% vs 1.82%), with statistically significant difference (all P<0.05), respectively. The detection rate of CIN2 was higher in the high-load group (28.44%) than in the medium-load group (25.32%) and the low load group (15.79%). (5) The detection rate of CIN3 in the HPV-positive TCT for the ASC-US populations was significantly higher in the HPV16/18-positive group than in the other subtypes of HPV-positive group (21.43% vs 8.33%, P<0.05). Conclusions:During cervical cancer screening in Shihezi region, we should strengthen the publicity of elderly women and uneducated people. CIN and cervical carcinoma in Shihezi region are closely associated with high-risk HPV infection, especially HPV16/18 infection. HPV-positive age is mainly concentrated in the age group of 40-49 years, and the detection rate of CIN and cervical cancer is the highest in the age group of 30-39 years and ≥60 years, respectively. The detection rate of ≥CIN2 in HPV16/18 fraction and high viral load population is higher than that of other HPV subtypes positive and low to medium load populations. How to effectively shunt HPV positive TCT is an important problem in ASC-US population, which needs further research.

Stratified research on related risk factors of CINⅡ + in CINⅠ patients diagnosed by endocervical curettage under colposcopy / 中华妇产科杂志

Objective:To estimate risks of cervical intraepithelial neoplasia (CIN) Ⅱ or worse (CINⅡ +) on loop electrosurgical excisional procedure (LEEP) specimens with the diagnosis of endocervical curettage (ECC) CINⅠ compared with biopsy CINⅠ, and also to investigate the hierarchical management scheme of ECC CINⅠ based on the relevant factors of CINⅡ + risk. Methods:(1) A retrospective computer-based research for subjects enrolled in the Obstetrics and Gynecology Hospital, Fudan University from Jan. 2013 to Jun. 2021 was performed. The case group comprised women with an ECC CINⅠ (ECC results of CINⅠ with colposcopy-directed biopsy results ≤CINⅠ), and the control group comprised women with a biopsy CINⅠ (colposcopy-directed biopsy results of CINⅠ with negative ECC findings) were divided after LEEP surgery and diagnosis in the next three months. The clinical data of all patients before LEEP were analyzed, and the pathological diagnosis between two groups after LEEP was compared. (2) Variables, including age, cytology, high-risk human papillomavirus (HR-HPV), ECC results, cervical transformation zone (TZ) and colposcopy impression, were included to describe the characteristics and compare the incidence of LEEP CINⅡ +. (3) Univariate analysis and Multivariate logistic regression method were used to analyze the related factors that affect the LEEP CINⅡ + in CINⅠ patients. Further, the specific risks caused by related factors and conduct a stratified study in LEEP CINⅡ + were analyzed. Results:(1) Overall, 2 581 women with ECC CINⅠ or biopsy CINⅠ diagnosis who underwent LEEP participated in the study with the mean age (43.6±9.5) years old. Chi square test found that the age and cytology of patients in ECC CINⅠ group were statistically different from those of biopsy CINⅠ group (all P<0.05). There was no significant difference in HR-HPV detection, TZ type and colposcopy impression between the two groups (all P>0.05). ECC CINⅠ comprised 957 women, with LEEP histopathology results revealing 288 (30.1%, 288/957) CINⅡ +, which was significantly higher than that of biopsy CINⅠ which was comprised 1 624 women, with LEEP histopathology results showing 333 (20.5%, 333/1 624) CINⅡ + ( χ2=30.31, P<0.001). (2) Compared by LEEP CINⅡ + with LEEP ≤CINⅠ group, there were no significant difference in the age, HR-HPV, colposcopy impression (all P>0.05); but there were significantly differences in cytology, ECC CINⅠ, type Ⅲ TZ (all P<0.001). Multivariate logistic regression analysis showed that atypical squamous epithelial cells (ASC-H; OR=2.77, 95% CI: 2.04-3.77), high-grade squamous intraepithelial lesions and worse (HSIL +; OR=2.93, 95% CI: 2.24-3.81), ECC CINⅠ ( OR=1.89, 95% CI: 1.56-2.29) and type Ⅲ of TZ ( OR=1.76, 95% CI: 1.45-2.11) were independent risk factors for LEEP CINⅡ + (all P<0.05). (3) When cytology was ≤low-grade squamous intraepithelial lesion (LSIL) and ≥ASC-H, the detection rate of CINⅡ + in ECC CINⅠ was significantly higher than that of biopsy CINⅠ (all P<0.001). In ECC CINⅠ, the rate of CINⅡ + with cytology ≤LSIL was significantly lower than that in cytology ≥ASC-H (56.0% vs 25.9%; χ2=49.38, P<0.001). In type Ⅰ/Ⅱ of TZ, the detection rate of CINⅡ + between ECC CINⅠand biopsy CINⅠ had no significantly different; while in type Ⅲ of TZ, there was significantly different (72.7% vs 46.2%; χ2=4.02, P=0.045). In ECC CINⅠ, type Ⅲof TZ was significantly higher in the rate of CINⅡ + than that of type Ⅰ/Ⅱ of TZ (72.7% vs 21.7%; χ2=16.38, P<0.001). When cytology ≥ASC-H, type Ⅲ of TZ and colposcopy impression of HSIL were combined, the rate of CINⅡ + in ECC CINⅠ was 6/6 while 1/3 in biopsy CINⅠ. Conclusions:Cytology ≥ASC-H, ECC CINⅠ and type Ⅲ TZ are the risk factors of LEEP CINⅡ +. However, cytology ≥ASC-H is more valuable in predicting LEEP CINⅡ + than ECC CINⅠ. For patients with ECC CINⅠ to perform LEEP, it is recommended that cytology ≥ASC-H is taken as the first level stratification, and type Ⅲ TZ is taken as the second level stratification. The colposcopy impression of patients is recommended for a reference parameter.

