Introduction: the intersection of COVID-19 and cancer—implications for patient vulnerability, disease progression, and oncogenic potential

The COVID-19 pandemic has posed unprecedented challenges to global healthcare systems, disproportionately affecting vulnerable populations, including cancer patients [1, 2]. Studies have consistently shown that individuals with cancer are at a heightened risk of contracting SARS-CoV-2 and experiencing more severe disease outcomes, including increased mortality and complications [3, 4]. This vulnerability is attributed to a combination of factors, including advanced age, preexisting comorbidities, and the immunosuppressive effects of cancer itself and its treatments, such as chemotherapy and radiotherapy [5, 6]. However, data on the precise influence of cancer type and treatment regimens on COVID-19 outcomes remain inconsistent, highlighting the need for further investigation.

Patients suffering from various diseases, particularly those related to cerebrovascular conditions and stroke, have also shown significant impacts from COVID-19 in multiple ways [7, 8]. Studies have already explored these connections, and further research holds promise for clarifying and addressing these links. This could play a crucial role in protecting vulnerable patient groups from severe outcomes associated with COVID-19 infections.

Beyond the immediate clinical risks, the pandemic has significantly disrupted cancer care. Delays in diagnoses, screenings, and treatments have led to an increase in advanced-stage cancer cases, potentially worsening long-term survival rates [9, 10]. Healthcare providers have faced difficult decisions in balancing the urgency of cancer treatment with the risks of SARS-CoV-2 exposure in immunocompromised patients [11, 12]. While vaccines and therapeutic advancements have facilitated a return to standard care, managing cancer in the context of COVID-19 remains a persistent challenge [10, 13].

The relationship between viral infections and cancer is well established, with several viruses, including human papillomavirus (HPV), hepatitis B and C (HBV, HCV), and Epstein-Barr virus (EBV), recognized as oncogenic agents [14–16]. These viruses contribute to tumorigenesis by interfering with tumor suppressor genes, promoting chronic inflammation, or inducing immune evasion. Emerging evidence suggests that coronaviruses, including SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV), may interact with cancer-related pathways. These interactions could potentially influence oncogenesis through mechanisms such as oxidative stress, immune dysregulation, and disruption of cell cycle regulation [14, 15]. SARS-CoV-1, for instance, has been shown to repress the tumor suppressor protein retinoblastoma (pRB) and interfere with cell-cell contact inhibition, raising concerns about whether SARS-CoV-2 might exert similar oncogenic effects [17, 18].

Long-term complications of SARS-CoV-2 infection, commonly referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or long COVID, have further implications for cancer patients [18]. Chronic inflammation, persistent immune dysfunction, and cellular stress—hallmarks of long COVID—may create a microenvironment conducive to tumorigenesis [19–21]. While direct evidence linking SARS-CoV-2 to cancer remains preliminary, these potential mechanisms warrant further investigation, particularly given the long-term health implications of the virus.

Understanding the interplay between COVID-19 and cancer is essential for guiding future research and healthcare policies. While observational studies have begun to explore potential connections, significant gaps remain due to limitations in data generalizability and comprehensiveness. Determining whether SARS-CoV-2 directly or indirectly influences cancer development and progression requires extensive, in-depth research to clarify the underlying mechanisms.

