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www.oncotarget.com Oncotarget, 2026, Vol. 17, pp: 1-29

Review

COVID vaccination and post-infection cancer signals: Evaluating

patterns and potential biological mechanisms

Charlotte Kuperwasser1,2 and Wafik S. El-Deiry3,4,5

1

Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA

2

Laboratory for the Convergence of Biomedical, Physical, and Engineering Sciences, Tufts University School of Medicine,

Boston, MA 02111, USA

3

Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Department of Pathology and Laboratory

Medicine, The Warren Alpert Medical School of Brown University, Providence, RI 029121, USA

4

Hematology-Oncology Division, Department of Medicine, Brown University Health and The Warren Alpert Medical School of

Brown University, Providence, RI 029121, USA

5

Legorreta Cancer Center at Brown University, The Warren Alpert Medical School of Brown University, Providence, RI 029121,

USA

Correspondence to: Charlotte Kuperwasser, email: charlotte.kuperwasser@tufts.edu

Wafik S. El-Deiry, email: wafik@brown.edu

Keywords: COVID; vaccine; cancer; infection; lymphoma; leukemia; sarcoma; carcinoma

Received: November 26, 2025 Accepted: December 26, 2025 Published: January 03, 2026

Copyright: © 2026 Kuperwasser and El-Deiry. This is an open access article distributed under the terms of the Creative Commons Attribution

License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source

are credited.

ABSTRACT

A growing number of peer-reviewed publications have reported diverse cancer

types appearing in temporal association with COVID-19 vaccination or infection. To

characterize the nature and scope of these reports, a systematic literature search from

January 2020 to October 2025 was conducted based on specified eligibility criteria.

A total of 69 publications met inclusion criteria: 66 article-level reports describing

333 patients across 27 countries, 2 retrospective population-level investigations

(Italy: ~300,000 cohort, and Korea: ~8.4 million cohort) quantified cancer incidence

and mortality trends among vaccinated populations, and one longitudinal analysis of

~1.3 million US miliary service members spanning the pre-pandemic through post- pandemic periods. Most of the studies documented hematologic malignancies (non- Hodgkin’s lymphomas, cutaneous lymphomas, leukemias), solid tumors (breast, lung,

melanoma, sarcoma, pancreatic cancer, and glioblastoma), and virus-associated

cancers (Kaposi and Merkel cell carcinoma). Across reports, several recurrent

themes emerged: (1) unusually rapid progression, recurrence, or reactivation of

preexisting indolent or controlled disease, (2) atypical or localized histopathologic

findings, including involvement of vaccine injection sites or regional lymph nodes,

and (3) proposed immunologic links between acute infection or vaccination and tumor

dormancy, immune escape, or microenvironmental shifts. The predominance of case- level observations and early population-level data demonstrates an early phase of

potential safety-signal detection. These findings underscore the need for rigorous

epidemiologic, longitudinal, clinical, histopathological, forensic, and mechanistic

studies to assess whether and under what conditions COVID-19 vaccination or

infection may be linked with cancer.

INTRODUCTION

The COVID-19 pandemic and the widespread

deployment of novel mRNA- and viral-vector based

vaccines have reshaped the landscape of human

immunology [1–4]. Never has such a large proportion

of the global population been exposed simultaneously to

nucleic acid–based immunogens, lipid nanoparticle (LNP)

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delivery systems, and repeated booster regimens over a

relatively short period. The unprecedented scale that

was marshaled in response to the COVID-19 pandemic

has generated and continues to generate extensive

clinical, molecular, and epidemiologic data, revealing

biological responses that extend beyond traditional

vaccine-induced immune activation and responses. These

include a spectrum of post-infection and post-vaccination

neurological, autoimmune, and inflammatory syndromes,

including myocarditis, immune-mediated neuropathies,

autoimmune cytopenias, systemic inflammatory responses

[5–7], as well as temporal co-occurrence with cancer

diagnoses, recurrences, or unexpectedly rapid disease

trajectories [8–11]. These events have prompted extensive

clinical investigation and underscore the capacity of

vaccine-induced immune activation to perturb immune

homeostasis in susceptible individuals. Importantly,

many of these conditions are characterized by cytokine

dysregulation, altered innate and adaptive immune

signaling, and tissue-specific inflammatory responses;

pathways that are also implicated in tumor initiation,

progression, and immune surveillance. The present

review focuses specifically on cancer-related observations

within this broader context of post-vaccination immune

perturbation.

