A Randomized Double-Blind Placebo-Controlled Phase I/II Clinical Trial of a Human Papillomavirus Therapeutic Vaccine, PepCan, for Reducing Head and Neck Cancer Recurrence

ABSTRACT Objectives Head and neck cancer (HNC) has a high recurrence rate. Safety and effectiveness of PepCan in reducing recurrence for HNC patients were assessed. Methods and analysis PepCan consists of four human papillomavirus 16 (HPV 16) E6 peptides and a Candida skin testing reagent (Candin®, Nielsen Biosciences) as a vaccine adjuvant. Since Candida was known to have a general immune stimulating effects, patients were recruited regardless of their HPV status. Men and women with HNC who had no evidence of disease after standard surgery, chemotherapy, and/or radiation treatments were enrolled. They were randomized at 3:1 to PepCan versus placebo. Seven intradermal injections of PepCan or placebo (saline) were given every 3 weeks (first 4 injections) or 3 months (last 3 injections). They were followed with two visits 6 months apart. Safety was assessed using Common Terminology Criteria for Adverse Events version 5, and efficacy was assessed based on not having recurrence within 2 years. In addition, immune responses were examined using enzyme-linked immunospot assay for HPV 16 E6 response, fluorescent-activated cell sorter analysis for peripheral immune cells, and T cell repertoire analysis. Peripheral cytokines and gut and oral microbiome were also analyzed. Results Seventeen patients were enrolled. The most common adverse events were grades 1 and 2 injection site reactions, and they occurred more frequently in the PepCan group ( p