Morphometric analysis of dendritic cells from anal mucosa of HIV-positive patients and the relation to intraepithelial lesions and cancer seen at a tertiary health institution in Brazil / Análise morfométrica das células dendríticas da mucosa anal de pacientes HIV-positivos e relação com as lesões intraepiteliais e o câncer numa instituição de saúde terciária no Brasil

PURPOSE: To morphometrically quantify CD1a+ dentritic cells and DC-SIGN+ dendritic cells in HIV-positive patients with anal squamous intraepithelial neoplasia and to evaluate the effects of HIV infection, antiretroviral therapy and HPV infection on epithelial and subepithelial dendritic cells. METHODS: A prospective study was performed to morphometrically analyze the relative volume of the dendritic cells and the relationship between anal intraepithelial neoplasia and cancer in HIV-positive patients from the Tropical Medicine Foundation of Amazonas, Brazil. All patients were submitted to biopsies of anorectal mucosa to perform a classic histopathological and immunohistochemical analysis, employing antibodies against CD1a and DC-SIGN for the morphometric quantification of dendritic cells. RESULTS: HIV-negative patients displayed a CD1a DC density significantly higher than that of HIV-positives patients (3.75 versus 2.54) (p=0.018), and in patients with severe anal intraepithelial neoplasia had correlated between DC CD1a density with levels of CD4 + cells (p: 0.04) as well as the viral load of HIV-1 (p: 0.035). A not significant rise in the median density of CD1a+ DC was observed in the HIV positive/ HAART positive subgroup compared to the HIV positive/ HAART negative subgroup. The CD1a+ DC were also significantly increased in HIV-negative patients with anorectal condyloma (2.33 to 3.53; p=0.05), with an opposite effect in HIV-positive patients. CONCLUSIONS: Our data support an enhancement of the synergistic action caused by HIV-HPV co-infection on the anal epithelium, weakening the DC for its major role in immune surveillance. Notoriously in patients with severe anal intraepithelial neoplasia, the density of CD1a+ epithelial dendritic cells was influenced by the viral load of HIV-1.(AU)

OBJETIVO: Quantificar morfometricamente as células dendríticas DC CD1a+ e DC DC-SIGN+ em pacientes HIV positivos portadores de neoplasia escamosa intraepitelial anal e avaliar os efeitos da infecção pelo HIV, da terapia antirretroviral e da infecção pelo HPV sobre as células dendríticas epiteliais e subepiteliais. MÉTODOS: Um estudo prospectivo foi realizado para analisar morfometricamente o volume relativo das células dendríticas e as relações entre neoplasia intraepitelial anal e o câncer em pacientes HIV positivos da Fundação de Medicina Tropical do Amazonas, Brasil.Todos os pacientes foram submetidos a biópsia da mucosa retal para realizar uma análise clássica histopatológica e imunohistoquímica utilizando anticorpos contra anti-CD1a e anti-DC-SIGN, para a quantificação morfométrica das células dendríticas. RESULTADOS: Os pacientes HIV negativos apresentaram densidade das DC CD1a+ significativamente maior do que a dos pacientes HIV positivos (3,75 versus 2,54) (p:0,018), e os pacientes com severa apresentaram correlação das DC CD1a com os níveis de células TCD4(p:0,04) assim como a carga viral do HIV-1 (p:0,035). Observamos no subgrupo HIV-positivo/HAART positivo elevação não significativa na mediana da densidade das DC CD1a+ em relação ao grupo HIV-positivo/HAART negativo. As DC CD1a+ também se elevaram nos pacientes HIV negativo portadores de condiloma anorretal(2,33 para 3,53; p:0,05), com efeito inverso nos pacientes HIV positivos. CONCLUSÕES: Nossos dados confirmam a potencialização da ação sinérgica representada pela coinfecção HIV-HPV sobre o epitélio anal, fragilizando as DC em sua função primordial de vigilância imune. Notoriamente nos pacientes com neoplasia intraepithelial anal grave, a densidade das DC CD1a+ epiteliais sofreu influência da carga viral do HIV-1.(AU)

The value of high-resolution anoscopy in the diagnosis of anal cancer precursor lesions in HIV-positive patients.