After nearly six years since the pandemic was

recognized in early 2020, the current world’s literature

addressing COVID-19 infection or vaccination and

cancer remains sparse, heterogeneous, and largely

limited to case reports and small case series, insufficient

to support definitive conclusions regarding causation

or quantification of risk. Package inserts for COVID19

vaccines posted by the Food and Drug Administration

(FDA) [12–15] specifically state that they have not

been evaluated for carcinogenicity or genotoxicity, nor

have they been studied after multiple vaccine doses and

boosters or in combination with subsequent SARS-CoV-2

infection.

During the COVID pandemic, it was predicted

that cancer rates would rise during and after COVID due

to reduced screening and reduced access to treatment

during the pandemic. However, rates of cancer among

younger individuals for example with early onset colon

cancer have been rising for two decades [16, 17]. Rates

of cholangiocarcinoma and endometrial cancer have been

rising as well. Cancer deaths exceeded 600,000 in US

for 1st time in 2024 and in 2025 are predicted to rise as

well [18]. As of the writing of this review, there are no

published population studies in the US with mortality or

cancer incidence follow-up beyond 42 days for outcomes

after Covid infection versus no Covid infection or Covid

vaccinated versus not Covid vaccinated. This is in part due

to lack of good quality databases that would have such

information. There is a National Cancer Institute (NCI)-

funded Covid and Cancer Consortium (CCC) but it has not

published on this topic specifically.

Against the backdrop of limited clinical evidence

and incomplete preclinical toxicology, a recent study

reported that SARS-CoV-2 mRNA vaccines may

actually sensitize tumors to immune checkpoint

blockade [19] prompting broad interpretation that

COVID-19 mRNA vaccination may actually potentiate

antitumor responses in patients with melanoma or non–

small cell lung cancer (NSCLC) undergoing immune

checkpoint inhibition. Moreover, in the analysis,

mRNA vaccination was associated with increased

Type I interferon signaling and elevated tumor PD-L1

expression. However, PD-L1 upregulation in the absence

of checkpoint inhibitor therapy is generally associated

with enhanced tumor immune evasion and resistance

to T-cell–mediated cytotoxicity, raising questions

about the biological interpretation of these findings.

Although interferon-based therapies have established

clinical utility in melanoma, the study did not provide

comparative analyses between interferon treatment and

the combination of mRNA vaccination with checkpoint

blockade. Furthermore, the study did not address key

limitations, alternative mechanistic explanations, or the

broader clinical context necessary to fully interpret the

reported effects.

This absence of evaluation of COVID19 vaccines

for carcinogenicity or genotoxicity motivated a systematic

review and synthesis of the available evidence from

2020–2025 concerning COVID-19 vaccination, SARS- CoV-2 infection, and cancer. Specifically, we sought to (i)

categorize malignancies reported in temporal proximity to

vaccination or infection, (ii) evaluate temporal and clinical

patterns across tumor types for relevant signals among

patients exposed to the COVID vaccines, and (iii) outline

plausible immunologic and molecular mechanisms that

could underlie these phenomena.

Across the published literature, we identified

reports involving hematologic malignancies, including

lymphomas and leukemias, solid tumors such as breast,

lung, pancreatic, and glial cancers, virus-associated

malignancies including Kaposi sarcoma and Merkel cell

carcinoma, and rare entities such as sarcomas, melanomas,

and adenoid cystic carcinomas. While the number of

studies or their temporal association does not establish

causation, understanding whether these associations

represent coincidence, immune dysregulation, or a broader

biologic effect linking infection, vaccination, and cancer

development is now of pressing importance.

Importantly, regarding reported adverse events

and potential risks, awareness of what has occurred,

even if ultimately this proves to be extremely rare, is

a necessary component of informed consent at a time

when there is no longer a public health emergency from

COVID-19. Cancer risk is likely based on heterogeneity

among individuals, the impact of genetics, environment,

and interacting social determinants of health that varies

among individuals and this is an area where this article

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could form a foundation for future studies to refine

individualized risk. As such, the goal of this article is

to systematically synthesize and contextualize findings

from the published literature regarding malignancies

temporally associated with COVID-19 vaccination or

SARS-CoV-2 infection, without attempting to estimate

risk, establish causality, or inform individual clinical or

vaccination decisions.

