Routine anal cytology screening for anal squamous intraepithelial lesions in an urban HIV clinic

OBJECTIVES: The purpose of this study is to describe our experience with routine anal cancer screening using anal cytology, determine risk factors for abnormal anal cytology, and determine if an association exists between cytology and histology in patients with HIV infection. METHODS: Demographics, CD4+ T-cell count, STD history, and cytology and histology data were extracted from medical charts of patients seen between November 1, 2002, and November 30, 2004. Analysis was done using chi2 for comparison of proportions and Student t test for continuous variables. Multivariate analysis was conducted using logistic regression controlling for age, race, sex, CD4+ T-cell nadir, and HIV exposure category. RESULTS: Overall, 276 of 560 of the clinic patients received a screening anal cytology during the study period. Of these patients, 11 were excluded from the analysis and 74 of 265 (27.9%) patients screened had an abnormal anal cytology. Mean age was 44 years, and 68% were men. Forty-nine percent were African American, 34% Caucasian, and 17% Hispanic. Those with an abnormal cytology were more likely to be Caucasian (P = 0.03), and be homosexual or bisexual (P = 0.02). They were also more likely to have a lower CD4+ nadir (142 cells/mm3 vs. 223 cells/mm3, P = 0.005) and CD4+ at time of anal cytology (353 cells/mm3 vs. 497 cells/mm3, P <0.001). Those with an abnormal anal cytology also had higher occurrence of anal disease on perianal visual inspection (30% vs. 9%, P <0.001) and were more likely to have a history of genital warts (23% vs. 12%, P = 0.02) or herpes (35% vs. 22%, P = 0.02). Two patients had anal intraepithelial neoplasia (AIN) I, 2 AIN II, 3 AIN III, and 2 squamous cell carcinoma in situ on histology. There was no apparent association between cytology and histology. CONCLUSION: Routine anal cytology screening is a feasible tool to incorporate into HIV care for patients regardless of gender and HIV risk factors. Its impact on morbidity and mortality warrant further study.     

The value of anal cytology and human papillomavirus typing in the detection of anal intraepithelial neoplasia: a review of cases from an anoscopy clinic

BACKGROUND: Previous studies have reached differing conclusions about the utility of anal cytology as a screening tool for anal intraepithelial neoplasia (AIN). There is a need also to establish whether HPV typing offers a useful adjunct to screening. METHODS: We analysed data from 99 consecutive homosexual/bisexual male patients (89 HIV-1 positive) who underwent high resolution anoscopy. Follow up visits for these patients were also included, giving a total of 160 anoscopic procedures. Comparison was made between results of anal cytology using the sampling method of Palefsky, and histological findings of biopsies taken from abnormal areas seen on high resolution anoscopic examination of the anal canal. Swabs taken concurrently with the cytology were analysed for the presence of human papillomavirus (HPV) DNA and compared with the cytological and histological findings. RESULTS: The sensitivity of the cytology was 83%, and the specificity 38% when compared with histology. At screening of 34 asymptomatic men, 83% had anal cytological dysplasia and 78% had AIN. There were no significant differences in the prevalence of hrHPV genotypes between different cytological or histological grades of abnormalities. CONCLUSION: Anal cytology by the Palefsky method is simple to undertake, has a sensitivity and specificity comparable with cervical cytology, and can therefore be used as the basis of a pilot screening project in centres with large cohorts of HIV positive homosexual men who have a high risk of developing anal carcinoma. HPV genotyping is not a useful adjunct to cytological screening.     

Anal human papillomavirus infection: a comparative study of cytology, colposcopy and DNA hybridisation as methods of detection.

