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.

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.

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.

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.

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.

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.

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.

Survival and treatment of AIDS patients 1984-1993: experience of a smaller east London HIV centre.

OBJECTIVE: To assess changes in survival from diagnosis of AIDS for patients managed in a small East London HIV clinic and the impact of therapeutic interventions on these survival patterns. DESIGN: Prospective observational study. SETTING: Grahame Hayton Unit, Royal London Hospital. SUBJECTS: 156 AIDS patients managed between 1984 and 1993. MAIN OUTCOME MEASURE: Survival from diagnosis of AIDS. RESULTS: Median survival for those diagnosed with AIDS before 1 January 1987 was 9.4 months compared with 27.2 months after 1 January 1987 (logrank chi 2 = 10.3, p = 0.001): CD4 count at time of AIDS and treatment with zidovudine or PCP prophylaxis were significantly associated with survival from time of AIDS. Of the 156 AIDS patients, 93 had been treated with zidovudine sometime during their follow up, 60 had received primary and 50 secondary Pneumocystis carinii pneumonia (PCP) prophylaxis. After controlling for gender, sexual orientation, age at time of AIDS, CD4 count at time of AIDS, diagnosis when first presenting to the clinic (AIDS/non-AIDS) and year of AIDS diagnosis, all patients who received either zidovudine or PCP prophylaxis had significant reductions in the risk of dying compared with those who received neither PCP prophylaxis nor zidovudine: a reduction in risk of dying between 71% (95% CI 40% to 86%) and 83% (95% CI 50% to 94%) was observed depending on the combination of zidovudine and PCP prophylaxis. CONCLUSION: A debate is currently taking place about the format and value of HIV service provision with increasing numbers of HIV infected individuals managed at smaller HIV clinics. Larger clinics concentrate clinical expertise on a single site and facilitate clinical trials. Smaller well run HIV units staffed by competent health professionals not only provide clinical outcomes similar to those obtained in the larger centres, but may also allow a more informal and intimate setting for HIV infected individuals who want to be treated nearer their area of residence.

Incidence of symptomatic urinary tract infections in HIV seropositive patients and the use of cotrimoxazole as prophylaxis against Pneumocystis carinii pneumonia.

OBJECTIVES: To determine the incidence of symptomatic urinary tract infections in HIV seropositive patients and to assess whether this varies with stage of disease, risk group or the use of co-trimoxazole as prophylaxis against Pneumocystis carinii pneumonia. METHODS: A retrospective case note review of 175 HIV-infected patients attending The Royal London Hospital between July 1988 and December 1992 was performed. A urinary tract infection was defined as a pure culture of > or = 10(5) colony forming units in a mid-stream specimen of urine from a patient with symptoms consistent with a urinary tract infection. RESULTS: Urinary tract infections occurred in 10 (5.7%) of 175 patients, with an incidence of 1.49 per hundred patient years. Urinary tract infections were significantly more common in patients with AIDS or a CD4 lymphocyte count below 0.2 x 10(9)/l (or both) when compared to those without AIDS and a CD4 lymphocyte count above 0.2 x 10(9)/l (5.4 vs. 0.5 urinary tract infections per hundred patient years, p = 0.00005). Women with AIDS or a CD4 count below 0.2 x 10(9)/l (or both) had an incidence of urinary tract infection of 18.5 per hundred patient years. No significant difference was found between the incidence of urinary tract infections in those taking co-trimoxazole as Pneumocystis carinii pneumonia prophylaxis and those taking alternative or no prophylaxis (2.6 vs 6.4 per hundred patient years, p = 0.39). CONCLUSIONS: Urinary tract infection represents a considerable health problem amongst HIV infected patients. Our data show that urinary tract infections are more common in patients with advanced compared with early HIV infection. Cotrimoxazole, when taken by patients as prophylaxis against Pneumocystis carinii pneumonia did not appear to reduce the incidence of urinary tract infection.

Changes in HPV infection in patients with anogenital warts and their partners.

OBJECTIVES--To investigate the relationship between clinical findings and the detection of human papillomavirus (HPV) DNA in a range of anatomical sites in patients with and without anogenital warts. SUBJECTS--Men and women with a clinical diagnosis of anogenital warts, or a current partner with anogenital warts. SETTING--A department of genitourinary medicine in central London. METHODS--The anogenital areas of the patients were thoroughly examined using a colposcope before and after application of acetic acid. Different types of specimens were taken from a variety of anatomical sites. Superficial skin sampling was performed by the application of slides covered with "Superglue" (SG) to clinically normal and abnormal areas of anogenital skin. The presence of human cells in the SG samples was confirmed by detection of the beta-globin gene using the polymerase chain reaction (PCR). HPV DNA was extracted from the specimens and amplified by using consensus primers with the PCR. HPV types 6, 11, 16, 18, 31 and 33 were identified by Southern blotting followed by hybridisation. RESULTS--In women, HPV DNA was detected in 83% of wart biopsies, 29% of cervical biopsies, 36% of cervical scrapes, 25% of urethral loop specimens, 37% of vaginal washes and 33% of rectal swab specimens. In men, HPV DNA was detected in 67% of wart biopsies, 37% of urethral loop specimens and 12% of rectal swab specimens. Of the SG samples containing the beta-globin gene, 49% from women and 50% from men contained HPV DNA. HPV DNA was not detected in buccal scrapes and serum samples from women or men. Of all specimens with detectable HPV DNA, there was evidence of a single HPV type in 41%, multiple types in 48% and undetermined types in 11%. Samples taken from different sites of a patient tended to have HPV types in common. Sexual partners, however, did not consistently have HPV types in common. CONCLUSIONS--HPV DNA was distributed widely in the anogenital area, in warts, acetowhite areas and clinically normal skin. The SG technique was well tolerated by patients and produced results consistent with other findings. Sampling from a single site of the genitalia on one occasion may significantly underestimate the infection rate with HPV. Multifocal infection of the anogenital area with HPV should be taken into consideration when interpreting epidemiological studies and management strategies.