RESULTS

This scoping review, covering the period of January

2020 until April 2025, was not designed to estimate cancer

risk or incidence, nor to draw causal inferences, but rather

to systematically assemble, categorize, and contextualize

published reports of malignancies temporally associated

with COVID-19 vaccination or SARS-CoV-2 infection.

It identified 69 publications [8, 20–87] describing

malignancies or malignant progression in temporal

association with COVID-19 vaccination or SARS-CoV-2

infection, encompassing a total of 333 patients (excluding

population-level studies [8, 20]. In addition, one

population-level publication which offered a longitudinal

assessment of cancer incidence across the pandemic and

immediate post-pandemic period was identified [86].

Among the 69 studies, most reports were single-patient

case reports or small series (55/69, 81%), with a small

number of systematic or narrative reviews (3/69, 4.5%),

mechanistic/experimental studies (2/69, 3%), and larger

case series, multicenter, or database-level analyses (8/69,

12%) (Table 1). Consistent with an early signal-detection

phase, the underlying evidence base is therefore heavily

weighted toward documenting occurrences of potentially

adverse events and hypothesis-generating case-level

observations rather than population-based epidemiologic

studies.

Geographic distribution

Reports originated from a wide range of countries

spanning Asia, Europe, the Middle East, Africa, and

North and South America. The countries with the highest

number of publications were Japan (n = 11) and the

United States (n = 11), followed by China (n = 7) and

Italy (n = 4). Additional single-patient cases or small

series were identified from Spain, South Korea, Saudi

Arabia, India, Nigeria, Brazil, Turkey, Singapore,

Lebanon, Egypt, Bulgaria, Taiwan, Ukraine, Iran, Russia,

Greece, Austria, Germany, Poland/Ukraine, as well as

multi-institutional or international collaborations. This

broad geographic distribution indicates that the reported

temporal associations between COVID-19 vaccination

or infection and oncologic events are not confined to a

particular region or healthcare system but have been

observed across diverse clinical settings and diagnostic

infrastructures around the globe.

Exposure types: Vaccination versus infection

Most publications identified in the search focused on

oncologic events occurring after COVID-19 vaccination

(56/69; 89%), with the remainder describing associations

following SARS-CoV-2 infection (5/69; 7%), and SARS- CoV-2 infection with prior vaccination (7/69; 10%). These

included case reports and mechanistic studies evaluating

post-infectious tumor behavior, immune perturbation, or

disease acceleration along with SARS-CoV-2 infection

but in the absence of vaccination or associated with a

SARS-CoV2 infection but with prior vaccination or

boosting. The predominance of vaccination-associated

case reports may reflect reporting patterns rather than

comparative biological risk, and the available data lack

sufficient individual-level detail to determine whether

or how oncologic responses differ between infection or

vaccination.

Across the published literature, reported vaccine

formulations and exposure types were heterogeneous

but could be grouped into broad platform categories

(Figure 1). Among vaccine-related reports, the majority

involved mRNA vaccines, with approximately 56%

following the Pfizer-BioNTech vaccine (BNT162b2) and

25% following the Moderna vaccine (mRNA-1273). An

additional 5% involved patients who had received both

Pfizer and Moderna products across different doses.

Adenovirus vector vaccines represented the next largest

category, including AstraZeneca (ChAdOx1/Covishield)

(5.8%), Johnson & Johnson (Ad26.COV2.S) (2.9%) and

the Russian, Sputnik-V (1.4%). Inactivated vaccines

(e.g., Sinopharm BBIBP-CorV, CoronaVac, or other

formulations) and studies in which the specific vaccine

type was not reported were least represented (2.6% and

1.1%, respectively). This distribution indicates that the

published literature is heavily weighted toward mRNA

vaccine platforms, particularly Pfizer-BioNTech and

Moderna, which together account for the vast majority

of vaccine-associated reports. This pattern closely

mirrors global vaccination practices where mRNA

vaccines were most widely deployed. The relatively

smaller representation of adenoviral vector vaccines

and inactivated platforms likely reflects both their more

limited use in certain regions and differential reporting

practices, rather than a comparative assessment of

biological risk.

