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Hypothesis:

Hypothesis: HPV E6 and COVID spike proteins cooperate in targeting tumor suppression by p53

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Wafik S. El-Deiry1,2,3,4,5

1 Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

2 Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

3 Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI 02912, USA

4 Legorreta Cancer Center at Brown University, Providence, RI 02912, USA

5 Hematology/Oncology Division, Department of Medicine, Lifespan Health System and Brown University, Providence, RI 02912, USA

Correspondence to:

Wafik S. El-Deiry, email: wafik@brown.edu

Keywords: HPV; COVID; p53; spike; cancer

Received: December 01, 2025     Accepted: December 26, 2025     Published: January 03, 2026

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.

ABSTRACT

Human Papilloma Virus (HPV) is a causative agent in several cancers including cervical cancer, head and neck cancer, anal cancer, penile, vulvar and vaginal cancers. HPV through its virus-encoded protein E6 and the cellular E6-Associated Protein (E6-AP) target the tumor suppressor p53 protein for degradation thereby contributing to cancer development after HPV infection. As viruses cause cancer, the author previously hypothesized that SARS-COV-2 virus may be associated with cancer. More recent insights on the present hypothesis have come from studies suggesting (1) Spike protein of SARS-COV-2 may suppress p53 function, (2) cancer has been associated with mRNA vaccines that produce Spike, and (3) a case mentioned by Dr. Patrick Soon Shiong of a patient who survived HPV-associated head and neck cancer, but the tumor recurred after COVID mRNA vaccination including with liver metastases. 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. The hypothesis can be further explored through epidemiologic and laboratory studies.