Hubbry Logo
Carcinogenic parasiteCarcinogenic parasiteMain
Open search
Carcinogenic parasite
Community hub
Carcinogenic parasite
logo
7 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Carcinogenic parasite
Carcinogenic parasite
Carcinogenic parasite
View on Wikipedia
from Wikipedia

Carcinogenic parasites are parasitic organisms that depend on other organisms (called hosts) for their survival, and cause cancer in such hosts. Three species of flukes (trematodes) are medically-proven carcinogenic parasites, namely the urinary blood fluke (Schistosoma haematobium), the Southeast Asian liver fluke (Opisthorchis viverrini) and the Chinese liver fluke (Clonorchis sinensis). S. haematobium is prevalent in Africa and the Middle East, and is the leading cause of bladder cancer (only next to tobacco smoking). O. viverrini and C. sinensis are both found in eastern and southeastern Asia, and are responsible for cholangiocarcinoma (cancer of the bile ducts). The International Agency for Research on Cancer declared them in 2009 as a Group 1 biological carcinogens in humans.[1]

Other parasites are also linked to various cancers. Among protozoan parasites, Toxoplasma gondii, Cryptosporidium parvum, Trichomonas vaginalis and Theileria are associated with specific cancer cells. Plasmodium falciparum can also be an indirect cause of cancer. Tapeworms such as Echinococcus granulosus and Taenia solium may directly or indirectly cause cancer. Liver flukes such as Opisthorchis viverrini and Platynosomum fastosum can cause cancer in domesticated animals. Roundworms such as Strongyloides stercoralis, Heterakis gallinarum, and Trichuris muris are known to cause cancer in animals.[2]

History

[edit]

A rat roundworm Gongylonema neoplasticum was the first parasite discovered—allegedly—to cause cancer. A Danish physician Johannes Fibiger discovered it in 1907, and experimentally showed that he could induce stomach cancer in rats using the roundworm infection in 1913. In 1914, he gave the name Spiroptera (Gongylonema) neoplastica, but later changed it to Spiroptera carcinoma.[3] Fibiger won the 1926 Nobel Prize in Physiology or Medicine "for his discovery of the Spiroptera carcinoma". However, his interpretation was later found to be false, and that the roundworm was not carcinogenic on its own.[4][5] Fibiger's Nobel Prize was described as "one of the biggest blunders made by the Karolinska Institute."[6]

The first true carcinogenic parasite discovered was Schistosoma haematobium. Theodor Maximillian Bilharz, a German physician at the Kasr el-Aini Hospital in Cairo recovered the adult fluke from a dead soldier in 1851. He named it Distomum haematobium. The disease is often called bilharzia in honour of the discoverer.[7] The infectivity and life cycle was discovered by Scottish physician Robert Thomson Leiper in 1915.[8] A British Surgeon Reginald Harrison, at the Liverpool Royal Infirmary, was the first to note its role in cancer. In 1889, he found that four people out of five cancer victims had bilharzia. A German physician Carl Goebel confirmed in 1903 that bladder tumour occurred in most bilharzia patients. By 1905, he was convinced that carcinoma of bladder was due to bilharzia.[9]

Group 1 carcinogens in human

[edit]

Three flukes, urinary blood fluke (Schistosoma haematobium), Southeast Asian liver fluke (Opisthorchis viverrini) and Chinese liver fluke (Clonorchis sinensis) are classified as Group 1 carcinogens, i.e. they are substantiated and directly cancer-causing agents.[1]

Schistosoma haematobium

[edit]

S. haematobium is a digenetic trematode found in Africa and the Middle East. It is the major agent of schistosomiasis, the most prevalent parasitic infection in humans.[10] It is the only blood fluke that infects the urinary tract, causing urinary schistosomiasis, and is the leading cause of bladder cancer (only next to tobacco smoking).[11][12] Its life cycle is transmission between humans and freshwater snail, species of Bulinus. The larvae live in water bodies from where they infect the hosts by penetrating the skin. Adults are found in the venous plexuses around the urinary bladder and the released eggs travels to the wall of the urine bladder causing haematuria and fibrosis of the bladder. The bladder becomes calcified, and there is increased pressure on ureters and kidneys (hydronephrosis). Inflammation of the genitals due to S. haematobium may contribute to the propagation of HIV.[13] Antigens produced by the eggs induce granuloma formation. Granulomata in turn coalesce to form tubercles, nodules or masses that often ulcerate. This creates the pathological lesions found in the bladder wall, ureter and renal; and also tumour, both benign and malignant.[14][15]

Opisthorchis viverrini

[edit]

O. viverrini is a food-borne liver fluke that mainly attacks the area of the bile duct. Infection with the parasite, called opisthorchiasis is the major cause of cholangiocarcinoma, a cancer of the bile ducts, in northern Thailand, the Lao People's Democratic Republic, Vietnam and Cambodia.[16] O. viverrini has three successive host for its life cycle – the first intermediate hosts are freshwater snails of the genus Bithynia, the second intermediate hosts are different cyprinid fish, and humans are the definitive hosts.[17] Generally opisthorchiasis due to O. viverrini is harmless without any clinical symptoms, but in rare cases, cholangitis, cholecystitis, and cholangiocarcinoma can develop. O. viverrini invades the bile ducts and, rarely, the gall bladder and pancreatic duct. Heavy infection can produce problems such as fibrosis in the liver, gall bladder and bile ducts.[18] Pathological effects on the bile ducts including inflammation, epithelial desquamation, goblet cell metaplasia, epithelial and adenomatous hyperplasia and periductal fibrosis collectively promote cholangiocarcinoma.[19] Though it is not immediately life-threatening, cancer develops after 30–40 years, and the ensuing death is rapid—within 3–6 months of diagnosis.[20]

