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Wildlife cancer: a conservation perspective

A Corrigendum to this article was published on 01 August 2009

This article has been updated


Until recently, cancer in wildlife was not considered to be a conservation concern. However, with the identification of Tasmanian devil facial tumour disease, sea turtle fibropapillomatosis and sea lion genital carcinoma, it has become apparent that neoplasia can be highly prevalent and have considerable effects on some species. It is also clear that anthropogenic activities contribute to the development of neoplasia in wildlife species, such as beluga whales and bottom-dwelling fish, making them sensitive sentinels of disturbed environments.


Cancer is an important cause of morbidity and mortality in several wildlife species. Virus-associated, carcinogen-related and novel transmissible tumours currently impact threatened and protected species. Cancer can affect conservation outcomes by reducing reproductive success, altering population dynamics (see Glossary) or directly or indirectly leading to population declines. In one species, the Tasmanian devil (Sarcophilus harisii), high cancer incidence threatens the species with extinction.

The links between animal and human health and scientific discovery are long standing. Viral oncogenesis is a familiar concept in both animal and human fields of medicine, and the study of animal viruses has led to important insights into the molecular basis of cancer. Discovering the transmissible effects of the Rous chicken sarcoma virus in 1911 (Ref. 1) led to the eventual identification of the SRC oncogene and its role in human cancer. Identification of the Ras oncogene originated from studies of murine leukaemia virus2 and our understanding of the crucial role Wnt signalling pathways have in carcinogenesis resulted from studies of mouse mammary tumour virus3. It is likely that animals, including wildlife, will continue to contribute to our understanding of cancer biology in the future. Novel allograft tumours in Tasmanian devils and dogs may influence the development of beneficial animal and human cancer immunotherapies, and wildlife that develop cancer from anthropogenic factors will continue to act as sentinels for animal and human health risks. What is learned about cancer through wildlife health monitoring will affect conservation of animals and wild places and affect human health, consistent with the One World, One Health concept (One World, One Health is a registered trademark of the Wildlife Conservation Society)4.

Cancer detection and prevalence

Cancer is a major cause of death in humans. The World Health Organization estimated that in 2007, 7.9 million human deaths globally (approximately 13% of the total number of deaths) were due to cancer5. However, despite its high incidence, cancer as a cause for human extinction is unlikely to warrant much consideration. Until recently, the same could have been said for most wildlife species. In the few surveys that summarized wildlife mortality data, trauma and starvation were most frequently reported as causes of death6,7. However, over the past few decades wildlife health monitoring has increased and we are now gaining an improved — and occasionally alarming — perspective about the presence and impact of cancer in endangered species, such as the Tasmanian devil, western barred bandicoot (Perameles bougainville) and Attwater's prairie chicken (Tympanuchus cupido Attwateri), and non-endangered species, such as the beluga whale (Delphinapterus leucas).

Evaluating health and diagnosing disease in wild animal populations poses several challenges. As in human medicine, data and sample collection in wildlife is performed by networks of professionals and non-professionals across many disciplines, including veterinarians, veterinary pathologists, biologists, epidemiologists and citizens in field stations, universities, zoos and communities. Access to live or deceased animals and sample collection can be complicated by environmental obstacles, such as thick jungle or wide dispersal of animals across oceans and vast savannahs, species-specific adaptations, such as flight, or tissue loss through environmental decomposition, predation or post-mortem scavenging. Cancer in wildlife is most commonly detected during post-mortem examination with confirmation through histopathology. Advanced cancer diagnostics, such as computed tomography and magnetic resonance imaging that are available for cancer detection and identification in humans are generally not accessible or are unavailable for wildlife. Techniques such as immunohistochemical staining are of value but have limited applicability in wildlife owing to the species-specific nature of protein targets and consequently the antibodies required for detection. Most animal cancer detection resources and the best developed networks exist in the companion animal and agriculture sectors. Relatively limited resources, human or financial, are dedicated to consistent or widespread wildlife health monitoring and disease diagnostics. For these reasons and those listed above, cancer in wildlife goes largely undetected.

