Parasitic worms, or helminths, are among the most common infectious agents globally, with an estimated 1.5 billion people infected, representing about 24% of the world’s population as of 2021. These infections primarily affect impoverished populations in tropical and subtropical regions, including sub-Saharan Africa, Asia, and South America. The main types of soil-transmitted helminths include roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura), and hookworms (Ancylostoma duodenale, Necator americanus). In addition, Schistosoma species cause schistosomiasis, affecting roughly 240 million people worldwide, associated with chronic disease and significant mortality.
Helminths and cancer are increasingly recognized as interconnected health concerns. Infection-associated cancers account for a significant portion of global malignancies, and helminth infections have drawn attention as possible contributors to carcinogenesis. Chronic inflammation, immune modulation, and tissue damage from long-standing helminth infections are suspected mechanisms linking these parasites to increased cancer risk. Well-documented examples include the association of Schistosoma haematobium with bladder cancer and liver fluke species with bile duct cancer.
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This article aims to explore the most recent scientific evidence (2020-2025) regarding the correlation between helminth infections and cancer development, assessing epidemiological data, molecular mechanisms, and clinical implications to provide a comprehensive understanding of this complex relationship.
Helminths and Human Health
Helminths are multicellular parasitic worms that infect humans and animals worldwide. They are broadly classified into three major groups based on their morphology and life cycle:
- Nematodes (roundworms): Cylindrical, bilaterally symmetrical worms with a complete digestive system and separate sexes. Examples include Ascaris lumbricoides, Hookworms (Ancylostoma, Necator), and Trichuris trichiura.
- Platyhelminths (flatworms): These include two subclasses:
- Trematodes (flukes): Leaf-shaped, usually hermaphroditic worms such as Schistosoma species, which are blood flukes with separate sexes.
- Cestodes (tapeworms): Segmented flatworms that inhabit the intestinal lumen, examples include Taenia solium and Diphyllobothrium latum.
Helminth infections occur through ingestion of contaminated water, soil, or food, or via skin penetration by larvae. Once inside the host, helminths colonize a variety of tissues including the intestinal tract, blood vessels, liver, and lungs.
The infection often persists chronically, leading to sustained tissue damage and inflammation. Helminths induce granulomatous reactions, fibrosis, and immune system modulation via secretion of immunoregulatory molecules. The resulting chronic inflammation and tissue remodeling underpin many helminth-associated pathologies with potential to contribute to carcinogenesis.
Common helminths linked to significant human disease include Schistosoma haematobium, which causes urogenital schistosomiasis and is associated with bladder cancer; liver flukes such as Opisthorchis viverrini and Clonorchis sinensis, which infect the bile ducts and have a strong epidemiologic link to cholangiocarcinoma; and intestinal nematodes, which contribute to malabsorption, anemia, and immune alterations that support chronic disease states.
What Is the Epidemiological Evidence Linking Helminths to Cancer?
Recent population-based studies continue to strengthen the evidence linking helminth infections, particularly Schistosoma haematobium and liver flukes, with increased cancer risk.
Schistosoma Haematobium and Bladder Cancer
Schistosoma haematobium infection is classified as a Group 1 biological carcinogen by the International Agency for Research on Cancer (IARC). It is endemic in sub-Saharan Africa and parts of the Middle East, affecting millions. Chronic infection leads to persistent inflammation, fibrosis, and granulomatous reactions in the bladder wall. Epidemiological data from regions with high prevalence of S. haematobium show a high incidence of squamous cell carcinoma (SCC) of the bladder, a histological subtype strongly associated with this parasite.
For example, studies from Egypt, Nigeria, Sudan, and Angola demonstrate that up to 40-50% of bladder SCC cases exhibit histological evidence of Schistosoma ova. National schistosomiasis control programs have led to reductions in S. haematobium prevalence and a shift in bladder cancer types toward urothelial carcinoma. However, diagnostic challenges and underreporting remain barriers to a comprehensive epidemiological picture.