This study aims to investigate the impact of SARS-CoV-2 infection, including acute COVID-19 and long COVID, on cancer progression, focusing on how immune dysregulation and genetic alterations contribute to oncogenesis. Additionally, it explores the distinct clinical outcomes observed in cancer patients, which result from the complex interplay between their malignancy, ongoing treatments, and viral pathophysiology. To address these issues, this article analyzes the challenges faced by cancer patients with acute and long-term COVID-19, particularly in symptom management and treatment complexities. Additionally, it examines the potential role of SARS-CoV-2 in cancer development and its long-term oncogenic risk. Furthermore, it investigates the genetic and immunological mechanisms underlying viral oncogenesis, with a specific focus on how SARS-CoV-2 may promote cancer progression. The study also assesses the variability in COVID-19 outcomes among cancer patients based on cancer type and treatment regimens. Furthermore, it proposes key strategies for advancing research on cancer care during global health crises, including addressing healthcare disruptions, treatment delays, and the prolonged effects of COVID-19. Ultimately, this work aims to provide a comprehensive understanding of the relationship between COVID-19 and cancer progression, highlighting the need for targeted clinical approaches to mitigate risks in cancer patients. By shaping future research priorities and healthcare policies, this study aims to enhance the resilience of cancer care during pandemics. Additionally, it evaluates the oncogenic potential of SARS-CoV-2 and recommends necessary adaptations in oncology practice to address emerging viral threats.

Persistent symptoms and treatment complexities in cancer patients with acute COVID-19 and long COVID

Given the continued global impact of cancer as a major public health challenge, understanding the interplay between cancer and COVID-19 is essential. Research has already investigated how COVID-19 affects cancer outcomes, associated risk factors, and healthcare disruptions (Table 1); however, further studies are required to deepen this understanding. For instance, a large cohort study analyzed electronic health records (EHRs) from over 500,000 adults, comparing outcomes such as mortality, ICU admissions, mechanical ventilation, and hospitalizations between patients with and without cancer [22]. In fully adjusted models, cancer patients receiving recent treatments exhibited an increased 30-day risk of death, ICU stays, and hospitalization. Conversely, cancer patients without recent treatment had comparable risks of mortality and ICU admission to non-cancer patients, though their risk of mechanical ventilation and hospitalization remained lower [22]. These findings underscore the importance of risk stratification based on recent treatments, highlighting the complexities of managing cancer care during the pandemic.

One potential research direction involves conducting longitudinal studies on individuals who have recovered from COVID-19 to assess cancer incidence over time. Given the inflammatory nature of SARS-CoV-2 and its effects on critical tumor suppressor genes [36], monitoring cancer rates in these survivors could help clarify any causal relationship between the virus and cancer development.

Cancer patients tend to be older and have more comorbidities than the general population, both of which are associated with adverse COVID-19 outcomes [22, 37]. Additional risk factors identified include male sex, severe obesity, and certain racial and ethnic backgrounds. Broader research has similarly emphasized the role of biological and socioeconomic factors in determining COVID-19 severity in both cancer and non-cancer patients [38]. For example, non-Hispanic Black patients did not exhibit an increased mortality risk after adjusting for comorbidities, highlighting the need for further investigation into how race and ethnicity influence health outcomes [39].

After accounting for factors such as age and comorbidities, mortality rates between cancer and non-cancer patients may be comparable. Studies, such as the Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS) registry, reported similar mortality rates between these groups once confounding factors were controlled, emphasizing the complex interplay of factors influencing COVID-19 outcomes [40].

The COVID-19 pandemic has had profound and far-reaching indirect effects on healthcare, particularly in the prevention and treatment of cancer [41]. Research highlights how the pandemic impacted cancer incidence and mortality, primarily through significant disruptions in healthcare services. These disruptions led to delays in cancer screening, diagnosis, and treatment, potentially reversing recent declines in cancer mortality rates [42]. For example, a study found that a one-year disruption, including a 26-week delay in treatment, could result in an additional 1,719 colorectal cancer (CRC) deaths in Australia between 2020 and 2044 [43]. Early detection through screenings is vital, particularly for cancers like colorectal, breast, and melanoma, but many countries postponed screenings during the pandemic [44]. Treatment delays also worsened outcomes; for example, a four-week delay in colon cancer surgery increases mortality risk by 6%, and delayed chemotherapy raises CRC mortality risk by 13% [45]. In Canada, average treatment initiation times for cancer patients increased from 4.5 weeks pre-pandemic to 44 days, significantly elevating death risks for those affected [46].

