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OBJECTIVES: Because current guidelines recognise high-grade anal squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), and recommend treatment of all HSILs although not all progress to cancer, this study aims to distinguish transforming and productive HSILs by grading immunohistochemical (IHC) biomarkers p16INK 4a (p16) and E4 in low-risk human papillomavirus (lrHPV) and high-risk (hr)HPV-associated SILs as a potential basis for more selective treatment.METHODS: Immunostaining for p16 and HPV E4 was performed and graded in 183 biopsies from 108 HIV-positive men who have sex with men. The causative HPV genotype of the worst lesion was identified using the HPV SPF10-PCR-DEIA-LiPA25 version 1 system, with laser capture microdissection for multiple infections. The worst lesions were scored for p16 (0-4) to identify activity of the hrHPV E7 gene, and panHPV E4 (0-2) to mark HPV production and life cycle completion.RESULTS: There were 37 normal biopsies, 60 LSILs and 86 HSILs, with 85% of LSILs caused by lrHPV and 93% of HSILs by hrHPV. No normal biopsy showed E4, but 43% of LSILs and 37% of HSILs were E4 positive. No differences in E4 positivity rates were found between lrHPV and hrHPV lesions. Most of the lesions caused by lrHPV (90%) showed very extensive patchy p16 staining; p16 grade in HSILs was variable, with frequency of productive HPV infection dropping with increasing p16 grade.CONCLUSIONS: Combined p16/E4 IHC identifies productive and nonproductive HSILs associated with hrHPV within the group of HSILs defined by the Lower Anogenital Squamous Terminology recommendations. This opens the possibility of investigating selective treatment of advanced transforming HSILs caused by hrHPV, and a 'wait and see' policy for productive HSILs. What's already known about this topic? For preventing anal cancer in high-risk populations, all patients with high-grade squamous intraepithelial lesions (HSILs) are treated, even though this group

Background: Men who have sex with men (MSM) are at high risk for sexually transmitted infections (STI) and often have sex while under the influence of drugs (sexualized drug use). We aimed to identify classes of MSM in Amsterdam and in surrounding urban regions with distinctive patterns of sexualized drug use and their association with STI.Methods: In this cross-sectional study, data on MSM were collected at STI clinics in the Netherlands between September-December 2017. Information on drug use, sociodemographics and sexual risk behavior, including lab-confirmed STI (chlamydia, gonorrhea, syphilis and HIV) was collected and compared between Amsterdam and surrounding urban regions. Latent class analysis was used to identify classes with similar drug use patterns, which were then linked to sexual behavior and STI.Results: We included 4461 MSM who were a median 35 years old (IQR = 27-47) and mostly Dutch (56.9 %). Use of all drugs was more often reported in Amsterdam compared to surrounding regions (p<0.001). We identified four different classes based on sexualized drug use among Amsterdam participants and three classes in surrounding regions. In both regions, polydrug use classes (compared to classes of no drug use; alcohol use; or few, various drugs) were defined by higher numbers of sexual partners (median range 8-15 vs 4-6, respectively) and higher STI prevalence (range 30.5%-31.8% vs 18.6%-22.8%, respectively).Conclusion: Given the high prevalence of risk behavior and STIs, MSM in urban settings partaking in sexualized polydrug use might benefit from tailored outreach, screening, and safe sex and drug use interventions.

New or important issues in this updated version of the 2013 European guideline on the management of lymphogranuloma venereum (LGV): EPIDEMIOLOGY: Lymphogranuloma venereum continues to be endemic among European men who have sex with men (MSM) since 2003. Lymphogranuloma venereum infections in heterosexuals are extremely rare in Europe, and there is no evidence of transmission of LGV in the European heterosexual population. AETIOLOGY AND TRANSMISSION: Chlamydia trachomatis serovars/genovars L2b and L2 are the causative strains in the majority of cases in Europe. CLINICAL FEATURES: Among MSM, about 25% of the anorectal LGV infections are asymptomatic. Genital infections among MSM are rare; the ratio of genital vs. anorectal LGV infections is 1 in 15. DIAGNOSIS: To diagnose LGV, a sample tested C. trachomatis positive with a commercial nucleic acid amplification test (NAAT) platform should be confirmed with an LGV discriminatory NAAT. TREATMENT: Doxycycline 100 mg twice a day orally for 21 days is the recommended treatment for LGV. This same treatment is recommended also in asymptomatic patients and contacts of LGV patients. If another regimen is used, a test of cure (TOC) must be performed.