Cryotherapy for Intra- and Perianal High-Grade Squamous Intraepithelial Lesions in HIV-Positive Men who have Sex with Men

Background Available treatment options for anal high-grade squamous intraepithelial lesions (HSIL) in HIV-positive men who have sex with men (MSM) are limited by low response rates and frequent recurrences. Cryotherapy is an established therapeutic option for several pre-malignant skin disorders. Methods This retrospective, non-randomized study included HIV-positive MSM who received intra- and/or perianal HSIL cryotherapy treatment between 30 December 2008 and 23 April 2015. Cryotherapy was applied in sessions 4-6 weeks apart for a maximum of five sessions. Patients received a follow-up high-resolution anoscopy (HRA) to assess treatment response. Complete and partial treatment responders were followed-up after 6 months and then every 6-12 months to investigate recurrent HSILs. Results Of 64 patients [median age 48 years; interquartile range (IQR) 42-56] included in the study, six were lost to follow-up. In total, 35 (60%) of 58 patients responded to treatment. Of 64 patients, 31 (48%) reported one or more side effects, of which anal pain or tenderness and mild blood loss were reported most frequently. A total of 19 patients who responded to cryotherapy were adequately followed-up for over 18 months, of whom 13 (68%) had recurrent HSILs. Conclusion Cryotherapy is capable of clearing HSIL in HIV-positive MSM, and treatment success rates are comparable with those reported for current treatment modalities. The treatment is well tolerated, and side effects are relatively mild. Future studies should therefore compare the efficacy and tolerability of cryotherapy with those of current treatment modalities in randomized controlled trial

HPV vaccination to prevent recurrence of Anal Intraepithelial Neoplasia in HIV+ MSM: a randomised, placebo-controlled multicentre trial.

OBJECTIVE: Anal cancer precursor lesions high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent among HIV+ men-who-have-sex-with-men (MSM). Treatment of HGAIN is frustrated by high recurrence rates. We investigated the efficacy of the quadrivalent human papillomavirus (qHPV) vaccine as post-treatment adjuvant in preventing HGAIN recurrence in HIV+MSM. DESIGN: Randomised, double-blind, placebo-controlled, multicentre trial. SETTING: Three HIV outpatient clinics in Amsterdam, the Netherlands. SUBJECTS: HIV+MSM with CD4 count >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 randomised 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 (received all vaccinations) and per-protocol analysis (all vaccinations and complete follow-up). RESULTS: We randomised 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 intention-to-treat analysis (absolute risk reduction -7.5 (95%CI -24.1-9.2)). This was similar in the per-protocol analysis. CONCLUSIONS: 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

Supplementary Data FS3 from Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV⁺ Men

Supplementary Figure S3: Type of T cells responding to HPV16 oncoproteins.</p

Supplementary Data FS1 from Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV⁺ Men

Supplementary Figure S1: Trial Flowchart.</p

Supplementary Data TS2 from Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV⁺ Men

Supplementary Table S2: T-cell responses determined by 4-day IFNγ-ELISPOT assay.</p

Supplementary Data FS2 from Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV⁺ Men

Supplementary Figure S2: HPV16-specific T cell responses at different dose levels and time points.</p

Supplementary Data TS3 from Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV⁺ Men

Supplementary Table S3: Representativeness of Study Participants.</p

Supplementary Data MS1 from Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV⁺ Men

Supplementary material 1: Rationale for intradermal administration of the vaccine, the use of pegylated interferon-alpha-2b (PegIntron) as adjuvant, immune assays.</p

Supplementary Data MS2 from Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV⁺ Men

Supplementary material 2: HPV-Typing of AIN lesions.</p