The pandemic also disrupted cancer research, with a third of clinical trials delayed or stopped, and two-thirds of labs closed, potentially delaying breakthroughs by 18 months [47]. Globally, public health campaigns like HPV vaccination were also interrupted, reducing coverage and increasing future cancer risks. For example, HPV vaccination rates in the UK dropped from 88% to 59%, and projections in the United States suggest up to 6,200 additional oropharyngeal cancer cases by 2100 due to the disruption [48].

The long-term impact of the pandemic on cancer care, emphasizing the need for future public health planning to address these indirect consequences. Understanding how large-scale crises reshape healthcare is essential for preparing for future emergencies and ensuring recovery in cancer care.

Early studies during the COVID-19 pandemic highlighted the heightened vulnerability of cancer patients. In the UK, it was found that 10% of hospitalized COVID-19 patients had a history of cancer, and this group exhibited a significantly higher in-hospital mortality rate compared to non-cancer patients [49]. The hazard ratio (HR) of 1.13 further underscored the increased risk faced by this demographic [50, 51]. This elevated mortality risk emphasizes the severity of COVID-19 outcomes in cancer patients and highlights the unique challenges they face, including delayed cancer treatments due to hospital resource shortages, disruption of ongoing cancer therapies, and lack of timely access to necessary diagnostic services [52]. For instance, during the pandemic, many oncology departments had to postpone elective surgeries, radiation treatments, and even chemotherapy regimens, leading to exacerbated disease progression [53, 54]. In some cases, these delays were further compounded by overwhelmed healthcare systems that struggled to manage both COVID-19 patients and cancer care. Additionally, cancer patients often face difficulty accessing routine imaging and laboratory diagnostics, which are essential for monitoring disease progression and making timely adjustments to treatment plans [55].

Moreover, the shortage of hospital beds, especially during peak COVID-19 surges, resulted in cancer patients being displaced from specialized cancer care units to general wards [1, 56], where the quality of care could be suboptimal for their specific needs. This reallocation of resources hindered the ability to deliver timely and appropriate interventions for cancer patients, worsening prognosis in many cases.

Additionally, many cancer patients experienced the compounding effect of being unable to receive routine care or attend cancer screenings, which resulted in delayed diagnoses and worsened outcomes [57]. The pandemic also led to the cancellation or postponement of cancer screening programs, such as mammograms and colonoscopies, which are critical for early detection of various cancers. This disruption in screening services has likely led to a surge in cancer diagnoses at more advanced stages, which are more difficult to treat and have worse survival rates. Moreover, the healthcare system’s overwhelming focus on COVID-19 cases led to an inadequate allocation of resources for cancer treatment centers, which worsened survival prospects for cancer patients. In some countries, cancer treatment units were repurposed as intensive care units for COVID-19 patients, deprioritizing ongoing cancer care [41, 53, 58]. This has significantly impacted patient outcomes, as the delay in critical treatments, such as immunotherapy or hormone therapy, can substantially alter the course of the disease.

Further investigations into age and cancer treatment outcomes revealed that although older cancer patients experienced worse absolute outcomes, younger cancer patients exhibited a disproportionately higher relative mortality risk when compared to non-cancer patients of the same age [59]. This observation challenges the prevailing belief that older age alone is the most significant factor in severe COVID-19 outcomes. Several factors, including cancer type, treatment intensity, and social interactions, may contribute to the elevated risk observed in younger cancer patients [60].

In regard to vaccination, despite the overall reduction in mortality due to vaccination, the efficacy of the vaccines was found to be lower in cancer patients, especially those with hematological malignancies [13, 29]. The delta variant surge in 2021 further widened the mortality gap between cancer patients and the general population, underscoring the need for targeted protective measures. Data spanning the pandemic, from the initial wave to the early Omicron variants (BA.1 and BA.2), illustrated how shifting variants, societal changes like the relaxation of lockdowns, and varying vaccine effectiveness influenced mortality risks over time [61].