Liver Flukes (Opisthorchis viverrini, Clonorchis sinensis) and Cholangiocarcinoma
Liver fluke infections are endemic in Southeast Asia and parts of China. Both O. viverrini and C. sinensis are classified as Group 1 carcinogens. Chronic infection induces inflammation, epithelial hyperplasia, and bile duct fibrosis, which increase the risk of cholangiocarcinoma (bile duct cancer). Several recent meta-analyses confirm a significantly elevated risk—up to 7 to 10-fold—for cholangiocarcinoma in infected individuals, supported by both case-control and cohort studies.
Meta-Analyses and Clinical Data from the Last 5 Years
Meta-analyses from 2020 to 2025 have consolidated data from multiple endemic regions, confirming the strong epidemiologic links between these helminths and associated cancers. They highlight that chronic helminth infections contribute to carcinogenesis primarily through sustained inflammation, oxidative stress, and immunomodulation. However, data gaps still exist, especially in molecular characterization and the impact of co-factors such as smoking or chemical exposure.
Contrasting Anticancer Properties of Helminths
Emerging evidence indicates that, despite some helminth infections being linked to cancer, parasite-derived molecules exhibit promising anticancer effects. These helminth components can modulate immune responses and the tumor microenvironment, offering potential pathways for novel cancer therapies.
Several experimental and preclinical studies have identified specific parasite antigens and proteins with immunomodulatory and antineoplastic properties. For example, antigens from Heligmosomoides polygyrus have been shown to regulate macrophage activity, enhancing immune control within the tumor microenvironment and inhibiting breast cancer cell growth. Similarly, compounds from Echinococcus granulosus stimulate macrophage polarization and promote inflammatory responses that can help activate antitumor immunity.
In colorectal cancer models, helminth-derived molecules such as those from Taenia crassiceps enhance the efficacy of chemotherapy by modulating inflammatory cytokines, recruiting natural killer (NK) cells and cytotoxic CD8+ T cells, and promoting tumor cell apoptosis. Parasite antigens from Trypanosoma cruzi and Toxoplasma gondii have also demonstrated efficacy in limiting tumor growth through stimulating Th1 immune responses and increasing CD8+ T cell density in tumors.
These findings underscore the dual role of helminths: while chronic infection can promote cancer, helminth-derived compounds might be harnessed as effective immunotherapies or anticancer agents. Future therapeutic development may isolate and utilize these bioactive molecules to improve cancer treatment outcomes. Patryk Firmanty Vet Sci. 2024 , Hongyu Li, Front. Immunol, 2025
Interactions Between Helminth Infections and Other Comorbidities in Cancer Patients
Helminth infections induce complex immune modulation characterized by expansion of regulatory T cells (Tregs) and secretion of anti-inflammatory cytokines such as IL-10 and TGF-β, fostering an immunosuppressive tumor microenvironment. This immune suppression hampers the activity of cytotoxic T lymphocytes and natural killer cells, impairing the host immune surveillance mechanisms necessary to control tumor growth. Additionally, helminth infections may downregulate tumor suppressor genes such as p53, exacerbating genomic instability and promoting carcinogenesis. As a result, infected cancer patients often exhibit more aggressive tumor behavior and reduced responsiveness to immunotherapy. Hongyu Li, Front. Immunol, 2025
Nutritional Deficits and Impact on Therapy
Persistent helminthiasis frequently causes malnutrition, anemia, and protein-energy deficiencies due to nutrient malabsorption and chronic blood loss. These nutritional impairments deteriorate patients’ physiological resilience and immune competence, undermining their ability to tolerate cytotoxic cancer therapies like chemotherapy and radiotherapy. Malnourished patients face greater risks of treatment-related toxicities, infections, and poor wound healing, all of which negatively influence treatment outcomes and survival rates. Fabrício Marcus Silva Oliveira, Exp Biol Med (Maywood). 2022
Increased Susceptibility to Secondary Infections and Clinical Challenges
Helminth-induced immune dysregulation and tissue damage increase vulnerability to bacterial, viral, and fungal coinfections in immunocompromised cancer patients, complicating clinical management. Overlapping toxicities from antihelminthic and cancer therapies require careful dosing adjustments and monitoring. Moreover, helminth infections can amplify systemic inflammation or trigger allergic reactions, further compromising treatment efficacy and patient quality of life. Comprehensive screening for helminth infections is crucial in endemic regions to optimize integrated management plans for cancer patients with comorbid parasitism. Fabrício Marcus Silva Oliveira, Exp Biol Med (Maywood). 2022
What Are the Challenges and Advances in Helminth Diagnosis?