OBJECTIVE--To compare anal cytology, colposcopy and DNA hybridisation as methods of detecting anal HPV infection. SUBJECTS AND DESIGN--Patients attending: (1) a genitourinary medicine (GUM) clinic with ano-genital warts; (2) a surgical out-patient department with anal fissure or haemorrhoids were examined for evidence of anal HPV infection. RESULTS--Considering GUM clinic attenders, 17% (38/225) and 40% (90/225) had perianal or anal canal warts respectively. Colposcopic examination revealed anal acetowhite lesions without warts in 28% (63/225). Cytological evidence of HPV infection was found in 98%, 83%, and 90% of patients with anal canal warts, perianal warts and acetowhite lesions respectively. Anal intraepithelial neoplasia (AIN) was documented in 22% of patients with anal canal warts compared with 6% with perianal warts (p less than 0.01). HPV DNA was detected from the anal brushings of 71%, 50%, 32%, and 29% of patients with anal canal warts, perianal warts, acetowhite lesions and a normal anal examination respectively. HPV type 6/11 was detected in the majority of HPV positive samples. Considering surgical out-patient attenders with no history or signs of anal warts, 25% showed cytological evidence of anal HPV infection and HPV DNA was detected from anal brushings in 3% (2/71). CONCLUSION--Anal examination with the colposcope is a useful method for detecting subclinical HPV infection. Anal cytology may prove helpful for detecting AIN, however, since koilocytosis was rarely seen, the specificity of the cytological criteria for anal HPV infection in the absence of AIN is uncertain. DNA analysis of anal brushings proved only moderately sensitive.     

High prevalence of anal squamous intraepithelial lesions in HIV-positive men despite the use of highly active antiretroviral therapy

BACKGROUND: The impact of highly active antiretroviral therapy (HAART) on the natural history of HPV infection and anal squamous intraepithelial lesions (SIL) in HIV-infected men who have sex with men (MSM) is poorly documented.GOAL The goal of this study was to evaluate the prevalence of anal HPV infection and SIL inpatients under HAART. STUDY DESIGN: Forty-five HIV-infected protease inhibitor-experienced MSM were enrolled in a cross-sectional study. Each patient provided anal samples for anal cytology, histology, and human papillomavirus (HPV) DNA testing. RESULTS: The patients had previously received HAART for a median of 32 months. Anal cytology was abnormal in 32 of 45 (71%) patients, including high-grade SIL in 10 patients (22%), low-grade SIL in 19 patients (42%), and atypical squamous cells of undetermined significance in 3 patients (7%). HPV DNA was detected 36/45 men (80%). The prevalence of anal SIL and HPV infection were similar in patients exhibiting a significant increase in CD4+ cell count after HAART initiation compared with those who did not. CONCLUSION: Our results demonstrate a high prevalence of anal SIL, including high-grade SIL, and anal HPV infection in HIV-infected MSM despite immune restoration under HAART.     

A comparison between cytology and histology to detect anal intraepithelial neoplasia.

INTRODUCTION--Anal intraepithelial neoplasia (AIN), which may be a precursor of anal carcinoma, has been identified on histology following minor anal surgical procedures, in particular the removal of perianal condylomata, in increasing numbers of homosexual and bisexual men. Anal cytology has recently been proposed as a useful method of identifying AIN lesions. OBJECTIVE--To compare anal cytology with histology as a method of detecting AIN. METHODS--215 homosexual and bisexual men attending a central London sexually transmitted diseases clinic had an anal cytological smear performed under standard conditions. The perianal area and anal canal were then examined using a colposcope, and areas macroscopically suggestive of intraepithelial neoplasia were biopsied. RESULTS--176 of the 215 patients were biopsied of whom 76 had AIN on histology. 154 of the 215 patients had an adequate anal smear of whom 46 and 85 had cytological features of both HPV and AIN, or HPV alone respectively. Including features of HPV alone as an abnormal smear, anal cytology, when compared with anoscopy and histology as the gold standard for diagnosing AIN, resulted in a sensitivity of 87.5%, a specificity of 16.3%, a positive predictive value of 37.4% and a negative predictive value of 69.6%. Restricting abnormal smears to those with features of both HPV and AIN resulted in a sensitivity of 33.9%, a specificity of 72.5%, a positive predictive value of 41.3% and a negative predictive value of 65.7%. CONCLUSION--Anal cytology is a sensitive but nonspecific method of identifying patients with biopsy proven AIN if cytological features of HPV alone are included as abnormal smears. Specificity is improved by restricting abnormal smears to those with features of both HPV and AIN but this markedly lowers the sensitivity of the test. At present, anoscopy and histology are required in addition to anal cytology to differentiate between patients who simply have anal condylomata and those who also have AIN.     

