Nuestra experiencia en el manejo diagnóstico-terapéutico a corto plazo del paciente con displasia anal / Our experience in the short-term diagnostic-therapeutic management of the patient with anal dysplasia

Introducción: La neoplasia intraepitelial anal (NIA) es una lesión premaligna del carcinoma escamoso anal. Los varones VIH que tienen sexo con varones, es la población de riesgo más afectada. La citología y anuscopia son los métodos mejor aceptados para su diagnóstico, aunque es controvertido qué pacientes deben completarlo con una biopsia. Tampoco está bien establecido qué pacientes deben someterse a tratamiento y cuál es el mejor. Con este estudio, queremos exponer nuestra experiencia en el manejo diagnóstico-terapéutico de la NIA a corto plazo. Métodos: Estudio observacional retrospectivo de pacientes con riesgo de NIA con una citología anal alterada a los que se les realizó una anuscopia de alta resolución con biopsia. Tras la confirmación histológica de displasia iniciaron tratamiento con ácido tricloroacético. Se comprobó su efectividad con una citología posterior. Se analizaron las variables demográficas de la muestra y los resultados de las pruebas diagnósticas y de tratamiento. Resultados: La mayoría eran varones VIH positivos (104/115) y el 50% mantenían relaciones sexuales con otros varones. Se incluyeron 115 pacientes con citología anal alterada, de los cuales el 92% presentaron displasia en la biopsia. El 97% con atipia de significado incierto en la citología presentaron displasia histológicamente. El 60% de los pacientes normalizó la citología tras el tratamiento. Conclusión: Se debe considerar de forma sistemática la detección precoz de la NIA en poblaciones de riesgo conocidas. Cualquier anormalidad citológica debe ser biopsiada. El ácido tricloroacético puede ser un tratamiento efectivo consiguiendo un alto porcentaje de regresión, aunque actualmente la información con la que contamos es de bajo nivel de evidencia. (AU)

Introduction: Anal intraepithelial neoplasia (AIN) is a premalignant lesion of anal squamous cell carcinoma. HIV-positive males who have sex with males, are the most affected at-risk population. Cytology and anuscopy are the best accepted methods for its diagnosis, although it is controversial which patients should complete it with a biopsy. Neither which patients should undergo treatment nor which is the best treatment is not well established. With this study, we would like to present our experience in the diagnostic-therapeutic management of AIN in the short term. Methods: Retrospective observational study of patients at risk of AIN with altered anal cytology who underwent high-resolution anuscopy with biopsy. After histological confirmation of dysplasia, they started treatment with trichloroacetic acid. Its effectiveness was verified by subsequent cytology. The demographic variables of the sample and the results of both diagnostic and treatment tests were analyzed. Results: The majority were HIV-positive males (104/115) and 50% had sexual relations with other men. We included 115 patients with altered anal cytology, of whom 92% had dysplasia on biopsy. 97% with atypia of uncertain significance on cytology had histological dysplasia. Cytology normalized after treatment in 60% of patients. Conclusion: Early detection of AIN should be routinely considered in known at-risk populations. Any cytological abnormality should be biopsied. Tricholoroacetic acid can be an effective treatment achieving a high percentage of regression, although currently, the information we have is of low level of evidence. (AU)

Our experience in the short-term diagnostic-therapeutic management of the patient with anal dysplasia.

INTRODUCTION: Anal intraepithelial neoplasia (AIN) is a premalignant lesion of anal squamous cell carcinoma. HIV-positive males who have sex with males, are the most affected at-risk population. Cytology and anuscopy are the best accepted methods for its diagnosis, although it is controversial which patients should complete it with a biopsy. Neither which patients should undergo treatment nor which is the best treatment is not well established. With this study, we would like to present our experience in the diagnostic-therapeutic management of AIN in the short term. METHODS: Retrospective observational study of patients at risk of AIN with altered anal cytology who underwent high-resolution anuscopy with biopsy. After histological confirmation of dysplasia, they started treatment with trichloroacetic acid. Its effectiveness was verified by subsequent cytology. The demographic variables of the sample and the results of both diagnostic and treatment tests were analyzed. RESULTS: The majority were HIV-positive males (104/115) and 50% had sexual relations with other men. We included 115 patients with altered anal cytology, of whom 92% had dysplasia on biopsy. 97% with atypia of uncertain significance on cytology had histological dysplasia. Cytology normalized after treatment in 60% of patients. CONCLUSION: Early detection of AIN should be routinely considered in known at-risk populations. Any cytological abnormality should be biopsied. Tricholoroacetic acid can be an effective treatment achieving a high percentage of regression, although currently, the information we have is of low level of evidence.