CONTEXT: Anal cancer, although a still rare disease, is being observed in ascending rates among some population segments known to be at risk for the development of the disease. Human papillomavirus (HPV) infection, immunodepression and anal intercourse are some factors associated with the development of the malignancy. Its similarities to cervical cancer have led to many studies aiming to establish guidelines for detecting and treating precursor lesions of anal cancer, with the goal of prevention. High-resolution anoscopy is routinely used for the diagnosis of anal cancer precursor lesions in many centers but the medical literature is still deficient concerning the role of this diagnostic modality. OBJECTIVES: To evaluate diagnostic validation and precision measures of high-resolution anoscopy in comparison to histopathological results of anal biopsies performed in HIV-positive patients treated at the Tropical Medicine Foundation of Amazonas, AM, Brazil. To observe any possible association between some risk factors for the development of anal cancer and the presence of anal squamous intraepithelial lesions. METHODS: A hundred and twenty-eight HIV-positive patients were submitted to anal canal cytological sampling for the detection of HPV infection by a PCR based method. High-resolution anoscopy was then performed after topical application of acetic acid 3% in the anal canal for 2 minutes. Eventual acetowhite lesions that were detected were recorded in respect to location, and classified by their tinctorial pattern, distribution aspect, relief, surface and vascular pattern. Biopsies of acetowhite lesions were performed under local anesthesia and the specimens sent to histopathological analysis. The patients were interviewed for the presence of anal cancer risk factors. RESULTS: The prevalences of anal HPV infection and of anal squamous intraepithelial lesions in the studied population were, respectively, 79% and 39.1%. High-resolution anoscopy showed sensibility of 90%, specificity of 19.23%, positive predictive value of 41.67%, negative predictive value of 75%, and a kappa coefficient of 0.076. From the analyzed lesions, high-grade squamous intraepithelial lesions was more frequently observed in association to dense (68%), flat (61%), smooth (61%), non-papillary (83%) and normal vascular pattern (70%) acetowhite lesions, while low-grade squamous intraepithelial lesions tended to be associated to dense (66%), flat-raised or raised (68%), granular (59%), non-papillary (62%) and normal vascular pattern (53%) acetowhite lesions. No statistical significance was observed as to the association of epidemiological characteristics and of most of the investigated anal cancer risk factors and presence of acetowhite lesions or anal squamous intraepithelial lesions. However, anal receptive sex and anal HPV infection were significantly associated to anal squamous intraepithelial lesions (P = 0.0493 and P = 0.006, respectively). CONCLUSION: High-resolution anoscopy demonstrated to be a sensitive, but not specific test for the detection of anal squamous intraepithelial lesions. Risk factors anal receptive sex and anal HPV infection were significantly associated to the presence of anal squamous intraepithelial lesions. Based on high-resolution anoscopy image data, acetowhite lesions relief and surface pattern were prone to distinguish between low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions.

The value of high-resolution anoscopy in the diagnosis of anal cancer precursor lesions in hiv-positive patients / Anuscopia de alta resolução: valor diagnóstico em lesões precursoras de câncer anal em pacientes soropositivos

CONTEXT: Anal cancer, although a still rare disease, is being observed in ascending rates among some population segments known to be at risk for the development of the disease. Human papillomavirus (HPV) infection, immunodepression and anal intercourse are some factors associated with the development of the malignancy. Its similarities to cervical cancer have led to many studies aiming to establish guidelines for detecting and treating precursor lesions of anal cancer, with the goal of prevention. High-resolution anoscopy is routinely used for the diagnosis of anal cancer precursor lesions in many centers but the medical literature is still deficient concerning the role of this diagnostic modality. OBJECTIVES: To evaluate diagnostic validation and precision measures of high-resolution anoscopy in comparison to histopathological results of anal biopsies performed in HIV-positive patients treated at the Tropical Medicine Foundation of Amazonas, AM, Brazil. To observe any possible association between some risk factors for the development of anal cancer and the presence of anal squamous intraepithelial lesions. METHODS: A hundred and twenty-eight HIV-positive patients were submitted to anal canal cytological sampling for the detection of HPV infection by a PCR based method. High-resolution anoscopy was then performed after topical application of acetic acid 3 percent in the anal canal for 2 minutes. Eventual acetowhite lesions that were detected were recorded in respect to location, and classified by their tinctorial pattern, distribution aspect, relief, surface and vascular pattern. Biopsies of acetowhite lesions were performed under local anesthesia and the specimens sent to histopathological analysis. The patients were interviewed for the presence of anal cancer risk factors. RESULTS: The prevalences of anal HPV infection and of anal squamous intraepithelial lesions in the studied population were, respectively, 79 percent and 39.1 percent. High-resolution anoscopy showed sensibility of 90 percent, specificity of 19.23 percent, positive predictive value of 41.67 percent, negative predictive value of 75 percent, and a kappa coefficient of 0.076. From the analyzed lesions, high-grade squamous intraepithelial lesions was more frequently observed in association to dense (68 percent), flat (61 percent), smooth (61 percent), non-papillary (83 percent) and normal vascular pattern (70 percent) acetowhite lesions, while low-grade squamous intraepithelial lesions tended to be associated to dense (66 percent), flat-raised or raised (68 percent), granular (59 percent), non-papillary (62 percent) and normal vascular pattern (53 percent) acetowhite lesions. No statistical significance was observed as to the association of epidemiological characteristics and of most of the investigated anal cancer risk factors and presence of acetowhite lesions or anal squamous intraepithelial lesions. However, anal receptive sex and anal HPV infection were significantly associated to anal squamous intraepithelial lesions (P = 0.0493 and P = 0.006, respectively). CONCLUSION: High-resolution anoscopy demonstrated to be a sensitive, but not specific test for the detection of anal squamous intraepithelial lesions. Risk factors anal receptive sex and anal HPV infection were significantly associated to the presence of anal squamous intraepithelial lesions. Based on high-resolution anoscopy image data, acetowhite lesions relief and surface pattern were prone to distinguish between low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions.

