Search

Background Anal symptoms may indicate serious pathology. Receptive anal intercourse (RAI) and sexually transmissible infections (STIs) may contribute to a higher prevalence of symptoms among gay and bisexual men (GBM). This study investigated associations with anal symptoms among GBM. Methods: The Study of the Prevention of Anal Cancer was a longitudinal study of anal human papillomavirus and related lesions in Sydney, Australia. GBM aged ≥35 years were recruited from community settings between September 2010 and August 2015. Information about anal symptoms (discharge, itch, pain defecating, lump, bleeding, ‘sores’, tearing, tenesmus), STIs and sexual behaviours was collected. High-resolution anoscopy (HRA) and STI testing were performed. Logistic regression analyses on baseline data were performed to assess associations with each symptom. Results: Among 616 participants (median age 49 years, 35.9% HIV positive), 35.3% reported at least one anal symptom within the past week and 65.3% were diagnosed with fistula, fissure, ulcer, warts, haemorrhoids and/or perianal dermatoses at HRA. Anal symptoms were not associated with anal chlamydia, gonorrhoea, warts or syphilis. Self-reported ‘sores’ were associated with previous anal herpes simplex virus (HSV; P < 0.001). ‘Sores’ (P < 0.001), itch (P = 0.019), discharge (P = 0.032) and lump (P = 0.028) were independently associated with ulceration. Among participants diagnosed with fissure, fistulae, haemorrhoids and perianal dermatoses, 61.9%, 100%, 62.0% and 63.9% respectively were asymptomatic. Only self-reported anal tear was independently associated with recent RAI. Conclusions: Previous anal HSV was the only STI associated with any symptom. Anal pathology was highly prevalent, but often asymptomatic. Anal symptoms do not appear to be useful markers of most anal pathology in GBM.

Background Incidence of anal cancer is highest in gay and bisexual men (GBM). Better understanding of the natural history of anal high-risk human papillomavirus (hrHPV) infection is needed for anal cancer prevention. Methods The Study of the Prevention of Anal Cancer was a 3-year study of Australian GBM, aged 35 years or older. We examined incidence, clearance, and risk factors for 13 hrHPV types at baseline and 3 annual visits. Results In 525 men with ≥ 2 visits, 348 (66.3%) acquired ≥ 1 incident hrHPV infection. HPV16 incidence rates were similar, but non-16 hrHPV incidence was higher in HIV-positive (51.8/100 person years [PY]) than HIV-negative men (36.5/100 PY, P Conclusions Higher incidence of non-16 hrHPV types, coupled with lower clearance of non-16 hrHPV types in those with past impaired immune function, is consistent with the greater role of non-16 hrHPV in anal cancer in HIV-positive people. Australia New Zealand Clinical Trials Registry ANZCTR365383.

Human papillomavirus (HPV) causes anal warts and anal squamous cell carcinoma (SCC). A higher incidence of anal cancer has been found among individuals previously diagnosed with anogenital warts. We aimed to investigate the association between anal warts and the presumed anal SCC precursor high-grade squamous intraepithelial lesion (HSIL), among participants in the Study of the Prevention of Anal Cancer (SPANC). SPANC was a longitudinal study of anal HPV infections and related lesions among gay and bisexual men (GBM) age 35 years and older, in Sydney, Australia. Anal cytology and high-resolution anoscopy were performed. Logistic regression was used to investigate the association between clinically diagnosed anal warts and intra-anal composite-HSIL (cytology and/or histology) at the baseline visit. The prevalence of HSIL within biopsies from intra-anal warts was calculated. Laser capture microdissection (LCM) and HPV-genotyping was performed on HSIL lesions. Among 616 participants at study entry, 165 (26.8%) and 51 (8.3%) had intra-anal and perianal warts, respectively. Warts were associated with composite-HSIL, even after adjustment for HIV status, age, lifetime receptive anal intercourse partner number, and smoking (perianal: aOR 2.13, 95% CI 1.17-3.87

Background: Anal high-grade squamous intraepithelial lesion (HSIL) can be histomorphologically categorized into anal intraepithelial neoplasia (AIN) grade 2 (AIN2) and grade 3 (AIN3). Different risk factors for these two categories have been described. We investigated whether there were also differences in lesion-specific human papillomavirus (HPV) genotypes. Methods: The Study of the Prevention of Anal Cancer (SPANC) recruited 617 gay and bisexual men (GBM); 36% of participants were HIV positive. At baseline, 196 men (31.8%) had histologic HSIL lesions. Tissue was available for genotyping in 171, with a total of 239 HSIL lesions (183 AIN3 and 56 AIN2). Using laser capture microdissection, each lesion revealed a maximum of one genotype. Results: High-risk HPV (HR-HPV) genotypes were found in 220 (92.1%) HSIL lesions, with no significant difference between AIN3 (93.4%) and AIN2 (87.5%). AIN3 lesions had significantly more HPV16 (42.1%) than AIN2 lesions (12.5%; P < 0.001) and AIN2 lesions had significantly more non-16 HR-HPV types (75.0%) than AIN3 lesions (51.4%; P = 0.002). These associations were similar for HIV-negative men with HPV16 in 51.1% AIN3 and 18.2% AIN2 (P = 0.001) and non-16 HR-HPV in 40.0% AIN3 and 75.8% AIN2 (P < 0.001). For HIV-positive men, HPV16 remained more frequently detected in AIN3 (33.3% vs. 4.4% for AIN2; P = 0.004), but there was no difference between AIN3 and AIN2 for non-16 HR-HPV (62.4% vs. 73.9%; P = 0.300). Conclusions: As HPV16 has the strongest link with anal cancer, the subcategorization of HSIL may enable stratification of lesions for anal cancer risk and guide anal HSIL management. Impact: Stratification of anal cancer risk by histologic HSIL grade.