Clonorchis sinensis

[edit]

C. sinensis is also a food-borne liver fluke. It is the most prevalent human trematode in Asia, and is found in Korea, China, Vietnam and also Russia. 85% of the cases are found in China.[21] It is transmitted similarly to O. viverrini, but the species of snails are varied, of which Parafossarulus manchouricus is the most common. The cyprinid fish hosts are also different.[22] General clonorchiasis is indicated with fatigue, abdominal discomfort, anorexia, weight loss, diarrhea, liver cirrhosis and jaundice. The most severe infections cause cholangiocarcinoma and hepatic carcinoma.[23]

Indirect or putative carcinogens

[edit]

Infection with malarial parasite Plasmodium falciparum is classified by IARC as probable (Group 2A) carcinogen. Schistosoma japonicum is a possible (Group 2B) carcinogen. There is a close association between the cat liver fluke Opisthorchis felineus and bile duct cancer among people in Russia.[24][25]

Toxoplasma gondii and eye cancer (intraocular lymphoma) was detected by PCR from two human cases.[26] Strongyloides stercoralis eggs and adult worms may be linked with gastric adenocarcinoma and colon adenocarcinoma in Korea.[27][2] Cryptosporidium parvum infection is associated with colorectal carcinoma.[28][29]

Carcinogens in animals

[edit]

The roundworm Trichuris muris infection can increase the number of tumours in mice.[30] Heavy infection with the trematode Platynosomum fastosum is associated with cholangiocarcinoma in cats.[31] Cryptosporidium parvum infection can be the cause of carcinoma in the gut of mice.[29][32]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Carcinogenic parasite

View on Grokipedia
from Grokipedia
Carcinogenic parasites are a group of parasitic helminths recognized for their ability to induce malignant tumors in humans through chronic infections that promote persistent inflammation, oxidative stress, and DNA damage. The International Agency for Research on Cancer (IARC) has classified three such parasites as Group 1 carcinogens—definite causes of cancer in humans: the trematode Schistosoma haematobium, which causes urinary bladder cancer, and the liver flukes Opisthorchis viverrini and Clonorchis sinensis, both associated with cholangiocarcinoma of the bile ducts. These infections collectively affect tens of millions globally, contributing significantly to cancer burdens in endemic regions of Africa, East Asia, and Southeast Asia, where poor sanitation, contaminated water, and consumption of raw freshwater fish facilitate transmission. Schistosoma haematobium, a blood fluke transmitted via skin penetration by cercariae in contaminated freshwater, primarily affects the urinary tract and is endemic in and parts of the . Chronic infection leads to granulomatous inflammation, epithelial hyperplasia, and production of carcinogenic nitrosamines, resulting in of the , which accounts for a substantial proportion of such cases in endemic areas. An estimated 251.4 million people required preventive treatment for overall in 2021, with over 90% in where S. haematobium is the predominant species, underscoring its role in both infectious and oncologic morbidity. In contrast, and are foodborne trematodes acquired through ingestion of undercooked or raw cyprinid fish harboring metacercariae, with infections concentrated in the River basin of and eastern Asia, respectively. These liver flukes reside in the for decades, inducing cholangiocarcinogenesis via mechanical obstruction, chronic proliferative , release of proinflammatory cytokines, and potential genotoxic metabolites that promote mutations in oncogenes like and tumor suppressors such as . Prevalence exceeds 10% in high-risk communities, with over 10 million cases of in alone and similar burdens from in and , leading to one of the highest global incidences of in affected populations. Preventive strategies, including mass drug administration with , improved sanitation, and education on safe food practices, have reduced transmission in some areas, but challenges persist due to socioeconomic factors and influences on intermediate hosts. Research continues to elucidate immune evasion tactics and synergistic cofactors like exposure, highlighting the need for integrated control to mitigate these ' carcinogenic potential.

Definition and Classification

Definition

A carcinogenic parasite is defined as a parasitic capable of inducing cancer in its host through prolonged interactions that promote oncogenic processes, primarily via chronic infection, persistent , or direct cellular damage. These parasites establish long-term infestations that disrupt normal host physiology, leading to pathological changes that favor tumorigenesis. Unlike incidental pathogens, carcinogenic parasites are distinguished by their ability to evade host immune clearance, resulting in sustained exposure of host tissues to harmful stimuli. Biologically, carcinogenic parasites are certain helminths—multicellular eukaryotic worms classified as platyhelminths (flatworms, including trematodes or flukes)—rather than , which are unicellular and less commonly associated with definitive carcinogenicity. Emphasis falls on trematodes, which exhibit complex life cycles involving multiple hosts: in intermediate hosts such as mollusks produces infective larvae, which then mature sexually in definitive hosts, often leading to chronic biliary or vascular infections in humans. This digenetic cycle facilitates persistent parasitism, contrasting with simpler direct life cycles in many or non-carcinogenic helminths. , while capable of causing , lack the strong epidemiological and mechanistic evidence for carcinogenicity seen in certain helminths. Nematodes (roundworms), such as common intestinal parasites like species, typically cause acute or self-resolving infections with nutritional impacts but without the chronic inflammatory milieu or cellular transformations that lead to neoplasia, and none are classified as carcinogenic. Pathologically, the criteria for carcinogenicity involve persistent that initiates a cascade of tissue alterations: chronic inflammation induces and release, driving remodeling such as and ; this progresses to , where normal epithelial cells transform into abnormal types more prone to ; ultimately, accumulated genetic instability culminates in neoplasia, characterized by uncontrolled proliferation and tumor invasion. According to the International Agency for Research on Cancer (IARC), infections with specific parasites meeting these criteria are classified as agents, carcinogenic to humans.