Establishing cancer prevalence is important if we are to understand the effect of cancer in wildlife species and its importance to conservation. However, determining valid cancer prevalence (or prevalence of any disease in wildlife) is not often achieved. Most wild animals live and die in anonymity without being documented in census data, without baseline health information or without the causes of morbidity and mortality ever being determined or recorded. An exception to this general rule are small, geographically isolated populations, such as the critically endangered island fox (Urocyon littoralis), for which population size and animal health can be feasibly monitored and valid disease prevalence can be established8. It is more common to determine disease prevalence relative to a sampled group. For example, beluga whales inhabit arctic and subarctic waters along the coasts of Alaska, Canada, Greenland and Russia. The southernmost extent of the range includes an isolated population in the St Lawrence river estuary (SLE) where population and health monitoring have been ongoing for 17 years9. In this population, cancer was the second leading cause of death overall (accounting for 18% of mortalities) with tumours identified in 27% of adult animals found dead9, a rate that is strikingly similar to that found in humans, in whom cancer is the second leading cause of mortality in the United States and accounts for 22.9% of all deaths5. In this case, cancer prevalence was determined for the local population rather than the species. As the SLE beluga whales are a well-characterized group, accurate data for epidemiological modelling can be applied to the local population; similar disease prevalence and epidemiological investigations can be performed in captive collections of animals (Box 1). In less well monitored or more dispersed populations, disease prevalence is often estimated from retrospective information in the absence of accurate population data, and in many cases small numbers of animals are assumed to be representative of the species as a whole, a situation that may or may not be accurate.

In wildlife with cancer, the focus is generally not on treatment but rather is directed at understanding tumour biology, prevention and intervention strategies in spontaneous tumours, as well as efforts to affect conservation policy or introduce mandatory environmental abatement in anthropogenically induced tumours. Research and resources for investigating wildlife cancer are extremely limited and successful outcomes for wildlife are more likely for tumours arising in association with anthropogenic activities and interventions that also affect humans. In one notable exception, intense activity is currently focused on Tasmanian devils, in which a spontaneous transmissible tumour is spreading to epidemic proportions resulting in devastating effects on the population. In this case, efforts are underway to manage the remaining animals and develop conservation strategies without which species extinction is predicted.

Transmissible allograft cancers

The Tasmanian devil survives only on the island state of Tasmania, Australia, and is threatened by extinction owing to a contagious cancer, devil facial tumour disease (DFTD)10,11,12,13. It presents as a focal or multicentric neuroendocrine tumour14,15 that generally affects the face and neck and progresses to cause considerable soft tissue disfigurement; metastasis, most commonly to regional lymph nodes or the lungs, occurs in up to 65% of the animals14. Complications associated with tumour growth or metastasis result in a mortality rate of 100% in affected animals. In the early 1990s, Tasmanian devils were considered to be common and the Tasmanian devil population was estimated at 150,000 individuals12; however, since its first observation in 1996 (Refs 13, 16), DFTD has decimated the Tasmanian devil population12 resulting in a population decline of 53%11 and the listing of the Tasmanian devil as an endangered species by the International Union for the Conservation of Nature and Natural Resources (IUCN) in 2008. Current disease modelling predicts declines of 90% across 60% of territories with diseased Tasmanian devils and a 70% reduction of the entire population over the next 10 years12,17,18. At these rates, extinction is a real possibility.

Evidence supports a novel mechanism of DFTD persistence and spread within the population: allograft transmission. Although initial transmission trials are not yet published, transplantation of cultured DFTD cells and surgically implanted tumour tissue has produced tumours in unaffected Tasmanian devils18. Further evidence supporting the allograft theory includes failure to identify pathogens (such as a virus) using routine light and electron microscopy14 Additionally, in all animals studied, karyotype analysis shows 13 rather than 14 chromosomes and consistent genetic aberrations, including loss of both sex chromosomes, no copies of chromosome 2, loss of 1 copy of chromosome 6 and the addition of 4 unidentified marker chromosomes (M1–M4) in tumour cells compared with host cells19. Furthermore, evaluation of multiple microsatellite and major histocompatibility complex (MHC) loci has confirmed genotypes that are identical in Tasmanian devil tumours but differ from their hosts, consistent with an exogenous tumour source20. Despite having a competent immune system21,22,23, ease of tumour spread is thought to be related to low MHC class I diversity and limited cell-mediated immunological reaction and activation (rather than the failure of immune cells to proliferate) to tumour cells in Tasmanian devils12,14,20.

Canine transmissible venereal sarcoma (CTVS) is the only other cancer in wildlife known to be naturally transmitted through an allograft24; the unintentional transfer of undiagnosed neoplastic cells through organ transplantation is the only comparison in humans25,26,27 CTVS was first described and transmitted between dogs in 1876 by Novinski (reviewed in Ref. 24). It is a histiocytic tumour28 that generally affects the external genital mucosa of sexually active dogs and is transmitted during breeding and the licking or sniffing of affected tissue24,29,30. The tumour is locally extensive more often than metastatic and in many animals it regresses within several months; morbidity rather than mortality is therefore more common in CTVS. The tumour is present in free-ranging dogs worldwide and is most prevalent in tropical and subtropical countries29. CTVS is thought to have developed in a wolf (Canis lupus) or East Asian breed of dog 200 to 2,500 years ago24,29,30,31, and on the basis of genetic markers, Murgia et al. suggest that CTVS arose from a single common ancestral neoplastic clone that subsequently diverged into the two current genetically distinct tumour subtypes that exist in dogs today24.

