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

Author:

Gosens Karien C.M.12ORCID,van der Burg Sjoerd H.3ORCID,Welters Marij J.P.3ORCID,Boekestijn Sanne3ORCID,Loof Nikki M.3ORCID,Quint Wim G.V.4ORCID,van Noesel Carel J.M.5ORCID,van der Wal Allard C.5ORCID,Richel Olivier16ORCID,Krebber Wilhelmus J.T.A.7ORCID,Melief Cornelis J.M.7ORCID,de Vries Henry J.C.28ORCID,Prins Jan M.1ORCID

Affiliation:

1. 1Amsterdam UMC, University of Amsterdam, Department of Internal Medicine, Division of Infectious Diseases, Amsterdam, the Netherlands.

2. 2Amsterdam UMC, University of Amsterdam, Department of Dermatology, Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam, the Netherlands.

3. 3Leiden University Medical Center, Department of Medical Oncology, Oncode Institute, Leiden, the Netherlands.

4. 4DDL Diagnostic Laboratory, Rijswijk, the Netherlands.

5. 5Amsterdam UMC, University of Amsterdam, Department of Pathology, Amsterdam, the Netherlands.

6. 6Radboud University Medical Center, Department of Internal Medicine, Nijmegen, the Netherlands.

7. 7ISA Pharmaceuticals, Oegstgeest, the Netherlands.

8. 8STI outpatient clinic, Department of Infectious Diseases, Public Health Service of Amsterdam (GGD Amsterdam), Amsterdam, the Netherlands.

Abstract

Abstract Purpose: Anal cancer is increasing in HIV+ men who have sex with men (MSM). Treatment options for its precursor, high-grade anal intraepithelial neoplasia (HGAIN), are suboptimal. In this phase I to II dose-finding study, we assessed the safety and efficacy of the human papillomavirus type 16 (HPV16) synthetic long peptide vaccine (SLP-HPV-01) in HIV+ MSM with HPV16-positive HGAIN. Patients and Methods: Four dosage schedules (1-5-10; 5-10-20; 10-20-40; and 40-40-40-40 μg) of SLP-HPV-01 were administered intradermally with a 3-week interval in 10 patients per dose level (DL). In each dose group, 5 patients also received 1 μg/kg pegylated IFNα-2b subcutaneously. Primary endpoints were safety and regression of HGAIN at 3, 6, and 12 months. Results: Eighty-one of 134 screened patients (60%) had HPV16-negative HGAIN lesions, leaving 53 eligible patients. Thirteen patients were excluded, leaving 40 men. The vaccine was well tolerated. One patient developed a generalized rash. The highest dosage level induced the strongest immune responses. There was no indication for stronger reactivity in the IFNα groups. Up to 18 months of follow-up, 8/38 intention-to-treat patients had a complete clinical and histologic response and one had a partial response (in total 9/38, 23.7%). At the highest dosage level, the clinical response was 4/10 (40%). Stronger immune responses were detected among clinical responders. Conclusions: The highest DL is safe, immunogenic, and associated with clinical responses to HPV16-induced lesions. However, as the majority of HGAIN is caused by the other HPV types, further studies should aim at pan-HPV vaccination to prevent or treat HGAIN.

Funder

ZonMw

Stichting Pathologie Onderzoek en Ontwikkeling

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

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