Cancer types and clinical spectrum

Approximately 43% (30/69) of publications

reported lymphoid malignancies, encompassing both

lymphomas and leukemias (Figure 2 and Table 2). These

included a wide spectrum of lymphoid neoplasms such as

diffuse large B-cell lymphoma (DLBCL), various T-cell

lymphomas (e.g., angioimmunoblastic T-cell lymphoma,

subcutaneous panniculitis-like T-cell lymphoma),

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chronic lymphocytic leukemia/small lymphocytic

lymphoma (CLL/SLL), and cutaneous T-cell lymphomas

(CTCL). Several reports emphasized unexpectedly

rapid progression, atypical presentations, or unusually

aggressive courses of disease.

Solid tumors accounted for 41% of publications

(28/69) and represented a diverse group of malignancies,

including melanoma, breast cancer, lung cancer,

glioblastoma and other glial tumors, sarcomas, and

various organ-specific carcinomas, such as pancreatic

cancer (Figures 2 and 3). In multiple reports, the authors

described unusually rapid onset, short-latency recurrence,

or aggressive clinical progression for tumor types such

as pancreatic adenocarcinoma and glioblastoma; features

that are atypical for these cancers highlighted as notable

temporal observations.

A subset of reports described tumor formation or

recurrence at or near vaccine injection sites, the deltoid

region, axilla, or draining lymphatic basins, including

cases where axillary lymphadenopathy coincided with

solid-tumor metastasis. Virus-associated malignancies

such as Kaposi sarcoma, Merkel cell carcinoma, and EBV- Table 1: Summary of reports linking COVID-19 vaccination or infection to cancer

Study type N % of Total

(N = 69) Comments

Case reports 48 75% Dominant study type; mostly single-patient descriptions

Case series 5 6% Typically 2-several patients

Systematic/narrative reviews 6 4% Summaries or literature syntheses

Cohort/retrospective/

observational population studies 8 12% Larger-scale data (e.g., population cohort, singlecenter

cohort)

Mechanistic/translational studies

(tissue, organoids, mouse) 2 3% Experimental or preclinical mechanistic work

Figure 1: Distribution of reported malignancies by COVID-19 vaccine type. Distribution of vaccine formulations among

vaccinated patients with reported cancer following COVID-19 immunization. Most cases involved Pfizer-BioNTech (BNT162b2; 56%)

and Moderna (mRNA-1273; 25%) vaccines, followed by AstraZeneca/ChAdOx1 (Covishield; 17%) and Johnson & Johnson/Ad26.

COV2.S (8%). A small fraction of reports involved Sinovac (CoronaVac), Sinopharm (BBIBP-CorV), or other inactivated vaccines, as

well as unspecified mRNA or COVID-19 vaccine types. The predominance of mRNA vaccines reflects their widespread global use during

the study period.

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positive lymphomas were also identified across several

reports. The remaining 16% of publications (11/69) were

categorized as other or unspecified, which included mixed

or indeterminate cases, non-malignant proliferations,

studies referencing “cancer”, “tumor”, or “malignancy”

without definitive histopathologic classification, and

population-level analyses in which tumor type was not

explicitly delineated.

Figure 2: Distribution of post-vaccination and post-infection malignancies by tumor type. Distribution of reports with

malignancy or tumor-like lesions temporally associated with COVID-19 vaccination, SARS-CoV-2 infection, or SARS-CoV-2 infection

and vaccination. Pie charts depict the proportional representation of major cancer categories observed. (A) Accross all studies. (B)

COVID-19 vaccination, (C) SARS-CoV-2 infection, and (D) combined SARS-CoV-2 infection and COVID-19 vaccination. Cancer types

were consolidated into seven high-level categories. Carcinoma includes: breast cancer, prostate cancer, colon cancer, pancreatic cancer,

lung cancer, Merkel cell carcinoma, GI neoplasia/polyposis. Lymphoma also includes lymphoid neoplasms, cutaneous lymphoproliferative

disorders, lymphoproliferative disorder. Other includes benign tumors, pseudotumors, mixed tumors, heart tumors, inflammatory and non- specific tumors (e.g., myofibroblastic).