Similarly to DFTD, experimental studies have confirmed that CTVS is a clonal cell allograft. Supporting evidence includes transmission trials32, common specific chromosomal anomalies, such as tumour markers (in particular the long interspersed nuclear element insertion near MYC24,31), and genetic comparisons of the MHC, microsatellites and mitochondrial DNA between tumour and host cells24. Impaired differentiation of dendritic cells, downregulation of classical MHC class I and absence of MHC class II24,33,34 (rather than low MHC diversity as in DFTD) are recognized as factors in host immune system evasion and successful transmission and progression in CTVS24,27,34. Circulating anti-tumour antibodies in affected dogs are implicated in natural tumour regression16,32, which if complete is associated with subsequent resistance29,32. Recent scientific interest in characterizing immunological reactions between the tumour and host, including the role of tumour and host cytokine expression, such as transforming growth factor-β1 (TGF-β1), interleukin-6 and interferon-γ, in this unique canine tumour includes consideration of the potential applicability of CTVS as an in vivo model for developing cancer immunotherapies in humans34,35.

Genetic diversity is a common topic of discussion and scientific debate in the conservation community. Low MHC diversity is implicated as a factor in disease susceptibility owing to its crucial role in immune system surveillance and resistance to infectious disease; it is of special concern in endangered species, such as the cheetah (Acinonyx jubatus). Low MHC diversity is thought to be important to the high susceptibility of cheetahs to infectious diseases, such as feline coronavirus36 and the unusually high acceptance of tissue allografts between cheetahs37. Low MHC diversity has been implicated in DFTD transmission and may have been important in the early development of CTVS24.

Current evidence and disease modelling suggest that transmission of DFTD and CTVS occurs in a frequency-dependent10,11,38,39 rather than a density-dependent manner. In frequency-dependent disease transmission models, transmission rate depends on the frequency of contact with an infected host and is independent of population size (for example, human sexually transmitted diseases are often modelled in this manner). If the modelling is correct, DFTD could therefore lead to the extinction of the Tasmanian devil despite its decreasing population density. In classical density-dependent disease transmission models (commonly applied to infectious diseases, such as measles or influenza) there is a population threshold below which disease is not maintained in the host40,41 and in which disease disappears in the absence of alternative disease reservoirs. Recent modelling by Hilker et al.42 suggests that there are certain conditions under which density-dependent disease transmission could lead to extinction in the absence of reservoirs, such as when there is a strong allee effect42 as is proposed in the predator–prey relationship between golden eagles and the critically endangered island fox43. If DFTD transmission were density rather than frequency dependent, extinction could also potentially occur under certain density-dependent conditions.

DFTD is incurable and unpreventable. In an effort to avoid species extinction, scientists and conservationists are considering establishing isolated assurance colonies of tumour-free animals in geographically restricted areas in Tasmania or zoos to guard against ongoing population declines44 while preventive therapies are developed and tested. It is a race against time to ensure the survival of the Tasmanian devil. As the population loses ground to the disease, the Tasmanian devil's crucial role as the top carnivorous marsupial in the Tasmanian ecosystem and its survival will be challenged by native predators, such as the spotted-tail quoll (Dasyurus maculates) and Eastern quoll (Dasyurus viverrinus), as well as introduced species, such as the fox and domestic cat (Felis catus)44. If efforts fail and the Tasmanian devil disappears, the Tasmanian devil's role in the Tasmanian ecosystem and its contribution to biodiversity will be lost forever and DFTD will represent the first known instance of a contagious cancer causing the extinction of a species.

Virus-associated tumorigenesis

The biology of DFTD and its devastating and rapid effects on the Tasmanian devil population are unique regardless of species. More commonly recognized mechanisms of tumorigenesis in both animals and humans include mutations of proto-oncogenes involved in cell cycle regulation, signal transduction and tumour suppression (such as Ras, Wnt or p53) or the effects of viral oncogenes, such as SRC. The effects and implications of oncogenic viruses and mechanisms of tumorigenesis in most wildlife species are poorly understood; however, in some species these issues and the consequences for conservation are in the process of being elucidated.

Attwater's prairie chickens and western barred bandicoots are endangered largely because of habitat destruction45,46 and, in the case of the bandicoot, introduced predators such as foxes (Vulpes vulpes) and domestic cats46. Wild Attwater's prairie chicken populations totalled less than 100 by the mid 1990s47 and fewer than several thousand western barred bandicoots are thought to survive today48. Captive breeding programmes in both species were established in the 1990s but have been hampered by cancer-causing oncogenic viruses.