IARC Classification

The International Agency for Research on Cancer (IARC) classifies carcinogenic hazards, including parasitic infections, into groups based on the strength of scientific evidence from human, experimental animal, and mechanistic studies, as outlined in the Preamble to the IARC Monographs. denotes agents carcinogenic to humans, requiring sufficient evidence of carcinogenicity in humans—typically from consistent findings across multiple high-quality epidemiological studies (e.g., cohort or case-control designs) that establish a causal association, while accounting for chance, bias, confounding, and biological plausibility. For parasites, this evidence often involves population-based data from endemic regions, demonstrating elevated cancer risks linked to infection prevalence and chronicity. Three parasitic infections are classified in Group 1: , , and . These were evaluated in IARC Monograph Volume 61 (1994), where sufficient human evidence showed S. haematobium infection causally associated with through studies in Egyptian and other African populations revealing odds ratios exceeding 10 in infected cases. Similarly, O. viverrini and C. sinensis infections were linked to via epidemiological data from and Korea/, respectively, with relative risks of 5 or higher in endemic cohorts. The classifications were reaffirmed without modification in Volume 100B (2012), following a re-evaluation of biological agents that confirmed the original evidence, and remain unchanged as of the 2025 IARC update. Group 2A includes agents probably carcinogenic to humans, based on limited in humans (positive associations not fully excluding chance, bias, or ) plus sufficient from experimental animals or strong mechanistic . An example relevant to parasites is caused by infection with in holoendemic areas, classified in Group 2A in Volume 104 (2012); limited human from African studies indicated an association with endemic , supported by animal models of lymphomagenesis. Group 2B encompasses agents possibly carcinogenic to humans, requiring limited evidence in humans with inadequate or no supporting animal data. Infection with Schistosoma japonicum falls into this group, as evaluated in Volume 61 (1994), with limited epidemiological evidence from Chinese populations suggesting links to and , but insufficient consistency or strength for higher classification. Unlike classifications for chemical carcinogens, which emphasize quantitative exposure metrics and dose-response curves, evaluations for carcinogenic parasites prioritize dynamics—such as , persistence, and transmission in human populations—drawing on serological, parasitological, and cohort from endemic settings to infer . This approach accounts for the binary nature of exposure (infected versus uninfected) and integrates host-parasite interactions, distinguishing it from viral or bacterial assessments that may focus more on viral integration or production.

History

Early Observations

Theodor Bilharz, a German pathologist, made one of the earliest key observations in 1851 during an in , , where he identified Schistosoma eggs in the urinary tract of a exhibiting and other urogenital symptoms. In a 1852 publication, Bilharz described the parasite as residing in the vesical veins and associating with chronic inflammation and tissue damage in the , though he did not explicitly link it to at the time. This discovery highlighted the parasite's role in endemic urinary disorders in , where —termed "endemic hematuria"—had been documented since ancient times but was now tied to a specific infectious agent. Throughout the , clinicians in schistosomiasis-endemic regions like reported elevated rates of severe bladder pathologies, including ulcerations and granulomatous lesions that predisposed patients to chronic complications, some retrospectively identified as precursors to . Sir , in his 1903 edition of Tropical Diseases: A Manual of the Diseases of Warm Climates, documented cases of in tropical areas, emphasizing the parasite's capacity to cause persistent and in the urinary tract. Early animal studies suggested parasitic links to , with reports noting liver tumors in animals infected with liver flukes such as . For instance, cholangiocarcinomas have been observed in infected cats and dogs concurrent with heavy fluke burdens. These findings paralleled human cases in but faced challenges in establishing due to factors like dietary habits, co-infections with other helminths, and environmental toxins that could independently promote hepatic lesions. Linking parasites directly to cancer proved difficult in these early accounts, as diagnostic tools were limited, and multifactorial influences—such as , repeated bacterial supers, and genetic predispositions—often obscured the parasites' specific contributions. Despite these hurdles, the patterns observed in endemic zones laid the groundwork for later epidemiological inquiries into parasite-induced oncogenesis. In the early , Egyptian clinicians began reporting associations between chronic S. haematobium infection and bladder malignancies in postmortem examinations.