The value of colposcopy in referral of cervical high-risk HPV positive women / 中国医师杂志

Objective:To investigate the clinical value of referral colposcopy in cervical high-risk human papillomavirus (HR-HPV) positive women in cervical cancer screening.Methods:Totally 2 445 cases, which were referred for colposcopic cervical biopsy for cervical HR-HPV positive in Karamay Central Hospital from January 2018 to November 2021 were collected. The status of cervical HR-HPV positive transferred colposcopy in different situations to identify high-grade squamous intraepithelial lesions (HSIL) and above (HISL+ ) was analyzed. The value of referral colposcopy in cervical HR-HPV positive women under different conditions was evaluated.Results:2 445 HR-HPV positive women were referred for colposcopic cervical biopsy, which confirmed 1 447 cases of negative for intraepithelial lesion or malignancy (NILM), 362 cases of low grade squamous intraepithelia lesion (LSIL), 510 cases of HSIL and 126 cases of squamous cell carcinoma (SCC); The complete coincidence rate between colposcopy diagnosis and pathological diagnosis was 67.08%(1 640/2 445), and the Kappa value of consistency test was 0.489. The sensitivity and specificity of colposcopy in the diagnosis of LSIL+ were 91.28% and 69.38%, and HSIL+ were 74.52% and 93.15%. The detection rates of HSIL+ in HPV16/18 positive and other 12 HPV positive patients with abnormal cervical liquid based cytology (TCT) were 64.78%(103/159) and 78.79%(364/462), respectively. The positive rates of HPV16/18 and 12 other HPV positive HSIL+ with normal TCT were 16.46%(82/498) and 6.56%(87/1 326), respectively. The rate of detecting HSIL+ in abnormal areas under colposcopy was 44.69%(534/1 195), and that in routine biopsy was 8.16%(102/1 250).Conclusions:Among the referred for colposcopic cases, the detection rate of HSIL+ was higher in cases with cervical HR-HPV positive and TCT abnormalities. Colposcopy has obvious value in identifying cervical lesions. The accurate diagnosis of cervical lesions is based on cervical biopsy under colposcopy.

