Virological and Serological Predictors of Anal High-grade Squamous Intraepithelial Lesions Among Human Immunodeficiency Virus-positive Men Who Have Sex With Men.

BACKGROUND: Our objective was to identify virological and serological predictors of anal high-grade squamous intraepithelial lesions (HSIL) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). METHODS: HIV-positive MSM were recruited from a longitudinal study during which anal self-swabs and serum were collected at up to 5 bi-annual visits. Swabs were human papillomavirus (HPV) genotyped, and the type-specific HPV viral load in the anal swabs was determined. Serum antibodies to the E6, E7, E1, E2, and L1 proteins of 7 high-risk HPV (hrHPV) types and HPV6 and 11 were analyzed. The participants who had a high-resolution anoscopy after the last study visit were included in the current analysis. Anal HSIL was diagnosed by histopathological examinations of anal biopsies. The causative HPV type of anal HSIL was determined in whole tissue sections (WTS) and by laser capture micro-dissection if more than one HPV-type was found in WTS. Multivariable logistic regression was used to study whether persistent anal HPV infections, HPV viral loads, and seropositivity for HPV were predictors of anal HSIL, either in general or caused by the concordant HPV type. RESULTS: Of 193 HIV-positive MSM, 50 (26%) were diagnosed with anal HSIL. HrHPV persistence in anal swabs was common, varying by hrHPV type between 3-21%. Anal HPV persistence was the only determinant independently associated with anal HSIL, both in general and by concordant, causative HPV type. CONCLUSIONS: Persistent HPV infections were strongly associated with anal HSIL, in general as well as for the concordant HPV type.

Detection Rate of High-Grade Squamous Intraepithelial Lesions as a Quality Assurance Metric for High-Resolution Anoscopy in HIV-Positive Men.

BACKGROUND: High-resolution anoscopy-guided biopsies are the gold standard for identifying anal intraepithelial neoplasia, but diagnosing high-grade squamous intraepithelial lesions depends on the skills of the anoscopist. OBJECTIVE: This study aims to validate the high-grade squamous intraepithelial lesion detection rate as a quality assurance metric for high-resolution anoscopy in HIV-positive men. DESIGN: This is a retrospective study. SETTING: This study was conducted at 3 HIV outpatient clinics in Amsterdam, The Netherlands. PATIENTS: HIV-positive men who have sex with men were selected for this study. MAIN OUTCOME MEASURES: We analyzed the high-grade squamous intraepithelial lesion detection rate per high-resolution anoscopy, the mean number of biopsies taken, and the mean high-grade squamous intraepithelial lesion rate per biopsy in time-subsequent groups for 7 anoscopists performing high-resolution anoscopy. RESULTS: Seven anoscopists performed high-resolution anoscopy in 1340 HIV-positive men who have sex with men. The overall high-grade squamous intraepithelial lesion detection rate for all 7 anoscopists combined increased significantly over time, from 27% to 40% (p < 0.001; OR, 1.15; 95% CI, 1.08-1.23 per 50 high-resolution anoscopies). The mean number of biopsies increased significantly from 1.4 (22% high-grade squamous intraepithelial lesions per biopsy) to 2.0 biopsies per patient (29% high-grade squamous intraepithelial lesions per biopsy) (p < 0.001). Three anoscopists showed a significant increase in proportion of high-grade squamous intraepithelial lesions per biopsy with increasing experience. LIMITATIONS: There were statistically significant differences, with limited clinical significance, in the characteristics of patient populations between anoscopists and clinics. CONCLUSIONS: We found significant variations in the high-grade squamous intraepithelial lesion detection rate among anoscopists performing high-resolution anoscopy in HIV-positive men who have sex with men. The high-grade squamous intraepithelial lesion detection rate and mean high-grade squamous intraepithelial lesion rate per biopsy can be used as a quality assurance metric to follow up the learning curve of high-resolution anoscopists. See Video Abstract at http://links.lww.com/DCR/A555.

HPV vaccination to prevent recurrence of anal intraepithelial neoplasia in HIV+ MSM.

OBJECTIVE: Anal cancer precursor lesions high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent among HIV+ MSM. Treatment of HGAIN is frustrated by high recurrence rates. We investigated the efficacy of the quadrivalent human papillomavirus (qHPV) vaccine as posttreatment adjuvant in preventing HGAIN recurrence in HIV+ MSM. DESIGN: Randomized, double-blind, placebo-controlled, multicentre trial. SETTING: Three HIV outpatient clinics in Amsterdam, the Netherlands. SUBJECTS: HIV+ MSM with CD4+ cell count more than 350 cells/µl, biopsy-proven intra-anal HGAIN successfully treated in the past year, and lesions still in remission at enrolment, as assessed by high-resolution anoscopy (HRA). INTERVENTION: Participants were randomized to three doses of qHPV (Gardasil-4, MSD) or placebo with vaccinations at 0, 2, and 6 months. HRA was repeated at 6, 12, and 18 months. MAIN OUTCOME MEASURE: The primary outcome was cumulative, biopsy-proven HGAIN recurrence rate at 18 months, evaluated in an intention-to-treat (ITT) (received all vaccinations) and per-protocol analysis (all vaccinations and complete follow-up). RESULTS: We randomized 126 participants of which 64 (50.8%) received qHPV and 62 (49.2%) placebo. All participants received three vaccinations, and in both groups for two participants follow-up was incomplete. We found no difference (P = 0.38) in cumulative HGAIN recurrence rates between the qHPV (44/64, 68.8%) and placebo group (38/62, 61.3%) in the ITT analysis [absolute risk reduction -7.5 (95% confidence interval (CI) -24.1 to 9.2)]. This was similar in the per-protocol analysis. CONCLUSION: Despite adequate serological responses to qHPV vaccination, short-term recurrence of HGAIN was not prevented. These findings do not support qHPV vaccination as a treatment adjuvant to prevent HGAIN recurrence in HIV+ MSM.

Nurse-led sexual health care: international perspectives.

Nurses as first-line care providers for the treatment of sexually transmitted infections are a relatively new concept in the United Kingdom (UK). However, for over 25 years, services in other countries have been empowering nurses to work as autonomous practitioners, capable of dealing with patients presenting with a range of sexual health conditions and issues without necessarily seeking the advice or input of a doctor. This paper will present the observations of nurse-led services in Amsterdam, Seattle and Sydney. It will discuss how service providers in the UK can learn from the experiences of international colleagues and will argue why trained and experienced genitourinary medicine nurses need to advance their role and be better integrated as first-line care providers.