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We evaluated the concordance between β-HPVs detected in external genital skin, anal canal, and oral cavity specimens collected simultaneously from 717 men that were participating in the multinational HIM Study. Viral genotyping was performed using the Luminex technology. Species- and type-specific concordance was measured using kappa statistics for agreement. Overall, concordance of β-HPVs across sites was low and mainly observed among paired genital/anal canal samples. When grouped by species, solely β-4 HPVs showed moderate concordance in genital/anal pairs (κ = 0.457), which could be attributed to the substantial concordance of HPV-92 in men from Brazil and Mexico (κ > 0.610). β-HPV type concordance was higher in Mexico, where HPV-19 was consistently concordant in all anatomic site combinations. Our analysis indicates that type-specific concordance across sites is limited to few viral types; however, these infections seem to occur more often than would be expected by chance, suggesting that although rare, there is agreement among sites.
Copyright © 2017 Elsevier Inc. All rights reserved.
OBJECTIVES - Globally, anal cancer incidence is rare, but is increasing in some world regions. Our objective was to assess differences in anal HPV natural history in three countries.
METHODS - Men aged 18-70 years were recruited from the US (n = 634), Mexico (n = 665), and Brazil (n = 731). Anal specimens were collected every six-months. HPV genotyping was assessed by Linear Array. Anal HPV prevalence was compared using the Fisher's exact test. HPV infection incidence rates (IR) and 95% confidence intervals (CI) were calculated.
RESULTS - Any anal HPV prevalence was highest among men from Brazil (24%) compared to Mexico (15%) and the US (15%). When stratified by sexual history, the prevalence of any HPV among MSM/MSMW was 43%, 37%, and 45% and 9%, 12%, and 10% for MSW from Brazil, Mexico, and US, respectively. Any HPV incidence was significantly higher among men from Brazil compared to US men (IRR = 2.4, 95% CI = 1.7-3.4) and comparable between men from Mexico and the US (IRR = 1.2, 95% CI = 0.8-1.8).
CONCLUSION - Men in Brazil and Mexico often have similar, if not higher incidence of anal HPV compared to men from the U.S., and may benefit from gender neutral HPV vaccine policies.
Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Our goal was to describe prevalence of β-HPVs at three anatomic sites among 717 men from Brazil, Mexico and US enrolled in the HPV Infection in Men (HIM) Study. β-HPVs were genotyped using Luminex technology. Overall, 77.7%, 54.3% and 29.3% men were positive for any β-HPV at the genitals, anal canal, and oral cavity, respectively. Men from US and Brazil were significantly less likely to have β-HPV at the anal canal than men from Mexico. Older men were more likely to have β-HPV at the anal canal compared to younger men. Prevalence of β-HPV at the oral cavity was significantly associated with country of origin and age. Current smokers were significantly less likely to have β-HPV in the oral cavity than men who never smoked. Lack of associations between β-HPV and sexual behaviors may suggest other routes of contact such as autoinoculation which need to be explored further.
Copyright © 2016 Elsevier Inc. All rights reserved.
OBJECTIVE - To conduct a systematic review and meta-analysis to evaluate the efficacy of peer-led interventions in reducing unprotected anal intercourse (UAI) among men who have sex with men (MSM).
METHODS - Randomized clinical trials (RCTs), quasi-experimental studies, pre- and post-intervention studies without control groups, and serial cross-sectional assessments involving peers delivering interventions among MSM and published as of February 2012 were identified by systematically searching 13 electronic databases and cross-referencing. Effect sizes (ES) were calculated as the changes of standardized mean difference (SMD) in UAI between groups or pre-post intervention.
RESULTS - A total of 22 studies met the eligibility criteria, including five RCTs, six quasi-experimental studies, six pre-and-post intervention studies, and five serial cross-sectional intervention studies. We used 15 individual studies including 17 interventions for overall ES calculation; peer-led interventions reduced UAI with any sexual partners in meta-analysis (mean ES: -0.27; 95% confidence interval [CI]: -0.41, -0.13; P<0.01). Subgroup analyses demonstrated a statistically significant reduction on UAI in quasi-experimental studies (mean ES: -0.30; 95% CI: -0.50, -0.09; P = 0.01) and serial cross-sectional intervention studies (mean ES: -0.33; 95% CI: -0.57, -0.09; P = 0.01), but non-significant reduction in RCTs (mean ES: -0.15; 95% CI: -0.36, 0.07; P = 0.18) or pre- and post-intervention studies (mean ES: -0.29; 95% CI: -0.69, 0.11; P = 0.15). Heterogeneity was large across these 15 studies (I2 = 77.5%; P<0.01), largely due to pre-and-post intervention studies and serial cross-sectional intervention studies.
CONCLUSIONS - Peer-led HIV prevention interventions reduced the overall UAI among MSM, but the efficacy varied by study design. More RCTs are needed to evaluate the effect of peer-led interventions while minimizing potential bias.
BACKGROUND - Carcinogenic human papillomaviruses (HPVs) cause a large proportion of anal cancers. Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) are at increased risk of HPV infection and anal cancer compared with HIV-negative men. We evaluated risk factors for HPV infection and anal precancer in a population of HIV-infected MSM.