Neoplasia intraepitelial escamosa cervical de alto grau: abordagem ambulatorial / High-grade cervical intraepithelial neoplasia: outpatient approach

As neoplasias intraepiteliais cervicais correspondem a alterações identificadas por rastreamento citológico cervical e estudo histológico, pós-biópsia incisional guiada por colposcopia ou procedimento diagnóstico excisional. Podem ser tratadas com abordagens conservadoras e procedimentos excisionais. A vacinação anti-HPV e o tratamento excisional oportuno constituem, respectivamente, prevenção primária e secundária contra o câncer do colo uterino.(AU)

Cervical intraephitelial neoplasms correspond to changes identified by cervical citological screening and histological study, post-incisional biopsy guided by colposcopy or excisional diagnostic procedure. They can be treated with conservative approaches and excision procedures. Anti-HPV vaccination and timely excional treatment are primary and secondary prevention against cervical cancer, respectively.(AU)

Perfil dos exames citopatológicos do colo do útero de mulheres residentes no estado de Minas Gerais / Profile of cytopathological examinations of the cerever of women resident in the state of Minas Gerais

Introdução: O diagnóstico precoce e referenciamento ao serviço especializado são essenciais para melhorar as taxas de cura e sobrevida das mulheres acometidas pelo câncer de colo de útero. Assim, a realização deste estudo tornará possível o levantamento de informações que serão essenciais para o desenvolvimento de medidas preventivas, que almejam contribuir com o desenvolvimento de ações de educação em saúde e o diagnóstico precoce para reduzir a morbimortalidade dessa enfermidade. Objetivo: Identificar o perfil dos resultados dos exames citopatológicos do colo do útero de mulheres residentes no estado de Minas Gerais a partir dos dados de exames correspondentes ao ano de 2019, utilizando as variáveis disponibilizadas pelo Sistema de Informação do Câncer. Métodos: Trata-se de um estudo retrospectivo, exploratório, quantitativo realizado por meio de base de dados secundários. Os dados foram submetidos à análise no software SPSS, versão 20.0. Realizou-se estatística descritiva (frequência absoluta, porcentagem, média e desvio padrão). Para verificar associação entre variáveis qualitativas foi utilizado teste qui-quadrado (x²) e exato de Fisher. A força das associações entre as variáveis foi aferida pelo risco relativo (RR) e intervalos de confiança (IC 95%). Resultados: As principais alterações presentes nos exames foram: alterações por células escamosas atípicas de significado indeterminado e lesão intraepitelial de baixo grau. Após análises estatísticas, notou-se que algumas alterações possuem risco maior de se desenvolverem no público fora da faixa etária preconizada, ou seja, entre mulheres com idade <25 anos ou >64 anos. Conclusão: O estudo realizado contribui para identificação do perfil atual vivenciado na área da saúde da mulher e possibilita a criação de condutas e ações que visem intervir frente aos resultados obtidos, impactando positivamente na realidade de Minas Gerais

Introduction: Early diagnosis and referral to a specialized service are essential to improve the cure and survival rates of women affected by cervical cancer. Thus, carrying out this study will make it possible to collect information that will be essential for the development of preventive measures, which aim to contribute to the development of health education actions and early diagnosis to reduce the morbidity and mortality of this disease. Objective: Identify the profile of the results of cervical cytopathological examinations of women residing in the State of Minas Gerais from the data of examinations corresponding to the year 2019, using the variables made available by the Cancer Information System.Methods: This is a retrospective, exploratory, quantitative study carried out by means of a secondary database. The data were submitted to analysis using the SPSS software, version 20.0. Descriptive statistics (absolute frequency, percentage, mean and standard deviation) were performed. To verify the association between qualitative variables, the chi-square test (x²) and Fisher's exact test were used. The strength of the associations between the variables was measured by the relative risk (RR) and confidence intervals (95% CI). Results: The main alterations present in the cytopathological exams performed were: changes due to atypical squamous cells of undetermined significance and low- grade intraepithelial lesion. After statistical analysis, it was noted that some changes have a higher risk of developing in the public outside the recommended age range, that is, among women aged <25 years or> 64 years. Conclusion: The study carried out contributes to the identification of the current profile experienced in the area of women's health and enables the creation of conducts and actions that aim to intervene in view of the results obtained, positively impacting the reality of Minas Gerais.

