Professor of Therapeutics-Epidemiology-Preventive Medicine, internist (Therapeutics Clinic, School of Medicine, NKUA, Alexandra Hospital) Theodora Psaltopoulou, biologist Alexandra Stavropoulou, Dr. Maria Kaparelou (medical oncologist), and Thanos Dimopoulos (former rector of NKUA, Professor of Therapeutics-Oncology-Hematology, Director of the Therapeutics Clinic, School of Medicine, NKUA, Alexandra Hospital) reported that during the first year of the pandemic, according to Professor of Intensive Care at University College London, Hugh Montgomery, colleagues began noticing unusually high numbers of people suddenly developing metastatic cancer, mainly breast and colorectal.
The prevailing explanation attributed this phenomenon to delays in medical check-ups and treatments due to the pandemic, which led to diagnoses at more advanced stages. However, as Montgomery pointed out: "Cancers don't evolve like that; they don't go from a small lump to terminal stage in three months."
This led him to explore a different hypothesis: Could respiratory viruses such as influenza and COVID-19 "awaken" dormant cancer cells and trigger metastasis?
A study recently published in Nature began with experiments on mice genetically programmed to carry dormant disseminated cancer cells. These cells, originating from the breast, had settled in the lungs and other organs.
Normally, these cells remain dormant for about a year before beginning to grow and form cancerous lesions. However, when the mice were exposed to a mild dose of the influenza virus, researchers observed that within days the cells were activated and began multiplying. Within two weeks, they had developed into metastatic tumors.
The same occurred when the mice were infected with a mouse-adapted version of SARS-CoV-2: within 28 days there was a "dramatic increase" in cancer cells.
"Viral infection significantly accelerates the growth of these cells," said John Alcorn, Professor of Pediatrics at the University of Pittsburgh.
To investigate whether the same happens in humans, researchers analyzed data from two major databases. In the first, the UK Biobank, which included more than 4,800 cancer survivors in remission, it was found that those who tested positive for COVID-19 in 2020 had nearly double the risk of dying from cancer compared to those who tested negative. The correlation was strongest in the first months after infection. In the second database, Flatiron Health, which contained data from about 37,000 women in remission from breast cancer, those who had contracted COVID-19 showed an increased likelihood of developing lung metastases, confirming the findings from the mouse experiments.
Influenza and COVID-19 trigger strong inflammation in the body, as the immune system attempts to fight the virus. Researchers focused on a specific protein, interleukin-6 (IL-6), which temporarily increases during infection. IL-6 plays a critical role in the body's defense, but in the presence of cancer cells it can enhance their growth.
In mice, IL-6 appeared to be a key factor in awakening dormant cancer cells. However, even after its levels returned to normal 15 days post-infection, the cells continued to grow, suggesting that secondary mechanisms were also at play. One of these seems to involve T lymphocytes: CD4 T cells suppress the activity of CD8 T cells, which are responsible for killing cancer cells. This creates an environment that allows cancer to spread unchecked.
Although the data point to a link between viral infections and metastasis, many questions remain. Researchers want to investigate whether the same is true for other viruses, as well as for different types of cancer and organs, such as the liver, where dormant cancer cells often settle.
Until answers are found, experts emphasize the value of prevention. Vaccination against influenza and COVID-19 does not eliminate the risk, but it significantly reduces the likelihood of severe infection.
Professor Montgomery stresses that caution should not turn into fear that restricts the lives of cancer survivors. Ultimately, how careful each person chooses to be is a personal decision.
This study sheds light on a new, concerning mechanism: respiratory infections are not merely temporary nuisances but may leave long-term effects, especially in those with a history of cancer.