In terms of ICU admissions, cancer patients were generally less likely to be escalated to the ICU compared to non-cancer patients [32]. However, this pattern was not observed in younger cancer patients, who, despite their increased mortality risk, were admitted to the ICU at similar rates to non-cancer patients [30]. This disparity suggests that factors beyond ICU admission rates may contribute to poor outcomes among cancer patients. This highlights the need for a more detailed exploration of ICU decision-making and the underlying causes of these outcomes [62].

The findings highlight the need for continued research into ICU escalation decisions and the specific drivers of poor outcomes for cancer patients admitted to the ICU with COVID-19. A more nuanced understanding of these elements could inform clinical guidelines, ultimately improving care and outcomes for this particularly vulnerable population [63].

Looking ahead, it is clear that cancer patients remain at high risk from COVID-19, necessitating ongoing mitigation efforts. These should include prioritizing vaccination for this group, regular testing of healthcare staff in high-risk environments, and ensuring timely access to antiviral treatments and therapeutic antibodies [64]. In the context of future pandemics, the study emphasizes the importance of systematic data collection for cancer patients, advocating for the use of national protocols to provide a comprehensive understanding of their specific risks. This approach would offer more robust insights than isolated cancer registries and would enhance preparedness and response strategies for high-risk groups.

Future clinical research on the impact of COVID-19 on cancer patients is essential for understanding and addressing their increased vulnerability to severe outcomes. Studies consistently show that cancer patients are at higher risk of adverse effects from COVID-19, influenced by factors such as pre-existing comorbidities, cancer stage, ongoing treatments, and immunosuppression [4, 65].

While the immediate effects of COVID-19 on multiple organ systems have been well documented, there is growing concern about the persistence of symptoms long after recovery, especially among cancer patients. Research draws parallels between long COVID and post-viral syndromes observed after past outbreaks [66, 67]. Long COVID, or post-acute sequelae of SARS-CoV-2 (PASC), is characterized by symptoms persisting for at least four weeks after diagnosis. Estimates of its prevalence in the general population vary widely, from 10% to around 90%, but data specific to cancer patients are limited, and the implications for their care and prognosis remain unclear [68, 69].

The severity of the initial COVID-19 infection appears to be a key factor in the development of long COVID, with patients who required hospitalization more likely to experience lingering symptoms. However, even those with mild or moderate infections have reported prolonged health issues, underscoring the complexity of the condition [70]. A study of few hundreds’ cancer patients found that 60% developed long COVID, with women more likely to report symptoms such as fatigue, sleep disturbances, and muscle pain. Surprisingly, cancer type, age, or initial infection severity did not predict long COVID, although hypertension was inversely associated with its development [33]. Hypertension, a known risk factor for severe acute COVID-19, appears to have a different role in long COVID, suggesting distinct mechanisms between the acute and post-acute phases of the disease. Furthermore, although men typically experience more severe COVID-19, women in this study were more likely to report long-term symptoms, pointing to possible influences from immune responses and hormonal factors [34, 71].

Fatigue was the most commonly reported symptom in cancer patients with long COVID, affecting 82%, consistent with reports from the general population. Other prevalent symptoms included sleep disturbances, muscle pain, and gastrointestinal issues. However, ongoing cancer treatments such as chemotherapy and radiotherapy may complicate symptom attribution, making it difficult to determine whether these are related to COVID-19 or cancer therapy [72, 73].

Long COVID poses significant concerns for cancer patients, particularly women, with fatigue and sleep disturbances being the most frequent symptoms [33, 74]. Although severe acute COVID-19 was associated with higher mortality, it did not reliably predict the development of long COVID [75]. Further research is critical to developing effective long-term management strategies tailored to the specific needs of cancer patients.

