The question of whether a COVID-19 infection increases an individual’s risk of developing cancer is a significant public health concern. The investigation into this potential link considers two pathways through which SARS-CoV-2 could influence cancer risk. The first involves a direct interaction between the virus and host cells, potentially causing oncogenic changes. The second focuses on the indirect, systemic effects of the infection, particularly the long-term inflammatory and immunological changes that could favor tumor growth. Understanding these mechanisms is necessary to assess the impact on cancer incidence and patient outcomes.
Is SARS-CoV-2 Directly Oncogenic?
The current scientific consensus does not support the idea that SARS-CoV-2 acts as a traditional oncogenic virus, such as Human Papillomavirus (HPV) or Hepatitis B virus (HBV). Established cancer-causing viruses integrate their genetic material into the host cell’s DNA, causing mutations or introducing viral oncogenes that drive uncontrolled cell division. SARS-CoV-2 is an RNA virus, and there is no strong evidence demonstrating its genome permanently integrates into the human cell nucleus.
The virus initiates infection by binding its spike protein to the Angiotensin-Converting Enzyme 2 (ACE2) receptor. This binding, coupled with the action of the host enzyme TMPRSS2, facilitates the virus’s entry. The goal of this cellular interaction is viral replication.
Despite the absence of genomic integration, researchers are exploring if the virus’s non-structural proteins interfere with cellular control mechanisms. Some studies suggest that SARS-CoV-2 proteins may interact with and promote the degradation of tumor suppressor proteins like p53 and the retinoblastoma protein (pRB). These proteins function as the cell’s natural brakes on division, and their inactivation is a frequent step in cancer development. This indirect action on cellular control pathways is a theoretical concern, but it differs significantly from the direct, mutation-inducing mechanism of established oncogenic viruses.
How Chronic Inflammation Could Promote Tumor Growth
The primary concern regarding cancer risk lies in the long-term, systemic effects of COVID-19, particularly the prolonged immune activation seen in post-acute sequelae of COVID-19 (Long COVID). Chronic inflammation is a well-established factor that promotes carcinogenesis. The acute infection can trigger a “cytokine storm,” an excessive release of pro-inflammatory signaling molecules such as Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α).
Even after the acute phase resolves, many individuals experience persistent, low-grade systemic inflammation marked by elevated cytokine levels. This sustained environment increases oxidative stress within tissues, damaging cellular DNA. Impaired DNA repair mechanisms, combined with chronic damage signals, increase the likelihood of accumulating genetic mutations that drive malignant growth.
The severe immune response to SARS-CoV-2 can also result in immune dysregulation that undermines the body’s ability to fight cancer. The infection is associated with T-cell exhaustion, where T-lymphocytes responsible for surveillance become functionally impaired. This failure of immune surveillance inhibits the body’s ability to detect and destroy nascent cancer cells. The inflammatory milieu may also reawaken dormant cancer cells, potentially leading to tumor growth or metastatic relapse.
Epidemiological Evidence and Current Research Gaps
Real-world data is largely dominated by the systemic disruption of healthcare during the pandemic. Initial large-scale epidemiological studies showed a drop in new cancer diagnoses during 2020, rather than an increase. For instance, one analysis reported a 65.2% decrease in new cancer diagnoses in April 2020 compared to the previous year, with breast cancer screenings declining by nearly 90%.
This reduction occurred because diagnoses were missed due to screening cancellations and patient hesitancy. Modeling estimates suggest these delays could result in an increased number of cancer deaths in the future, including a projected 7.9% to 9.5% increase in breast cancer deaths and a 15.5% to 16.6% increase in colorectal cancer deaths over five years. The lack of a significant “rebound” in 2021 suggests many cancers were missed entirely or diagnosed at a later, more advanced stage.
Current research faces a significant time lag. Since cancer development typically takes many years, the long-term effects of chronic inflammation from COVID-19 are only beginning to appear in population data. Preliminary signals have emerged, such as an increase in incidence rates for certain cancers in a Southern Italian study during 2020–2022. However, it is challenging to separate a true biological effect from the diagnostic catch-up that followed the initial lockdown. Definitive quantification of the biological risk requires several more years of observation to distinguish viral pathology effects from delayed medical care consequences.
COVID-19’s Effect on Cancer Detection and Care
The pandemic’s primary impact on cancer outcomes stems from the disruption of the healthcare system. Lockdowns and public health measures led to an abrupt halt to routine preventative care, with an estimated 9.4 million cancer screenings, including mammograms and colonoscopies, missed across the United States. This delay meant that when cancers were eventually found, they were often at a more advanced stage, requiring more aggressive and less successful treatment.
The pandemic also directly affected treatment for active cancer patients. Healthcare resources were diverted to manage the surge of COVID-19 cases, leading to significant decreases in cancer management visits, surgical capacity, and chemotherapy administration. A substantial reduction was seen in major cancer surgeries, such as mastectomies and colectomies, during peak pandemic periods.
A practical challenge complicating diagnosis is the overlap between symptoms of Long COVID and those of various malignancies. Persistent fatigue, unexplained weight loss, and chronic cough are characteristic of Long COVID, but are also common signs of cancer. This symptomatic ambiguity can lead to misdiagnosis or a delay in the crucial investigation of a potential malignancy.