A randomized double-blind placebo-controlled phase I/II clinical trial of a human papillomavirus therapeutic vaccine, PepCan, for reducing head and neck squamous cell carcinoma recurrence.

Abstract

Copyright: © 2026 Bivens et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Objectives: The main goals were to assess safety and efficacy (i.e., recurrence reduction).

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 < 0.0001). Two patients had allergic reactions (grade 2 and grade 3), at the 6th vaccination, which were considered to be a dose-limiting toxicity. No serious adverse events were reported. In the intention-to-treat analyses, 45% (5/11) had non-recurrence in the PepCan group while 80% (4/5) had non-recurrence in the placebo group (p = not significant). Those who received PepCan and experienced non-recurrence showed a trend of having higher new peripheral T cell immune responses to human papillomavirus type 16 E6 (p = 0.05). Pre-vaccination T helper type 1 cells were higher in the PepCan non-recurrence group compared to the PepCan recurrence group (p = 0.01).

Methods: PepCan consists of four human papillomavirus type16 E6 peptides and a Candida skin testing reagent. Patients with head and neck squamous cell carcinoma who had no evidence of disease after standard of care treatments were randomized at 3:1 to PepCan versus placebo (saline). Seven intradermal injections were given followed with two observational visits. Safety was assessed using CTCAE version 5, and efficacy was assessed based on not having recurrence within 2 years. In addition, immune responses and oral and gut microbiome were assessed.

Conclusions: PepCan was well tolerated. PepCan does not seem to be effective in reducing recurrence; however, the results are inconclusive given the small patient numbers.