Factors associated with clinical and sub-clinical anal human papillomavirus infection in homosexual men.

OBJECTIVES--(I) to determine the relative sensitivities of clinical examination, cytology and HPV DNA hybridisation for the detection of anal human papillomavirus infection; and (ii) to examine various factors which may influence presentation of anal human papillomavirus infection in homosexual men. METHODS AND RESULTS--112 unselected homosexual men attending a Sydney STD clinic for routine screening underwent a complete anogenital and physical examination, during which blood samples (for haematological, serological and immunological investigations), rectal swabs (for culture of anal pathogens) and anal scrapes of the dentate line (for cytology and HPV DNA hybridisation) were collected. Papanicolaou-stained anal smears were examined for cytological abnormalities, including those indicative of HPV infection or anal intraepithelial neoplasia (AIN). HPV DNA was detected by high stringency dot hybridisations using radiolabelled HPV 6, 11, 16 and 18 DNA probes. Visible anal condylomata, situated either externally or in the anal canal, were present in 26% of these men; 46% had cytological evidence of HPV infection, and 19% of the smears showed evidence of mild to moderate dysplastic changes (AIN I-II). Detectable HPV DNA was present in 40% of the anal scrapes. By combining these results, a total of 73 men (65%) were found to have at least one of the indicators of HPV infection. These data, together with that relating to HIV antibody, immune status and past or present infection with other STDs, was correlated with information obtained from a questionnaire administered to the patients at the time of their clinical examination. CONCLUSIONS--In this study cytology was found to be slightly more sensitive than HPV DNA dot hybridisation for the detection of HPV infection in the anal canal, providing the full range of HPV-associated cytological changes were accepted as a basis for diagnosis. Clinical anal lesions were more likely to be detected in young men, men who had symptomatic HIV infection and those with a history of past anal wart infection. The latter group also had a higher incidence of cytologically apparent HPV infection in their anal smears. There was a significant association between the detection of HPV 16/18 and the presence of anal dysplasia, but there were no significant correlations between HPV infection or anal dysplasia and HIV antibody, immune function status, sexual practices or history of other STDs.     

Anal cytological abnormalities and anal HPV infection in men with Centers for Disease Control group IV HIV disease.

OBJECTIVE: To characterise risk factors for abnormal and cytology and anal human papilloma virus (HPV) infection in homosexual/bisexual men with advanced HIV related immunosuppression. DESIGN: Cross sectional study of men with Centers for Disease Control group IV HIV disease. SETTING: The University of California San Francisco, AIDS Clinic. PATIENTS: 129 homosexual or bisexual men with group IV HIV disease. METHODS: A questionnaire was administered detailing tobacco, alcohol and recreational drug use, medical history, and sexual practices. Anal swabs for cytology and HPV studies were obtained, as was blood for CD4 levels. MAIN OUTCOME MEASURES: Abnormal anal cytology and anal HPV infection. RESULTS: Abnormal anal cytology was detected in 39% of subjects and anal HPV infection in 93% as measured by polymerase chain reaction (PCR). Risk factors for abnormal cytology in multivariate analysis included HPV 16/18 infection (measured by PCR, RR = 2.1, 95% CI = 1.2-3.5) and intravenous drug use (RR = 1.8, 95% CI = 1.2-2.7). Infection with HPV 6/11 also had significantly elevated RRs in a separate model. Cigarette smoking, alcohol use, recreational drug use, and low CD4 level were associated with abnormal anal cytology in univariate analysis, as was infection with multiple HPV types and high levels of hybrid capture group B viral DNA. CONCLUSIONS: Anal cytological abnormalities and HPV infection are common among homosexual/bisexual men with group IV HIV disease. In this study population, the main risk factors for abnormal cytology were HPV infection and intravenous drug use.     

