Background The incidence of high-risk human papillomavirus (HR-HPV)–induced anal cancer is increasingly problematic among HIV-positive patients. Anal cancer is preceded by precursor lesions, anal intraepithelial neoplasia (AIN). AIN detection requires high-resolution anoscopy, a cumbersome and time-consuming procedure. We aggregated evidence on anal swab–based tests to detect AIN in HIV-positive patients. Methods We searched MEDLINE and EMBASE for cross-sectional studies on AIN detection with anal cytology, HR-HPV DNA detection, HPV E6/E7 mRNA analysis, and P16INK4a and Ki-67 immunostaining. Summary estimates of sensitivity and specificity were calculated using bivariate logistic regression. Cytology was reported using the terms squamous intra-epithelial lesion (SIL) for AIN and high-grade SIL (HSIL) for high-grade AIN (HGAIN). Results We included 22 studies. Using cytology with a cutoff of any SIL to detect HGAIN, we detected a sensitivity of 82% (95% CI, 74%–87%) and specificity of 45% (95% CI, 44%–66%); with the cutoff of HSIL, the sensitivity was 44% (95% CI, 45%–67%) and the specificity was 79% (95% CI, 69%-87%). The sensitivity of HPV DNA to detect HGAIN was 91% (95% CI, 82%–95%) and the specificity was 27% (95% CI, 21%–33%). For MSM, the positive predictive value (PPV) of cytology with a cutoff of any SIL was 36% (95% CI, 23%–50%) and the negative predictive value (NPV) was 87% (95% CI, 78%–93%), whereas cytology with a cutoff of HSIL had a PPV of 62% (95% CI, 50%–73%) and an NPV of 78% (95% CI, 65%–87%). The PPV of HR-HPV DNA detection was 37% (95% CI, 20%–57%) and the NPV was 87% (95% CI, 79%–93%). Conclusions Given its sensitivity, cytology with a cutoff of any SIL could be considered as a triaging method, whereas cytology with a cutoff of HSIL had better specificity and could be used for quality assurance. HR-HPV DNA detection had poor specificity and PPV, making it unsuitable for triage.

BackgroundPre-exposure prophylaxis (PrEP) is highly effective for preventing HIV infections, but is not yet implemented in the Netherlands. As the attitudes of health-care professionals toward PrEP can influence future PrEP implementation, we studied PrEP knowledge and beliefs and their association with PrEP acceptability among professionals in clinics for sexually transmitted infection (STI professionals) and HIV treatment centers (HIV specialists). In addition, we examined preferred regimens, attitudes toward providing PrEP to key populations and to reimbursement of PrEP costs.MethodsAn online questionnaire was distributed among 24 public health STI clinics and 27 HIV treatment centers nationwide in the Netherlands between January and August 2015. The acceptability of PrEP was measured on a 7-point Likert scale ranging from 1 = low to 7 = high acceptability. Univariable and multivariable linear regression analyses were used to explore associations between demographic characteristics, PrEP knowledge, beliefs about PrEP, and PrEP acceptability.ResultsIn total, 209 people (143 STI professionals and 66 HIV specialists) completed the questionnaire. The mean acceptability of PrEP implementation was 4.28 (SD 1.68) among STI professionals and 4.42 (SD 1.67) among HIV specialists. The mean score on self-perceived knowledge related to PrEP efficacy was 3.90 (SD 1.57) among STI professionals and 5.68 (SD 1.08) among HIV specialists (p-value of <0.001). Beliefs associated with lower PrEP acceptability among both groups were the fear that PrEP use will lead to a decrease in condom use and an increase in STI, the high costs of PrEP and ethical issues regarding prescribing antiretroviral medication to healthy individuals. No preference for a daily or an event-driven regimen was detected. Most participants deemed the following groups to be eligible for PrEP: men who have sex with men (MSM) who regularly get post-exposure prophylaxis, MSM who never used condoms with casual partners and MSM with an HIV-positive partner with a detectable viral load. Over half of the participants indicated that PrEP users should partly (54.1%) or fully (35.4%) pay the costs of PrEP.ConclusionIn 2015, PrEP acceptability was only moderate among Dutch STI professionals and HIV specialists, which is far from an optimal setting. Addressing barriers to PrEP acceptability in educational programs for various types of health-care professionals is needed to successfully implement PrEP in the Netherlands.

IntroductionAnal cancer precursors, or high-grade anal intraepithelial neoplasia (HGAIN), are highly prevalent in HIV-seropositive (HIV+) men who have sex with men (MSM). Around 30% of lesions regress within 1 year, but current histopathological assessment is unable to distinguish between HGAIN likely to regress and HGAIN likely to persist or progress to cancer. We aim to assess if host cell DNA methylation markers can predict regression of HGAIN, thus determining the need for immediate treatment or active surveillance. This could reduce overtreatment and the associated anal and psycho-sexual morbidity.Methods and analysisThis is an active surveillance cohort study in three centres located in Amsterdam, the Netherlands, in 200 HIV+ MSM diagnosed with HGAIN. Participants will not be treated, but closely monitored during 24 months of follow-up with 6 monthly visits including cytology, and high-resolution anoscopy with biopsies. The primary study endpoint is histopathological regression of each baseline HGAIN lesion at the end of the study. Regression is defined as ≤low grade anal intraepithelial neoplasia in the exit biopsy at 24 months. Regression proportions in lesions with low versus high methylation levels (ASCL1, ZNF582), other biomarkers (HPV genotype, HPV-E4, p16INK4A, Ki-67) and immunological markers at baseline will be compared. Main secondary endpoints are the histological and clinical outcome (ie, the number of octants affected by HGAIN) of each baseline HGAIN lesion and overall HGAIN disease (i.e., all lesions combined) after each visit. The health-related quality of life of the study group will be compared with that of a control group of 50 HIV+ MSM receiving regular HGAIN treatment.Ethics and disseminationEthics approval was obtained from the Institutional Review Board of the Academic Medical Center (Amsterdam, The Netherlands; reference no. 2021_099). Participants are required to provide written informed consent. Findings will be disseminated through publication in peer-reviewed scientific journals and presentations at international scientific conferences; dissemination to policy makers and the target patient group will be achieved through our (inter-)national network, professional associations and collaboration with a patient representative organisation.Trial registration numberNL9664.

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