Background Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL). Methods The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology cHSIL) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs. Results Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5–13.5 per 100 PY). Significant bivariate predictors of higher incidence included age Conclusion These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments. Clinical Trials Registration Australia New Zealand Clinical Trials Registry (ANZCTR365383).

ObjectivesSexually transmitted infection (STI) notifications are increasing among older individuals. Many older gay and bisexual men (GBM) are sexually active and have multiple partners. We aimed to investigate the prevalence, incidence and predictors of anal chlamydia, anal gonorrhoea and syphilis in older GBM.MethodsThe Study for the Prevention of Anal Cancer (SPANC) was a prospective cohort study of HPV infections and related anal lesions among community-recruited GBM age ≥ 35 years in Sydney, Australia. At baseline and subsequent annual visits, recent STI diagnoses were collected via questionnaire (‘interval diagnoses’) and STI testing occurred (‘study visit diagnoses’). Baseline STI prevalence was calculated using study visit diagnoses. Incidence of anal chlamydia and gonorrhoea was calculated using interval and study visit diagnoses. Syphilis incidence was calculated using interval diagnoses. Univariate and multivariate analysis using Cox proportional hazards were undertaken to investigate the association between risk factors and incident STI.ResultsAmong 617 GBM, the median age was 49 years (range 35–79) and 35.8% (n=221) were HIV-positive. At baseline, STI prevalence was: anal chlamydia 2.3% (n=14); anal gonorrhoea 0.5% (n=3) and syphilis 1.0% (n=6). During 1428 person-years of follow-up (PYFU), the incidence (per 100 PYFU) of anal chlamydia, anal gonorrhoea and syphilis was 10.40 (95% CI 8.82 to 12.25), 9.11 (95% CI 7.64 to 10.85) and 5.47 (95% CI 4.38 to 6.84), respectively. In multivariate analysis, HIV-positivity, higher number of recent condomless receptive anal intercourse partners and baseline methamphetamine use were associated with each STI. Sex with ‘fuck-buddies’ was associated with anal chlamydia and gonorrhoea. Age was not associated with any STI.DiscussionThere was a high incidence of STI among SPANC participants. Age should not be used as a proxy for sexual risk and older GBM require a detailed sexual behaviour and recreational drug use history. Interventions that specifically target STI risk among older GBM should be considered.

ObjectiveHigh-risk human papillomavirus (HRHPV) causes anal cancer, which disproportionately affects gay and bisexual men (GBM). We examined sexual behaviours associated with incident anal HRHPV in an observational cohort study of GBM in Sydney, Australia.MethodsGBM aged 35 years and above were enrolled in the Study of the Prevention of Anal Cancer. Detailed information on sexual practices in the last 6 months, including receptive anal intercourse (RAI) and non-intercourse receptive anal practices, was collected. Anal human papillomavirus (HPV) testing was performed at the baseline and three annual follow-up visits. Risk factors for incident HRHPV were determined by Cox regression using the Wei-Lin-Weissfeld method.ResultsBetween 2010 and 2015, 617 men were recruited and 525 who had valid HPV results at baseline and at least one follow-up visit were included in the analysis. The median age was 49 years (IQR 43–56) and 188 (35.8%) were HIV-positive. On univariable analysis, incident anal HRHPV was associated with being HIV-positive (pConclusionGBM living with HIV and those who reported RAI were at increased of incident anal HRHPV. Given the substantial risk of anal cancer and the difficulty in mitigating the risk of acquiring anal HRHPV, HPV vaccination should be considered among sexually active older GBM.Trial registration numberANZCTR365383.

Recreational drug use (RDU) among gay and bisexual men (GBM) is associated with higher-risk sexual behaviours, however this has not been well defined among older GBM. We investigated the association between RDU and sexual behaviours among older GBM in Sydney, Australia. 617 GBM aged 35–79 years self-reported their RDU in the past 6 months and sexual behaviours. Age-stratified univariable associations between RDU and behaviour were examined. GBM aged 35–44 years were the most likely to report RDU, with rates decreasing with increasing age (Ptrend < 0.001). Associations between RDU and higher-risk sexual behaviours were most consistently found among GBM aged 35–54 years.