Human papillomavirus DNA in the urogenital tracts of men with gonorrhoea, penile warts or genital dermatoses.

OBJECTIVE: To assess the presence of human papillomavirus (HPV) DNA in urethral and urine specimens from men with and without sexually transmitted diseases. DESIGN: Prospective study. SETTING: Two London departments of genitourinary medicine PATIENTS: 100 men with urethral gonorrhoea, 31 men with penile warts and 37 men with genital dermatoses. METHODS: Urethral and urine specimens were taken, HPV DNA extracted and then amplified using the polymerase chain reaction. HPV types 6, 11, 16, 18, 31 and 33 were identified using Southern blotting followed by hybridisation. RESULTS: HPV DNA was detected in 18-31% of urethral swab specimens and in 0-14% of urine specimens. Men with penile warts had HPV detected in urethral swabs more often than did men in the other two clinical groups. "High risk" HPV types were found in 71-83% of swab specimens and in 73-80% of urine specimens containing HPV DNA. CONCLUSIONS: HPV is present in the urogenital tracts of men with gonorrhoea, penile warts and with genital dermatoses. In men with urethral gonorrhoea, detection of HPV in urethral specimens is not related to the number of sexual partners, condom usage, racial origin or past history of genital warts. HPV DNA in the urethral swab and urine specimens may represent different aspects of the epidemiology of HPV in the male genital tract. The preponderance of HPV types 16 and 18 in all three groups of men may be relevant to the concept of the "high risk male".

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.

Detection of human papillomavirus DNA in the urogenital tracts of men with anogenital warts.

Increasing evidence suggests that human papillomavirus (HPV) infection of the female anogenital tract is multifocal. Less is known of the distribution of HPVs in men. To investigate this, a prospective study was conducted of 116 men consecutively attending a clinic for ablative treatment of anogenital warts. Wart tissue, urethral swabs, and urine were obtained from each patient. HPV DNA was extracted from the specimens and amplified using the polymerase chain reaction (PCR). HPV types 6, 11, 16, 18, 31, and 33 were identified using Southern blotting of the PCR product, followed by hybridization. HPV DNA was detected in 112 (96.6%) of 116 wart specimens and there was urethral infection with HPV in 26 (22.4%) of the men. Eleven (61.1%) of 18 urethral specimens taken with a loop and 22 (20.0%) of 116 urethral specimens taken using a cotton-tipped swab contained HPV DNA. One (6.3%) of 16 urine samples tested contained HPV DNA. HPV types 6 and 11 were found in the urethra most commonly when warts were seen near the urinary meatus, although HPV occurred in the urethras of men without clinically apparent meatal warts. The proportion of urethral samples with HPV DNA, including HPV types 16, 18, 31, and 33, was independent of the location of visible warts at the time of sampling.

Penile dermatoses: a clinical and histopathological study.

OBJECTIVE: To assess the spectrum of genital dermatological conditions affecting men and compare the clinical and histopathological diagnoses. DESIGN: Prospective study over a one year period. SETTING: A central London teaching hospital. PATIENTS: Seventy one patients with unresponsive penile dermatoses attending a specific internal referral clinic within the department of genitourinary medicine and 36 patients undergoing penile biopsy following attendance at other departments within the same hospital. METHODS: Full dermatological assessment of patients attending the specific clinic. Standard histopathological methods were used in the diagnosis of biopsy specimens. OUTCOME MEASURED: Clinico-pathological diagnosis of cutaneous penile abnormalities. RESULTS: Description of the range and relative frequency of penile dermatological conditions. The most common histopathological diagnosis was of non specific dermatitis. Twenty seven percent (16 of 61) of patients attending the specific clinic and 33% (12 of 36) of men attending other departments had conditions requiring long term follow up. CONCLUSIONS: The ranges of penile dermatoses presenting to the different departments were broadly similar. Penile biopsy was shown to be a safe and clinically informative procedure. In the genitourinary clinic setting, clinical diagnosis prior to biopsy was found frequently to be inaccurate.

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.

Granuloma annulare of the penis.

Granuloma annulare is an uncommon skin condition, most often found on the extremities of young females. A case of granuloma annulare occurring on the penis of a 61 year old man is reported and the current literature associating granuloma annulare and conditions likely to present to genitourinary clinics is reviewed.