Navigating Uncharted Waters: Could COVID-19 and/or Certain COVID-19 Vaccines Promote Malignancy?

Abstract

Cancer is a complex and dynamic disease. The "Hallmarks of Cancer" were proposed by Hanahan and Weinberg (2000) as a set of biological capabilities acquired by human cells as they make their way from normalcy to neoplastic transformation. These capabilities include self-sufficiency in proliferative signaling, insensitivity to growth-suppressive signals and immune surveillance, ability to evade cell death, enabling replicative immortality, reprogramming energy metabolism, inducing angiogenesis, and activating tissue invasion and metastasis. Underlying these capabilities are genome instability, which expedites their acquisition, and inflammation, which fosters their function/s. Additionally, cancer exhibits another dimension of complexity: a heterogeneous repertoire of infiltrating and resident host cells, secreted factors, and extracellular matrix, known as the tumor microenvironment, that through a dynamic and reciprocal relationship with cancer cells supports immortality, local invasion, and metastatic dissemination. This staggering intricacy calls for caution when advising all people with cancer (or a previous history of cancer) to receive the COVID-19 primary vaccine series plus additional booster doses. Moreover, because these patients were not included in the pivotal clinical trials, considerable uncertainty remains regarding vaccine efficacy, safety, and the risk of interactions with anticancer therapies, which could reduce the value and innocuity of either medical treatment. After reviewing the available literature, we are particularly concerned that COVID-19 vaccination may predispose some (stable) oncologic patients to cancer progression, recurrence and/or metastasis. This hypothesis is based on biological plausibility (i.e., induction of lymphopenia and inflammation; downregulation of ACE2 expression; activation of oncogenic cascades; sequestration of tumor suppressor proteins; dysregulation of the G4-RNA-protein binding system and type I IFN responses; unsilencing of LINE-1 retrotransposons) together with growing anecdotal evidence and reports filed to Vaccine Adverse Effects Report System (VAERS) suggesting that some cancer patients experienced disease exacerbation or recurrence following COVID-19 vaccination. In light of the above, and because some of these concerns also apply to cancer patients infected with SARS-CoV-2, we encourage the scientific and medical community to urgently evaluate the impact of both COVID-19 and COVID-19 vaccination on cancer biology, adjusting public health recommendations accordingly. INTRODUCTIONA number of estimates and modelling studies highlight the millions of lives that COVID-19 vaccines might have saved globally (1-6). Yet, the COVID-19 crisis has negatively impacted the health and wellbeing of many people, particularly those living with cancer. Three years into the pandemic, healthcare authorities keep recommending that people with active and prior cancer get vaccinated against COVID-19 (7). Booster doses are encouraged (7,8) because vaccine effectiveness wanes...