Gosens Karien C M, van der Burg Sjoerd H, Welters Marij J P, Boekestijn Sanne, Loof Nikki M, Quint Wim G V, van Noesel Carel J M, van der Wal Allard C, Richel Olivier, Krebber Wilhelmus J T A, Melief Cornelis J M, de Vries Henry J C, Prins Jan M
Amsterdam UMC, University of Amsterdam, Department of Internal Medicine, Division of Infectious Diseases, Amsterdam, the Netherlands.
Amsterdam UMC, University of Amsterdam, Department of Dermatology, Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam, the Netherlands.
Clin Cancer Res. 2023 Oct 13;29(20):4109-4117. doi: 10.1158/1078-0432.CCR-22-3361.
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.
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.
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.
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.
在男男性行为的HIV阳性者（MSM）中，肛管癌的发病率正在上升。其前驱病变，即高级别肛管上皮内瘤变（HGAIN）的治疗选择并不理想。在这项I期至II期剂量探索性研究中，我们评估了16型人乳头瘤病毒（HPV16）合成长肽疫苗（SLP-HPV-01）在HPV16阳性HGAIN的HIV阳性MSM中的安全性和疗效。
SLP-HPV-01的四种剂量方案（1-5-10；5-10-20；10-20-40；以及40-40-40-40μg）以皮内注射的方式给药，每3周为一个间隔，每个剂量水平（DL）有10名患者。在每个剂量组中，5名患者还皮下注射1μg/kg聚乙二醇化干扰素α-2b。主要终点是3、6和12个月时HGAIN的安全性和消退情况。
134名筛查患者中有81名（60%）患有HPV16阴性HGAIN病变，剩余53名符合条件的患者。13名患者被排除，最终有40名男性。疫苗耐受性良好。1名患者出现全身性皮疹。最高剂量水平诱导出最强的免疫反应。在干扰素α组中没有更强反应性的迹象。长达18个月的随访中，38名意向性治疗患者中有8名有完全的临床和组织学反应，1名有部分反应（总共9/38，23.7%）。在最高剂量水平，临床反应为4/10（40%）。在临床反应者中检测到更强的免疫反应。
最高剂量水平是安全的、具有免疫原性的，并且与对HPV16诱导病变的临床反应相关。然而，由于大多数HGAIN是由其他HPV类型引起的，进一步的研究应旨在进行泛HPV疫苗接种以预防或治疗HGAIN。