Formal Recognition

The formal recognition of certain parasitic infections as carcinogenic to humans was established through the evaluations of the International Agency for Research on Cancer (IARC), a specialized agency of the (WHO). In its 1994 monograph (Volume 61), IARC classified infection with as a carcinogen, indicating sufficient evidence of carcinogenicity in humans, primarily based on epidemiological data from endemic areas in showing a strong association with of the urinary . This classification relied on case-control and cohort studies demonstrating elevated cancer risks in infected populations, marking a pivotal in acknowledging parasitic infections as environmental s. Subsequent IARC evaluations expanded this recognition to liver flukes. was classified as (carcinogenic to humans) in the 1994 , while was classified as Group 2A (probably carcinogenic to humans). was upgraded to in the 2009 (Volume 100B, published 2012). This upgrade was supported by new epidemiological , including cohort and case-control studies from and Korea that quantified the dose-response relationship between intensity/duration and incidence. The WHO has reinforced these classifications through its broader framework for control, emphasizing the oncogenic risks of parasitic infections since the via programs like the Special Programme for Research and Training in Tropical Diseases (TDR), established in 1975 and expanded to address cancer linkages in endemic regions. These efforts integrated parasite control into strategies, highlighting the impact in high-burden areas of and .

Mechanisms of Carcinogenesis

Chronic Inflammation Pathway

Chronic parasitic infections, particularly those involving helminths such as schistosomes and liver flukes, initiate primarily through sustained inflammatory responses in affected tissues. The process begins with mechanical damage to epithelial linings caused by egg deposition or direct worm attachment; for instance, eggs of become trapped in the bladder wall, releasing antigens that provoke a robust immune reaction, while adult flukes like adhere to biliary epithelium, causing ulceration and abrasion. This damage triggers the release of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which recruit immune cells such as macrophages and to the site, amplifying the inflammatory cascade. Over time, this persistent promotes , characterized by excessive deposition from activated fibroblasts and stellate cells, leading to tissue remodeling and scarring that disrupts normal cellular architecture. The progression from chronic to involves the generation of reactive oxygen and nitrogen species by infiltrating immune cells, which indirectly contribute to cellular transformation. Notably, inflammatory cells produce and other mediators that facilitate the formation of endogenous nitrosamines, potent carcinogens that induce and subsequent DNA alterations, fostering metaplastic and dysplastic changes. In the urinary tract affected by schistosomes, this manifests as of the , while in the impacted by flukes, it results in periductal and cholangiocellular proliferation, both heightening susceptibility to malignant conversion. These tissue-specific responses underscore how localized drives organ-targeted oncogenesis without direct parasitic . Experimental evidence from animal models robustly supports this inflammation-to-cancer link. In Syrian hamsters infected with O. viverrini, chronic biliary leads to cholangiofibrosis and cholangiocarcinomas, with histopathological analyses revealing progressive epithelial and correlating with elevation and nitrosative stress. Similarly, models of schistosomal demonstrate that egg-induced granulomatous in the promotes fibrotic lesions and neoplastic transformation, affirming the pathway's causality . These findings highlight the central role of unresolved in parasitic .

Genotoxic Effects

Carcinogenic parasites exert direct genotoxic effects through the release of secretions and metabolites that interact with host DNA, leading to strand breaks, adducts, and mutations independent of host immune responses. In liver flukes such as Opisthorchis viverrini and Clonorchis sinensis, excretory-secretory products including proteases contribute to mechanical abrasion of biliary epithelium, while metabolites like oxysterols generate reactive oxygen species (ROS) that cause oxidative DNA damage, including single- and double-strand breaks in cholangiocytes. Similarly, Schistosoma haematobium eggs release antigens and catechol-estrogens that form DNA adducts in urothelial cells, promoting genotoxicity as evidenced by increased DNA migration in comet assays. Key molecules involved include ROS, which arise from parasite-derived oxysterols during infection and induce base modifications and strand breaks, facilitating mutagenesis. In O. viverrini infections, these processes are linked to mutations in oncogenes such as (approximately 17% frequency) and tumor suppressors such as TP53 (approximately 44% frequency in human cases) in induced cholangiocarcinomas. For S. haematobium, egg secretions directly cause chromosomal aberrations, such as breaks and instability in exfoliated urothelial cells, as observed in cytogenetic analyses of infected individuals. These genotoxic actions differ from host-mediated inflammatory damage by relying on parasite-specific molecules that bypass immune activation; for instance, S. haematobium egg antigens induce DNA adducts via estrogen-like pathways, driving cellular dysplasia without requiring cytokine involvement. In vitro studies further confirm this direct toxicity, where purified schistosome egg extracts elevate ROS levels and chromosomal instability in bladder cells, underscoring the parasites' role in initiating oncogenic transformations at the molecular level.

