Oncotarget

Research Papers:

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

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Oncotarget. 2026; 17:291-305. https://doi.org/10.18632/oncotarget.28892

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Emily Bivens1, Omar Atiq2,3, Teresa Evans1, Milan Bimali4, Ginger Brown5, Jasmine Crane1, Nadia Darwish1, Jennifer L. Faulkner5, Rangaswamy Govindarajan2, Aaron Johnson5, Alongkorn Kurilung6, Oxana Lazarenko1, Yong-Chen William Lu1, Keanna Marsh1, Mauricio Moreno3, Intawat Nookaew6, Michael Robeson6, Jumin Sunde3, David Ussery6, Emre Vural3, Mindy Wilman5 and Mayumi Nakagawa1

1 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

2 Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

3 Otolaryngology – Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

4 Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

5 College of Medicine and Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

6 Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

Correspondence to:

Mayumi Nakagawa, email:[email protected]

Keywords: human papillomavirus; head and neck cancer; therapeutic vaccine; adjuvant; clinical trial

Received: January 19, 2026     Accepted: May 21, 2026     Published: June 05, 2026

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.

ABSTRACT

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.