Search

Introduction Optimal screening for detection of anal precancer has not been established, and most studies involve very high-risk populations. We evaluated high-risk human papillomavirus (HPV) testing and anal cytology to detect high-grade anal intraepithelial neoplasia ( > AIN2) in a cohort with mostly moderate risk factors for AIN. Materials and Methods Patients > 35-years-old undergoing anal biopsy for various lesions received HPV testing by Roche cobas and a subset by Hologic APTIMA HPV assays with concurrent anal ThinPrep cytology. Biopsies were blindly reviewed by 3 authors, and consensus diagnosis was compared with HPV and cytology results. Sensitivity and specificity for > AIN2 detection by HPV testing and cytology ( > ASC-US) were calculated. Results Among 64 patients, 19 (29.7%) showed > AIN2 on biopsy. All patients were tested by cobas, and 35 (54.7%) were positive. A subset of 39 patients were also tested by APTIMA, and 18 (46.2%) were positive. Positive cytology ( > ASC-US) was present in 37 (57.8%) patients, with 27 (73.0%) of these positive by cobas. HPV testing alone yielded 75.0% and 84.2% sensitivity for APTIMA and cobas, respectively; specificity was 66.7% and 57.8%. Sensitivity and specificity of cytology alone was 78.9% and 51.1%. Combined HPV testing and cytology had a sensitivity and specificity of 91.7% and 37.0% for APTIMA and 94.7% and 40.0% for cobas. Conclusions Combined HPV testing and cytology had the highest sensitivity for > AIN2 detection, with a performance comparable to cervical cancer screening tests, suggesting this strategy may represent a viable screening option in a population with moderate risk factors for AIN.

Anal squamous cell cancer has a precancerous stage of high-grade squamous intraepithelial lesion (HSIL). Some centers still use the terminology of anal intraepithelial neoplasia (AIN) where HSIL covers AIN2 and AIN3. Techniques that may be used for screening to prevent anal cancer aim to detect HSIL with high sensitivity and specificity and relatively low cost. Cytology and human papillomavirus detection are currently available; however, both have insufficient sensitivity and specificity to be reliable screening techniques, especially in the highest-risk groups for anal cancer. Biomarker tests are under consideration. High resolution anoscopy (HRA) is the gold standard for detecting anal precancer lesions; however, it is expensive and labor-intensive. For these reasons, there is a lack of national screening strategies for anal cancer. Guidelines quickly become out of date in this rapidly changing field: the German-Austrian 2015 guidelines are the most current.

Background: Anal intraepithelial neoplasia grade 2 (AIN2) and AIN grade 3 (AIN3) are commonly grouped together as high grade squamous intraepithelial lesions (HSIL). We assessed risk factors for HSIL-AIN2 and HSIL-AIN3 in a cohort of homosexual men. Methods: At the baseline visit in the Study for the Prevention of Anal Cancer (SPANC), all men completed a questionnaire and underwent anal swabbing for cytology and HPV genotyping, followed by high resolution anoscopy. Results: Composite-HSIL prevalence was 47% and 32% among 220 HIV-positive and 396 HIV-negative men, respectively. HSIL-AIN3 (37.7% versus 24.7%; p

Resumen Introduccion La neoplasia intraepitelial anal se considera una lesion precursora del carcinoma escamoso anal. La poblacion de mayor riesgo de padecer esta lesion son pacientes inmunodeprimidos, especialmente los infectados por el virus de la inmunodeficiencia humana (VIH), con practicas de sexo anal. El objetivo de este estudio fue describir los habitos sexuales de los pacientes atendidos en la consulta de infecciones de transmision sexual (ITS) en nuestro servicio, a los que se les realizo una citologia anal, asi como la presencia de otras ITS. Material y metodos Se realizo un estudio descriptivo de aquellos pacientes a los que, de acuerdo con nuestro protocolo, se les realizo una citologia anal entre 2008 y 2011. Asimismo, se realizo una encuesta sobre habitos sexuales y cribado de otras ITS. Finalmente, se llevo a cabo un estudio descriptivo y analitico bivariado valorando la distribucion de la alteracion citologica y el grado de displasia anal. Resultados Se incluyeron un total de 347 citologias anales, con un 48,1% de citologias alteradas. Se encontraron diferencias estadisticamente significativas entre la presencia de condilomas perianales/endoanales, la infeccion por VIH, la infeccion por Chlamydia trachomatis y la presencia de alteracion citologica. Conclusion La displasia anal tiene una alta prevalencia en nuestro medio en determinados grupos con habitos sexuales de riesgo, pero probablemente este infradiagnosticada por su caracter subclinico y la falta de un protocolo de cribado bien establecido.