Perfil do rastreamento do câncer do colo do útero em Campo Grande, Mato Grosso do Sul: um estudo avaliativo do período 2006-2018 / Perfil de seguimiento del cáncer de cuello uterino en Campo Grande, Mato Grosso do Sul, Brasil: un estudio evaluativo del periodo 2006-2018 / Profile of cervical cancer screening in Campo Grande, Mato Grosso do Sul, Brazil: an evaluative study, 2006-2018

Objetivo: Avaliar a cobertura e a qualidade do rastreamento do Programa de Controle do Câncer do Colo do Útero (PCCCU) em Campo Grande, Mato Grosso do Sul, Brasil, 2006-2018. Métodos: Estudo descritivo da tendência da série histórica de exames citopatológicos para rastreamento do CCU em mulheres residentes em Campo Grande. Foram descritas características demográficas das mulheres avaliadas e a qualidade dos exames realizados nos cinco últimos anos do período. Analisou-se a tendência temporal por modelos de regressão polinomiais. Resultados: Foram registradas 578.417 citologias, das quais 1,8% apresentaram alterações citológicas pré-malignas/malignas. Na faixa etária-alvo do programa, verificou-se redução de 48,4% no número de exames realizados. A positividade dos exames variou entre 2,2% e 3,3% e aumentou o percentual de amostras insatisfatórias. Conclusão: O programa de rastreamento de CCU apresenta fragilidades que necessitam ser superadas, como baixa cobertura da população-alvo, crescimento do número de amostras insatisfatórias e baixo índice de positividade.

Objetivo: Evaluar la cobertura y calidad del tamizaje del programa de control de cáncer cervicouterino en Campo Grande, MS, Brasil, entre 2006-2018. Métodos: Estudio descriptivo de la serie histórica de exámenes citopatológicos en mujeres de Campo Grande. Se realizó un análisis descriptivo de las características demográficas de las mujeres y la calidad de los exámenes realizados en los últimos cinco años del período. La tendencia temporal se analizó mediante modelos de regresión polinómica. Resultados: Se registraron 578.417 citologías, de las cuales el 1,8% mostró alteraciones citológicas. En la población objetivo del programa, hubo reducción del 48,4% en el número de pruebas realizadas. La positividad de las pruebas varió entre 2,2% y 3,3% y aumentó el porcentaje de muestras no satisfactorias. Conclusión: El programa de cribado tiene debilidades que es necesario superar, como baja cobertura de la población objetivo, crecimiento del número de muestras insatisfactorias y baja tasa de positividad.

Objective: To assess the coverage and quality of screening by the Cervical Cancer Control Program in Campo Grande, Mato Grosso do Sul, Brazil, between 2006 and 2018. Methods: This was a descriptive study of the cytology screening time series among women living in Campo Grande. A descriptive analysis of the demographic characteristics of these women and the quality of the tests performed in the last five years of the period was carried out. Temporal trends were analyzed using polynomial regression models. Results: 578,417 cytology tests were recorded, of which 1.8% showed pre-malignant/malignant cytological changes. There was a 48.4% reduction in the number of tests performed in the Program's target age group. Test positivity varied between 2.2% and 3.3% and the percentage of unsatisfactory samples increased. Conclusion: The cervical cancer screening program has weaknesses that need to be overcome, such as low coverage of the target population, growth in the number of unsatisfactory samples and a low positivity rate.

Riesgo de desarrollar LIE-AG en pacientes con tamizaje inicial positivo para VPH y citología cervicovaginal negativa en seguimiento hasta 10 años: revisión sistemática y metaanálisis / Risk of developing H-SIL in patients with initial positive screening for HPV and negative cervicovaginal cytology in follow-up up to 10 years: systematic review and meta-analysis

Resumen Introducción: El cáncer de cérvix es el segundo en frecuencia y el tercero en mortalidad; la infección por el virus del papiloma humano (VPH) está asociada al riesgo de cáncer; sin embargo, no se conoce el riesgo acumulado a 1, 2, 3, 5 y 10 años. Objetivo: Determinar el riesgo de las pacientes VPH positivo con evaluación inicial citológica negativa para desarrollar lesión intraepitelial de alto grado a lo largo del tiempo. Método: Se realizó una revisión sistemática de artículos en inglés y español de los últimos 20 años, usando las bases de datos PubMed, Cochrane, LILACS, ProQuest y Embase. Se incluyeron ensayos clínicos aleatorizados en los que se determinaba el estado VPH y se realizaba seguimiento con citología cervicovaginal a 1, 2, 3, 5 y 10 años en mujeres de 20-64 años. Resultados: Se incluyeron siete ensayos clínicos aleatorizados, con un total de 98.521 mujeres, de ellas 8820 VPH positivo y 89.701 VPH negativo al ingreso, seguidas hasta por 10 años con citología cervicovaginal, encontrando que la infección por VPH es un factor de riesgo para desarrollar lesiones intraepiteliales de alto grado a 2, 5 y 10 años, con un riesgo relativo de 110.94 (79.41-154.97), 83.65 (55.22-126.73) y 29.71 (5.72-154.33), respectivamente. Conclusiones: La infección por VPH es un factor de riesgo importante para el desarrollo de lesiones intraepiteliales de alto grado a 2, 5 y 10 años.

