Data from Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of Anal Intraepithelial Neoplasia in HIV+ Men

Abstract Purpose: Anal cancer is increasing in HIV-positive men who have sex with men (MSM). Treatment options for its precursor, high-grade anal intraepithelial neoplasia (HGAIN), are suboptimal. In this phase I-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-positive 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 mg) of SLP-HPV-01® were administered intradermally with a three-week interval in 10 patients per dose level. In each dose group, five patients also received 1 µg/kg pegylated interferon-alpha-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 IFN-α groups. Up to 18 months of follow-up, 8/38 intention-to-treat patients had a complete clinical and histological response (CR) and one had a partial response (PR) (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 dose level 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.