Confirmed Human Carcinogenic Parasites

Schistosoma haematobium

Schistosoma haematobium is a dioecious trematode belonging to the family , responsible for urogenital , also known as bilharziasis. Its complex life cycle requires an intermediate host, specifically freshwater snails of the genus Bulinus, and humans as the definitive host. Eggs excreted in infected human urine hatch in fresh water to release free-swimming miracidia, which penetrate the snail host and undergo to form sporocysts and then infective cercariae. These cercariae are released into the water, where they actively penetrate during contact with infested freshwater, such as during bathing, washing, or agricultural activities. Once inside the human host, the cercariae transform into schistosomula, migrate via the bloodstream to the venous plexuses surrounding the and pelvic organs, and mature into adult worms within 4-6 weeks. Paired adult worms (males and females) reside in these venules, where females produce 20-30 eggs daily that embed in the wall, causing granulomatous , or are passed in urine to continue the cycle. The parasite is endemic in 54 countries, primarily in and parts of the , where poor and reliance on contaminated water sources facilitate transmission. Globally, at least 253.8 million people required preventive treatment for in 2023, with over 90% of cases in , and S. haematobium accounts for the majority of urogenital infections, infecting an estimated 110 million individuals (as of 2022). Prevalence is highest among school-aged children and populations in rural, low-income communities, with infection rates exceeding 50% in some hyperendemic foci in countries like , , and . Chronic infections often begin in childhood and persist without treatment, leading to long-term morbidity including urinary tract obstruction and increased susceptibility to secondary infections. Chronic S. haematobium infection is a well-established risk factor for squamous cell carcinoma of the bladder (SCCB), particularly in endemic regions where it accounts for 30-75% of bladder cancer cases. The parasite's eggs induce persistent inflammation and epithelial metaplasia in the bladder mucosa, promoting neoplastic transformation over decades. Case-control studies in high-prevalence areas like Egypt and Iraq report odds ratios for bladder cancer ranging from 3- to 7-fold higher among individuals with a history of schistosomiasis compared to uninfected controls, even after adjusting for confounders such as age and occupation. For instance, in Alexandria, Egypt, the adjusted odds ratio was 1.72 for urinary schistosomiasis history, but broader reviews indicate higher risks (up to 10-fold) in heavily infected cohorts. Longitudinal observations in endemic populations show that individuals with long-standing, untreated infections develop bladder pathology such as granulomatous inflammation and fibrosis, with a small proportion progressing to SCCB after decades, with peak cancer incidence in the 40-60 age group and a male-to-female ratio of 5:1. Diagnosis of S. haematobium infection relies on detecting eggs in urine via microscopic examination, ideally using filtration methods on midday urine samples when egg shedding peaks. Visible or microscopic hematuria is a hallmark early symptom, present in up to 60% of infected individuals and detectable via urine dipsticks, particularly in children. In cases of suspected complications like fibrosis or malignancy, cystoscopy allows direct visualization of characteristic "sandy patches" or granulomas on the bladder wall, often confirmed by biopsy revealing viable or calcified eggs. Serological tests for antibodies or circulating anodic antigen can support diagnosis in low-burden infections but are less specific. Beyond environmental exposure to infested water, risk factors for severe disease and cancer progression include high infection intensity, malnutrition, and co-infections like , which exacerbate immune responses. Smoking acts as a significant co-carcinogen, with studies in showing synergistic effects that elevate odds ratios to over 4-fold in smokers with compared to non-smokers. Genetic polymorphisms in detoxification enzymes, such as NQO1 and , may further modulate susceptibility in infected populations. Early treatment can interrupt progression, but reinfection remains common without improved water hygiene.

Opisthorchis viverrini

Opisthorchis viverrini is a trematode , commonly known as the Southeast Asian , that infects the of humans and is classified as a by the International Agency for Research on Cancer due to its association with . The parasite's life cycle involves two intermediate hosts: the first is a (e.g., species) where eggs released in develop into miracidia, which hatch and penetrate the snail to form sporocysts and rediae, ultimately producing cercariae. These cercariae then encyst as metacercariae in the flesh of cyprinid , such as Puntius or Hampala species, serving as the second intermediate host. Humans acquire the infection primarily through the consumption of raw or undercooked fish containing metacercariae, a dietary practice prevalent in endemic areas of and , particularly dishes like pla som or koi pla. Once ingested, the metacercariae excyst in the and migrate to the bile ducts, where they mature into adult flukes within two months, residing for decades and releasing eggs that are excreted in feces to perpetuate the cycle. Epidemiologically, O. viverrini affects an estimated 8-10 million people across the lower Basin (as of 2021), with the highest in northeastern and parts of , where up to 70% of individuals in some communities may be infected. Longitudinal studies, such as those initiated in the 1980s in , , have tracked dynamics and associated outcomes, revealing persistent high burdens despite control efforts, with rates in surveyed cohorts declining from around 40-50% in the early 1980s to lower levels in recent decades but remaining a concern. These studies underscore the parasite's endemicity in rural communities reliant on River ecosystems, where environmental factors like flooding facilitate transmission. The infection is strongly linked to (CCA), a cancer, with meta-analyses estimating a 4- to 6-fold increased risk among infected individuals compared to uninfected controls. In , approximately 5,000 CCA cases annually are attributed to O. viverrini, representing a significant portion of the global burden in high-endemicity regions where incidence rates can exceed 100 per 100,000 person-years. This association arises from chronic biliary inflammation and oxidative damage induced by the parasite, mechanisms shared with other carcinogenic flukes like . Key risk modifiers for CCA development include the duration and intensity of ; adult flukes can persist for over 20 years, with typically manifesting 30-40 years post- in long-term cases. Higher infection intensity, measured as eggs per gram of (EPG), correlates with elevated risk, where individuals with >6,000 EPG face up to 14-fold greater odds of CCA compared to uninfected persons. These factors highlight the importance of early to mitigate cumulative exposure in endemic populations.