Abstract Introduction: Cervical cancer is the second in frequency and the third in mortality, infection by the human papillomavirus (HPV) is associated with the risk of increased cancer; however, the cumulative risk of 1, 2, 3, 5 and 10 years is not known. Objective: To determine the risk of HPV-positive patients with negative initial cytological evaluation for developing high-grade intraepithelial lesion over time. Method: A systematic review of articles in English and Spanish in the last 20 years was carried out, using the PubMed, Cochrane, LILACS, ProQuest and Embase databases. Randomized clinical trials were included in which HPV was performed and subsequent follow-up with cervicovaginal cytology at 1, 2, 3, 5 and 10 years in women aged 20-64 years. Results: Seven randomized clinical trials were included, a total of 98,521 women, 8820 with positive HPV and 89701 negative on admission and followed up for up to 10 years with cervicovaginal cytology. Finding that HPV infection is a risk factor for developing high-grade intraepithelial lesion at 2, 5 and 10 years with a relative risk of 110.94 (79.41-154.97), 83.65 (55.22- 126.73) and 29.71 (5.72-154.33), respectively. Conclusions: HPV infection is an important risk factor for the development of high-grade intraepithelial lesion at 2, 5 and 10 years.

Differences in HPV infection and HPV-related lesions between the cervix and anus in hiv-positive women / Diferenças na infecção por HPV e lesões HPV-relacionadas entre colo uterino e ânus em mulheres hiv positivas

Introduction: the prevalence of cervical and anal human papillomavirus (HPV) infection in women infected with human immunodeficiency virus (HIV) is high. However, little is known about the differences in the susceptibility of these infections and related lesions. The aim of this study was to describe the association between the prevalence of cervical and anal HPV infection and HPV-related lesions in HIV-positive women. Methods: this study included 88 HIV-positive women attending an outpatient clinic in a university hospital. Ectocervical, endocervical, and anal samples were collected for colpocytology and anal cytology. A polymerase chain reaction-based technique was used to detect HPV deoxyribonucleic acid in endocervical and anal swab samples. Results: the cervical and anal HPV positivity rates were 35.21% and 78.8%, respectively. The presence of HPV-related lesions on colpocytology was associated with anal HPV positivity (P = 0.027). The ratio between cervical HPV infection and cervical HPV-related lesions was 2.5. The ratio between anal HPV infection and anal HPV-related lesions was 4.3. Overall, 30% had concomitant HPV DNA in the cervix and anus. Conclusion: there are differences in the susceptibility of infections and related lesions between the cervix and anus. Despite a higher incidence of anal HPV, the progression to HPV-related lesion does not occur via the same manner in the cervix and anus. Moreover, cervical HPV-related lesions in HIV-positive women may serve as a cue for anal preventive strategies, and further investigations in these women may be useful.

Introdução: as infecções cervicais e anais pelo papilomavírus humano (HPV) em mulheres infectadas com o vírus da imunodeficiência umana (HIV) são muito prevalentes. Entretanto, pouco se sabe sobre as diferenças na suscetibilidade entre essas infecções e as lesões HPV-relacionadas. Objetivo: descrever a associação entre as prevalências de infecção cervical e anal pelo HPV e lesões relacionadas em mulheres HIV-positivas. Metodologia: este estudo incluiu 88 mulheres HIV-positivas atendidas em ambulatório de hospital universitário. Amostras ectocervicais, endocervicais e anais foram coletadas para colpocitologia e citologia anal. Uma técnica baseada na reação em cadeia da polimerase foi usada para detectar o ácido desoxirribonucléico (DNA) do HPV em amostras de swabs endocervical e anal. Resultado: as taxas de positividade do HPV cervical e anal foram de 35,21% e 78,8%, respectivamente. As lesões relacionadas ao HPV na colpocitologia foram associadas à positividade anal para o HPV (P = 0,027). A proporção entre infecção cervical por HPV e lesões cervicais relacionadas foi de 2,5. A proporção entre a infecção anal por HPV e as lesões anais relacionadas foi de 4,3. 30% tinham DNA-HPV concomitante no colo do útero e ânus. Conclusão: existem diferenças na suscetibilidade de infecções e de lesões relacionadas entre o colo e o ânus. Apesar de maior incidência de HPV anal, a progressão para lesões relacionadas não ocorre da mesma forma no colo e no ânus. Além disso, lesões cervicais relacionadas ao HPV em mulheres HIV positivas podem servir como pista para estratégias preventivas anais. Investigações adicionais podem ser úteis.