Diagnosis, follow up, and treatment of anal intraepithelial neoplasia are complex and not standardized. This may be partly caused by poor communication of biopsy and cytology findings between pathologists and clinicians as a result of a disparate and confusing terminology used to classify these lesions. This article focuses on general aspects of epidemiology and on clarifying the current terminology of intraepithelial squamous neoplasia, its relationship with human papilloma virus infection, and the current methods that exist to diagnose and treat this condition.

Key points Anal intraepithelial lesions are caused by chronic infection with oncogenic types of human papillomavirus. Their incidence and prevalence are increasing, especially among patients with HIV infection. Their natural history is not well known, but high-grade intraepithelial lesions seem to have an important risk to progress to squamous cell carcinoma. Their treatment can be achieved by many ways (surgery, coagulation, imiquimod, etc.) but there is a high rate of recurrent lesions. Pretherapeutic evaluation should benefit from high-resolution anoscopy. Periodic physical examination and anal cytology may probably be interesting for screening the disease among patients with risk factors. Vaccine against oncogenic types of papillomavirus may prevent the development of anal intraepithelial neoplasia.

To reduce computational complexity, 2-D images of tumors are firstly preprocessed following our method to form two 1-D sequences, called horizontal and vertical landscapes, and then their fractal dimension is estimated using Higuchi’s fractal dimension. We validate application of this method for grading Anal Intraepithelial Neoplasia (AIN) tumors using 120 images of histological slices graded by an experienced pathologist. The method is easy and quick and we demonstrate that it may be successfully applied for differentiation between AIN stages. It can easily be adapted to other histological specimen. Of course, like any other semiautomatic method it may support the pathologist’s decision.

Anal human papilloma virus (HPV) infection causes significant pathology, including condylomata as well as low- and high-grade anal intraepithelial lesions, the precursors of invasive cancer. Men who have sex with men, women with concomitant high-grade cervical/vulvar disease, and immunocompromised patients are particularly vulnerable. The incidence of anal cancer is increasing in men and women, but human immunodeficiency virus-infected patients regardless of immune reconstitution are at greatest risk. A critical review of the literature and evidence-based, comparative analysis and discussion of treatment modalities for anal HPV related diseases was undertaken. Anal cytology screening for high-grade dysplasia has been shown to be sensitive and cost-effective in men who have sex with men; any abnormal anal cytology result should be followed with high-resolution anoscopy. Condylomata must be considered a marker for intraanal HPV disease, and patients should be screened for concomitant high-grade dysplasia. A variety of topical and ablative treatment modalities are available, including pharmacologic, targeted ablation of lesions and surgery. Treatment modality is directed not only by the extent and location of disease but also by available expertise and resources. Currently, there is no pharmacologic therapy approved by the Food and Drug Administration for intraanal HPV-related disease. Once treated, recurrence over time remains high, and patients should be closely monitored.

It is well known that human papillomaviruses (HPV) induce a variety of tumorous lesions of the skin. HPV-subtypes also cause premalignant lesions which are termed anal intraepithelial neoplasia (AIN). The clinical classification of AIN is of growing interest in clinical practice, due to increasing HPV infection rates throughout human population. The common classification approach is based on subjective inspections of histological slices of anal tissues with all the drawbacks of depending on the status and individual variances of the trained pathologists. Therefore, a nonlinear quantitative classification method including the calculation of the fractal dimension and first order as well as second order image statistical parameters was developed. The absolute values of these quantitative parameters reflected the distinct grades of AIN very well. The quantitative approach has the potential to decrease classification errors significantly and it could be used as a widely applied screening technique.