A study of anal intraepithelial neoplasia in HIV positive homosexual men

OBJECTIVES: To determine the prevalence of high grade anal intraepithelial neoplasia (HGAIN), the value of anal cytology in screening for HGAIN, and the characterisation of epidemiological factors and human papillomavirus (HPV) types. METHODS: Prospective cohort study of HIV positive homosexual men. Subjects were interviewed, underwent STD, anal cytological, and HPV screening at enrolment and at subsequent follow up visits with anoscopy and biopsy at the final visit. 57 enrolled, average CD4 count 273 x 10(6)/l (10-588); 41 completed the cytological surveillance over the follow up period (181 visits, average follow up 17 months), 38 of these had anoscopy and anal biopsy. RESULTS: Oncogenic HPV types were detected in 84% and high grade dyskaryosis in 10.5% (6/57) at enrollment. There was a 70% incidence of high grade dyskaryosis during follow up in patients with negative/warty or low grade dyskaryosis at enrollment. Anoscopy correlated with histology in high grade AIN lesions (sensitivity 91%, specificity 54%) and cytology was 78% sensitive (18/23) for HGAIN on biopsy. CONCLUSIONS: AIN and infection with multiple oncogenic HPV types are very common among immunosuppressed HIV positive homosexual men. Apparent progression from low to high grade cytological changes occurred over a short follow up period, with no cases of carcinoma. All 23 cases of HGAIN were predicted by cytology and/or anoscopy. Future studies focusing on the risk of progression to carcinoma are needed before applying anal cytology as a screening tool for AIN in this population.     

Anal carcinoma in human immunodeficiency virus‐positive men: results of a prospective study from Germany

Background Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)‐associated potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)‐positive men who have sex with men (MSM). There is a paucity of data published on the progression of high‐grade AIN to invasive cancer as well as on clinical and virological characteristics comparing anal margin and anal canal carcinoma. Objectives To search for anal carcinoma and AIN in a large series of HIV‐positive MSM, to assess treatment response of anal carcinoma, and to analyse lesional HPV spectrum of anal cancers. Methods Detection of anal carcinoma and AIN was performed using cytology, high‐resolution anoscopy, and histology in case of abnormal findings. Additionally, HPV analyses for 36 high‐ and low‐risk α‐HPV types were performed in patients with anal carcinoma. Results In total, 446 German HIV‐positive MSM were examined within an observation period of 5 years and 10 months. Of these, 116 (26·0%) patients had normal findings, 163 (36·5%) had low‐grade AIN, 156 (35·0%) had high‐grade AIN, and 11 (2·5%) had anal carcinoma as evidenced by the highest grade of cytology/histology. Five patients with anal cancer, who had refused treatment of their precancerous lesions, had progressed from high‐grade AIN to invasive cancer within a median time of 8·6 months. All anal cancers carried high‐risk α‐HPV types. All five squamous cell carcinomas (SCCs) of the anal canal were HPV16 positive. In contrast, only one of the four anal margin SCCs were HPV16 positive (HPV31, HPV33 and HPV33 + HPV68 were found in the other three anal margin SCCs). HPV59 was found in two adenocarcinomas, one of which additionally carried HPV33. In contrast to the cancer biopsies, a broad spectrum of surface high‐ and low‐risk HPV types was found in anal swabs of the patients. Surgical excision resulted in long‐term disease control of all anal margin carcinomas, whereas combined chemoradiotherapy in carcinomas of the anal canal was associated with high recurrence rates, high toxicity, and high mortality. Conclusions Anal carcinoma and AIN are frequent in HIV‐positive men, even in patients participating in anal cancer prevention programmes. High‐grade dysplasia in these patients can progress to invasive cancer within a short period of time. Anal margin carcinoma and anal canal carcinoma differ substantially in their lesional HPV spectrum, prognosis and treatment response.     

