Squamous Cell Carcinoma of the Anus (SCCA) is a rare cancer that is heavily associated with high-risk human papillomavirus infection (HRHPV) of the squamocolumnar junction (SCJ) of the anus. Treatment of SCCA ranges from chemotherapy and radiation for early stage cancer, and surgical interventions such as abdominoperineal resection for later stage cancer. Patients who present with late-stage metastatic SCCA have a five-year survival rate of 32%, emphasizing the crucial need for early detection. Given its rarity in the general population (approximately 1 to 2 cases per 100,000 people), screening guidelines to allow for early detection of SCCA have not been fully established, and remains the subject of continuous debate amongst clinicians, researchers, and public health practitioners. A major challenge in establishing SCCA screening guidelines is slow progression of symptoms. 20-33% of patients diagnosed with SCCA were clinically asymptomatic at the time of their diagnosis. Patients who reported symptoms usually noted mild symptoms, which mimicked ones found in other anal disorders. For instance, early stage cases of SCCA frequently manifest as bleeding in the anus, but in the absence of other serious symptoms, patients and clinicians often assume hemorrhoids as a cause. As SCCA is a rare disease with that frequently presents with seemingly benign symptoms, if any, few studies have addressed the complexities of concerns in regards to preventive screening of SCCA. Using “Principles and Practice of Screening for Disease” by Wilson and Jungner, this thesis intends to discuss known screening strategies for SCCA and explore knowledge gaps in need of further study before definitive guidelines for SCCA screening can be established. Wilson and Jungner do not specifically address the issue of SCCA; rather, they provide a framework for establishing guidelines for disease screening. This thesis will examine the current understanding of SCCA gained in literature and will apply them to the ten tenets that Wilson and Jungner uphold as necessary criteria that should be considered in order to craft an appropriate screening methodology for a specific disease. These tenets address issues ranging from the severity of the disease in question, available treatments for the disease, and the economic perspective relating the cost of screening to the cost of treatment and management. Analysis of the ten tenets of Wilson and Jungner in relation to SCCA has revealed the need for the cancer research community to gain a better understanding of the role of high-grade intraepithelial lesions, which may act as a precursor to the development of SCCA; however, a significant portion of persons afflicted with HSIL have demonstrated the ability to spontaneously clear them. In addition, this thesis identified a need to gain a better understanding of HPV, especially in chronic variants. Further research to develop SCCA screening guidelines should also evaluate and weigh the effectiveness and practicality of different screening techniques; certain techniques such as anal cytology may be easily implemented on a massive scale, but may be less accurate. Though a rare disease, the progressive yearly increase in incidence (2.2% per year) of SCCA indicates that comprehensive screening guidelines are urgently needed. Using an analysis of a tried and true framework for establishing disease screening guidelines set by Wilson and Jungner, this thesis intends to contribute to the development of a standardized set of screening guidelines for SCCA. In doing so, we hope to allow SCCA to be managed in a manner that minimizes the impact on patients’ quality of life in a cost-effective manner.

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No. of bitstreams: 1 Tese - Felicidad Santos Gimenez.pdf: 1802898 bytes, checksum: 245aa4c3338753c4ecf130b72b8adf62 (MD5) Previous issue date: 2009-07-20 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / BACKGROUND: The anal cancer incidence, about 1,5% of malignant tumors of the gastrointestinal tract, has increased among men who have sex with men (MSM) which have contracted the human immunodeficiency virus (HIV+), to 70/100.000 people with the same behavior. The development of this cancer is a consequence of the interaction of several factors, among them, human papilomavirus (HPV) infection, immunodepression and anal sex practice. The similarities to the cervical cancer development (low and high grade precursor lesions, which can be early diagnosed) have inspired many studies performed in order to establish guidelines for the detection and treatment of precursor lesions of anal cancer, intending its prevention. The high-resolution anoscopy (HRA) is routinely used in this diagnosis; however, medical literature is even deficient concerning to the role of this diagnostic modality in the detection of precursor lesions of anal cancer. Taking these facts into account, this study has the intention of checking the validity of this test by comparing it to histopathology results of HIV+ patients of the Fundação de Medicina Tropical do Amazonas (FMT-AM). METHODS: The patients included (128) underwent a proctologic examination with the collection of anal channel cells, and using the Polimerase Chain Reaction (PCR) technique, it