Background Anal dysplasia is a potentially chronic disease that affects HIV-seropositive and-seronegative men who have sex with men (MSM) and transgender women. Novel approaches to AIN screening could improve healthcare through access to timely care and treatment since appropriate training and equipment are currently required for screening and follow-up. To pioneer new ideas, the foundation for new technology relies on collecting data to design new tools. Recently, Raman spectroscopy (RESpect), a laser-based technology, has identified unique anal tissue fingerprints. We assessed anal tissue for RESpect phenotypes for differences in HIV-serodiscordant couples. Methods HIV-serodiscordant couples were enrolled in a clinical study to assess anal biopsy specimens as per IRB guidelines. Anal tissue was flash-frozen and mounted onto aluminum reflective slides which were then subjected to RESpect point scans accumulations. RESpect information was processed using asymmetric least squares to baseline the data and subjected to principal component analysis (PCA). Results To date, data from 2 couples showed that PCA distinguishes between HIV+ and HIV- individuals of the couples. In HIV+ individuals, PCA also distinguishes AIN from normal tissue. Conclusions RESpect has shown to identify not only AIN amongst all individuals but also suggested there may be a unique HIV effect in the RESpect data from anal tissue. Further work on RESpect could provide groundbreaking information towards the design of a RESpect monitoring instrument to diagnose and follow patients for AIN. Supported in part by R21CA216830 and U54MD007584.

Background: Intra-anal lesions caused by human papillomavirus (HPV) can be classified as low-grade squamous intraepithelial lesions (LSIL) or high-grade squamous intraepithelial lesion (HSIL). The latter can be further subclassified histomorphologically as anal intraepithelial neoplasia (AIN)2 or AIN3. It is not known whether morphological differences within and between these categories are associated with different high-risk HPV (HR-HPV) genotypes. Methods: In a natural history study of anal HPV-related lesions in gay and bisexual men, we identified the presumed causal genotype of all HSIL present at baseline, utilizing laser capture microdissection. For comparison, we also analyzed randomly selected flat LSIL (fLSIL) and negative biopsies. Results: 244 distinct lesions from 175 men were analyzed: 149 AIN3, 64 AIN2 and 31 flat LSIL (fLSIL). HR-HPV genotypes were found in 139 (93.3%) AIN3, 55 (85.9%) AIN2 and 8 (25.8%) fLSIL. HPV16 was found in 59 (39.6%) AIN3, 11 (17.2%) AIN2 and 1 (3.2%) fLSIL. HR-HPV types were not significantly more common in AIN3 than AIN2 (p=0.08) but HPV16 was (p=0.001). HR-HPV genotypes were significantly more common in HSIL than in LSIL (p

Anal intraepithelial neoplasia (AIN) is a precancerous condition of growing concern, due to the strong interrelation of AIN with infections caused by human papillomaviruses (HPV) and HIV. Several HPV-subtypes induce a variety of tumorous skin lesions and cause different stages of dysplasia and even cancer. The histological classification of AIN is becoming more and more important in clinical practice, due to increasing HPV infection rates throughout human population. Histological slices of anal tissues are commonly classified by individual inspections with all the unavoidable differences of the training status and variances of the individual. Therefore, a quantitative classification method including the calculations of first order as well as second order image statistical parameters in combination with data mining was developed. The results of several classifiers were compared to each other and it turned out that at least two classifiers had very high correct classification rates with very low errors. So it was possible to classify the distinct grades of AIN with high accuracy. The quantitative approach has the potential to minimize individual classification errors significantly and it will enable the establishing of a quantitative screening technique.

