Anal intraepithelial neoplasia and squamous cell carcinoma in HIV-infected adults.

Anal cancer is one of the most common non-AIDS-defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV-infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV-related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV-infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV-infected adults.

Indian-born patients attending a sexual health clinic in Australia have differing characteristics to their Australian-born counterparts.

We report a retrospective cross-sectional study from Western Sydney that assessed the sexual health characteristics of Indian-born patients attending sexual health services compared with Australian-born controls. The sexual health needs of Indian-born patients differed significantly from controls with those born in India reporting more sexual dysfunction and controls having more sexually transmitted infections (STI). These issues should be considered when delivering services to people from culturally and linguistically diverse backgrounds.

Prevalence and associations of larger burden of intra-anal high-grade squamous intraepithelial lesions at baseline in an Australian cohort of gay and bisexual men: The Study of the Prevention of Anal Cancer.

OBJECTIVES: To investigate factors associated with larger burden of intra-anal high-grade squamous intraepithelial lesions (HSIL) in a natural history study of HSIL. METHODS: 617 gay and bisexual men (GBM) attended a baseline visit. High-resolution anoscopy-directed biopsy was performed of suspected HSIL. GBM with biopsy-confirmed HSIL (bHSIL) affecting a single-octant were compared with those who had bHSIL affecting a larger area. RESULTS: Of 196 men with bHSIL at baseline, 73 (37.2 %) had larger bHSIL burden. Larger burden was independently associated with anal HPV16 detection (aOR 2.06, 95 % CI 1.09-3.89, p = 0.026) and infection with a greater number of high-risk HPV types (aOR per type increase 1.25, 95 % CI 1.05-1.49, p-trend = 0.010). CONCLUSION: The observation that men with a larger burden of HSIL also had more risk factors for anal cancer suggests this group may warrant closer observation to ensure earlier detection, and thus improved prognosis, of individuals whose HSIL may progress to anal cancer.

Anal human papillomavirus genotype diversity and co-infection in a community-based sample of homosexual men.

OBJECTIVES: To determine the prevalence and risk factors for anal human papillomavirus (HPV) infection in community-based cohorts of homosexual men in Sydney, Australia. METHODS: A cross-sectional study in consecutively presenting participants in the positive Health and Health in Men cohorts in 2005. HPV testing was performed on anal PreservCyt specimens collected from 316 homosexual men (193 HIV-negative, 123 HIV-positive) using the Digene Hybrid Capture 2 (HC-2) assay for detection of low-risk (LR) and high-risk (HR) genotypes. HPV genotype testing was also performed on a subset of 133 men (93 HIV-negative, 36 HIV-positive) using Roche Linear Array (LA) assay. RESULTS: HC-2 detected HPV infection in 79% of men (LR 55%, HR 69%). HIV-positive men were more likely than HIV-negative men to have LR-HPV (OR 3.5, 95% CI 2.1 to 5.7) and HR-HPV (OR 5.5, 95% CI 3.0 to 10.2). LA detected HPV infection in 95% of men (LR 85%, HR 77%). HIV-positive men had a mean of 7.1 HPV types compared to 4.2 in HIV-negative men; the difference was significant for both LR-HPV (p<0.001) and HR-HPV (p<0.001). HPV-16 was detected in 36% of HIV-positive and 27% of HIV-negative men. There was no consistent trend in HPV prevalence with increasing age. HR-HPV detection was associated with anal bleeding for HIV-positive men and anal warts for HIV-negative men. CONCLUSIONS: Anal HPV infection was nearly universal in this community-based sample of homosexual men. A wide variety of HPV genotypes were detected, and co-infection with multiple genotypes was common. Anal HPV infection is more prevalent and more diverse in HIV-positive than HIV-negative homosexual men.

Association of anal symptoms with anal high grade squamous intraepithelial lesions (HSIL) among men who have sex with men: Baseline data from the study of the prevention of anal cancer (SPANC).

BACKGROUND: The association between anal high-grade squamous intraepithelial lesion (HSIL) and anal symptoms has not been systematically investigated. METHODS: The Study of Prevention of Anal Cancer is a prospective cohort study of men who have sex with men (MSM) ≥ 35 years old in Sydney, Australia. Self-reported symptoms were collected. Anal cytology and high-resolution anoscopy were undertaken. Using baseline visit data, men negative for squamous intra-epithelial lesion (SIL) were compared with men diagnosed with composite-HSIL (cytology and/or histology). Logistic regression analyses were performed to assess the association of symptoms with HSIL. RESULTS: Among 414 MSM included (composite-HSIL (n = 231); negative for SIL (n = 183)), 306 (73.9%) reported symptom(s) within the last 6 months. There was no association between any symptom and composite-HSIL. A significant association between anal lump and a larger burden of HSIL (at least 2 intra-anal octants) (anal lump within last month: p = 0.014; anal lump within last 6 months: p = 0.010) became non-significant after adjusting for HIV-status and recent anal warts (anal lump within last month: p = 0.057; anal lump within last 6 months: p = 0.182). CONCLUSIONS: Among MSM age 35 years and older, most anal symptoms are not a useful marker of anal HSIL.