Clonorchis sinensis

Clonorchis sinensis, commonly known as the Chinese liver fluke, is a trematode parasite endemic to , particularly , , and northern Vietnam. Its life cycle mirrors that of other liver flukes like Opisthorchis species, involving freshwater snails as the first intermediate host where eggs hatch into miracidia, develop through sporocysts and rediae, and emerge as cercariae; these then encyst as metacercariae in the flesh of second intermediate hosts, primarily freshwater of the family. Unlike Opisthorchis viverrini, which has a more restricted host range, C. sinensis infects over 31 species of and , facilitating broader transmission in regions with diverse practices. Humans and other piscivorous mammals acquire the infection by consuming raw or undercooked infected , allowing the adult flukes to mature in the , where they can persist for decades. Epidemiologically, C. sinensis infects an estimated 12-15 million people worldwide (as of 2020), with over 85% of cases concentrated in , where prevalence exhibits urban-rural gradients driven by dietary habits and sanitation levels. In , infection rates are notably high in southern provinces such as and , with hotspots in the region, where surveys have documented prevalence exceeding 16% in some communities due to widespread consumption of raw . Rural areas often show higher burdens owing to traditional and undercooked meal preparation, though urban migration and market access contribute to sustained transmission in peri-urban zones. The International Agency for Research on Cancer (IARC) classifies chronic C. sinensis as , carcinogenic to humans, primarily due to its association with intrahepatic . The parasite's carcinogenicity manifests through a dose-response relationship, where higher worm burdens correlate with elevated risk of intrahepatic , as evidenced by epidemiological studies showing odds ratios increasing from 1.7 for light infections to over 14 for heavy burdens. Globally, nearly 5,000 cases of are attributed annually to C. sinensis infection, predominantly in East Asian endemic areas. Pathologically, adult flukes induce chronic mechanical irritation and inflammatory responses in the bile ducts, leading to periductal characterized by deposition and epithelial . This progresses to bile duct obstruction, causing stasis, recurrent cholangitis, and eventual of biliary .

Other Potential Carcinogenic Parasites

Indirect Mechanisms

Indirect mechanisms of carcinogenesis involve parasites that indirectly elevate cancer risk by modulating host immunity, facilitating co-infections with oncogenic agents, or inducing systemic physiological disruptions, rather than exerting direct genotoxic or inflammatory effects on tissues. These pathways often manifest in settings of chronic infection where the parasite compromises host defenses, allowing secondary oncogenic processes to dominate. A primary mechanism is , which enables viral oncogenesis by impairing the host's ability to control latent oncogenic viruses. For instance, chronic infection with the intestinal nematode can breach the gut mucosal barrier, facilitating enhanced transmission and proviral load of human T-lymphotropic virus type 1 (HTLV-1), a known oncogenic . This interaction increases the risk of HTLV-1-associated adult T-cell / (ATLL) in co-infected individuals, as the parasite-induced immune dysregulation—particularly reduced Th2 responses and activity—exacerbates HTLV-1 replication and progression to malignancy. Similarly, in HIV-infected hosts, parasitic co-infections such as those with Strongyloides or protozoans like amplify , heightening susceptibility to virus-driven cancers like or through synergistic CD4+ T-cell depletion and chronic immune activation. Observational studies in endemic regions, such as and , have documented associations between Strongyloides-HTLV-1 co-infection and HTLV-1-associated diseases. In HIV-parasite co-infections, studies from indicate higher parasite prevalence in patients with advanced (CD4+ ≤50 cells/mm³), though direct links to increased malignancies require further confirmation due to confounding factors like antiretroviral therapy access. Despite these associations, evidence for causality remains limited, with most data derived from epidemiological observations rather than mechanistic interventions. The International Agency for Research on Cancer (IARC) has not classified or similar parasites in this context as carcinogenic (, 2A, or 2B), reflecting insufficient direct evidence and challenges in isolating indirect effects from confounders like or concurrent infections. Further prospective studies are needed to delineate these pathways and inform preventive strategies in high-burden areas.

Putative Human Cases

Several parasites have been investigated for potential links to human cancers, though the evidence remains suggestive and inconclusive, warranting further epidemiological research. Toxoplasma gondii, a protozoan parasite affecting up to one-third of the global population, has shown associations with tumors, particularly , in multiple seroprevalence studies. A 2022 meta-analysis of case-control studies reported a pooled (OR) of 1.96 (95% CI, 1.37–2.80) for tumors among individuals with T. gondii exposure, indicating a modestly elevated , though factors like immune status could influence results. These findings stem from higher seropositivity rates in patients compared to controls, with prospective cohort data also suggesting a potential link, but causality has not been established due to the observational nature of the evidence. A 2023 case-control study in further supported this association, finding higher T. gondii seropositivity in patients (OR 2.0, 95% CI 1.1–3.6). Another candidate is , a trematode causing fascioliasis. Systematic reviews indicate strong experimental data in animal models demonstrating F. hepatica-induced liver and , with one report of (HCC) in cattle, yet no confirmed human epidemiological evidence links it to HCC or other cancers. For instance, a preliminary study in found negative for F. hepatica antibodies in all 13 tested HCC patients, highlighting the lack of direct associations in endemic areas. Overall, these parasites fall outside the International Agency for Research on Cancer (IARC) classifications for carcinogenicity ( or 2), placing them in Group 3 (not classifiable) or unevaluated, based on insufficient human data despite promising animal models. Researchers emphasize the need for large-scale cohort studies to clarify these associations, as current evidence relies heavily on designs prone to and low statistical power.

