image: Figure 2: Schematic depicting hypothesized cooperation between HPV and COVID in suppressing p53 and contributing to cancer.
Credit: Copyright: © 2026 El-Deiry. 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.
“Thus, the present hypothesis is that virally encoded proteins such as HPV-E6 or SARS-COV-2 Spike may cooperate in suppressing host defenses including tumor suppressor mechanisms involving p53.”
BUFFALO, NY – January 13, 2026 – A new hypothesis article was published in Oncotarget (Volume 17) on January 3, 2026, titled “Hypothesis: HPV E6 and COVID spike proteins cooperate in targeting tumor suppression by p53.”
Written by Wafik S. El-Deiry, Oncotarget Editor-in-Chief, from The Warren Alpert Medical School of Brown University and from Lifespan Health System and Brown University, the paper proposes that two viral proteins, HPV E6 and SARS-CoV-2 spike, could jointly reduce the activity of p53, a protein that helps protect cells from becoming cancerous. HPV is already known to drive several cancers, and the hypothesis suggests that additional pressure on p53 could matter for cancer risk or recurrence in some settings.
HPV can promote cancer development in part by using its E6 protein, together with a human partner protein called E6-AP, to drive the downregulation of p53. When p53 is weakened, damaged cells may be more likely to survive and continue growing. The new hypothesis asks whether SARS-CoV-2 viral influence could further reduce p53 function in people already affected by HPV.
The article highlights studies suggesting that the SARS-CoV-2 spike protein may suppress p53 activity and discusses observations that have raised questions about cancer outcomes after COVID-19 infection or vaccination in certain contexts. It also notes that a search of the literature did not identify clear evidence of direct molecular cooperation between HPV and COVID-19 in suppressing p53, which underscores the need for further studies.
“I listened to an interview (https://www.youtube.com/watch?v=tnVMjp9mCA0&t=2s) of Dr. Patrick Soon-Shiong by Chris Cuomo where I learned about a patient named Jim Johnson with a history of HPV-related head and neck cancer who by 2022 had survived his HPV-related cancer for 7 years and then he took the COVID vaccine.”
To investigate the presented hypothesis, Dr. El-Deiry proposes epidemiological studies that analyze cancer incidence and recurrence in HPV-positive groups with prior SARS-CoV-2 infection or COVID mRNA vaccination. It also proposes laboratory studies to assess whether HPV E6 and SARS-CoV-2 spike combined reduce p53 function more than either factor alone.
Overall, the hypothesis was formulated to focus attention on an HPV and SARS-CoV-2 shared biological target, p53, and to encourage careful studies that separate coincidence from causation. By outlining specific approaches, it aims to help researchers evaluate whether combined viral pressures on tumor-suppressor pathways could contribute to cancer progression.
DOI: https://doi.org/10.18632/oncotarget.28823
Correspondence to: Wafik S. El-Deiry – wafik@brown.edu
Keywords: HPV, COVID, p53, spike, cancer
Click here to sign up for free Altmetric alerts about this article.
________
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
X
Facebook
YouTube
Instagram
LinkedIn
Pinterest
Spotify, and available wherever you listen to podcasts
Click here to subscribe to Oncotarget publication updates.
For media inquiries, please contact media@impactjournals.com
Journal
Oncotarget
Method of Research
News article
Subject of Research
Not applicable
Article Title
Hypothesis: HPV E6 and COVID spike proteins cooperate in targeting tumor suppression by p53
Article Publication Date
3-Jan-2026
COI Statement
W.S.E-D. is a co-founder of Oncoceutics, Inc., a subsidiary of Chimerix (Chimerix was acquired by Jazz Pharmaceuticals), p53-Therapeutics, Inc. and SMURF-Therapeutics, Inc. Dr. El-Deiry has disclosed his relationships and potential conflicts of interest to his academic institution/employer and is fully compliant with NIH and institutional policy that manage these potential conflicts of interest.