Background: Gay and bisexual men (GBM) are at disproportionately high risk of anal cancer. The precursor lesions, high-grade squamous intraepithelial lesions (HSIL), are very common and it is evident that not all HSIL progresses to cancer. The serologic response to anal human papillomavirus (HPV) in GBM has not been well characterized. Methods: The Study of the Prevention of Anal Cancer is an ongoing cohort study of GBM ages 35 years and older. At six visits over three years, anal samples are collected for cytology, HPV DNA testing, and histology. Baseline serum was tested for HPV L1, E6, and E7 antibodies for 10 HPV types. Seroprevalence and associated predictors were analyzed. Results: A total of 588 of 617 participants were included in this analysis. A total of 436 (74.2%) were seropositive for at least one of the 10 HPV types. Almost half had L1 antibodies to HPV6 (48.5%), over a third to HPV11 (36.4%) and HPV16 (34.5%). HIV-positive men were more likely to be HPV L1 seropositive. HSIL detection was highest among participants who were HPV serology and DNA positive. There was a borderline significant association between presence of HPV16 E6 antibodies and prevalent HSIL (OR = 2.97; 95% confidence interval, 0.92–9.60; P = 0.068). Conclusions: HPV L1 seropositivity was common in this cohort of older GBM. These results suggest that HPV L1 seropositivity, in conjunction with anal HPV DNA detection, predicts concurrent HSIL. The apparent association between HPV16 E6 antibodies and prevalent HSIL is a finding with potential clinical significance that needs further exploration. Impact: HPV seropositivity with concurrent DNA detection predicted anal HSIL detection. Cancer Epidemiol Biomarkers Prev; 27(7); 768–75. ©2018 AACR.

Objective: HPV causes ~90% of anal cancer and HPV16 is the type most commonly associated with anal cancer. Gay and bisexual men (GBM) are at greatly increased risk. We investigated patterns of vaccine-preventable anal HPV in older GBM. Methods: The Study of the Prevention of Anal Cancer (SPANC) is an ongoing, prospective cohort study of HIV-positive and HIV-negative Australian GBM. Participants completed questionnaires and underwent an anal swab for HPV genotyping using Roche Linear Array. We analysed baseline data from SPANC by HPV type, mean number of types, stratified by age and HIV status. Results: Anal HPV results from 606 (98.2%) of 617 participants (median age 49 years, 35.7% HIV-positive) showed 525 (86.7%) had â¥1 HPV type and 178 (29.4%) had HPV16. Over one third of participants (214, 35.3%) had no nonavalent vaccine-preventable types detected. Two (0.3%) participants had all quadrivalent types and none had all nonavalent vaccine types. HIV-positive participants (p

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

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.

ObjectiveGay, bisexual and other men who have sex with men (GBMSM), particularly HIV-positive GBMSM, are at increased anal cancer risk compared with the general population. This study examined the psychological and quality of life (QoL) impact of receiving abnormal anal cancer screening results during the baseline visit of the Study of the Prevention of Anal Cancer (SPANC).MethodsSPANC was a prospective cohort study of the natural history of anal human papillomavirus (HPV) and associated abnormalities in GBM aged 35 years and over. Participants completed questionnaires including aspects of health-related QoL (HR-QoL) and psychosocial functioning at baseline. Participants underwent procedures including an anal swab for cytology, and high-resolution anoscopy with biopsy of any possibly HPV-related abnormality. Questionnaires were readministered 2 weeks and 3 months after participants were given cytology and histology results. Perceived test result served as the study factor.ResultsParticipants with perceived abnormal results (n=232) reported poorer HR-QoL (mean difference=1.8; p=0.004) and lower utility-based QoL (mean difference=0.02; p=0.018) 2 weeks after screening than individuals with perceived normal results (n=268). These differences did not persist at 3-month follow-up. A greater proportion of participants who perceived their results as abnormal reported feeling worse than usual about their anal health and anal cancer fear (p’sConclusionsProviding abnormal results may cause psychological distress and impact HR-QoL, with sustained intrusive thoughts, increased cancer worry and perceived cancer risk. The potential for psychological harm needs to be considered when implementing anal cancer screening programmes.

Contains fulltext : 215651.pdf (Publisher’s version ) (Open Access) OBJECTIVE: The aim of the study was to develop recommended techniques and quality assurance metrics for the practice of Digital Anal Rectal Examination (DARE). MATERIALS AND METHODS: The International Anal Neoplasia Society undertook a literature review and, using the AGREE II technique, developed guidelines for performing DARE. RESULTS: A consensus was formed regarding the optimum conditions and characteristics of DARE. Several Quality Assurance metrics were developed. CONCLUSIONS: Digital Anal Rectal Examination is a cheap and potentially universally available technique, which has the potential to facilitate the early diagnosis of anal cancers, when they are most amenable to treatment. These guidelines provide a basis for teaching the technique and may be used as for evaluation research.