Anal intercourse: a risk factor for anal papillomavirus infection in women?

OBJECTIVE--To determine whether anal intercourse is a risk factor for anal HPV infection in women. DESIGN--Results derived from clinical examination, anal cytology and HPV DNA hybridisation were correlated with data obtained from a questionnaire administered to the patients at the time of their clinical examination. SETTING--A sexually transmitted diseases (STD) clinic in Sydney, Australia. SUBJECTS--31 women attending the clinic for HPV related problems. METHODS AND RESULTS--A thorough history was elicited from each woman followed by physical examination of the anogenital region. Cervical and anal scrapes were collected for cytology and HPV DNA hybridisation. Of the 15 women who practised anal intercourse, a total of 12 (80%) had either clinical or subclinical HPV infection. Seven had overt anal warts, situated either internally or externally in the anal canal; and further 5 women had evidence of subclinical HPV infection as determined by positive cytological and/or HPV DNA hybridisation results on their anal scrapes. The women who did not have a history of anal intercourse had a lower (7/16, 43%), but not statistically significant, rate of anal HPV infection: five had anal warts and two had subclinical evidence of infection. No correlations were found between anal HPV infection and genital (cervical, vulval or vaginal) HPV infection; nor between the HPV typing patterns of women in either group. CONCLUSION--The results obtained from these women do not indicate a close relationship between anal intercourse and the presence of detectable anal HPV infection.     

Anale intraepitheliale Neoplasie und Analkarzinom

Anal dysplasia is common in HIV patients, especially in HIV-positive men having sex with men (MSM). High-grade anal dysplasia can progress to invasive anal cancer. As in cervical carcinoma, there is a cause and effect relationship between anal cancer and human papillomavirus (HPV) infection, especially with high-risk types such as HPV16. Several experts have recommended screening programs for anal cancer, including anal cytology along the lines of the Pap smear in women. Such screenings should only be performed if pathological findings result in further diagnostic steps and, if necessary, appropriate treatment. Clinical inspection, lesion biopsy, and treatment of anal dysplasia are performed under high-resolution anoscopy. Anal cancer is divided into cancer of the anal margin and cancer of the anal canal. This classification is important because of the difference in treatment regimens. Early cancer of the anal margin is excised akin to squamous cell cancer of the exposed skin, whereas cancer of the anal canal is treated by radiochemotherapy. HIV-positive and HIV-negative patients have similar response rates to combined radiochemotherapy. However, side effects, especially acute post-irradiation skin toxicity, early local recurrences, and abdominoperineal rectal excision are more common in HIV-positive patients. Physicians working in the field of HIV/AIDS should regularly screen their patients for the presence of anal dysplasia and anal cancer. Basic diagnostic workup includes clinical inspection of the perianal area, digital rectal examination, and anal cytology.     

HPV-induzierte Erkrankungen bei HIV-positiven Patienten

Since the introduction of highly active antiretroviral therapy (HAART), opportunistic infections by bacteria and fungi have been reduced in human immunodeficiency virus (HIV)-positive patients. However, diseases caused by human papilloma virus (HPV) have become more frequent despite HAART. There is an increased incidence of anal and cervical carcinomas, their precancerous lesions such as anal/cervical intraepithelial neoplasia, and condylomas and oral warts. In order to prevent anal carcinomas, HIV-positive patients should receive proctoscopic examinations regularly. The examination should include anoscopy and smears for cytology and HPV polymerase chain reaction.     