Accurate diagnosis of helminth infections is critical for effective treatment and control but remains challenging, particularly in resource-limited settings. Several approaches are currently employed, each with strengths and limitations:
Microscopy-Based Methods
Microscopic examination of stool samples remains the standard diagnostic tool for soil-transmitted helminths (STHs) such as Ascaris lumbricoides, Trichuris trichiura, and hookworms. The Kato-Katz thick smear technique is widely recommended for quantifying eggs but has limited sensitivity, especially in low-intensity infections. Other methods like spontaneous tube sedimentation (STS) and agar plate culture (APC) enhance detection sensitivity but require trained personnel and laboratory infrastructure.
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Recent advances include the use of digital whole slide imaging combined with deep learning algorithms. In a 2024 study, AI-supported digital microscopy of Kato-Katz smears significantly improved the diagnostic accuracy for common STHs, detecting many light-intensity infections missed by manual microscopy. This approach allows remote analysis via cloud services and shows promise for field applicability in endemic areas with basic lab facilities.
Serological and Immunological Tests
Serology detects host antibodies against helminth antigens and includes ELISA and rapid diagnostic tests. These methods are useful for tissue-dwelling or less accessible parasites, such as Schistosoma and Fasciola, where stool egg detection may be less reliable. However, antibody persistence post-treatment and cross-reactivity with other parasites can confound interpretation. Recent developments focus on identifying specific antigenic targets to increase specificity for active infections.
Molecular Diagnostics (PCR-based Methods)
Polymerase chain reaction (PCR) and real-time PCR assays detect parasite DNA in stool, urine, or blood samples, offering high sensitivity and specificity. Molecular diagnostics have become essential in low-prevalence settings and for species differentiation. Advances include multiplex PCR allowing simultaneous detection of multiple helminth species and portable PCR devices enhancing point-of-care potential. However, these remain costly and require laboratory infrastructure not broadly available in endemic regions.
Point-of-Care and Emerging Technologies
Novel diagnostic tools under research include loop-mediated isothermal amplification (LAMP), biosensors, and microfluidic devices, aiming for rapid, low-cost, and field-friendly detection. Emerging AI-driven digital microscopy platforms also promise to overcome human resource limitations. Yet, validation studies and wider implementation are needed to realize their full potential.
Limitations in Resource-Limited Settings
Diagnostics face significant challenges in endemic, low-resource areas, including scarcity of trained personnel, lack of laboratory infrastructure, reagent supply issues, and difficulties in maintaining cold chains. The low intensity of many infections in control program settings reduces test sensitivity, complicating surveillance efforts. Integration of newer digital and molecular diagnostics into existing health systems remains limited by costs and technical requirements.
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Clinical Implications and Future Research
Managing helminth infections in cancer patients presents unique challenges due to immunosuppression caused by both cancer and its treatments. Coinfections can exacerbate patient morbidity and complicate therapeutic regimens, requiring careful diagnosis and treatment strategies . Antihelminthic drugs such as albendazole and praziquantel are effective and generally safe but may require adjustments in immunocompromised patients .
Public health screening and control programs remain critical in endemic regions to reduce helminth prevalence and associated cancer risks. Preventive chemotherapy, improved sanitation, and health education contribute to lowering infection burdens .
