Karien C M Gosens1, Ramon P van der Zee, Matthijs L Siegenbeek van Heukelom, Vita W Jongen, Irina Cairo, Arne van Eeden, Carel J M van Noesel, Wim G V Quint, Hella Pasmans, Marcel G W Dijkgraaf, Henry J C de Vries, Jan M Prins. 1. Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity (AII), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands Department of Pathology, Cancer Center Amsterdam (CCA), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands Department of Infectious Diseases, Public Health Service of Amsterdam (GGD Amsterdam), Amsterdam, The Netherlands Department of Dermatology, OLVG, Amsterdam, The Netherlands DC Klinieken Lairesse, Amsterdam, The Netherlands Department of Pathology, Cancer Center Amsterdam (CCA), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands DDL Diagnostic Laboratory, Rijswijk, The Netherlands Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands Department of Epidemiology and Data Science, Amsterdam Public Health Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands STI Outpatient Clinic, Department of Infectious Diseases, Public Health Service of Amsterdam (GGD Amsterdam), Amsterdam, The Netherlands. Authors contributed equally.
Abstract
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%) receivedqHPV 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.
RCT Entities:
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.
Authors: Fernando Dias Gonçalves Lima; Ramon P van der Zee; Stèfanie Dick; Carel J M van Noesel; Johannes Berkhof; Maarten F Schim van der Loeff; Jan M Prins; Renske D M Steenbergen; Henry J C de Vries Journal: BMJ Open Date: 2022-08-03 Impact factor: 3.006