Imiquimod leads to a decrease of human papillomavirus DNA and to a sustained clearance of anal intraepithelial neoplasia in HIV-infected men

Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)-associated precursor lesion of anal carcinoma, is highly prevalent in HIV-infected men having sex with men (MSM). This prospective follow-up study evaluated the long-term results of imiquimod treatment of AIN in 19 HIV-infected MSM. Standardized follow-up examinations included high-resolution anoscopy, anal cytology/histology, HPV typing, and DNA load determination for HPV types 16, 18, 31, and 33. Mean follow-up time was 30.3 months. A total of 74% (14/19) of the patients remained free of AIN at the previously treated site. Five patients (26%) had recurrent high-grade AIN after a mean time of 24.6 months. At the end of follow-up, the numbers of HPV types as well as high-risk HPV-DNA loads were significantly lower than before therapy. During follow-up, 58% of all patients (11/19) developed new anal cytological abnormalities in previously normal, untreated anal regions. 55% of these new AIN lesions were high-grade lesions and most of them were located intra-anally and associated with high-risk HPV types not detectable before therapy. These results demonstrate that imiquimod leads to a high rate of long-term clearance of AIN in HIV-positive men together with a prolonged decrease of high-risk HPV-DNA load. However, new AIN lesions associated with previously undetected HPV types frequently occur in untreated areas.     

Influence of genital infection on cervical cytology

OBJECTIVE: To ascertain whether the presence of genital infection adversely affects smear quality. METHOD: A prospective study of all patients having cytology performed. The presence of genital infection was recorded and compared with the smear result. RESULTS: The presence of genital infection was not associated with inadequate cytology. Inflammatory changes were found in association with symptomatic candidiasis, trichomoniasis, Chlamydia trachomatis infection, primary herpes simplex, and the finding of 21-30 polymorphs per high power field (averaged over 10 fields) on cervical samples. Inadequate cytology was significantly associated with the smear taker. CONCLUSION: The presence of genital infection at the time of cytology does not increase the rates of inadequacy, and opportunistic cytology should not be deferred as the patient may default from further appointments.


     

Papillomavirus-induced anogenital lesions in 121 HIV seropositive men. Clinical, histological, viral study, and evolution]

OBJECTIVE: To determine the prevalence of the Human Papillomavirus (HPV) in Human Immunodeficiency Virus (HIV) infected men, using clinical examination and molecular hybridization in situ. PATIENTS AND METHODS: From May 1995 to May 1997 we studied the prevalence, clinical and histological characteristics, the types and the evolution of the HPV lesions among 121 HIV-infected men. The HPV DNA was determined by molecular hybridization in situ, using biotinylated probes which recognized HPV types 6/11, 16/18 and 31/33/35 in 79 p. 100 (5/19) of the patients (17 biopsies). RESULTS: Sixteen per cent (19/121) of the patients are HPV infected: genital warts in 37 p. 100 (7/19), anal warts in 37 p. 100 (7/19), and ano-genital warts in 26 p. 100 (5/19) of the patients. In every case of anal codyloma, intracanalar lesions were found. In 47 p. 100 (9/19) of the cases, histological exam showed an intra-epithelial neoplasia. The HPV types 6/11, 16/18 and 31/33/51 were positive in 53 p. 100 (9/17), 35 p. 100 (6/17) and 35 p. 100 (6/17) biopsies respectively. High-risk types of HPV have been noted in 71 p. 100 (12/17) of the biopsies. The evolution of the clinical lesions was: recovering in 47 p. 100 (9/19) of the patients (after 3 months of treatment), recurrence in 16 p. 100 (3/19) of the anal warts (after 1 to 3 months of treatment), stabilization in 16 p. 100 (3/19) of the genital warts (after 6 months of treatment) and extension in 11 p. 100 (2/19) of the anogenital warts (after 3 months of treatment). CONCLUSION: The high prevalence of condyloma and dysplasia emphasizes the importance of the anogenital exam in HIV-positive patients. In case of anal lesions, anuscopy and biopsy are required. We insist on the need to closely follow these patients with HPV lesions in order to adapt treatment. Anal cytology and HPV-DNA detection by Hybrid Capture Assay, should be developed for screening and prevention of the malignant transformation of HPV lesions in this population.     