Cribado de neoplasia intraepitelial anal en pacientes con infección por virus de la inmunodeficiencia humana / Anal intraepithelial neoplasia screening in patients with human immunodeficiency virus infection

Introducción: la incidencia de cáncer anal ha aumentadoen los últimos años, por lo que el cribado y la detecciónprecoz de la neoplasia intraepitelial anal (AIN) en pacientesde riesgo son una necesidad.Métodos: se realizó un estudio observacional descriptivode pacientes homosexuales (HSH) o mujeres con neoplasiacervical intraepitelial grado III (CIN III), con infección porvirus de la inmunodeficiencia humana (PVIH), incluidos enun programa de cribado de detección de AIN entre marzode 2016 y septiembre de 2019.Resultados: se realizaron 695 citologías anales, 156 conresultados de lesión de bajo grado (LSIL) o lesión de altogrado (HSIL) (22,4 %), y 116 anoscopias de alta resolución(HRA), el 75,3 % de los pacientes con citología alterada. Sehan obtenido 403 biopsias, el 84 % de ellas patológicas; 197biopsias evidenciaron AIN I (49 %) y 96, AIN II y III (24 %); 44eran condilomas (11 %); y el 16 %, mucosa normal.Conclusión: la alta prevalencia de lesiones premalignas y lamejoría del estadiaje de las lesiones tras tratamiento recomienda dicho protocolo. (AU)

Anal PAP, HPV tests and magnifying chromoendoscopy with biopsies in the diagnosis of anal intraephitelial neoplasia / Papanicolau anal, testes de HPV e cromoendoscopia de ampliação com biópsias no diagnóstico de neoplasia intraepitelial anal

Abstract Introduction: Anal intraepithelial neoplasia (AIN) is the most likely precursor of squamous cells cancer which represents 90% of anal cancers. The use of biomolecular tests as a screening method has been extended by gynecology. Given the similarities that exist between the HPV disease in the lower genital tract and anorectal sectors, it is expected that HPV tests can provide information for the diagnosis, treatment and follow-up for AIN-affected patients. Objectives: Comparing the performance of anal cytology, PAP and HPV tests (Hybrid Capture and Papillocheck) against the histology of the diagnosis of low- and high-grade AIN in risk groups. Material and methods: A cross-sectional study was carried out to evaluate diagnostic methods for low- and high-grade AIN in 73 patients. Samples for anal PAP, Papillocheck and Hybrid Capture were taken from all patients who then, regardless of the results, underwent magnifying chromoendoscopy (MCE) along with biopsy. Diagnostic test performances and their 95% confidence intervals (CI: 95%) were calculated as well as the likelihood ratio for each test. Results: Of the 73 patients, 49 (67%) were women. The average age of the patients was 38 years. In 38 patients (52%), the histology was positive with 10 (14%) grade II AIN or higher. There were no statistically significant differences in sensitivity nor in specificity for low- and high-grade AINs between any of the tests. Conclusion: Anal PAP, the Hybrid Capture test (HC2, Qiagen) and PapilloCheck (Greiner Bio One) were highly sensitive but not specific for low- and high-grade AINs. Therefore, a biopsy should be conducted against a positive result of any of the tests to confirm AIN and the degree of dysplasia. The screening method selection depend on the availability but also costs of the test should be considered, since all the diagnostic tests have similar performance.

