“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 p53 protein plays a central role in preventing cancer by responding to cellular stress and DNA damage. When activated, it can repair damaged DNA or trigger cell death, preventing the survival of potentially malignant cells. Loss of p53 function is a hallmark of many cancers.
HPV is well known to inactivate p53 through its E6 protein, which promotes p53 degradation. This mechanism contributes to HPV-associated cancers, including cervical, anal, and head and neck cancers. SARS-CoV-2, while not traditionally classified as an oncogenic virus, has been shown to interfere with immune function and, in some cases, with cellular pathways that involve p53.
A recent article by Dr. Wafik El-Deiry of The Warren Alpert Medical School of Brown University, published in Oncotarget, proposes a scientific hypothesis suggesting that proteins from HPV and SARS-CoV-2 may both interfere with the body’s tumor-suppressing mechanisms, potentially compounding their effects on cancer-related pathways.
The Hypothesis: HPV E6 and SARS-CoV-2 Spike Proteins May Cooperatively Suppress p53
In the paper, titled “Hypothesis: HPV E6 and COVID spike proteins cooperate in targeting tumor suppression by p53,” Dr. El-Deiry proposes that the SARS-CoV-2 spike protein, whether introduced via infection or mRNA vaccination, may suppress p53 activity in a manner that complements the effects of HPV E6. In individuals with persistent HPV infection, this combined interference could further reduce p53 function, weakening tumor suppression mechanisms.
The Mechanistic Rationale: Dual Viral Impact on p53 and Immune Regulation
The proposed mechanism involves two converging effects on p53. HPV E6 promotes the degradation of p53 protein, while the SARS-CoV-2 spike protein may suppress its transcriptional function. This dual action could further compromise the cellular ability to detect and respond to oncogenic stress.
The hypothesis also considers the broader immunological environment. SARS-CoV-2 infection has been shown to alter innate immune responses, which may indirectly accelerate progression of HPV-related neoplasia or other pre-cancerous states.
The Supporting Observations
Although the hypothesis remains untested, it is based on several converging observations. Laboratory research has shown that the SARS-CoV-2 spike protein can reduce p53-related gene activity, like p21, DR5, and MDM2, and weaken the response of cancer cells to therapy. In addition, a clinical case shared in a public interview by Dr. Patrick Soon-Shiong involved a patient with long-term remission from HPV-associated head and neck cancer who experienced recurrence and liver metastases after COVID-19 vaccination. While this does not establish causality, it illustrates the kind of clinical context in which the hypothesis could be further explored.
The Impact: Potential Implications for Cancer Risk in HPV- Positive Individuals
If validated, this hypothesis may have implications for cancer surveillance in HPV-positive individuals, particularly in the context of SARS-CoV-2 exposure or vaccination. However, as emphasized by the author, there is currently no clinical evidence linking COVID-19 vaccination to increased cancer risk.
This hypothesis is intended to encourage further epidemiological and mechanistic investigations, not to alter clinical recommendations. It proposes a framework for evaluating whether co-exposure to two common viruses may jointly impair p53-mediated tumor suppression in a subset of patients.
Future Perspectives and Conclusion
Dr. El-Deiry outlines two avenues for future research: population-based studies to assess cancer outcomes in HPV-positive individuals following SARS-CoV-2 infection or vaccination, and laboratory experiments to model the combined effects of HPV E6 and spike protein on p53 activity in human cells.
At present, the hypothesis remains speculative but biologically plausible. It highlights the importance of continued research at the intersection of oncology, virology, and immunology, particularly as we learn more about the long-term consequences of widespread viral exposure.
Click here to read the entire hypothesis published by Oncotarget.
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Oncotarget is an open-access, peer-reviewed journal that has published primarily oncology-focused research papers since 2010. These papers are available to readers (at no cost and free of subscription barriers) in a continuous publishing format at Oncotarget.com.
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