Pathways of IFN-alpha Activation in Patients with Cervical Intraepithelial Neoplasia (CIN) / Vias de ativação de IFN-alfa em pacientes com Neoplasia Intraepitelial Cervical (NIC)

Abstract Objective The aim of the present study was to compare the local and systemic expression of the factors linked to the interferon alpha (IFN-α) activation pathway in different degrees of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods A total of 128 patients with CIN I, CIN II, CIN III and cervical cancer was evaluated. The real-time polymerase chain reaction (RT-PCR) technique was used to evaluate the gene expression of IFNR1, IFNR2, IFN-α, oligoadenylate synthase (2'5′OAS), cytokine signal suppressor 1 (SOCS) 1, SOCS3, signal transducer and transcription activator 1 (STAT1), and IRF9 from 128 biopsies. A total of 46 out of 128 samples were evaluated by flow cytometry for IFNAR1, IFNAR2, STAT1, IRF7 and IFN-α in peripheral blood cells. Results Patients with CIN II and III (63 samples) had a low local expression of IFNR1, but not IFNR2. Patients with some degree of injury showed high expression of SOCS1 and SOCS3. Systemically, patients with CIN II and III (20 samples) had a significant increase in IFNR1, IFNR2, STAT1, IRF7, and IFN-α in helper, cytotoxic T lymphocytes, and in monocytes. Conclusion Patients with high-grade lesions have increased systemic expression of IFN-α and its activation pathways in helper and cytotoxic T lymphocytes, as well as in monocytes due to an exacerbation of the immune response in these patients. This phenomenon is not accompanied by resolution of the lesion due to a defect in the IFN-α activation pathway that revealed by low local IFNAR1 expression and high local expression of SOCS1 and SOCS3.

Resumo Objetivo O objetivo do presente estudo foi comparar a expressão local e sistêmica dos fatores ligados à via de ativação do interferon alfa (IFN-α) em diferentes graus de neoplasia intraepitelial cervical (NIC) e câncer cervical (CA) Métodos Foram avaliados 128 pacientes com NIC I, NIC II, NIC III e CA. A técnica de reação de cadeia de polimerase em tempo real (RT-PCR, na sigla em inglês) foi realizada para avaliar a expressão gênica do receptor de interferon (IFNR) 1, IFNR2, IFN-α, 2′-5′- oligoadenilato sintetase (2′5′OAS), supressor de sinalização de citocina (SOCS)1, SOCS3, transdutor de sinal e ativador de transcrição 1 (STAT1) e fator regulador de interferon 9 (IRF9) das 128 biópsias. Das 128 amostras, 46 foram avaliadas por citometria de fluxo para IFNAR1, IFNAR2, STAT1, IRF7 e IFN-α em células de sangue periférico. Resultados Pacientes com NIC II e III (63 amostras) tiveram baixa expressão local de IFNR1 mas não de IFNR2. Pacientes com algum grau de lesão apresentaram alta expressão de SOCS1 e SOCS3. Sistemicamente, os pacientes com NIC II e III (20 amostras) tiveram um aumento significativo de IFNR1, IFNR2, STAT1, IRF7 e IFN-α em linfócitos T auxiliares, citotóxicos e monócitos. Conclusão Pacientes com lesões de alto grau apresentam expressão sistêmica aumentada de IFN-α e suas vias de ativação em linfócitos T auxiliares e citotóxicos, bem como em monócitos, devido à exacerbação da resposta imune nesses pacientes. Este fenômeno não é acompanhado pela resolução da lesão devido a um defeito na via de ativação do IFN-α que é revelado pela baixa expressão local de IFNR1 e alta expressão local de SOCS1 e SOCS3.