Resumo Introdução: A neoplasia intraepitelial anal é o precursor mais provável do câncer de células escamosas, que representa 90% dos tumores anais. O uso de exames biomoleculares como método de triagem foi ampliado pela ginecologia. Considerando-se as semelhanças entre as apresentações de HPV no trato genital inferior e anorretal, espera-se que os exames de HPV possam fornecer informações para o diagnóstico, tratamento e acompanhamento dos pacientes com neoplasia intraepitelial anal. Objetivo: Comparar o desempenho da citologia anal, Papanicolau, exames para HPV (teste de captura híbrida e Papillocheck) e histologia no diagnóstico de neoplasia intraepitelial anal de baixo e alto grau em grupos de risco. Material e métodos: Foi realizado um estudo transversal para avaliar métodos de diagnóstico de neoplasia intraepitelial anal de baixo e alto grau em 73 pacientes. Amostras para Papanicolau anal, Papillocheck e captura híbrida foram coletadas de todos os pacientes; independentemente dos resultados desses exames, todos foram submetidos a cromoendoscopia de ampliação (CEA) e biópsia. O desempenho dos exames e seus intervalos de confiança de 95% (95% CI) foram calculados, bem como a razão de verossimilhança para cada teste. Resultados: Dos 73 pacientes, 49 (67%) eram mulheres. A idade média dos pacientes foi de 38 anos. A histologia foi positiva em 38 pacientes (52%), dos quais dez (14%) apresentaram neoplasia intraepitelial anal grau II ou superior. Não foram observadas diferenças estatisticamente significativas na sensibilidade ou especificidade para as neoplasias intraepiteliais anal de baixo e alto grau entre qualquer um dos exames. Conclusão: O Papanicolau anal, o teste de captura híbrida (HC2, Qiagen) e o Papillocheck (Greiner Bio One) foram altamente sensíveis, mas não específicos para neoplasia intraepitelial anal de baixo e alto grau. Portanto, uma biópsia deve ser realizada após um resultado positivo em qualquer um dos testes para confirmar o diagnóstico de neoplasia intraepitelial anal e seu grau. A seleção do método de triagem depende da disponibilidade, mas os custos devem ser considerados, uma vez que todos os testes apresentam desempenho semelhante.

Ablación de las neoplasias intraepiteliales escamosas anales de alto grado, precursoras del cáncer anal, con coagulación infrarroja / Ablation of high-grade anal squamous intraepithelial neoplasms, anal cancer precursors, with infrared coagulation

Introducción: Las neoplasias intraepiteliales anales de alto grado (AIN-AG) sin tratamiento progresan a carcinoma anal escamoso invasor (CAE) en 8-13% de los casos. Esto disminuye al 1,2% con la ablación dirigida por anoscopía de alta resolución (AAR). El tratamiento ideal de la AIN-AG no está establecido. Goldstone, en 2005 introdujo el coagulador infrarrojo (CIR) para la ablación de estas lesiones y demostró que tiene tanta efectividad como la cirugía, aunque menor morbilidad y la ventaja de no requerir quirófano. No hemos encontrado publicaciones con esta técnica en nuestro medio. El objetivo de este trabajo es evaluar los resultados de la ablación de las AIN-AG con CIR, las complicaciones del método y la recurrencia temprana. Diseño: Observacional, retrospectivo, con base de datos prospectiva. Pacientes y Método: Se incluyeron individuos con AIN-AG en conducto anal y/o región perianal diagnosticadas en el Consultorio de Detección Temprana de Displasia Anal del Hospital Juan A. Fernández mediante biopsia dirigida por AAR y tratadas con CIR con el aparato Redfield®, entre marzo 2013-agosto 2014 previo consentimiento informado escrito. Tras infiltración con anestesia local las lesiones fueron coaguladas con repetidos pulsos de 1,5 segundos hasta visualizar los vasos de la submucosa. Se controló entre los 3 y 6 meses con AAR y biopsia de lesiones sospechosas. Resultados: Fueron 14 pacientes (10 hombres que tienen sexo con hombres, todos VIH-positivos y 4 mujeres, 2 VIH-positivas). Edad mediana: 37,5 (rango 20-59) años. La AIN-AG se localizaba en el conducto anal en 11 pacientes y en la región perianal en 3. En la AAR diagnóstica todos presentaban sólo un área de AIN-AG. El procedimiento fue bien tolerado. Una paciente VIH-positiva presentó secreción purulenta a los tres días de la ablación, que se trató con antibióticos. Esta paciente y otro más tuvieron dolor post-procedimiento manejado con anti-inflamatorios no esteroides. En la AAR de control se hallaron 2 (14,3%) recurrencias, una interpretada como persistencia por margen insuficiente de una lesión extendida y otra diagnosticada al momento de realizar CIR, que no había sido observada en la AAR realizada 1 mes antes. La eficacia por lesión individual tratada fue del 92,9%. Conclusiones: El tratamiento de las AIN-AG en el consultorio mediante CIR es bien tolerado, tiene mínimas complicaciones y resulta efectivo en el corto plazo. Es necesario un seguimiento más prolongado para evaluar la tasa de recidiva y la utilidad para prevenir la progresión al CAE. (AU)