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Specific examples of cancers and their

association with COVID vaccination

Lymphoma

Cavanna et al. [26] reports the review of a series of

eight patients who developed Non-Hodgkin’s Lymphoma

after COVID-19 vaccination (Table 3), including four

males and four women. Five patients were vaccinated with

the BNT162b2 vaccine (Pfizer), one with the ChAdOx1

nCOV-19 vaccine (AstraZeneca, Cambridge, UK), one

with mRNA 1273/Spikevax (ModernaTX) and one patient

with the recombinant replication-incompetent adenovirus

type 26 (Ad26) viral-vector-based COVID-19 vaccine

(Janssen Pharmaceuticals, Beerse, Belgium). One of the

NHL cases presented with large right axillary adenopathy

shortly after COVID-19 vaccination (Figure 3A).

Sekizawa et al. [28] describe a case of marginal

zone B-Cell lymphoma in an 80-year-old Japanese woman

who presented with a right temporal mass that appeared

the morning after she was administered her first mRNA

COVID-19 vaccination (BNT162b2) (Figure 3B). The

mass gradually decreased in size but persisted over 6

weeks after her first vaccination (3 weeks after her second

vaccination). At her first visit, ultrasound revealed the

size of the mass to be 28.5 Å~ 5.7 mm, and computed

tomography revealed multiple lymphadenopathies in the

right parotid, submandibular, jugular, and supraclavicular

regions. This case brings up the possibility that an initial

mass may not be composed entirely of cancer cells and

may have an element of a host response that may limit the

progression depending on immune or other factors. In this

case, the patient had marginal zone B-cell lymphoma after

BNT162B2 COVID-19 vaccination.

Sarcoma

Bae et al. [21] reported the development of high

grade sarcoma after the second dose of the Moderna

vaccine. A 73-year-old female with a past medical history

of hypertension, hyperlipidemia, and renal angiomyolipoma

status post resection in 2019 presented with worsening

right upper arm swelling for the past two weeks. She

noticed the swelling two to four days after receiving her

second dose of the Moderna vaccine within 1 cm from the

prior injection site. Physical examination was remarkable

for a 6 cm, circular, mobile, soft mass present in the

right upper arm. (Figure 3C). Li et al. [23] reported the

development of classic cutaneous Kaposi’s sarcoma in a

79-year-old male following the first dose of the ChAdOx1

nCov-19 vaccine, without prior SARS-CoV-2 infection or

history of HIV infection. The patient developed multiple

reddish-blue papules on his legs and feet, confirmed

as KS through histopathology (Figure 3D). Treatment

included radiotherapy and sequential chemotherapy with

doxorubicin. The potential reactivation of latent HHV-8 by

the vaccine is suggested through mechanisms involving the

SARS-CoV-2 spike protein and adenovirus vector, which

may induce immune responses and inflammatory pathways.

Carcinoma

Abue et al. [32] describe a case series of 96 patients

with the diagnosis of pancreatic ductal adenocarcinoma

(Figure 3E). Repeated COVID-19 booster vaccinations

were associated with worse overall survival in the patients

with pancreatic cancer. Analysis revealed that high levels

of IgG4, induced by vaccination, correlate with a poor

prognosis. Sano [36] described an 85-year-old woman

who presented with an asymptomatic skin lesion in the

right chest within one month immediately after the 6th

dose of (Pfizer-BioNTech) vaccination. The patient had

been diagnosed with right breast cancer two years prior

and underwent partial mastectomy, hormone therapies, and

was deemed to be in remission. The lesion was confirmed

as a skin metastasis deemed to have developed through

potential local recurrence at surgical margins (Figure 3F).

Melanoma

Wagle et al. [56] described a 49-year-old Indian

male who developed rapidly progressive vision loss

Table 2: Clinicopathologic spectrum of lymphomas in post-vaccination reports

Lineage Subtypes Key features

T-cell lymphomas

CTCL, LyP, ALCL, AITL, SPTCL,

TFH-type, PCGDTCL, T-ALL,

T- cellNOS

Dominated by cutaneous and TFH-derived entities; several at

injection sites; many indolentor self-resolving (CD30+

).

B-cell lymphomas DLBCL, Follicular, MZL, CLL Primarily DLBCL; often nodal or axillary post-mRNAvaccine;

typically de novo; most treated with R-CHOP.

NK/NK-T-cell

lymphomas ENKL (nasal-type), NK/T overlap EBV+

nasal lesions; one partial response to SMILE +

radiation; suggest EBV reactivation.

Mixed/

Unspecified LPDs

Large “unspecified/other” cohort

from systematic review (Cui 2024)

and PCLDs

Aggregate data without cell-lineage resolution; largely

literature or registry series.