Could a particularly bad respiratory infection set the stage for lung cancer?
“This is further evidence that respiratory viruses can be associated with more than just the infection itself,” says James DeGregori, PhD, a professor of biochemistry and molecular genetics at the University of Colorado Anschutz School of Medicine and the interim director of the University of Colorado Cancer Center in Aurora, Colorado.
How Respiratory Viral Infections May Prime Lung Cancer
To assess how lung injury from respiratory illnesses could impact cancer risk over time, researchers examined the effects of severe COVID-19 and influenza in both mice and humans.
First, the investigators determined that mice who experienced severe lung infections from influenza or COVID were more likely to later develop lung cancer, and more likely to die from it.
To see if serious respiratory infections in humans might have the same effect, researchers looked at data including 76 million adults from the United States, Lebanon, and Saudi Arabia who’d been hospitalized for COVID-19 but had no history of cancer before 2022. The scientists tracked the subjects’ health data, including any new cancer diagnoses, from that point forward.
The investigators observed that people who’d been hospitalized with COVID-19 were more likely to have a lung cancer diagnosis, experiencing a 24 percent increase in risk — regardless of whether they smoked or used to smoke or had other health conditions that could raise the likelihood of lung cancer.
“That is considered a pretty significant increase in lung cancer, particularly considering the relatively short time window,” says the study author Jie Sun, PhD, a professor of medicine and the codirector of the Beirne B. Carter Center for Immunology Research at the University of Virginia School of Medicine in Charlottesville, Virginia.
“The COVID-19 pandemic provided us a unique context to study this,” Dr. Sun says, “because so many people got so sick with the same virus at the same time.”
Viruses Can Trigger Inflammation That Leaves the Door Open for Cancer
DeGregori says that severe viral infections trigger changes in immune system cells that usually protect lung tissue. This state of chronic inflammation could make it easier for cancer to develop later.
“The findings basically show a ‘memory’ function within the lung environment. So the environment of the lung seems to be switched because of this infection, and that switch within the lung is more conducive to cancer initiation or progression,” he says.
The New Research Has Some Limitations
Sun says this study is the first to establish a causal link between prior viral infection and the development of lung cancer. But the study has some limitations.
For example, participants who were hospitalized or diagnosed with COVID-19 before January 2022 would have likely had medical imaging and follow-up care, which could have had an impact on the results, says Charlotte Kuperwasser, PhD, a professor of developmental, molecular, and chemical biology at Tufts University School of Medicine in Medford, Massachusetts, who has researched the link between COVID-19 infection, vaccination, and cancer risk.
“This would have increased the likelihood of imaging and incidental findings,” she explains. “In addition, patients who developed severe COVID may have already had undiagnosed lung cancer, premalignant lung lesions, chronic lung disease, or immune dysfunction, which was why they developed such a severe case.”
“The lack of information about prior COVID vaccination or why if patients received COVID vaccination they still developed severe pneumonia is important to understand better and reconcile with the mouse data,” he says.
But the mouse data does clarify one point: “It is clear the COVID virus per se isn’t the culprit, as other viral infections causing severe pneumonia in mice also showed increased lung cancer.”
Steps for Protecting Yourself From Viral Infections and Potential Cancer Risk
The researchers say their findings underscore the importance of vaccination, and urge healthcare providers to consider close monitoring of people with a history of severe COVID, flu, or pneumonia for lung cancer screening purposes.
“Severe viral infections are not only harmful in the acute phase, but may also contribute to the development of chronic diseases, including cancer. Therefore, it is important to protect ourselves from severe infections whenever possible,” says Sun.
People at high risk of severe illness from a viral infection should also talk to their healthcare team about medications like Tamiflu (for flu) or Paxlovid (for COVID-19) to prevent a mild infection from becoming more serious.
People may want to take other precautions as well. “If I was a cancer survivor, I would definitely not only make sure I’m vaccinated, but I’d probably avoid a context where I thought there was a really high risk of getting infected. But everyone’s always got to make their own choices about risk,” says DeGregori.