Carcinogenic Parasites in Animals

Veterinary Examples

In veterinary medicine, several parasites have been documented to induce cancers in domestic and wild animals through mechanisms such as chronic inflammation and tissue damage, paralleling pathways observed in human infections. One prominent example is Spirocerca lupi, a nematode that causes esophageal sarcomas in dogs, particularly in endemic regions like South Africa and Israel, where the parasite migrates to the esophageal wall, forming fibro-inflammatory nodules that can undergo malignant transformation into fibrosarcomas or osteosarcomas. Another case involves Heterakis gallinarum and related Heterakis species in poultry, such as chickens and pheasants, leading to cecal neoplasms including leiomyomas and fibrosarcomas; these arise from persistent nodular typhlitis in the ceca, with reports documenting 8–16 spontaneous cases in gallinaceous birds. Liver flukes like Clonorchis sinensis in cats and dogs similarly provoke cholangiocarcinomas by inducing chronic biliary inflammation and epithelial proliferation in the liver. Fasciola hepatica, a trematode affecting ruminants such as cattle and sheep, is also associated with cholangiocarcinoma through chronic cholangitis and fibrosis in the liver. Prevalence of these parasitic cancers is notably high in affected and populations within endemic areas; for instance, S. lupi infections show prevalences ranging from 10% to over 80% in dogs from endemic regions of , while C. sinensis affects a significant proportion of cats and dogs in subtropical southern , with rates exceeding 30% in reservoir hosts. In flocks, Heterakis infections are common, occurring in up to 20–50% of backyard or free-range birds in temperate climates, though neoplastic transformation remains rarer at around 1–5% of infected cases based on necropsy surveys. Diagnosis of these parasitic cancers often relies on necropsy findings, which reveal characteristic lesions such as esophageal nodules with parasitic remnants in S. lupi cases or cecal masses with embedded nematodes in Heterakis infections; histopathological examination confirms through evidence of and . Zoonotic risks are elevated for liver fluke-associated cancers, as C. sinensis transmits via contaminated fish to humans, posing a foodborne threat from infected domestic cats and dogs, whereas S. lupi and Heterakis present minimal direct risk due to host specificity. These conditions contribute to substantial economic losses in , estimated at billions annually from reduced productivity, including lower , decreased yield, and higher mortality in infected , sheep, and herds; for example, parasitic infections, including those from s, cause over $21 billion in global production losses annually, with infections estimated at $3 billion worldwide.

Comparative Oncology Insights

Comparative oncology reveals striking parallels in the carcinogenic mechanisms induced by parasites across humans and animals, particularly through chronic inflammation and that drive epithelial cell proliferation and DNA damage. In rodent models, such as hamsters infected with , the inflammatory response closely mimics human development, with elevated levels and tissue remodeling leading to bile duct and , providing a translational bridge for understanding human fluke-associated liver cancers. Similarly, excretory/secretory products from parasites like promote shared pathways of cellular transformation in both cats and humans, underscoring conserved host-parasite interactions that facilitate oncogenesis. Key differences highlight the utility of animal models while revealing limitations in direct extrapolation. Latency periods for tumor development are markedly shorter in animals—often months in for O. viverrini-induced compared to decades in humans—allowing accelerated study of disease progression but necessitating caution in interpreting long-term human risks. Species-specific susceptibilities further differentiate outcomes; for instance, hamsters exhibit high vulnerability to Opisthorchis due to robust inflammatory responses in the , whereas mice show resistance, reflecting variations in immune modulation that parallel human genetic diversities in endemic regions. These disparities emphasize the need for multi-species modeling to capture the spectrum of parasitic . Animal models offer substantial research value by enabling preclinical testing of interventions, such as the drug , which has demonstrated efficacy in reducing tumor burden in parasite-infected hosts. In O. viverrini-infected hamsters, administration prevents progression by eliminating adult worms and mitigating associated inflammation and fibrosis, informing dosing strategies for human prevention programs. Such models have been instrumental in evaluating drug impacts on precancerous lesions, accelerating the translation of therapies from veterinary to human . Zoonotic potential amplifies the relevance of comparative insights, as and domestic animal reservoirs sustain transmission cycles that pose emerging risks to human populations. For liver flukes like C. sinensis and O. viverrini, infections in cats and dogs serve as amplifiers, facilitating spillover to humans via contaminated aquatic environments, with studies in these models revealing how environmental factors exacerbate carcinogenic outcomes across species. This interconnected underscores the importance of approaches in surveilling and controlling parasite-driven cancers.