Aspiration cytology of cutaneous metastatic melanoma and epidermoid carcinoma of the penis

Aspiration biopsy cytology is an accurate, safe, innocuous alternative to excisional biopsy in diagnosing the nature of concomitant superficial nodules or lymphadenopathy in patients with known cutaneous malignancy. In patients with penile cancer, aspiration biopsy cytology may avoid the morbidity (30-50%) and mortality (3%) of groin dissection staging. A positive aspirate is conclusive of Stage III tumor and, in patients with occult nodal metastases, may lead to early curative lymphadenectomy. In the present study of 28 patients with known cutaneous malignant melanoma, the aspiration biopsy cytology of 31 superficial nodules resulted in a cytologic diagnosis of metastasis in 29 nodules from 26 patients. In the management of patients with known melanoma, the positive cytology of superficial nodules is conclusive of metastatic disease and requires an accurate radiologic study to establish or exclude disseminated disease. Surgical removal of a metastatic superficial nodule is indicated when the lesion is considered localized disease and the patient, having been accurately examined, is determined to be apparently free of disease in other sites and organs. When systemic diffuse melanoma is found, the excision of metastatic superficial nodules is unnecessary. Positive aspiration cytology may avoid risk from ill-judged surgical procedures and indicate appropriate palliative treatment of the disease.     

Blind sampling is superior to anoscope guided sampling for screening for anal intraepithelial neoplasia

OBJECTIVES: Anal cytology smears are either collected "blind" (swab inserted 4 cm into anal canal and rotated) or guided through an anoscope (transformation zone visualised and then sampled). We compared these smear techniques with respect to sample quality and patient acceptability. METHODS: Using a paired, random sequence clinical trial, 151 homosexual men (n = 95 HIV positive) underwent both smear techniques at a single visit; smear order was randomised and specimens were read blind. Both techniques utilised a Dacron swab, with water lubrication. Cytological specimens were prepared using a liquid based collection method (ThinPrep). The outcome measures were cytological specimen adequacy, cytological classification, presence of rectal columnar, squamous and metaplastic cells, contamination, patient comfort and acceptability, and volume of fluid that remained after the ThinPrep procedure. RESULTS: Regardless of smear order, guided smears were less likely to detect higher grade abnormalities than blind smears (15 v 27 cases, p = 0.001). Controlling for smear order, guided smears were more likely to be assessed as "unsatisfactory" for cytological assessment (OR 6.93, 95% CI 1.92 to 24.94), and contain fewer squamous (OR 0.20, 95% CI 0.04 to 0.94) and metaplastic cells (OR 0.12, 95% CI 0.03 to 0.54) than blind smears; there were no other statistically significant differences between techniques. Regardless of smear technique, first performed smears were more likely to detect a higher grade abnormality than second performed smears (23 v eight cases, p < 0.001). CONCLUSIONS: Blind cytology smears are superior to anoscope guided smears for screening for anal neoplasia in homosexual men.     