METHODS - Our study included 305 MSM at an HIV/AIDS clinic in the Kaiser Permanente Northern California Health Maintenance Organization. Logistic regression was used to estimate associations of risk factors comparing men without anal HPV infection; men with anal HPV infection, but no precancer; and men with anal precancer.
RESULTS - Low CD4 count (<350 cells/mm(3)) and previous chlamydia infection were associated with an increased risk of carcinogenic HPV infection (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.28-10.40 and OR, 4.24; 95% CI, 1.16-15.51, respectively). History of smoking (OR, 2.71 95% CI, 1.43-5.14), duration, recency, and dose of smoking increased the risk of anal precancer among carcinogenic HPV-positive men but had no association with HPV infection.
CONCLUSIONS - We found distinct risk factors for anal HPV infection and anal precancer. Risk factors for HPV infection and anal precancer are similar to established risk factors for cervical cancer progression.
OBJECTIVE - Anal cancer incidence is high in HIV-infected MSM. Screening for anal intraepithelial lesions and cancers is performed at specialized clinics and relies on high-resolution anoscopy (HRA) and anal cytology. Both approaches have limited reproducibility and sensitivity for detecting anal cancer precursors. We evaluated biomarkers for human papillomavirus (HPV)-related disease in a population of HIV-infected MSM.
METHODS - A cross-sectional screening study with passive follow-up included 363 MSM followed at a HIV/AIDS clinic. All men had anal cytology samples taken and were evaluated using HRA and anal biopsies. Using a composite endpoint of biopsy results and cytology, we compared the performance of HPV16/18 genotyping, HPVE6/E7 mRNA expression, and p16/Ki-67 cytology to detect high-grade anal intraepithelial neoplasias (AINs).
RESULTS - For all biomarkers analyzed, there was a significant trend of increasing percentage of men testing positive with increasing severity of disease (P < 0.001). HPV DNA testing had the highest sensitivity for anal intraepithelial neoplasia grade 2 and anal intraepithelial neoplasia grade 3 (AIN3), followed by p16/Ki-67, HPVE6/E7 mRNA testing, and HPV16/18 genotyping. The highest Youden's index was observed for HPVE6/E7 mRNA testing, followed by HPV16/18 genotyping, p16/Ki-67 cytology, and HPV DNA testing. Increasing the threshold for positivity of p16/Ki-67 to five or more positive cells led to significantly higher specificity, but unchanged sensitivity for detecting AIN3.
CONCLUSION - Molecular features of anal disease categories are similar to those of corresponding cervical lesions. Biomarkers evaluated for cervical cancer screening may be used for primary anal cancer screening or to decide who should require immediate treatment vs. expectant management.
BACKGROUND - Little is known about the associations between CD4(+) cell counts, human immunodeficiency virus (HIV) load, and human papillomavirus "low-risk" types in noncancerous clinical outcomes. This study examined whether CD4(+) count and HIV load predict the size of the largest anal warts in 976 HIV-infected women in an ongoing cohort.
METHODS - A linear mixed model was used to determine the association between size of anal wart and CD4(+) count and HIV load.
RESULTS - The incidence of anal warts was 4.15 cases per 100 person-years (95% confidence interval [CI], 3.83-4.77) and 1.30 cases per 100 person-years (95% CI, 1.00-1.58) in HIV-infected and HIV-uninfected women, respectively. There appeared to be an inverse association between size of the largest anal warts and CD4(+) count at baseline; however, this was not statistically significant. There was no association between size of the largest anal warts and CD4(+) count or HIV load over time.
CONCLUSIONS - There was no evidence for an association between size of the largest anal warts and CD4(+) count or HIV load over time. Further exploration on the role of immune response on the development of anal warts is warranted in a larger study.
BACKGROUND - Perianal fistulas are a debilitating manifestation of Crohn's disease (CD) in the pediatric population and present a management challenge. The aims of this study were to describe our experience using endoscopic ultrasound (EUS) to guide management of perianal CD (PCD) in a pediatric population, and determine whether using EUS to monitor healing after seton placement improves outcomes.
METHODS - We conducted a retrospective study of 2 cohorts: pediatric subjects with PCD who underwent EUS and pediatric subjects who underwent seton placement between 2002 and 2007.
RESULTS - In all, 25 children underwent a total of 42 EUS procedures. Of 28 EUSs performed to evaluate suspected perianal disease, complex fistulizing disease was identified in 15 (54%). Setons were placed after most EUSs demonstrating complex fistulizing disease and after none demonstrating superficial or no fistulizing disease. Of 14 EUSs performed to monitor healing around a seton, 7 (50%) demonstrated persistent peri-seton inflammation. Setons were more often left in place after an EUS revealing persistent inflammation (86% versus 0%), and the patients were more likely to have a biologic initiated or changed (57% versus 0%). Among all subjects who underwent seton placement, time from seton removal to recurrence was longer for those followed by EUS compared to those followed by physical exam only; however, we were not powered to test for statistical significance.
CONCLUSIONS - EUS to guide the combined medical and surgical management of PCD is feasible in the pediatric population. Larger prospective studies are needed to determine if EUS-directed management improves outcomes in pediatric patients with PCD.