Background: There is debate about the accuracy of anal cytology and high-resolution anoscopy (HRA), in the diagnosis of anal human papillomavirus (HPV)-related squamous intraepithelial lesions (SIL). Few studies have performed both simultaneously in a large sample of high-risk individuals. Methods: At baseline in a community-based cohort of HIV-infected and uninfected homosexual men ages ≥35 years in Sydney, Australia, all men underwent anal swabbing for cytology and HPV genotyping, and HRA-guided biopsy. We evaluated the separate and combined diagnostic accuracy of cytology and histology, based on a comparison with the prevalence of HPV16 and other high-risk (HR) HPV. We examined trends in HPV prevalence across cytology–histology combinations. Results: Anal swab, HRA, and HPV genotyping results were available for 605 of 617 participants. The prevalence of cytologically predicted high-grade SIL (HSIL, 17.9%) was lower than histologically diagnosed HSIL (31.7%, P < 0.001). The prevalence of composite-HSIL (detected by either method) was 37.7%. HPV16 prevalence was similar in men with HSIL by cytology (59.3%), HSIL by histology (51.0%), and composite-HSIL (50.0%). HPV16 prevalence was 31.1% in men with composite-atypical squamous cells suggestive of HSIL, to 18.5% in men with composite-low-grade SIL, to 12.1% in men with composite-negative results (Ptrend < 0.001). Conclusions: Significantly more HSIL was detected when a composite cytology–histology endpoint was used. Increasing grade of composite endpoint was associated with increasing HPV16 prevalence. Impact: These data suggest that a composite cytology–histology endpoint reflects meaningful disease categories and is likely to be an important biomarker in anal cancer prevention. Cancer Epidemiol Biomarkers Prev; 25(7); 1134–43. ©2016 AACR.

BACKGROUND Studies regarding the performance of anal cytology in which both the screening test (cytology) and the diagnostic test (high-resolution anoscopy [HRA]) are performed in all members of a screening population are rare. The authors evaluated the performance of liquid-based anal cytology in a cohort of homosexual men in Sydney, New South Wales, Australia. METHODS The Study of the Prevention of Anal Cancer (SPANC) is a 3-year prospective study of the natural history of anal human papillomavirus infection in homosexual men aged ≥35 years. At baseline, all participants underwent a liquid-based anal cytology test and HRA at the same clinical visit. Biopsies were obtained for histological assessment if lesions suspicious for human papillomavirus infection were visible during HRA. Using any cytological abnormality as the threshold, the sensitivity, specificity, and positive and negative predictive values were calculated against histologically diagnosed high-grade squamous intraepithelial lesions (HSILs). RESULTS Among 617 men recruited, the median age was 49 years (range, 35-79 years) and 35.7% were positive for the human immunodeficiency virus. Overall, the sensitivity of cytology was 83.2%, the specificity was 52.6%, the positive predictive value was 45.8%, and the negative predictive value was 86.7%. Specificity improved with increasing age (P for trend =.041). Sensitivity was significantly higher in men with >1 anal octant of biopsy-confirmed HSIL (92.9% vs 77.7%; P = .010), and in those who had ≥10 metaplastic cells present on their cytology slides (87.5% vs 70.2%; P = .007). CONCLUSIONS Anal cytology was found to have a higher specificity in older men while maintaining sensitivity. Sensitivity was higher among those with more extensive HSILs and men with metaplastic cells present on cytology. Cancer Cytopathol 2016;124:415–24. © 2016 American Cancer Society.

Background The ThinPrep Imaging System (TIS) is an accurate time-saving method of reading cervical ThinPrep slides in screening programs. As anal and cervical cytology are morphologically similar, TIS can potentially be used for anal cytology. We assessed the performance of TIS on anal ThinPrep slides from homosexual men in a natural history study of human papillomavirus-related anal abnormalities. Methods Four hundred nineteen anal cytology slides were processed by TIS and classified by a cytologist as either No further review (slide archived) or Manual review (slide requiring full manual screen). The results were compared with the original manual screening report for all slides and specifically for those screening episodes accompanied by a high-grade squamous intraepithelial lesion (HSIL) on concurrent biopsy. Results One hundred seventy six of 419 (42.0%) slides were classified as No further review, with a trend of decreasing proportions as the degree of severity of the cytological abnormality increased. Thirteen (27.7%) slides with an original unsatisfactory report were classified as No further review. Eighty two (92.1%) of those with biopsy HSIL and cytological abnormality were classified for Manual review, including all 45 (100%) with cytological HSIL. Conclusion The cervical algorithm of TIS performed best on anal samples when HSIL was present both cytologically and histologically. The 27.7% unsatisfactory slides classified as No further review may indicate need for use of different criteria from cervical cytology. Because of the high prevalence of abnormalities, and hence the large proportion of slides needing manual review, the cytologist time-saving would compare unfavorably with use of TIS in cervical screening. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