References

  1. https://pmc.ncbi.nlm.nih.gov/articles/PMC5233816/
  2. https://monographs.iarc.who.int/list-of-classifications/
  3. https://www.who.int/news-room/fact-sheets/detail/schistosomiasis
  4. https://publications.iarc.who.int/_publications/media/download/2056/8378c730bd7c5c5a781a1f592ba7f4449e44f219.pdf
  5. https://pmc.ncbi.nlm.nih.gov/articles/PMC10938900/
  6. https://www.parasite-journal.org/articles/parasite/full_html/2012/02/parasite2012192p101/parasite2012192p101.html
  7. https://monographs.iarc.who.int/agents-classified-by-the-iarc/
  8. https://monographs.iarc.who.int/wp-content/uploads/2019/07/Preamble-2019.pdf
  9. https://publications.iarc.who.int/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Schistosomes-Liver-Flukes-And-Em-Helicobacter-Pylori-Em--1994
  10. https://pmc.ncbi.nlm.nih.gov/articles/PMC6225400/
  11. https://publications.iarc.who.int/_publications/media/download/2061/fdd7b21a52b5d846c7f0436b2911bc5515689842.pdf
  12. https://www.ncbi.nlm.nih.gov/books/NBK487776/
  13. https://www.ncbi.nlm.nih.gov/books/NBK304354/
  14. https://pmc.ncbi.nlm.nih.gov/articles/PMC88908/
  15. https://www.nature.com/articles/s41572-021-00300-2
  16. https://pmc.ncbi.nlm.nih.gov/articles/PMC11668550/
  17. https://journals.lww.com/ctg/fulltext/2021/01000/association_of_chronic_opisthorchis_infestation.6.aspx
  18. https://parasitesandvectors.biomedcentral.com/articles/10.1186/1756-3305-3-60
  19. https://www.sciencedirect.com/science/article/abs/pii/S1089860304001132
  20. https://tdtmvjournal.biomedcentral.com/articles/10.1186/s40794-022-00161-x
  21. https://pmc.ncbi.nlm.nih.gov/articles/PMC10970119/
  22. https://pubmed.ncbi.nlm.nih.gov/8180954/
  23. https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.13-232751
  24. https://doi.org/10.1016/j.mrfmmm.2011.10.009
  25. https://doi.org/10.1016/j.ijpara.2012.10.023
  26. https://pubmed.ncbi.nlm.nih.gov/22553348/
  27. https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.2910500407
  28. https://pmc.ncbi.nlm.nih.gov/articles/PMC12406355/
  29. https://www.cdc.gov/dpdx/schistosomiasis/index.html
  30. https://pmc.ncbi.nlm.nih.gov/articles/PMC6658823/
  31. https://journals.asm.org/doi/10.1128/cmr.12.1.97
  32. https://pmc.ncbi.nlm.nih.gov/articles/PMC11097794/
  33. https://www.who.int/data/gho/data/themes/topics/schistosomiasis
  34. https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0012456
  35. https://pubmed.ncbi.nlm.nih.gov/9569060/
  36. https://www.nature.com/articles/bjc1998197
  37. https://www.cancercontrol.info/cc2016/is-stoping-schistosoma-haematobium-associated-bladder-cancer-a-feasible-goal/
  38. https://www.cdc.gov/schistosomiasis/hcp/diagnosis-testing/index.html
  39. https://emedicine.medscape.com/article/228392-workup
  40. https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2018.00223/full
  41. https://pubmed.ncbi.nlm.nih.gov/24035474/
  42. https://pmc.ncbi.nlm.nih.gov/articles/PMC2635548/
  43. https://www.sciencedirect.com/science/article/pii/S2352771425000424
  44. https://pmc.ncbi.nlm.nih.gov/articles/PMC5956617/
  45. https://elifesciences.org/articles/59755
  46. https://www.sciencedirect.com/science/article/pii/S1471492220303627
  47. https://www.cell.com/trends/parasitology/fulltext/S1471-4922%2820%2930362-7
  48. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X%2816%2930301-1/fulltext
  49. https://pmc.ncbi.nlm.nih.gov/articles/PMC3682777/
  50. https://pmc.ncbi.nlm.nih.gov/articles/PMC3739706/
  51. https://pmc.ncbi.nlm.nih.gov/articles/PMC3010517/
  52. https://www.mdpi.com/2414-6366/7/10/313
  53. https://www.sciencedirect.com/science/article/pii/S1876034120304950
  54. https://www.ncbi.nlm.nih.gov/books/NBK532892/
  55. https://www.journalofinfection.com/article/S0163-4453(25)00122-7/fulltext
  56. https://pubmed.ncbi.nlm.nih.gov/20549239/
  57. https://etd.ohiolink.edu/acprod/odb_etd/ws/send_file/send?accession=osu1366378549&disposition=inline
  58. https://idpjournal.biomedcentral.com/articles/10.1186/2049-9957-1-4
  59. https://pmc.ncbi.nlm.nih.gov/articles/PMC9627039/
  60. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02579/full
  61. https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.832430/full
  62. https://www.mdpi.com/2076-0817/9/11/904
  63. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091452
  64. https://pubmed.ncbi.nlm.nih.gov/35152168/
  65. https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.33443
  66. https://pmc.ncbi.nlm.nih.gov/articles/PMC10182190/
  67. https://pmc.ncbi.nlm.nih.gov/articles/PMC5040415/
  68. https://pubmed.ncbi.nlm.nih.gov/29768560/
  69. https://www.researchgate.net/publication/306079987_Association_of_Fasciola_hepatica_Infection_with_Liver_Fibrosis_Cirrhosis_and_Cancer_A_Systematic_Review
  70. https://doi.org/10.1016/j.vetpar.2019.108935
  71. https://pmc.ncbi.nlm.nih.gov/articles/PMC10373346/
  72. https://doi.org/10.1007/s00261-004-0193-4
  73. https://monographs.iarc.who.int/wp-content/uploads/2018/06/mono100B-11.pdf
  74. https://pmc.ncbi.nlm.nih.gov/articles/PMC4000364/
  75. https://doi.org/10.1186/1756-3305-4-180
  76. https://www.merck-animal-health.com/blog/2024/05/21/merck-animal-health-the-global-economic-impact-of-parasites-in-cattle/
  77. https://www.mdpi.com/2076-2615/13/10/1599
  78. https://pmc.ncbi.nlm.nih.gov/articles/PMC10215612/
  79. https://doi.org/10.1186/s13027-023-00522-x
  80. https://pmc.ncbi.nlm.nih.gov/articles/PMC7796817/
Add your contribution
Related Hubs
User Avatar
No comments yet.