OBJETIVO: Avaliar se o grau de neoplasia intra-epitelial anal (NIA) está associado ao tipo do HPV em doentes HIV positivo, já que esses apresentam imunodepressão durante longos períodos. MÉTODOS: Identificamos os tipos do HPV, pelo método da reação em cadeia da polimerase (PCR), e realizamos exame anatomo-patológico para avaliar o grau de NIA em 39 homens HIV positivo portadores de condilomas acuminados perianais. RESULTADOS: Observamos NIA de alto grau em nove (23,1%) e NIA de baixo grau em 30 doentes (76,9%). Os tipos virais mais observados foram os não oncogênicos 6 e 11 em 64% e os oncogênicos 16, 18 e 31 em 20,5%. Não identificamos o tipo viral em quatro doentes (10,2%), embora o teste revelasse a presença do DNA viral. Comparando o padrão histológico e os tipos virais, observamos que os tipos não oncogênicos do HPV também podem estar associados ao desenvolvimento de NIA de alto grau. CONCLUSÃO: Os resultados obtidos nas condições de execução deste estudo permitem concluir que tanto os tipos oncogênicos como os não oncogênicos de HPV podem estar associados ao desenvolvimento de NIA de alto grau em doentes HIV positivo. OBJECTIVE: We decided to evaluate if grade of anal intraepithelial neoplasia (AIN) was associated to the HPV type in HIV positive patients, since this group of patients has immunodeficiency over long periods. We identified HPV types by PCR (polimerase chain reaction) and histological examination to determine the AIN grade in 39 HIV positive males with anal condylomata acuminata. RESULTS: We observed high grade AIN (HAIN) in 9 (23.1 percent) and low grade AIN (LAIN) in 30 patients (76.9 percent). The most frequent HPV types were 6 and 11 (64 percent) and oncogenic types 16, 18 and 31 appeared in 20.5 percent of patients. We could not identify viral type in four patients (10.2 percent) despite tests revealing presence of viral deoxiribonucleic acid. Comparing AIN grades with viral types we observed that non-oncogenic types can also be associated with HAIN lesions. CONCLUSION: These results allowed us to conclude that both oncogenic and non-oncogenic HPV types can be associated with HAIN lesions in HIV positive patients.

Summary Anal intra-epithelial neoplasia (AIN) is a pre-malignant condition, which over time may progress to invasive anal squamous cell carcinoma. There is no standard treatment for AIN, but one of the therapeutic options available is photodynamic therapy (PDT). There are very few published studies of the efficacy of PDT, but it has been shown to produce downgrading of high-grade dysplasia in the anal region. The aim of the study was to evaluate the role of PDT in the treatment of AIN. Fifteen patients who received anal PDT between 2004 and 2013 were identified; twelve of these had AIN, two had intra-epithelial adenocarcinoma and one had dysplasia with high-risk human papillomavirus. After a median follow-up of nineteen months, ten of these have had at least one follow-up with aceto-white staining. Six of these ten patients had a complete response to PDT, although three subsequently had some recurrence. Three further patients had a partial response to PDT. There were no major therapeutic complications. Our findings suggest that PDT is a safe and feasible treatment option for AIN, associated with reasonable response rates and relatively little morbidity. Further research into the efficacy of PDT for AIN is required.

was infused intravenously and both normal appearing tissue and the area of concern were imaged and recorded using the pCLE probe. The area of concern was then biopsied and the biopsies were read by a single pathologist. The pCLE images were examined by a single physician familiar with pCLE technology. Results: 12 patients were enrolled. Average age was 50 years. Five of the 12 patients had lesions with features of high grade dysplasia on biopsy (Anal Intraepithelial Neoplasia 2 or 3 (AIN2/3)). Normal squamous tissue was wellimaged in all patients in non-suspicious areas of "control". Confocal findings in areas of concern included the following: 1) pleomorphic cells with loss of regular squamous architecture (5/5 patients 100%) 2) dark spots, potentially representing gland formation (3/5 patients 60%) 3) large or torturous blood vessels (4/5 patients 80%). 4) Dark bands (1/ 5 patients 20%). Quality of imaging was deemed adequate and interpretable in all patients with HGAIN lesions. Conclusions: Distinctive features on pCLE can be found in lesions suspicious for HGAIN in a population of HIV-infected males. If sensitive and specific, pCLE may obviate the need for anal biopsy allowing real-time treatment.