16 Apr COVID-19 and Lung Cancer Risk: New Research Identifies a Biological Mechanism
Prof. Gileles-Hillel
MedicalResearch.com interview with
Prof. Alex Gileles-Hillel, M.D.
Senior Pediatric Pulmonologist and researcher
Hadassah Medical Center and Senior Lecturer at The Hebrew University of Jerusalem
together with co-investigators Cayleigh Wallace, Hong Yue, Ph.D., Wei Li, Ph.D.,
and David Gozal, M.D., M.B.A., Ph.D. (Hon) of Marshall University
MedicalResearch.com: What is the background for this study? What type of lung cancer risk may be impacted by COVID exposure?
Response: Clinicians have observed that many COVID-19 survivors develop interstitial lung fibrosis, a condition characterized by scarring of lung tissue that is known to increase the risk of lung cancer, particularly non-small cell lung cancer such as adenocarcinoma.
To explore this link mechanistically, we used a urethane carcinogenesis model in mice, which is a well-established model for lung adenocarcinoma. In this model, tumors are predominantly pulmonary adenomas and adenocarcinomas, allowing us to study how lung injury and inflammation may promote tumor development. These parallels suggest that COVID-related lung injury and fibrosis could similarly increase the risk of lung adenocarcinoma.
MedicalResearch.com: What are the main findings?
Response: Our study identifies a potential biological mechanism linking COVID-19 to increased lung cancer risk. We found that COVID-19 survivors have a modest but statistically significant increased risk of lung cancer, and that the risk is more pronounced in individuals with preexisting risk factors, particularly smokers. The SARS-CoV-2 spike protein may initiate a cascade of lung injury, inflammation, and fibrosis — a process mediated in part by activation of thymidine phosphorylase (TYMP) and downstream STAT3 signaling, which promotes a tumor-supportive environment.
Importantly, we did not observe a similar increase in bladder or oral cancers, suggesting a lung-specific effect related to viral-induced lung injury.
MedicalResearch.com: Are other cancers also influenced by the mechanism you describe?
Response: STAT3 is a well-known pathway that promotes a pro-tumor inflammatory environment and has been implicated in many cancers, including brain, lung, pancreatic, renal, colorectal, endometrial, cervical, ovarian, breast, and prostate cancers, as well as melanoma, glioma, head and neck cancers, lymphoma, and leukemia.
However, in our study, we did not find an association between prior COVID-19 infection and increased risk of bladder or oral cancers. This suggests that while the STAT3 pathway is broadly relevant in cancer biology, the effect of COVID-19 appears to be more specific to the lungs, likely due to direct viral injury in lung tissue.
MedicalResearch.com: Does COVID vaccination impact the findings?
Response: Yes. We found that prior COVID-19 vaccination was associated with a reduced risk of developing lung cancer. This supports the idea that preventing severe infection — and therefore reducing lung injury and inflammation — may lower long-term cancer risk.
MedicalResearch.com: What should patients and clinicians take away from your report?
Response: COVID-19 survivors — particularly those who experienced more severe disease — may benefit from closer long-term monitoring for lung health and cancer risk. For patients who smoke, this is an especially important opportunity to pursue smoking cessation, as smoking significantly amplifies the observed risk.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Several important questions remain. Is the increased risk limited to severe COVID-19, or does it extend to milder infections? We suspect severity plays a key role. Can TYMP be targeted therapeutically to reduce lung cancer risk or progression? Could early interventions during viral pneumonia reduce long-term fibrosis and subsequent cancer risk? Further research is needed to better define risk groups and develop targeted prevention strategies.
No disclosures.
Citation
Wallace C, Gileles-Hillel A, Cox A, Gozal D, Li W and Yue H (2026) Thymidine phosphorylase promotes SARS-CoV-2 spike protein-driven lung tumor development. Front. Immunol. 17:1798566. doi: 10.3389/fimmu.2026.1798566
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Last Updated on April 16, 2026 by Marie Benz MD FAAD