COVID-19 may increase lung cancer risk through inflammatory pathways in lungs

Researchers have linked severe acute respiratory syndrome coronavirus 2 infection to molecular changes in lung tissue that may promote tumour development, supported by clinical data showing higher cancer incidence in affected patients

A multidisciplinary study led by researchers at Marshall University Joan C. Edwards School of Medicine, Huntington, West Virginia, USA and the Hebrew University of Jerusalem, Israel, has identified a potential association between COVID-19 and an elevated risk of lung cancer, with evidence that the virus may induce molecular changes in lung tissue that favour tumour development.

The study has combined human clinical data with mechanistic investigations in animal and cellular models to examine how COVID-19 may contribute to long-term pulmonary pathology. The authors have focused on biological processes that extend beyond acute infection to explore how persistent alterations in the lung microenvironment could influence carcinogenesis.

“Our findings suggest that COVID-19 may do more than cause acute illness – it may also create biological conditions in the lung that could contribute to increased cancer risk over time,” said Dr. Wei Li, professor of biomedical sciences and co-corresponding author of the study. 

“Understanding these pathways is critical as we continue to study the long-term health impacts of the virus,” he said.

Central to the findings is the identification of a role for thymidine phosphorylase, a protein involved in angiogenesis and tissue remodelling. The researchers have reported that thymidine phosphorylase may interact with the spike protein of severe acute respiratory syndrome coronavirus 2 – the virus responsible for the disease COVID-19 – to trigger inflammatory and fibrotic responses within the lung. These processes have long been associated with tumour initiation and progression, particularly in tissues exposed to chronic injury.

The study has shown that this interaction may activate signalling pathways linked to tumour growth while also reshaping the immune landscape of the lung. Such immune modulation could reduce tumour surveillance capacity and create conditions that allow malignant cells to establish and proliferate. The authors have suggested that these findings provide a plausible mechanistic bridge between viral infection and cancer biology.

To complement the experimental work, the team has analysed clinical data derived from the TriNetX Research Network, a large-scale federated database of electronic health records. The analysis has indicated a higher incidence of lung cancer among individuals with a documented history of COVID-19, with the strongest association observed in current and former smokers. This observation aligns with established knowledge that smoking primes the lung for oncogenic transformation and may exacerbate the effects of additional insults such as viral infection.

The authors have emphasised that the epidemiological findings do not establish causality and require validation through longitudinal studies with extended follow-up. However, the convergence of clinical and mechanistic evidence strengthens the case for further investigation into COVID-19 as a potential modifier of cancer risk.

“The collaboration between basic and translational scientists and clinicians enabled the identification of mechanisms underlying epidemiological evidence linking COVID-19 infection to the potential increased risk of lung cancer,” said Dr. David Gozal, vice president for health affairs and dean of the Joan C. Edwards School of Medicine. 

“This is exactly the type of research the School of Medicine aims to expand in the coming years,” he concluded.

The findings have provided a framework to guide future research into the long-term oncological consequences of COVID-19. In particular, the identification of thymidine phosphorylase as a potential mediator offers a target for therapeutic intervention and risk stratification.

The study has been led by co-first authors Dr. Cayleigh Wallace and Dr. Alex Gileles-Hillel, with senior oversight from Dr. Li Yue and Dr. Hong Yue.

For further reading please visit: 10.3389/fimmu.2026.1798566