The molecular impact of SARS-CoV-2 on cancer development

SARS-CoV-2, the virus responsible for COVID-19, is a positive-sense, single-stranded RNA (ss-RNA) virus with a genome size of 26–32 kilobases [76]. Unlike retroviruses, which encode reverse transcriptase, SARS-CoV-2 does not have the capacity to convert RNA into DNA. However, it possesses critical molecular components, including the spike (S) protein, which enables viral entry into human cells. The receptor-binding domain (RBD) of the spike protein, located in the S1 subunit, interacts specifically with angiotensin-converting enzyme 2 (ACE2) receptors on human cell surfaces, facilitating viral invasion (Table 2) [77, 78]. Mutations in the spike protein, particularly within the RBD, can impair antibody recognition, increasing the risk of reinfection and diminishing vaccine efficacy.

Mendelian randomization and the oncogenic potential of SARS-CoV-2: unraveling causal links between viral infections and cancer

The mutagenic effects of SARS-CoV-2 provide a unique insight into the complex relationships between viral infections, immune responses, and oncogenesis [121]. A key tool for studying these connections is Mendelian randomization (MR), an epidemiological method that uses genetic variants as instrumental variables to infer causal relationships between exposures, such as viral infections, and outcomes like cancer risk [122, 123]. MR helps minimize confounding factors and reverse causality, offering a more robust method to establish causality in epidemiological studies. This approach has been previously applied to identify associations between COVID-19 and various chronic conditions, including type 2 diabetes, and cancer risk factors like alterations in gut microbiota and autoimmune diseases such as rheumatoid arthritis [124, 125]. Recent applications of MR to explore potential links between COVID-19 and cancer have provided important insights into how viral infections might contribute to oncogenesis [123].

Recent MR studies have begun to identify genetic predispositions that link COVID-19 with specific cancers (Table 3). For instance, lung adenocarcinoma has emerged as one of the cancers potentially associated with SARS-CoV-2 infection. Genetic data from critically ill and hospitalized COVID-19 patients suggest that cancer risk may increase with the severity of the disease [126, 127]. Critically ill patients demonstrate an elevated risk for cancers such as HER2-positive breast cancer, esophageal cancer, CRC, stomach cancer, and colon cancer [128]. Notably, even patients with less severe disease—those hospitalized but not requiring intensive care—show increased risks for HER2-positive breast cancer, esophageal cancer, and stomach cancer [129].

An intriguing discovery is that individuals with milder SARS-CoV-2 infections, who do not require hospitalization, exhibit a higher risk of stomach cancer, while their risk of head and neck cancer is relatively lower [152, 153]. These variations suggest that the immune response to SARS-CoV-2, even in milder cases, may paradoxically foster an inflammatory environment that supports oncogenesis.

The relationship between COVID-19 severity and cancer risk is multifaceted and, at times, counterintuitive. Milder COVID-19 cases have been linked to an increased risk of gastric cancer, possibly due to immune responses that manage viral replication but cause chronic inflammation in the gastric mucosa [154, 155]. Chronic inflammation is known to promote mutagenic environments, increasing the likelihood of DNA damage and cellular changes that predispose tissues to malignant transformation [99, 156]. Furthermore, the immune dysregulation triggered by SARS-CoV-2 infection may interfere with normal tumor-suppressive mechanisms, contributing to cancer development (Table 3).

The role of viral infections in cancer development: implications of COVID-19 for long-term cancer risk

Viral infections have long been recognized as significant contributors to cancer development, with approximately 15% of all cancer cases worldwide linked to carcinogenic viruses [15]. Research exploring the relationship between viruses and cancer began in the mid-1960s, following the discovery of the first human oncogenic virus [171]. This breakthrough led to extensive investigations into how viruses contribute to tumorigenesis. Today, several viruses are strongly associated with specific cancer types, underscoring the profound impact of viral infections on cancer risk [172].