Background: High-grade anal intraepithelial neoplasia (HGAIN) without treatment progresses to invasive squamous cell carcinoma (SCC) in 8-13% of cases, and that incidence decreases to 1,2% with ablation targeted with high resolution anoscopy (HRA). The ideal treatment for HGAIN is not established yet. Goldstone, in 2005 introduced the infrared coagulator (IRC) for the ablation of these lesions, and with great experience demonstrated that it is as effective as surgery but has less morbidity and the advantage of not requiring the operating room. To our knowledge there are not publications with this technique in our country. The aim of this study is to assess the results of HGAIN ablation with CIR, the method complications, and early recurrence. Design: Observational, retrospective study, with prospective database. Patients and Methods: Individuals with HGAIN in the anal canal or the perianal region, diagnosed with biopsy targeted with HRA and treated with the IRC in the Anal Dysplasia Clinic of the Hospital Juan A. Fernández, between March 2013 and August 2014, were included. After written informed consent, HRA was repeated in the outpatient clinic to localize the area to be treated with the IRC Redfield®. After local anesthesia the lesions were coagulated with repeated 1.5 seconds pulses until the submucosa vessels were visualized. Control with HRA and biopsy of suspicious lesions was performed between 3-6 months of the procedure. Results: Fourteen patients (10 men who have sex with men, all HIV-positive, and 4 women, 2 HIV-positive). Median age: 37.5 (range 20-59) years. The HGAIN was localized at the anal canal in 11 patients, and in the perianal region in 3. In the diagnostic HRA all patients presented only one area of HGAIN. The procedure was well tolerated. Only one HIV-positive woman presented purulent discharge 3 days after ablation, and was treated with antibiotics. The latter and another patient had post-procedure pain, managed with non-steroidal anti-inflammatory drugs. In the control HRA, 2 (14,3%) recurrences were found, 1 was interpreted as persistency due to insufficient margin of a extended lesion, and 1 diagnosed during the CIR of other lesion, that had went unaware at the initial HRA performed one month before. The efficacy for individual lesion treated was 92.9%. Conclusions: The treatment of HGAIN with IRC in the outpatient department is well tolerated, has minimal complications, and is effective in the short term. It is necessary a longer surveillance to assess the recurrence rate and the usefulness for preventing progression to SCC. (AU)

[Usefulness of human papillomavirus testing in anal intraepithelial neoplasia screening in a risk behaviour population]. / Utilidad de la detección del virus del papiloma humano en el cribado de neoplasia intraepitelial anal en pacientes con conductas de riesgo.

INTRODUCTION: The incidence of intraepithelial anal neoplasia is increasing in certain risk behaviour groups, and human papillomavirus (HPV) infection is involved in its pathogenesis. The systematic use of anal cytology, and more recently HPV detection by hybrid capture and genotyping, have been introduced into screening programs in recent decades. MATERIAL AND METHODS: A retrospective cohort study was carried out on individuals with risk behaviours of developing intraepithelial anal neoplasia and who attended Sexually Transmitted Infections clinics in the Dermatology area of the Hospital Costa del Sol from January 2010 to December 2012. The intraepithelial anal neoplasia screening was performed using anal cytology and HPV genotyping. RESULTS: Half (50%) of the study population were HIV positive. A high frequency of anal dysplasia and presence of HPV in cytology (82.1%) and genotype (79%) was found. A statistically significant association (P<.005) was obtained between the presence of high-risk HPV genotypes and the presence of high-grade dysplasia in the second directed cytology. HPV genotyping enabled 17 cases (22%) of severe dysplasia to be identified that were under-diagnosed in the first cytology. CONCLUSION: Cases of high-grade dysplasia can be under-diagnosed by a first anal cytology. Detection of HPV can supplement this procedure, leading to the identification of those patients most at risk of developing high-grade anal dysplasia.