was researched the presence of HPV. Afterwards, HRA and topical anal application of Acetic Acid 3% during 2 minutes were performed. The acetowhite areas (AWA) detected were recorded concerning to their localization, classified by their color pattern, focal or coalescent aspect, relief, surface and vascular pattern. Facing the image characteristics of the observed lesions, these were classified into normal, low-grade squamous intraepithelial lesion (LSIL) or high-grade squamous intraepithelial lesion (HSIL) to the development of anal cancer. In addition, biopsies of the AWA were performed under local anesthesia, to undergo histopathologic analysis. RESULTS: Fro The HRA showed sensibility of 90%, specificity of 19,23%, positive predictive value of 41,66%, negative predictive value of 75%, and kappa coefficient of 0,076. Im the analyzed lesions it was found in the HSIL a more frequent visualization of 68% dense AWA, 61% flat, 61% smooth, 83% no-papillary and 70% normal vascular pattern, while in the LSIL they were 66% dense AWA, 68% flatraised or raised, 59% granular, 62% no-papillary and 53% normal vascular pattern. Gender, age, level of education and skin color did not represent associated factors to the development of AW lesions or to anal squamous intra-epithelial lesions (ASIL). The risk factors implied in the anal carcinogenesis were taking these factors into account, there was not statistic significance in the occurrence of AW lesions. Even though, to ASIL, it was demonstrated a relevance between anal sex adepts (p = 0,0493) and the presence of HPV infection (p = 0,006). CONCLUSIONS: The HRA has demonstrated to be sensible, but not specific in the detection of ASIL. In addition, it was not found association between HRA results histopathologic and the presence of HPV anal infection. The prevalence of HPV in the studied population was 79% and the prevalence of ASIL was 39,1%. Based on image data, the relief and surface pattern were able to distinguish between LSIL and HSIL, while the other characteristics did not show relevance. / INTRODUÇÃO: A incidência do câncer anal, cerca de 1,5% dos tumores malignos do trato digestório, vem aumentando em homens que fazem sexo com homens acometidos pelo vírus da imunodeficiência humana (HIV+), para até 70/100.000 pessoas com os mesmos hábitos. O desenvolvimento desse câncer é decorrente de vários fatores, dentre eles, a infecção pelo papilomavírus humano (HPV), a imunodepressão e a prática do sexo anal. As similitudes com o desenvolvimento do câncer cervical (presença de lesões precursoras de baixo e alto grau, que podem ser diagnosticadas precocemente) têm inspirado a realização de vários estudos para estabelecer rotinas de detecção e tratamento das lesões precursoras desse câncer, visando a sua prevenção. A anuscopia com magnificação de imagem (AMI) faz parte dessa rotina diagnóstica, porém a literatura médica ainda é escassa a respeito do papel desempenhado por essa modalidade. Este estudo pretende verificar a validade do exame comparando-o com o resultado da histopatologia, nos pacientes HIV+ atendidos na Fundação de Medicina Tropical do Amazonas (FMT-AM). MÉTODOS: Os 128 pacientes foram submetidos ao exame proctológico com coleta de células do canal anal e através da técnica da reação da cadeia de polimerase (PCR), pesquisou-se a presença do HPV. A seguir, realizou-se AMI com aplicação tópica anal de ácido acético 3% por 2 minutos. As lesões acetobrancas (ACB) detectadas foram anotadas quanto à sua localização, classificadas quanto à qualidade tintorial, ao aspecto focal ou coalescente, ao relevo, à superfície e ao padrão vascular. Diante das características imagenológicas das lesões observadas, essas foram classificadas em normais, lesões de baixo (LSIL) ou alto grau (HSIL) para o desenvolvimento do câncer anal. Foram feitas biópsias sob anestesia local das lesões ACB, para exame histopatológico. RESULTADOS: A AMI apresentou sensibilidade de 90%, especificidade de 19,23%, valor preditivo positivo de 41,66%, valor preditivo negativo de 75%, e coeficiente kappa de 0,076. Das lesões analisadas foi encontrado nas HSIL, uma visibilização mais freqüente de 68% ACB denso, 61% plano, 61% lisa, 83% não-papilar e 70% do padrão vascular normal, enquanto que as LSIL foram 66% ACB denso, 68% plano-elevado ou elevado, 59% granular, 62% não-papilar e 53% de padrão vascular normal. Gênero, idade, escolaridade e cor da pele não representaram fatores associados ao desenvolvimento de lesões ACB e lesões intraepiteliais escamosas anais (ASIL). Para os fatores de risco, implicados na carcinogênese anal e, em relação a esses fatores, não houve significância estatística na ocorrência de lesões ACB. No entanto, para as ASIL, demonstrou-se relevância entre os adeptos do sexo anal (p = 0,0493) e a presença de infecção pelo HPV (p = 0,006). CONCLUSÃO: A AMI demonstrouse sensível, porém não específica na detecção das ASIL. Não foi encontrada a associação entre os resultados histopatológicas da AMI e a presença de infecção anal pelo HPV. A prevalência de HPV na população estudada foi de 79% e a de ASIL foi de 39,1%. Baseado nos dados imagenológicos, o padrão de relevo e superfície puderam fazer distinção entre LSIL e HSIL, enquanto que as outras características não apresentaram relevância.