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has added new complexities to understanding the relationship between viral infections and long-term health outcomes, including potential cancer risks [105]. With increasing concerns about long COVID—where individuals experience prolonged symptoms months after the acute phase of infection—questions have arisen regarding its possible role in elevating long-term cancer risk [99].

Furthermore, the relationship between viral infections and cancer risk is complex, with significant public health implications [172]. Understanding how viral infections, such as SARS-CoV-2, contribute to cancer development is essential for developing effective interventions to mitigate this risk (Table 4).

COVID-19 outcomes in cancer patients—variability across cancer types and treatments

The outcomes of COVID-19 in cancer patients vary significantly based on the type of cancer and the treatments they have undergone (Table 5) [223]. While cancer patients generally face higher mortality rates from COVID-19, these data must be interpreted with caution due to variability in reporting methods. Some studies report overall mortality rates, while others focus on short-term mortality (e.g., 30-day mortality) [27]. Additionally, the strain on healthcare systems has varied across regions, complicating direct comparisons. Despite these discrepancies, the general trends indicate that cancer patients, particularly those undergoing recent or active treatments, remain at heightened risk [224, 225].

Organizing future research on cancer care during global crises: addressing healthcare disruptions, treatment delays, and long COVID

The COVID-19 pandemic has highlighted vulnerabilities in global healthcare systems, particularly in cancer care. It has disrupted cancer treatments, delayed early detection, and impeded preventive measures, leading to lasting impacts on patient outcomes [41]. Looking ahead, research must focus on strategies to ensure the resilience of cancer care systems during global crises (Figure 1). Several key research areas focused on mitigating the long-term effects of healthcare disruptions, improving treatment accessibility, and addressing the challenges posed by long COVID in cancer patients are outlined below and in Figure 1.

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Figure 1. 

Key research areas in response to the challenges posed by the COVID-19 pandemic on cancer care. COVID-19: coronavirus disease 2019

Temporal epidemiological association between the COVID-19 pandemic and the increase in cancer incidence

The COVID-19 pandemic has profoundly impacted global health systems, not only through the direct effects of the virus but also by disrupting essential healthcare services, including cancer prevention, diagnosis, and treatment [1, 2]. Recent epidemiological data suggest a temporal association between the pandemic and an increase in cancer incidence across various regions, with this association being multifactorial (Figure 2). Factors such as delays in screening, interruptions in treatment, and reduced access to healthcare services have all contributed to this rise.

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Figure 2. 

Temporal association between the COVID-19 pandemic and increased cancer incidence. COVID-19: coronavirus disease 2019

A key factor driving the increase in cancer incidence is the delay in diagnoses resulting from the strain placed on healthcare systems. As hospitals became overwhelmed with COVID-19 patients, many elective medical procedures, including routine cancer screenings, were postponed or canceled. This was observed across several countries, including the United States, Italy, Spain, and the United Kingdom, where screening programs for breast, colorectal, and cervical cancers experienced significant declines during the early phases of the pandemic [3–5]. For example, a dramatic drop in cancer screenings was reported in the United States in 2020, with CRC screenings decreasing by more than 80% in some states [6]. This delay in diagnosis led to the identification of cancers at more advanced stages, contributing to higher incidence rates in the years following the pandemic.

Patient behavior also played a crucial role in the observed temporal association. Fear of contracting COVID-19 in healthcare settings caused many individuals to avoid medical consultations and screenings, particularly in regions with high COVID-19 mortality rates [7]. In countries like Brazil and India, where healthcare systems were significantly strained by the pandemic, the number of cancer diagnoses initially fell. However, the postponement of treatments and failure to diagnose cancers early likely resulted in a rise in mortality rates in the years that followed [8, 9]. Vulnerable populations, such as the elderly and individuals with preexisting comorbidities, were particularly affected, as they are at higher risk for certain cancers. As a result, delays in diagnosis and treatment were compounded, and the full impact on cancer incidence may not be fully understood until comprehensive post-pandemic data is available.

