Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV+ Men
©2023 American Association for Cancer Research..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Clinical cancer research : an official journal of the American Association for Cancer Research - 29(2023), 20 vom: 13. Okt., Seite 4109-4117 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gosens, Karien C M [VerfasserIn] |
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| Links: |
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| Themen: |
Cancer Vaccines |
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| Anmerkungen: |
Date Completed 23.10.2023 Date Revised 07.11.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1158/1078-0432.CCR-22-3361 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360402585 |
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| 100 | 1 | |a Gosens, Karien C M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV+ Men |
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| 500 | |a Date Revised 07.11.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2023 American Association for Cancer Research. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a van der Burg, Sjoerd H |e verfasserin |4 aut | |
| 700 | 1 | |a Welters, Marij J P |e verfasserin |4 aut | |
| 700 | 1 | |a Boekestijn, Sanne |e verfasserin |4 aut | |
| 700 | 1 | |a Loof, Nikki M |e verfasserin |4 aut | |
| 700 | 1 | |a Quint, Wim G V |e verfasserin |4 aut | |
| 700 | 1 | |a van Noesel, Carel J M |e verfasserin |4 aut | |
| 700 | 1 | |a van der Wal, Allard C |e verfasserin |4 aut | |
| 700 | 1 | |a Richel, Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Krebber, Wilhelmus J T A |e verfasserin |4 aut | |
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| 700 | 1 | |a de Vries, Henry J C |e verfasserin |4 aut | |
| 700 | 1 | |a Prins, Jan M |e verfasserin |4 aut | |
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