The long-term effects of SARS-CoV-2, the virus that causes COVID-19, are a major public health concern. A primary question is whether infection with the virus directly increases the risk of developing cancer. Research into the relationship between COVID-19 and carcinogenesis is complex and ongoing, as scientists work to distinguish between a biological cause and factors related to pandemic-era healthcare disruptions. Understanding these potential biological and systemic connections is important for future disease management and surveillance.
Current Scientific Understanding of the Link
The clinical data on a direct link between SARS-CoV-2 infection and cancer incidence remains preliminary, given the relatively short time the virus has been circulating globally. Initial large-scale population studies often showed a temporary decline in new cancer diagnoses. However, this was largely attributed to widespread interruptions in screening programs during the early pandemic period, not a true reduction in cancer development.
More recent epidemiological analyses are beginning to suggest a potential association, particularly for certain cancer types. A three-year follow-up of individuals with SARS-CoV-2 infection showed an elevated risk for developing cancers related to the Human Papillomavirus (HPV), such as cervical and anal cancers, with some risks increasing by over 67% compared to uninfected groups. Mendelian randomization studies, which look at genetic markers to infer causal relationships, suggested a possible causal effect between severe COVID-19 and an increased risk for specific malignancies, including stomach, esophageal, and HER2-positive breast cancers.
One analysis in an Italian region noted a significant increase in new cancer diagnoses in the years following the pandemic’s onset, contrasting with reports of decreased diagnoses elsewhere. For example, diagnoses of brain and skin cancers increased by 300% in 2022 compared to pre-pandemic levels in 2017 in this cohort. While these findings do not definitively establish causation, they raise concerns that the virus may either initiate cancer or accelerate the progression of pre-existing, undetected disease. The observed trends underscore the need for sustained, long-term surveillance to fully characterize any direct biological influence the virus may have on cancer development.
Biological Mechanisms of Potential Interaction
The theoretical pathways by which SARS-CoV-2 could influence cancer development center on its persistent effects on the body’s internal environment. The inflammatory response triggered by the infection is a primary area of concern. Acute COVID-19 is often characterized by a “cytokine storm,” an excessive release of pro-inflammatory molecules like interleukin-6.
Even after recovery, some individuals experience a sustained, low-grade inflammatory state, often associated with Long COVID. This chronic inflammation can create a microenvironment conducive to tumor formation by promoting cell proliferation, inhibiting cell death, and potentially leading to DNA damage. Persistent inflammatory signaling can activate oncogenic pathways, such as the NF-κB and PI3K/AKT pathways, which are drivers of cancer progression.
Infection with SARS-CoV-2 causes lasting immune dysregulation, which is a major factor in cancer risk. The virus can lead to lymphopenia (a reduction in circulating lymphocytes) and cause functional exhaustion in cytotoxic T-cells and Natural Killer (NK) cells. These immune cells are normally responsible for immunosurveillance—the body’s mechanism for detecting and destroying nascent cancer cells.
Impaired immunosurveillance allows abnormal cells to evade detection and grow unchecked. The infection can also impact cellular control mechanisms, such as through oxidative stress, which damages cellular macromolecules and DNA repair mechanisms. Evidence suggests the virus can interfere with tumor suppressor proteins, such as the retinoblastoma protein (Rb), which regulates the cell cycle and prevents uncontrolled growth.
Indirect Factors Affecting Cancer Progression
The most immediate and well-documented impact of the pandemic on cancer outcomes relates to systemic disruptions in healthcare access and delivery. Stay-at-home orders, public health measures, and the burden on hospitals caused a massive drop in routine cancer screening worldwide. At the peak of the pandemic in early 2020, screenings for breast, colorectal, prostate, and lung cancers plummeted. Rates for mammography and colonoscopy dropped by as much as 85% and 75%, respectively, in some regions compared to the previous year.
This widespread suspension of preventative services led to a significant deficit of diagnosed cases, estimated at over 149,000 potentially undiagnosed cancers in the United States over the first two years of the pandemic. The consequence of these delays is known as stage migration, where cancers are detected at a later, more advanced stage. Studies have shown an increase in the diagnosis of larger tumors, such as clinical stage T4 colorectal cancer, and a higher proportion of metastatic breast cancer cases.
Patient behavior, often referred to as “medical distancing,” also contributed, as many individuals avoided hospitals and clinics out of fear of contracting the virus. This led to delays in seeking help for symptoms and interruptions in established treatment plans, including chemotherapy, radiation, and surgeries. The combined effects of delayed diagnosis and interrupted treatment are projected to increase cancer-related mortality for several years, independent of any direct biological effect the virus may have.