The pandemic has also been associated with significant changes in lifestyle behaviors, such as increased smoking, alcohol consumption, and physical inactivity, all of which are well-established risk factors for several types of cancer [10, 11]. Studies conducted in countries like the United States, the United Kingdom, and Canada have shown an increase in tobacco use during the pandemic, likely due to heightened stress and the closure of smoking cessation programs [12, 13]. Additionally, disruptions in dietary habits, increased sedentary behavior, and reduced physical activity were observed worldwide, further contributing to an increased cancer risk. For example, the incidence of lung and CRCs during the pandemic may reflect the compounded effects of these lifestyle changes [14, 15]. In Italy, for instance, a sharp rise in alcohol consumption in 2020 has been linked to an increase in alcohol-related cancers, such as liver and esophageal cancers.

Certain types of cancer appear to have been disproportionately impacted by the COVID-19 pandemic. In countries such as the United Kingdom and Italy, the incidence of lung cancer—strongly associated with smoking—and CRC, linked to dietary and lifestyle factors, increased in the years following the onset of the pandemic [16, 17]. On the other hand, some cancer types, particularly those reliant on early detection programs such as breast cancer, experienced a temporary decline in incidence due to postponed screenings [18, 19]. However, an anticipated surge in diagnoses is expected in the future, as delayed cases are detected. In countries like France and Germany, for example, breast cancer diagnoses sharply fell in 2020, but these declines are expected to reverse as delayed diagnoses are made in the years ahead [20, 21].

Discussion, conclusions, and future directions

The interplay between cancer and COVID-19 has revealed significant challenges, particularly for immunocompromised patients who face increased risks from both acute infection and long-term complications [72, 281]. The pandemic has exacerbated vulnerabilities in cancer care, disrupting treatments and delaying diagnoses, thereby contributing to poorer outcomes [41]. These challenges underscore the urgent need to understand the mechanisms through which SARS-CoV-2 may influence cancer progression and to develop robust mitigation strategies tailored to protect this high-risk group. Additionally, the long-term health consequences of COVID-19, including the emerging phenomenon of long COVID, highlight the necessity of sustained monitoring and comprehensive healthcare planning for cancer patients during and after pandemics [66, 282]. Future research should focus on identifying personalized intervention strategies to mitigate the long-term consequences of SARS-CoV-2 in oncology settings, ensuring that affected individuals receive continuous and adaptive care.

Addressing the unique vulnerabilities of cancer patients requires a multifaceted approach that integrates vaccination, timely treatment, and ongoing support for individuals experiencing persistent symptoms [283, 284]. Given the potential oncogenic risks associated with SARS-CoV-2, continued research into its long-term effects on cancer patients is essential. Such research will not only enhance our understanding of COVID-19’s broader health impacts but will also inform future public health strategies, ensuring that cancer patients receive appropriate protection and care during future pandemics. Effective data collection, alongside the refinement of clinical guidelines, will be crucial for improving patient outcomes and strengthening healthcare system preparedness. Furthermore, integrating AI and machine learning models to predict cancer risk in post-COVID-19 patients could provide valuable insights into early detection and preventive strategies.

A growing body of research investigating the role of viral infections in cancer development underscores the significance of viruses, such as SARS-CoV-2, in modulating long-term health risks, including cancer susceptibility [91, 285]. While traditional oncogenic viruses, such as HPV and HBV, have well-established links to cancer, emerging evidence suggests that SARS-CoV-2 may also exhibit oncogenic potential. This may occur through mechanisms such as chronic inflammation, CS, immune dysregulation, and autophagy disruption [88, 156]. These findings raise critical concerns regarding the potential for SARS-CoV-2 to increase cancer risk, particularly as long COVID becomes an area of significant clinical focus. However, the precise molecular pathways linking COVID-19 to oncogenesis remain poorly understood, necessitating further investigation into the cellular and molecular consequences of SARS-CoV-2 infection. Exploring the interactions between viral proteins and key oncogenic pathways, such as the p53 and PI3K-AKT signaling axes, will be essential for elucidating the mechanistic basis of SARS-CoV-2-driven tumorigenesis.

