{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:11:02Z","timestamp":1789593062077,"version":"build-2803163510"},"posted":{"date-parts":[[2026,1,12]]},"group-title":"Oncology","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Head and neck cancer (HNC) has a high recurrence rate. Safety and effectiveness of PepCan in reducing recurrence for HNC patients were assessed.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>\n                    PepCan consists of four human papillomavirus 16 (HPV 16) E6 peptides and a\n                    <jats:italic>Candida<\/jats:italic>\n                    skin testing reagent (Candin\u00ae, Nielsen Biosciences) as a vaccine adjuvant. Since\n                    <jats:italic>Candida<\/jats:italic>\n                    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.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    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 (\n                    <jats:italic>p<\/jats:italic>\n                    &lt;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 (DLT). No serious adverse events were reported. In the intention-to-treat analysis (ITT), 45% (5\/11) had non-recurrence in the PepCan group while 80% (4\/5) had non-recurrence in the placebo group. For the per-protocol (PP) analysis, non-recurrence was 56% (5\/9) for PepCan and 80% (4\/5) for placebo. These differences were not statistically significant. Those who received PepCan and experienced non-recurrence had higher new T cell immune responses to HPV 16 E6 (\n                    <jats:italic>p<\/jats:italic>\n                    =0.05 for ITT and\n                    <jats:italic>p<\/jats:italic>\n                    =0.02 for PP). Pre-vaccination T helper type 1 cells were higher in the PepCan non-recurrence group compared to the PepCan recurrence group (\n                    <jats:italic>p<\/jats:italic>\n                    =0.01 for ITT and PP).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>PepCan is safe although DLT can occur after multiple injections of PepCan. PepCan does not seem to be effective in reducing recurrence; however, the results are inconclusive given the small patient numbers.<\/jats:p>\n                  <jats:p>\n                    What is already known on this topic\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Head and neck cancer (HNC) has a high recurrence rate after reaching no evidence of disease status after standard therapies including chemotherapy, radiation, immunotherapy and survey. However, no intervention is available to reduce recurrence.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                  <jats:p>\n                    What this study adds\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>A therapeutic human papillomavirus vaccine called PepCan was tested in a clinical trial and has been shown to be safe.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                  <jats:p>\n                    How this study might affect research, practice or policy\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>If a sufficiently powered study demonstrates efficacy in reducing recurrence rate, then how HNC patients are treated after achieving the no evidence of disease status will change.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.09.26343801","type":"posted-content","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T16:45:14Z","timestamp":1768236314000},"source":"Crossref","is-referenced-by-count":1,"title":["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"],"prefix":"10.64898","author":[{"given":"Emily","family":"Bivens","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Atiq","sequence":"additional","affiliation":[{"name":"Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA"},{"name":"Otolaryngology \u2013 Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Bimali","sequence":"additional","affiliation":[{"name":"Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginger","family":"Brown","sequence":"additional","affiliation":[{"name":"College of Medicine & Winthrop P. 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