Beyond infection control, the molecular biology of helminths offers promising avenues for novel cancer therapies. Parasite-derived antigens exhibit immunomodulatory properties that may be harnessed as vaccines or immunotherapies, potentially enhancing conventional cancer treatments . Experimental combination therapies show promise in improving tumor response and reducing side effects .
Current research gaps include understanding helminth immune modulation mechanisms in diverse cancers, optimizing helminth antigen-based therapies, and establishing standardized clinical protocols. Future studies should focus on multi-center clinical trials, gene editing approaches to increase antigen safety, and integration of helminth-based treatments with existing oncology protocols . Sitotaw et al., 2022. Norasyikeen et al., 2024.Hedley et al., 2023. Li et al., 2025.
Written by Aharon Tsaturyan, MD, Lead of OncoDaily Volunteers, Editor at OncoDaily Intelligence Unit.
FAQ
What are helminths and how common are helminth infections worldwide?
Helminths are parasitic worms that infect about 1.5 billion people globally, approximately 24% of the population (WHO, 2023). These infections mainly affect impoverished populations in tropical and subtropical regions, such as sub-Saharan Africa, Asia, and South America. The major groups include nematodes (roundworms), trematodes (flukes), and cestodes (tapeworms).
How do parasitic worm infections contribute to cancer development?
Chronic helminth infections cause persistent inflammation, immune modulation, and tissue damage that can contribute to carcinogenesis. Parasitic eggs or larvae provoke granulomatous reactions, fibrosis, and oxidative stress, creating a tumor-promoting environment.
Which types of cancer are most associated with helminth infections?
Schistosoma haematobium infection is strongly linked with squamous cell carcinoma of the bladder, while liver flukes such as Opisthorchis viverrini and Clonorchis sinensis are linked with cholangiocarcinoma (bile duct cancer).
What is the link between Schistosoma haematobium and bladder cancer?
S. haematobium eggs deposited in the bladder wall cause chronic inflammation and tissue remodeling. This triggers molecular changes including dysregulation of tumor suppressor p53, promoting neoplastic transformation. The infection skews immune responses towards a Th2 profile, facilitating carcinogenesis. Studies report up to 40-50% of bladder squamous cell carcinomas from endemic areas contain schistosome eggs (Ishida et al., 2018).
How do liver fluke infections increase the risk of bile duct cancer?
Liver flukes cause chronic epithelial hyperplasia and fibrosis in bile ducts. The resulting inflammation and cellular proliferation increase mutation risk, significantly elevating cholangiocarcinoma incidence, with a 7 to 10-fold increased risk in infected individuals (meta-analyses 2020-2025).
What molecular mechanisms explain how helminths promote carcinogenesis?
Helminths secrete immunomodulators that suppress cytotoxic immune cells, induce oxidative DNA damage, and alter signaling pathways that regulate cell proliferation and apoptosis. Molecular mimicry and cross-reacting antigens further dysregulate host responses.
Can helminth infections have anticancer effects or therapeutic potential?
Yes, some helminth-derived molecules can modulate immune responses beneficially, showing promise as immunotherapies or cancer vaccines. Parasite antigens from Heligmosomoides polygyrus and others have demonstrated tumor growth inhibition in preclinical models.
How do helminth infections influence cancer treatment outcomes?
Helminth coinfections may worsen prognosis by immunosuppression, malnutrition, and increased infection risk. They can reduce chemotherapy and immunotherapy efficacy, complicating clinical management.
What are the challenges in managing helminth infections in cancer patients?
Challenges include diagnosis in immunocompromised hosts, drug interactions between antihelminthics and cancer therapies, managing side effects, and ensuring adequate nutritional support.
What are the current research gaps and future directions in helminth-cancer studies?
Further studies are needed on helminth molecular mechanisms, standardized screening, helminth antigen-based therapies, and integrated infection-cancer control strategies through multi-center clinical trials.