Longitudinal studies are essential to clarify the relationship between COVID-19 and cancer risk, with an emphasis on monitoring immune responses, inflammatory markers, and cellular stress in recovered patients. Investigating mechanisms such as CS, chronic inflammation, and immunosuppression will provide valuable insights into how SARS-CoV-2 may alter tumor-suppressive pathways, potentially fostering an environment conducive to cancer development [177]. Additionally, MR studies can help identify populations with a genetic predisposition to increased cancer risk following SARS-CoV-2 infection [126]. As the world continues to navigate the pandemic’s aftermath, the potential long-term oncogenic risks posed by COVID-19 highlight the need for interdisciplinary research to inform preventive strategies and therapeutic interventions aimed at mitigating future cancer incidences linked to viral infections. Future efforts should include large-scale biobanking and genome-wide association studies (GWAS) to uncover genetic susceptibilities that may predispose individuals to post-COVID-19 malignancies, facilitating early intervention measures.

The molecular impact of SARS-CoV-2 on cancer development presents a complex and multifaceted challenge. The virus has been implicated in dysregulating key cellular pathways, such as the RAAS and epigenetic mechanisms, both of which are recognized contributors to oncogenesis [286]. SARS-CoV-2’s interactions with tumor suppressors and oncogenes, as well as its role in promoting inflammation and oxidative stress, align with established cancer-promoting mechanisms [287]. However, definitive evidence directly linking SARS-CoV-2 to tumorigenesis remains elusive. Continued exploration of virus-encoded circRNAs, inflammatory cytokines, and viral proteins is critical for understanding their impact on cancer-related gene networks and for developing novel therapeutic strategies to mitigate the potential oncogenic effects of COVID-19 [81, 104]. Additionally, single-cell transcriptomics and spatial proteomics could provide unprecedented insights into how SARS-CoV-2 reshapes the tumor microenvironment, potentially driving malignancies in predisposed individuals.

Future research should prioritize investigating the long-term oncogenic potential of SARS-CoV-2, particularly in cancer survivors and individuals with a history of chronic infection. Comparative studies examining SARS-CoV-2’s oncogenic mechanisms alongside those of established oncogenic viruses will be valuable in identifying shared and unique pathways. Integrative omics approaches, coupled with mechanistic studies of viral protein function, will aid in the identification of biomarkers and pathways relevant to both cancer progression and prevention [288, 289]. Additionally, research into SARS-CoV-2-induced epigenetic changes and molecular interactions between viral proteins and host cell factors will be pivotal in unveiling the full spectrum of its influence on cancer development [102]. This research will ultimately guide personalized care and cancer surveillance strategies. Developing predictive models based on multi-omics data will be crucial for stratifying patients at higher risk for post-viral malignancies and tailoring precision oncology approaches.

Ensuring the continuity and resilience of cancer care during global crises is paramount, as demonstrated by the widespread disruptions experienced during the COVID-19 pandemic [273]. Future research must prioritize strategies that mitigate healthcare interruptions, improve access to screenings and treatments, and address the unique challenges cancer patients face in the context of long COVID. Advancing telemedicine, developing adaptable screening methods, and leveraging digital health innovations will help sustain essential services during crises [290]. Furthermore, targeted efforts to reduce healthcare disparities and explore the long-term effects of COVID-19 on cancer patients are crucial to improving patient outcomes [291]. By integrating real-time epidemiological surveillance with AI-driven predictive modeling, healthcare systems can proactively identify emerging risks and implement timely interventions. Establishing an international research consortia focused on post-viral oncology will be instrumental in accelerating discoveries and translating findings into clinical practice, ensuring a more resilient and equitable healthcare future.