Parasitic Infections as Determinants of Cancer Risk and the Oncologic Safety of Antiparasitic Therapy: A Systematic Review and Meta-Analysis

Background: Parasitic infections remain highly prevalent worldwide and have increasingly been recognized as contributors to infection-related carcinogenesis. Chronic helminth and protozoan infections can induce persistent inflammation, immune dysregulation, and tissue injury, creating a microenvironment conducive to malignant transformation. However, the magnitude of cancer risk associated with parasitic diseases and the oncologic safety of antiparasitic therapy have not been comprehensively synthesized.

Objectives: This systematic review and meta-analysis aimed to evaluate the association between parasitic infections and cancer risk and to assess the oncologic safety and potential protective effects of antiparasitic therapy.

Methods: A systematic literature search of PubMed, Scopus, Web of Science, Embase, and the Cochrane Library was conducted from inception to December 2025 following PRISMA 2020 guidelines. Observational and interventional studies reporting cancer outcomes in parasitic infections or following antiparasitic therapy were included. Data were extracted independently by two reviewers, and study quality was assessed using the Newcastle–Ottawa Scale and Cochrane risk-of-bias tool. Random-effects meta-analysis was performed to estimate pooled risk ratios (RR) with 95% confidence intervals (CI).

Results: Thirty-two studies met inclusion criteria, with 18 contributing to quantitative synthesis. Parasitic infections were associated with a significantly increased overall cancer risk (pooled RR = 3.12; 95% CI 2.01–4.84; I² = 56%). Trematode infections demonstrated the strongest association with malignancy, particularly cholangiocarcinoma, while schistosomiasis showed a robust link with bladder cancer. Protozoan infections exhibited weaker but significant associations, including the relationship between Plasmodium falciparum and endemic Burkitt lymphoma. Evidence from longitudinal studies indicated that antiparasitic therapy was oncologically safe and associated with reduced incidence of infection-related cancers in endemic regions. Preliminary findings also suggested potential anticancer effects of selected antiparasitic agents.

Conclusions: Parasitic infections represent important yet underrecognized determinants of cancer risk, especially in endemic settings. Antiparasitic therapy appears safe from an oncologic perspective and may contribute to cancer prevention by interrupting chronic infection-driven carcinogenic pathways. Further prospective studies and clinical trials are warranted to clarify causal relationships and explore therapeutic repurposing of antiparasitic drugs in oncology.