CONTEXTO: O câncer anal, muito embora ainda seja uma doença rara, vem sendo observado com frequência ascendente em alguns grupos populacionais considerados sob risco para o desenvolvimento da doença. Infecção pelo vírus do papiloma humano (HPV), imunossupressão e o sexo anoreceptivo são alguns dos fatores associados ao desenvolvimento da neoplasia. Suas semelhanças com o câncer do colo do útero levaram muitos estudos voltados para o estabelecimento de regras para a detecção e tratamento de lesões precursoras do câncer anal, tudo com o objetivo de prevenir a doença. A anuscopia com magnificação de imagem é rotineiramente utilizada para o diagnóstico de lesões precursoras do câncer anal em muitos centros, mas a literatura médica ainda é escassa a respeito do papel a ser desempenhado por essa modalidade diagnóstica. OBJETIVOS: Avaliar as medidas de validação e precisão diagnósticas da anuscopia com magnificação de imagem em comparação com resultados histopatológicos de biopsias anais realizadas em pacientes HIV-positivos tratados na Fundação de Medicina Tropical do Amazonas, Manaus, AM, Brasil. Observar qualquer possível associação entre alguns fatores de risco para o desenvolvimento do câncer anal e a presença de lesões intraepiteliais escamosas anais. MÉTODOS: Cento e vinte e oito pacientes HIV-positivos foram submetidos a coleta de material celular anal para a realização da detecção da presença de HPV pela reação em cadeia da polimerase. Anuscopias com magnificação de imagem foram realizadas após a aplicação tópica de ácido acético a 3 por cento no canal anal por 2 minutos. As lesões acetobrancas eventualmente observadas foram registradas com respeito a sua localização e classificadas quanto ao seu padrão tintorial, aspecto de distribuição, relevo, características de sua superfície e vascularidade. Foram realizadas biopsias das lesões acetobrancas sob anestesia local e os espécimes foram remetidos para estudo histopatológico. Os pacientes foram entrevistados em relação à presença de fatores de risco para o câncer anal. RESULTADOS: As prevalências de infecção anal pelo HPV e de lesões intraepiteliais escamosas anais na amostra populacional estudada foram de 79 por cento e 39,1 por cento, respectivamente. A sensibilidade e a especificidade da anuscopia com magnificação de imagem foram, respectivamente, de 90 por cento e 19,23 por cento, enquanto que o valor preditivo positivo foi de 41,67 por cento, o valor preditivo negativo foi de 75 por cento e o coeficiente kappa de 0,076. Com respeito às lesões analisadas de alto grau foram mais frequentemente observadas em associação com lesões acetobrancas densas (68 por cento), planas (61 por cento), lisas (61 por cento), não-papilíferas (83 por cento) e com padrão vascular normal (70 por cento), enquanto que lesões de baixo-grau tenderam a se associar a lesões aetobrancas densas (66 por cento), plano-elevadas ou elevadas (68 por cento), granulares (59 por cento), não-papilíferas (62 por cento) e de padrão vascular normal (53 por cento). Não se observou significância estatística na associação entre características epidemiológicas e a maioria dos fatores de risco para o câncer anal e a presença de lesão acetobrancas ou de lesões intraepiteliais escamosas anais. Entretanto, o sexo anorreceptivo e a detecção de infecção anal por HPV, segundo a técnica da reação da cadeia de polimerase, associaram-se significantemente com lesões intraepiteliais escamosas anais (P = 0,0493 e P =0,006, respectivamente). CONCLUSÕES: A anuscopia com magnificação de imagem demonstrou ser um método diagnostico sensível, mas inespecífico para a detecção de lesões intraepiteliais escamosas anais. Os fatores de risco sexo anorreceptivo e infecção anal pelo HPV associaram-se significantemente à presença de lesões intraepiteliais escamosas anais. Com base nos achados da anuscopia com magnificação de imagem, o relevo e o aspecto morfológico da distribuição das lesões acetobrancas na superfície do canal anal tenderam a permitir a distinção entre lesões de baixo e alto grau.