Perianal and Vulvar Extramammary Paget Disease: A Report of Six Cases and Mapping Biopsy of the Anal Canal

Treatment of perianal and vulvar extramammary Paget disease (EMPD), rare intraepithelial malignancies, is often challenging because of its potential to spread into the anal canal. However, there is still no consensus regarding the optimal resection margin within the anal canal. Between 2004 and 2014, six patients (three with perianal EMPD and three with vulvar EMPD) in which the spread of Paget cells into the anal canal was highly suspected were referred to our department. To evaluate the disease extent within the anal canal, preoperative mapping biopsy of the anal canal was performed in five out of six patients. Two patients were positive for Paget cells within the anal canal (one at the dentate line and the other at 0.5 cm above the dentate line), whereas in three patients, Paget cell were present only in the skin of the anal verge. Using 1 cm margin within the anal canal from the positive biopsy sites, we performed anal-preserving wide local excision (WLE), and negative resection margins within the anal canal were confirmed in all five patients. The remaining one patient with perianal EMPD did not undergo mapping biopsy of the anal canal because preoperative colonoscopy revealed that the Paget cells had spread into the lower rectum. Therefore, WLE with abdominoperineal resection was performed. During the median follow-up period of 37.3 months, no local recurrence was observed in all patients. Our small case series suggest the usefulness of mapping biopsy of the anal canal for the treatment of perianal and vulvar EMPD.     

Anal human papillomavirus DNA screening by Hybrid Capture II in human immunodeficiency virus-positive patients with or without anal intercourse

High risk human papillomaviruses (HPVs) have emerged as risk factors for anal carcinoma, of which incidence is higher in HIV-positive patients than in the general population. The aim of our study was to investigate the prevalence and risk factors for anal HPV infections in HIV-positive patients with or without history of anal intercourse. Fifty HIV 1-infected patients (36 men and 14 women) were tested at entry and followed-up every 3 months for one year for the presence of anal HPV DNA by the Hybrid Capture II trade mark assay. A series of 50 HIV-negative subjects matched for age and sex served as controls. At enrollment, anal HPV DNA was present in 29/50 HIV-positive patients (58 %) and in 3/50 control subjects (6 %). High risk (HR) HPV genotypes were detected in 20/50 HIV-positive patients (40 %) with no difference in homosexual men and other HIV-positive patients. Risk factors for HPV infection were CD4 + cell counts less than 500/microL (RR: 2.13 [95 % CI: 1.0-4.7]) and history of anogenital warts (RR: 2.36 [95 % CI: 1.2-4.6]). The HPV load was higher in patients with CD4+ < or = 500/microL than in patients with CD4 + > 500/microL (p < 0.04). During the follow-up, anal HR HPV DNA was repeatedly identified at high levels in 5 HIV-positive patients. There is some convincing evidence that HIV-positive patients with low CD4+ cells, whatever the routes of HIV transmission, have a high rate of anal HPV infection and might be at increased risk of developing anal neoplastic lesions. Identifying HR HPV infection might be warranted in immunosuppressed patients.     

Botulinum toxin A in anal fissures: a modified technique

BACKGROUND: Anal fissures are common and painful. Botulinum toxin A (BTXA) is considered to be the most potent non-surgical treatment; however, no attention has been paid to associated hyperhidrosis. AIM: To compare traditional BTXA treatment of muscular spasticity in anal fissures with combined treatment of spasticity and focal hyperhidrosis of the anal fold and perianal skin. SETTING: Outpatient department of a dermatological hospital. PATIENTS AND METHODS: Ten patients with chronic anal fissures (of more than 6 months duration who failed to respond to conservative treatment and who had refused surgery) associated with focal hyperhidrosis as assessed by Minor's sweat test were investigated in an open, two-armed trial. Intramuscular injections of 20-25 U BTXA (Botox) were performed in group A (n = 5). In group B (n = 5) those injections were combined with intracutaneous injection of 30-50 U BTXA to treat focal hyperhidrosis. Mean follow-up was 5 months. RESULTS: Five of five patients in group B but only two of five patients in group A experienced a complete remission despite the fact that relief of pain was evident in eight of 10 patients within 2 weeks. Patient satisfaction with treatment was high but slightly better in group B. CONCLUSIONS: This open trial suggests that combined therapy of both muscular spasticity and focal hyperhidrosis may provide better results than intramuscular injections alone in anal fissure therapy with BTXA.