Background Anal high-grade intraepithelial lesions (HSIL) precede the development of HPV-associated anal cancer and so present a target for early intervention and cancer prevention. Spontaneous HSIL clearance is associated with systemic CD4 T-cell response to the HPV oncogene E6. Pomalidomide may enhance immune responses to HPV and be therapeutic in HSIL. Methods This phase II single centre study (NCT3113942) recruited participants with persistent (>12 months) biopsy-proven anal HSIL. Therapy was oral pomalidomide, 2mg for 21 of 28 days for up to 6 months. Primary outcome was response at end therapy (CR defined as histological clearance; PR as ≥ 50% reduction in area); secondary included response after 6 further months observation. Immune activation markers (CD38, HLA DR) were assessed with flow cytometry and antigen-specific CD4+ T-cell responses to HPV E6 and E7 with OX40 immunoassay. Results 26 participants were enrolled, 24 were evaluable for response. All male; median age 54 (range 41-74). All AIN3 HSIL, median duration HSIL 37 months (15-86), median octants 2 (0.5-5); HPV16 in 55%; multiple high risk HPV types in 50%. Overall response (CR+PR) was 52% (CI: 31-73) at end therapy, increasing to 63% (95% CI 40-81) after 6 further months observation. Adverse events (AEs) were mild and self-limited, including cytopenias, constipation, and rash. Over 137 cycles (c), attributable grade 3/4 events were grade 3 neutropenia (4 c) and grade 3 angina (1 c). Systemic CD4 T-cell responses to HPV E6 but not E7 increased significantly during therapy, peaking day 14 of therapy: baseline 0.06%, (IQR 0.01 – 0.12%), median increase day 14 0.13% (IQR: 0.02 – 0.26%), p = 0.001. Activation of CD4 and CD8 cells increased significantly during therapy. Parameters returned to baseline after therapy. Conclusion Low dose oral pomalidomide was well tolerated and induced durable continuing clearance of anal HSIL of multiple genotypes in even in chronic extensive disease. Induction of HPV-specific CD4+ responses and immune activation support an immunological mechanism of action. Immunotherapy with pomalidomide is a promising approach to prevention of anal cancer and potentially other HPV cancers. Clinical trial identification NCT3113942. Legal entity responsible for the study Kirby Institute, University of New South Wales, Sydney, Australia. Funding Cancer Institute of New South Wales. Disclosure All authors have declared no conflicts of interest.

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.

Anal cytology has been suggested as a screening test for the anal cancer precursor high-grade squamous intraepithelial lesion (HSIL). We aimed to assess the prevalence and predictors of initial unsatisfactory anal cytology tests ('unsats'). The Study of the Prevention of Anal Cancer is a natural history study of anal human papillomavirus (HPV) and precancerous lesions among gay and bisexual men (GBM) of at least 35 years in Sydney, Australia. At each study visit, an anal swab is collected for cytological testing. Unsats are defined as slides with fewer than 2000 nucleated squamous cells and no abnormal cells. Among 617 GBM enrolled, the median age was 49 (range: 35-79) years and 220 (35.7%) were HIV positive. Initial unsats occurred in 61 (9.9%, 95% confidence interval: 7.6-12.5%), and 29 (4.7%, 95% confidence interval: 3.2-6.7%) remained unsatisfactory on repeat cytology. Initial unsats were associated with fewer lifetime anal-receptive partners with a condom (P=0.007); fewer recent anal-receptive sexual partners without a condom (P=0.005); never having had anal chlamydia (P=0.023) or gonorrhea (P=0.003); HIV-negative status (P=0.002); fewer total (P=0.002), low-risk (P=0.005), and high-risk (P=0.015) HPV types detected; lack of anal HPV18 detection (P=0.001); never having anally douched (P

ObjectivesTo define minimum standards for provision of services and clinical practice in the investigation of anal cancer precursors.MethodsAfter initial face to face meetings of experts at the International Papillomavirus meeting in Lisbon, September 17 to 21, 2015, a first version was drafted and sent to key stakeholders. A complete draft was reviewed by the Board of the International Anal Neoplasia Society (IANS) and uploaded to the IANS Web site for all members to provide comments. The final draft was ratified by the IANS Board on June 22, 2016.ResultsThe essential components of a satisfactory high-resolution anoscopy (HRA) were defined. Minimum standards of service provision, basic competencies for clinicians, and standardized descriptors were established. Quality assurance metrics proposed for practitioners included a minimum of 50 HRAs per year and identifying 20 cases or more of anal high-grade squamous intraepithelial lesions (HSILs). Technically unsatisfactory anal cytological samples at first attempt in high-risk populations should occur in less than 5% of cases. Where cytological HSIL has been found, histological HSIL should be identified in ≥ 90% of cases. Duration of HRA should be less than 15 minutes in greater than 90% of cases. Problematic pain or bleeding should be systematically collected and reported by 10% or lesser of patients.ConclusionsThese guidelines propose initial minimum competencies for the clinical practice of HRA, against which professionals can judge themselves and providers can evaluate the effectiveness of training. Once standards have been agreed upon and validated, it may be possible to develop certification methods for individual practitioners and accreditation of sites.