[Screening of anal intraepithelial neoplasia in risk groups: descriptive study of sexual habits and other sexual transmitted infections]. / Cribado de neoplasia intraepitelial anal en grupos de riesgo: estudio descriptivo sobre hábitos sexuales y otras infecciones de transmisión sexual.

BACKGROUND: Anal intraepithelial neoplasia is considered a precursor lesion of anal squamous carcinoma. The population with increased risk of this conditions are immunocompromised individuals, especially HIV-infected, with anal sex practices. The aim of this study was to describe the sexual habits of patients who were seen in sexually transmitted infections (STIs) consult in our service in whom anal cytology was performed as well as the association of anal dysplasia to other STIs. MATERIAL AND METHODS: We performed a retrospective cohort study that included those patients in whom, according to our protocol, anal cytology was performed between 2008 and 2011. Also we conducted a survey on sexual habits and screening for other STIs. Finally, we conducted a descriptive and analytical study assessing bivariate distribution of cytological alterations and grade of anal dysplasia. RESULTS: A total of 347 anal cytologies were performed, and 48.1% were abnormal. Statistically significant differences were found between the presence of condylomata perianal/endoanal, HIV infection, Chlamydia trachomatis infection and the presence of cytologic alterations. CONCLUSION: There was a high incidence of anal dysplasia in our group of individuals with risky sexual habits; however, it is probably underdiagnosed due to its subclinical nature and lack of a well-established screening protocol.

[Practical considerations for high resolution anoscopy in patients infected with human immunodeficiency virus]. / Consideraciones prácticas de la anoscopia de alta resolución en pacientes infectados por el virus de la inmunodeficiencia humana.

Anal cancer is uncommon in the general population, however its incidence is increasing significantly in certain risk groups, mainly in men who have sex with men, and particularly those infected with human immunodeficiency virus. High resolution anoscopy technique is currently considered the standard in the diagnosis of anal intraepithelial neoplasia, but at present there is no agreed standard method between health areas. High resolution anoscopy is an affordable technique that can be critical in the screening of anal carcinoma and its precursor lesions, but is not without difficulties. We are currently studying the most effective strategy for managing premalignant anal lesions, and with this article we attempt to encourage other groups interested in reducing the incidence of an increasing neoplasia.

Neoplasia intraepitelial anal / Anal intraepithelial neoplasia

RESUMEN Introducción: el virus del papiloma humano se asocia a las neoplasias cervicales y epiteliales anales. Objetivos: determinar la prevalencia de neoplasia intraepitelial anal (NIA) y las características clínicas en mujeres que acuden al consultorio de patología cervical en el Hospital Regional de San Lorenzo. Materiales y Métodos: estudio observacional, descriptivo, prospectivo realizado en 900 mujeres que acudieron al consultorio de patología cervical en el Hospital Regional de San Lorenzo, en los años 2012-2013 mediante colposcopía y citología anal. Resultados: Se encontraron 60 casos (8,5%) de NIA. Las características de las pacientes con NIA fueron: grupo etario predominante 19 a 25 años, 50% de práctica de relaciones sexuales anales, 25% con tabaquismo, inicio de las relaciones sexuales antes de los 16 años (70%), 2 a 4 parejas sexuales (81,6%). El riesgo de NIA en pacientes con hábitos sexuales anales fue significativo: OR 1,91 (IC95% 1,09-3,36) (p 0,01). Conclusiones: la prevalencia de NIA en mujeres fue 8,5%. Se halló asociación significativa con hábito de relaciones sexuales anales.

ABSTRACT Introduction: Human papillomavirus associated with cervical and anal epithelial neoplasia. Objectives: To determine the prevalence clinic of anal intraepithelial neoplasia (AIN) and the clinical characteristics in women attending the out patient of cervical pathology in the Regional Hospital of San Lorenzo. Material and Methods: An observational, descriptive, prospective study of 900 women attended the out patient clinic of cervical pathology in the Regional Hospital of San Lorenzo, in the years 2012-2013 through anal cytology and colposcopy. Results: 60 cases (8.5%) of NIA where found. The characteristics of the patients with NIA were: predominant age group 19-25 years, 50% of them sexual practicing anal intercourse, 25% smoking, initiation of sexual intercourse before 16 year of age (70%), 2-4 sexual pairs (81.6%). NIA risk in patients with anal sexual habits were significant: OR 1.91 (95% CI 1.09 to 3.36) (p 0.01). Conclusions: The prevalence of AIN in women was 8.5%. Significant association was found with anal sexual intercourse.