Australian dentists' perspectives on rapid HIV testing.

BACKGROUND: Fourteen per cent of people living with HIV in Australia, as in other countries, are not aware of their infection or their infective status. Dentists have the necessary expertise and are well-placed for access by those sections of the population who would not normally access screening for HIV. METHODS: A national cross-sectional online survey of 532 Australian dentists was conducted during the period June to October 2013. We surveyed dentists' understanding and willingness to undertake rapid HIV testing (RHT). RESULTS: The majority of respondents (65.1%) believed that RHT was needed in dental clinics, with approximately two-thirds of respondents indicating that RHT should be made available immediately. If RHT was to be undertaken in a dental setting, 51.1% of dentists thought that it should be conducted on saliva only, as opposed to blood or blood/saliva. Only 21.9% of dentists would currently be comfortable advising a patient of a reactive (i.e. positive) result indicative of HIV infection, with male dentists (26.1% comfortable) more comfortable than female dentists (17.5% comfortable) (p = 0.009). CONCLUSIONS: The majority of respondents were willing to provide RHT in their community settings. However, our data indicate that dentists would need additional training in HIV medicine, test administration and giving reactive results.

Serum myoglobin and creatine kinase enzymes in acute myocardial infarction treated with Anistreplase.

AIMS: To compare plasma myoglobin concentration and cardiac enzyme activity with electrocardiographic (ECG) changes in two groups of patients (reperfused and non-reperfused) participating in a placebo-controlled randomised double blind trial of treatment of myocardial infarction (MI) with intravenous thrombolytic therapy (Anistreplase). METHODS: Twenty two patients with confirmed MI obeying strict inclusion and exclusion criteria were studied. Plasma myoglobin was measured by radioimmunoassay and creatine kinase enzyme (CK and CKMB) by NAC activated and NAC activated/immunoinhibition methods respectively in all patients before and at frequent intervals after injection of Anistreplase or placebo. Patients were divided into reperfused (R) and non-reperfused (NR) groups on the basis of ECG criteria. Reperfusion was diagnosed if the measured ST segment elevation fell by greater than or equal to 50% at 2 hours post dosing. RESULTS: The time to peak (TTP) myoglobin was significantly less in the R group compared with the NR group but there was considerable overlap in the range of values. The area under the enzyme time curves (AUCs) and summed ST segment epsilon ST elevations were significantly smaller in the R compared with the NR group. CONCLUSIONS: Although TTP myoglobin results were significantly lower in the R group, TTP myoglobin will probably not be useful as an non-invasive indicator of reperfusion because of the overlap in values between the two groups. The significant reduction in the AUC and epsilon ST only in the R group suggests decreased infarct size. However, in this small preliminary study reperfusion did not occur more frequently with Anistreplase than without.

Ciprofloxacin as a cause of Clostridium difficile-associated diarrhoea in an HIV antibody-positive patient.

Ciprofloxacin is an uncommon cause of pseudomembranous colitis. A case is described in which diarrhoea was associated with the presence of clostridial toxin in an HIV-infected patient and the possible implications are discussed.

Medical and social aspects of sexual assault of males: a survey of 100 victims.

Sexual assault of males is an infrequently reported and a poorly understood phenomenon. Details of 100 victims who sought assistance from a nationwide agency set up specifically to provide help for such individuals are reported here. Twenty eight victims were aged 16 years or over at the time of assault. The assailants were known by 72 of the victims and were perceived by the victim to have a heterosexual orientation in 72% of these cases. Attacks were often multiple and in 33 cases involved disruption of skin or mucous membranes. Twenty victims received threats about the possibility of transmission of the human immunodeficiency virus and 17 victims sought medical advice following the assault, most commonly from their general practitioner. It is suggested that greater opportunities for medical and psychological support should be given to male victims of sexual assault.

Getting to the bottom of anal itch - a cautionary tale.

Peri-anal rash is common and may appear macroscopically benign. In HIV-positive men, however, more serious pathology may be revealed by a biopsy. The high prevalence of human papillomavirus infection in these men predisposes them to pre-cancerous lesions of the peri-anal and anal skin. We report an unusual case of dual pathology in the anal region, which highlights the need to thoroughly investigate peri-anal symptoms in HIV-positive men.

