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Randomized Controlled Trial
. 2021 Sep 1;35(11):1753-1764.
doi: 10.1097/QAD.0000000000002928.

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

Karien C M Gosens  1   2 , Ramon P van der Zee  1   2   3 , Matthijs L Siegenbeek van Heukelom  1 , Vita W Jongen  4 , Irina Cairo  5 , Arne van Eeden  6 , Carel J M van Noesel  7 , Wim G V Quint  8 , Hella Pasmans  9 , Marcel G W Dijkgraaf  10 , Henry J C de Vries  1   11 , Jan M Prins  2
Affiliations
Randomized Controlled Trial

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

Karien C M Gosens et al. AIDS. .

Abstract

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.

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Conflict of interest statement

M.G.W.D. has a family member working at MSD. H.J.C.d.V. received money or goods for research from Medigene, Gilead and MSD, money for presentations from Abbott and Janssen and money for advice from Medigene and Novartis. All other authors have no conflicts of interest to declare.

Preliminary results were previously presented at: International Anal Neoplasia Society Scientific Meeting in Amsterdam, The Netherlands, 1--3 November 2019 (oral presentation).

Dutch HIV Treating Physicians Scientific Meeting Amsterdam, The Netherlands, 17 January 2020 (oral presentation).

International Papillomavirus Society Conference (digital) 20–24 July 2020 (poster).

Figures

Fig. 1
Fig. 1
Trial profile.
Fig. 2
Fig. 2
Proportion of participants free of recurrent high-grade anal intraepithelial neoplasia.
Fig. 3
Fig. 3
Human papillomavirus type-specific IgG antibody concentrations before first (pre) and 3 months after last vaccination (post).
See this image and copyright information in PMC

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