Objective: Human papillomavirus–related anal cancer rates are increasing and are particularly high in gay, bisexual and other men who have sex with men (GBM/MSM), especially HIV-positive individuals. Although screening programs for high-risk populations have been advocated, concerns about possible adverse psychological consequences exist. This study aimed to investigate GBM/MSM's experience, understanding and emotional response to screening techniques for anal cancer to determine how best to minimise psychological distress in future programs. Methods: In-depth qualitative face-to-face interviews were conducted with 21 GBM/MSM participating in the “Study of the Prevention of Anal Cancer” in Sydney, Australia, between June 2013 and June 2014. Nonrandom, purposive sampling was used to ensure heterogeneity with respect to HIV status and screening test results. Framework analysis method was used to organise the data and identify emerging themes. Results: Knowledge about anal cancer, human papillomavirus and the link between them was limited. Abnormal screening results affected participants' sense of well-being and were associated with anxiety and concern about developing anal cancer. HIV-negative men receiving abnormal results showed higher levels of distress compared to their HIV-positive counterparts. Consultations with general practitioners about abnormal results had an important role in increasing participants' understanding and in moderating their anxiety. Conclusion: Anal cancer screening should be accompanied by health education around anal cancer, its aetiology and the meaning of associated test results. Simple and effective communication strategies should be encouraged. Collaboration with general practitioners could assist the process of education and reporting test results.

Background The majority of anal carcinomas are caused by human papillomavirus (HPV) 16. Identifying which of the high-grade squamous intraepithelial lesions (HSIL) are caused by HPV16 may enable targeted management of those most likely to progress. Methods In a natural history study of anal HPV-related lesions in gay and bisexual men, HPV typing of all baseline histologic HSIL was performed utilizing laser capture microdissection (LCM). The results were compared with HPV types detected by Cobas 4800 in matched anal swabs. We calculated the performance of Cobas testing in identifying HSIL caused by HPV16. Results 158 men had both lesion and swab genotyping. Overall 54 men (34%) had HPV16 identified as the causal genotype of at least one HSIL by LCM. 51 of these had HPV16 detected on their anal swabs (sensitivity of 94%). Of the 104 men with non-HPV16 HSIL biopsies, 73 had swabs negative for HPV16 (specificity of 70%). 51 of 82 men with swabs positive for HPV16 had HPV16 positive biopsies (positive predictive value - 62%). 73 of 76 men without HPV16 detected on their swabs had only non-HPV16 HSIL biopsies (negative predictive value (NPV) - 96%). Conclusions In men with prevalent histologic HSIL, Cobas testing of a concurrent anal swab has high sensitivity for detecting those with HPV16-associated HSIL and a high NPV. HPV testing with the Cobas platform may have a role in the identification and management of those with HSIL caused by HPV16 and who are at highest risk of development of anal carcinoma.

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

In a natural history study of anal human papillomavirus (HPV) infection and HPV-related lesions among homosexual men in Sydney, Australia, we identified 15 examples of papillary immature metaplasia (PIM) in anal biopsy samples. PIM has previously been described in the cervix, but not in the anal canal. PIM is a form of exophytic low-grade squamous intraepithelial lesion (eLSIL) also known as condyloma. In contrast to the maturing keratinocytes and koilocytosis seen in conventional eLSIL, the slender papillary structures of PIM have a surface population of immature squamous cells. In our anal samples PIM was characterized by close proximity to conventional eLSIL, was negative for p16 (p16) expression, and revealed the presence of a single low-risk HPV genotype (either 6 or 11) in laser capture microdissected lesions. The clinical significance of recognizing PIM lies in preventing misdiagnosis as high-grade squamous intraepithelial lesion, (the presumed precursor to anal cancer), due to the morphologic immaturity of the cell population. In routine practice, awareness of anal canal PIM and p16 immunostaining will prevent this. Further study of the natural history of anal canal PIM is needed.

Objective To determine the prevalence of antibody to herpes simplex virus type 2 (HSV-2) in patients attending a general public antenatal clinic and three public sexually transmitted disease (STD) clinics in Sydney. Background Highly specific tests for herpes simplex type 2 antibody, using the glycoprotein G2, have been recently introduced, allowing determination of past asymptomatic infection. Overseas studies have confirmed the long held suspicion that asymptomatic infection is more common than clinical genital herpes. The seroprevalence of HSV-2 in antenatal and STD clinic patients varies markedly in different countries. These are the first data available for Australia by means of this highly specific test. Design Cross-sectional study of seroprevalence in these two patient groups. Sera used in the antenatal study were those submitted for routine antenatal screening for viral markers. Participants Two hundred and twenty-nine consecutive patients attending the Westmead Hospital antenatal clinics, and 107 consecutive patients attending three public STD clinics. Hypotheses That Australian populations show a relatively high prevalence of past asymptomatic infection with HSV-2; and that higher rates of infection will be found in patients attending STD clinics and with past or current histories of STDs. Main outcome measures Comparison of HSV-2 seroprevalence between antenatal clinic patients and STD clinic patients; and associations of HSV-2 antibody with age, sex, occupation, country of birth, a history of current or past STDs and antibody to HSV-1. Results Antibody to HSV-2 was found in 14.5% of antenatal clinic patients and 40% of STD clinic patients. None of the antenatal patients and less than half of the seropositive STD clinic patients reported clinical genital herpes. Associations with age, socioeconomic status and previous HSV-1 infection were less marked than in studies from the United States. Female STD clinic patients had a significantly higher seroprevalence than males and three times the seroprevalence of age-matched antenatal clinic patients. The correlation between HSV-2 antibody and current gonorrhoea was more marked than that between HSV-2 and other STDs. Conclusion Asymptomatic infection with HSV-2 is quite common in Australian antenatal patients and more common in patients with STDs, who have higher rates of sexual exposure.