Setting up a support service for male prostitutes in London.

Estimating the number of male prostitutes working at any given time is fraught with difficulties. We suggest that perhaps around 600-700 men were selling sex in London in 1989. We report some preliminary observations gained during the setting up of a specific service for male prostitutes. Of 32 male prostitutes seen, 26 worked as rent-boys, 4 worked through agencies and 2 worked independently from home. Forty-one per cent had evidence of at least one sexually transmissible disease and 3 of 16 men tested (19%) were human immunodeficiency virus (HIV) positive.

Human papillomavirus DNA in the urogenital tracts of men with genital dermatoses: evidence for multifocal infection.

In an attempt to assess the multifocal nature of anogenital HPV infection in men, skin biopsies, urethral swabs and urine specimens were obtained from 100 men with genital dermatoses. The specimens were examined for the presence of human papillomavirus (HPV) types 6, 11, 16, 18, 31 and 33 using the polymerase chain reaction and Southern blotting techniques. HPV DNA was detected in one or more specimens from 39 patients, that is 29 of 100 biopsy specimens, 21 (25%) of 85 urethral swab specimens and 6 (10%) of 59 urine specimens. HPV DNA was more common in men with at least 20 lifetime sexual partners and in those who gave a history of anogenital warts. Twelve (18%) of 66 biopsy specimens with no histological evidence of warty change or neoplasia had detectable HPV DNA. HPV DNA was detected no more frequently in the urethral and urine specimens from men with histological evidence of warts or neoplasia than from men without such changes. HPV types 6 and 11 were most common in biopsy specimens with histological changes of typical HPV infection. HPV type 16 was commonest in biopsy specimens with neoplasia and type 18 with other changes. Furthermore, 'high-risk' HPV types were found proportionately more often in urethral swab and urine specimens than in biopsy specimens. There was generally a poor correlation between the detection of HPV DNA at the different sites. A greater understanding of the role of HPV in the production of genital abnormalities is required in order to develop a rational approach to the management of these patients.

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.

Anogenital warts and condom use--a survey of information giving.

OBJECTIVE: To examine information giving by genitourinary medicine (GUM) consultants about the use of condoms for patients with anogenital warts (AGW). METHOD: 228 GUM consultants in the UK and Ireland were sent a questionnaire concerning the information about condom use which they usually discuss with patients with AGW. The survey was carried out in 1994. RESULTS: There was a 46% response rate. Most consultants indicated giving information specifically with regard to the prevention of transmission of human papilloma virus (HPV), and not only in the context of safe sex. With regard to current AGW, consultants were more likely to discuss, than not to discuss, use of condoms with patients with regular sexual partners in terms of benefit, uncertain benefit, or no benefit. However, no significant difference in the likelihood of discussing, or not discussing, these issues was found for current AGW for patients without regular partners. For both groups, benefit of using condoms for current AGW was more likely to be discussed than no benefit. The majority of consultants indicated that they would discuss condom use after disappearance of AGW as being of uncertain benefit. However, many consultants also indicated discussing use of condoms for a specific period or an indefinite period of time, including many of those who specific discussing uncertain beneficial use of condoms after disappearance of AGW. The most common duration of condom use chosen for discussion was until 3 months after disappearance of AGW. CONCLUSION: GUM consultants vary in the information they give about condom use specifically to prevent transmission of HPV. This survey suggests a need for evaluation by GUM physicians of management guidelines relating to information given about condom use for AGW, including utilising the available scientific evidence as well as dealing with issues of uncertainty.

Scrotal ulceration in HIV-positive patients.

Four patients with scrotal ulceration were seen during a period of 9 months. All of them were HIV-positive homosexual men with coexisting skin conditions. Herpes simplex virus was not isolated from any of the ulcers, but a variety of bacteria was recovered. It is suggested that multiple factors peculiar to HIV-positive individuals may account for the development of such ulcers.

Effect of alpha-glucosidase inhibition on glucose profiles in insulin dependent diabetes.

A single-blind comparison of the effectiveness of miglitol (BAY-m-1099) and placebo in controlling postprandial hyperglycaemia was performed in 13 insulin dependent diabetics. Each subject received placebo and miglitol for four weeks, with an intervening two week placebo (washout) period, and underwent a 9.5 hr glycaemic profile after each four week treatment period. The area under the glucose curve was significantly (p less than 0.01) reduced by miglitol although no reduction in fasting blood glucose, HbA1, plasma lipids, insulin dosage or weight was observed. Side effects were not appreciably more common when patients received miglitol than when receiving placebo.