Coinfection of Epstein-Barr virus, cytomegalovirus, herpes simplex virus, human papillomavirus and anal intraepithelial neoplasia in HIV patients in Amazon, Brazil

OBJECTIVE: The prevention of anal cancer is a goal of worldwide Aids support centers. Despite the efforts that have been made and progress in the antiretroviral therapy, effective disease control remains elusive. Difficulty in preventing anal cancer may result from the ineffectiveness of highly active antiretroviral therapy on the human papillomavirus (HPV) since the coinfection with HIV and HPV appears to increase the risk of HPV-infected cells, becoming cancerous. METHODS: We evaluated 69 HIV-positive and 30 HIV-negative male patients who underwent cytological evaluation by RT-PCR for the presence of HPV, Epstein-Barr virus, cytomegalovirus and herpes virus types (HSV) 1 and 2, and histopathology analysis of the anal canal. RESULTS: The prevalence of anal intraepithelial neoplasia was 35% and it was restricted to HIV-positive patients. Patients infected with high-risk HPV and with fewer than 50 TCD4 cells/µL showed an anal intraepithelial neoplasia rate of 85.7% compared to those with TCD4 cells > 200 cells/µL (p<0.01). The rate of viral coinfection was 16.9% of the sexual transmitted diseases cases and it was correlated with HIV-1 viral load of more than 10.001 copies/mL (p=0.017). The rate of AIN in coinfected patients was 36.4% (p=0.047). CONCLUSIONS: In this study, at the main institution for the treatment of HIV/AIDS in the Amazon region of Brazil, anal coinfection with HPV, cytomegalovirus, HSV-1, HSV-2 and Epstein-Barr virus occurred only in HIV-positive patients and it was directly influenced by the viral load of HIV-1. In this study, anal viral coinfection showed no additional risk for the development of anal intraepithelial neoplasia. (AU)

OBJETIVO: A prevenção do câncer anal tem sido aplicada pelos centros de apoio a pacientes com Aids em todo o mundo. Apesar dos esforços empregados, o eficaz controle da doença permanece distante. A dificuldade na prevenção do câncer anal pode resultar, em parte, da ineficácia da ação da terapia antirretroviral sobre o papilomavírus humano (HPV), pois a coinfecção com HIV e HPV parece aumentar o risco das células infectadas pelo HPV em tornarem-se cancerosas. MÉTODOS: Foram avaliados 69 HIV-positivos e 30 pacientes HIV-negativos do sexo masculino, que foram submetidos à avaliação citológica anal por real time-PCR para a presença de HPV, vírus Epstein-Barr, citomegalovírus e herpes vírus tipos (HSV) 1 e 2 além da análise histopatológica de fragmento de mucosa do canal anal. RESULTADOS: A prevalência de neoplasia intraepitelial anal foi de 35% e foi restrita a pacientes HIV-positivos. Os pacientes infectados com o HPV de alto risco e com contagem inferior a 50 células TCD4/µL mostraram taxa de neoplasia intraepitelial anal de 85,7%. A diferença foi significativa quando comparado a pacientes com células TCD4 > 200 células/µL (p<0,01). A taxa de coinfecção viral foi de 16,9% dos casos de doenças sexualmente transmissíveis e diretamente correlacionada à carga viral HIV-1 superior a 10,001 cópias/mL (p=0,017). A taxa de neoplasia intraepitelial anal em pacientes coinfectados foi de 36,4% (p=0,047). CONCLUSÕES: Neste estudo, realizado na principal instituição para o tratamento de HIV/Aids na região amazônica do Brasil, a coinfecção anal com HPV, citomegalovírus, HSV-1, HSV-2 e vírus Epstein-Barr ocorreu somente em pacientes HIV-positivos e foi influenciada pela carga viral do HIV-1. Neste estudo, a coinfecção viral anal não representou risco adicional ao desenvolvimento da neoplasia intraepitelial anal. (AU)