In a cross-sectional study of 140 homosexual men attending a sexually transmissible diseases clinic, the association between the presence of antibody to the human immunodeficiency virus (HIV) and the presence of proctitis, as determined by histologic examination, as well as past or present exposure to other pathogens and details of sexual practices was analyzed. Significant associations with HIV seropositivity were found with the number of lifetime partners, positive treponemal serology, and evidence of previous infection with herpes simplex virus. However the major and unique finding was the strong and independent association between proctitis diagnosed by histologic criteria and seropositivity for HIV. Whether this is cause or effect awaits further elucidation.

OBJECTIVE--To determine the prevalence of rectal spirochaetosis in homosexual men attending a sexually transmissible diseases clinic and investigate the association between their presence and sexual practices, HIV infection and enteric flora. DESIGN--The study included 144 male homosexual subjects who each completed a questionnaire, underwent physical examination, proctoscopy and investigations for STD and HIV screening, rectal biopsies and collection of faecal samples. SETTING--The Sexual Health Centre, Sydney Hospital, Sydney, Australia. RESULTS--Spirochaetes were detected in 39% of the rectal biopsies, using histological criteria. Logistic regression analysis showed that rectal spirochaetosis was significantly associated with: oral-anal contact. (P < 0.05, OR 3.45, 95% CI 1.48-8.05); detection of 3-5 different non-pathogenic protozoa in faeces (P < 0.01, OR 11.68, 95% C.I. 2.33-58) and a positive HIV antibody test (P < 0.01) OR 4.48, 95% C.I. 1.28-15.72). CONCLUSIONS--These findings indicate that rectal spirochaetosis is relatively common in homosexual men. The association with non-pathogenic protozoa is most likely attributable to the common mode of transmission viz oral-anal contact. However it is difficult to determine whether the association with HIV infection is cause or effect because of the limitations in the study design. Further information is required to determine the clinical significance of infection with these organisms.

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.

In a study of bowel parasites in 128 Australian homosexual men attending a sexually transmitted diseases (STD) clinic, Entamoeba histolytica was detected in 37%, Giardia intestinalis in 3% and at least one protozoan in 81% of the group. There was no evidence of pathogenicity of E. histolytica, nor was there any association between the detection of E. histolytica and sexual practices, gastrointestinal symptoms, proctitis, human immunodeficiency virus antibody result or T-cell subset values. However it was noted that those subjects with an elevated IgM > 4 g/l were more likely to harbour E. histolytica trophozoites than those with a level below 4 g/l (OR 6.54, 95% CI 1.3–32.8). Travel to South-East Asia, India, China, Africa, South America or the Pacific islands in the previous 3 years emerged also as an independent factor (OR 2.70, 95% CI 1.12–6.53) associated with detection of E. histolytica.

The prevalence and manifestations of anogenital human papillomavirus (HPV) infection in 154 men, all of whom were the sexual partners of women with either overt anogenital warts or cervical HPV-related abnormalities, were assessed using clinical, histopathological and molecular criteria. Detailed examination of the anogenital region using a colposcope was supplemented by the use of 5% acetic acid to detect possible foci of subclinical HPV infection. Biopsies of warts and aceto-white lesions were examined histopathologically and by HPV DNA hybridization using radiolabelled HPV 6/11 and 16/18 DNA probes. More than two-thirds of the men had clinical indications of genital HPV infection: 37% had apparent macroscopic warts, almost invariably in combination with aceto-white lesions; while 34% had aceto-white lesions only. The overwhelming majority of these lesions (92%) were located on the penis only. However, only 49% of the macroscopic and 29% of the aceto-white lesions showed histological features consistent with a conclusive diagnosis of HPV infection; while the corresponding figures for HPV DNA positivity were 72% and 56% respectively. Current HPV infection was strongly associated with a past history of anogenital warts, but there was little or no correlation between the manifestions of HPV infection in the male and female sexual partners.

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.

To determine the significance of overt anogenital warts as indicators of human papillomavirus (HPV) infection of the cervix, 177 women attending a Sydney STD clinic were screened for evidence of cervical HPV infection using clinical criteria together with cytology and HPV DNA dot hybridization. HPV DNA probing was also performed on biopsies of 50 exophytic warts. A very high prevalence of both anogenital warts (40%), and of cervical HPV infection (58%) was indicated in this group of women. In the exophytic warts, HPV types 6/11 were most commonly detected, whereas the rates of detection of types 6/11 and 16/18 in the cervix were similar. Of the 87 women with evidence of cervical HPV infection, 57 (66%) had a history of either past or current overt exophytic anogenital warts; while the corresponding figure for the 90 women with no evidence of cervical infection was 45 (50%). Cytological evidence of dysplasia (CIN I–III) was detected in 13 (7%) of the cervical smears: of these, 4 were positive for HPV 16/18 only, 2 for 6/11 only and 4 for both 6/11 and 16/18.

Objective To determine the prevalence of antibody to herpes simplex virus type 2 (HSV-2) in patients attending a general public antenatal clinic and three public sexually transmitted disease (STD) clinics in Sydney. Background Highly specific tests for herpes simplex type 2 antibody, using the glycoprotein G2, have been recently introduced, allowing determination of past asymptomatic infection. Overseas studies have confirmed the long held suspicion that asymptomatic infection is more common than clinical genital herpes. The seroprevalence of HSV-2 in antenatal and STD clinic patients varies markedly in different countries. These are the first data available for Australia by means of this highly specific test. Design Cross-sectional study of seroprevalence in these two patient groups. Sera used in the antenatal study were those submitted for routine antenatal screening for viral markers. Participants Two hundred and twenty-nine consecutive patients attending the Westmead Hospital antenatal clinics, and 107 consecutive patients attending three public STD clinics. Hypotheses That Australian populations show a relatively high prevalence of past asymptomatic infection with HSV-2; and that higher rates of infection will be found in patients attending STD clinics and with past or current histories of STDs. Main outcome measures Comparison of HSV-2 seroprevalence between antenatal clinic patients and STD clinic patients; and associations of HSV-2 antibody with age, sex, occupation, country of birth, a history of current or past STDs and antibody to HSV-1. Results Antibody to HSV-2 was found in 14.5% of antenatal clinic patients and 40% of STD clinic patients. None of the antenatal patients and less than half of the seropositive STD clinic patients reported clinical genital herpes. Associations with age, socioeconomic status and previous HSV-1 infection were less marked than in studies from the United States. Female STD clinic patients had a significantly higher seroprevalence than males and three times the seroprevalence of age-matched antenatal clinic patients. The correlation between HSV-2 antibody and current gonorrhoea was more marked than that between HSV-2 and other STDs. Conclusion Asymptomatic infection with HSV-2 is quite common in Australian antenatal patients and more common in patients with STDs, who have higher rates of sexual exposure.

Trichinosis is a serious but understudied medical problem in the Arctic. Forty-nine consecutive cases in the Inuit population of northeastern Canada are described. Most developed the disease after eating raw walrus, and the clinical presentation of most of these cases differed from previously reported descriptions of classic trichinosis due to Trichinella spiralis. Unlike the classic syndrome of a brief period of diarrhea followed by fever, myalgia, muscle weakness, and edema, the most common presentation in these cases was a prolonged diarrhea without fever and with brief muscle symptoms. High peripheral eosinophilia, high Trichinella antibody serotiters, and little direct or indirect evidence of muscle invasion in many of those with the chronic diarrheal presentation suggest a new clinical syndrome due to a different species of Trichinella seen in the Arctic or to reinfection with Trichinella.

Mongolian gerbils were susceptible to infection with Giardia lamblia cysts from patients. Inoculation of gerbils with 5 x 10(3) cysts each resulted in an infection characterized by the intermittent release of cysts for up to 39 days. The mean number of cysts released per gerbil in a 2-hr period was 8.8 x 10(2) (range, 0-5 x 10(3)). The highest number of trophozoites found in the intestine was on day 15 after infection, when the mean number of trophozoites per gerbil was 6.36 x 10(6). Administration of cysts from different patients to gerbils resulted in a similar pattern of cyst release during the first 30 days of infection. Mongolian gerbils were also susceptible to infection with cultured trophozoites (Portland 1 strain). The pattern of cyst release and the number of trophozoites in the intestines of orally and duodenally inoculated gerbils were similar. Gerbils were protected against reinfection with G. lamblia for up to eight months after primary infection.

Histologic evidence of intestinal spirochetosis (IS) was found in 22 of 41 (53.7%) rectal biopsy specimens from homosexual men attending a sexually transmitted diseases clinic. Serpulina pilosicoli was cultured from 11 of the IS-positive biopsy specimens (50%) and from 2 specimens (10.5%) in which spirochetes were not observed. The association between seeing spirochetes in biopsy specimens and isolating S. pilosicoli was statistically significant, clearly indicating that this spirochete is the agent of IS.