Reticuloendotheliosis viruses (REVs), a group of avian gammaretroviruses that are similar to mammalian type C retroviruses47,49, are associated with lymphomas in Attwater's prairie chickens. REVs have been isolated from Attwater's prairie chickens at every captive breeding facility50. Natural infection most often causes runting, immunosuppression or a non-neoplastic syndrome associated with high mortality in young birds and B or T cell lymphomas inadults. Experimental infection with REV APC-566 is oncogenic in Japanese quail (Coturnix coturnix japonica) and specific pathogen-free chickens and turkeys, causing cancer (primarily lymphoma) as early as 6 weeks after hatching in inoculated quail embryos and 58 days and 13 weeks post-inoculation in domestic chickens and turkeys, respectively49. Infected Attwater's prairie chickens can be chronically and significantly infected and appear to be clinically healthy for months before disease expression, acting as reservoirs for virus replication and transmission to susceptible birds50.

Western barred bandicoots infected with bandicoot papillomatosis carcinomatosis virus type 1 (BPCV1), a novel oncogenic virus that contains genetic material from both papilloma and polyoma viruses, develop cutaneous and mucocutaneous hyperplasias, as well as papillomas, some of which undergo malignant transformation to squamous cell carcinoma51,52. In a review of 42 western barred bandicoots with lesions, hyperplasias (71%), carcinomas in situ (41%) and squamous cell carcinoma (48%) were all common, as was the presence of concurrent benign and malignant lesions in individuals (36%)52. Histologically, positive indirect immunohistochemistry for conserved papillomavirus capsid antigens and identification of viral crystalline arrays in affected keratinocyte nuclei with transmission electron microscopy support a causal relationship between the virus and tumour development52.

Virus-associated debilitation and tumour-associated death in REV- and BPCV1-infected Attwater's prairie chickens and western barred bandicoots, respectively, have led to limited population growth and are a risk to the survival of each species. The potential for disease transmission from captive to free-ranging remnant populations has implications for release and reintroduction efforts. Unlike the situation for Attwater's prairie chickens and western barred bandicoots, confirming the effect of virus-associated neoplasia in most wildlife species is often much more challenging. For example, in the marine environment, increases in spontaneous benign and malignant tumours have been identified over the past two decades41,53,54,55,56. Several viruses seem to have a role in the formation of these tumours but causal relationships remain to be confirmed, and understanding short- and long-term population effects will require ongoing and expanded monitoring.

Green turtles (Chelonia mydas) around the globe are dying from herpes-associated fibropapillomatosis6,54,55,56,57. These turtles are listed by the IUCN as endangered owing to several factors, including habitat disturbance or destruction, over-harvesting of animals and eggs, boat strike and entanglementin fishing nets that lack turtle excluder devices. In some parts of their range fibropapillomatosis-associated death is now also considered to be a contributing factor to overall population decline. In well-monitored populations, such as those along the coasts of Florida and the Caribbean and Hawaiian Islands, fibropapillomatosis is thought to be an epidemic55,58 and dramatic increases in prevalence of as much as 92% since the early 1980s have been observed56,59. Given its global distribution, some have suggested that the disease probably reflects a worldwide panzootic54,55,58. Fibropapillomatosis is most commonly observed in green turtles but has been described for all sea turtle species, including the critically endangered leatherback (Dermochelys coriacea)60, Kemp's ridley (Lepidochelys kempii)61, and hawksbill (Eretmochelys imbricata)62 turtles.

Fibropapillomatosis in sea turtles is characterized by benign nodular to papilliferous, fibropapillomas and fibromas rather than fibrosarcomas (which are observed but with less frequency)63. Tumours generally arise in the dermis but can be found in internal organs, such as the lung, liver, kidney and heart. Tumours in non-cutaneous sites may reflect metastasis from primary cutaneous tumours or multicentric development that is secondary to systemic virus dissemination, as the virus has been detected with real-time PCR in tumours in cutaneous and non-cutaneous sites63,64. Herpes viral inclusions are seen with variable frequency in tumour epithelium55,63,65. Debilitation and death from fibropapillomatosis occurs when tumour growth interferes with crucial functions such as feeding, sight and mobility.

The cause, environmental persistence and mode of natural transmission, as well as the cofactors and mechanisms of tumorigenicity of marine turtle fibropapillomatosis, are under investigation. Transmission studies and consensus in the scientific community favours a new chelonian alpha herpesvirus as its cause66,67. Viral DNA is consistently found in tumours and tissues of tumour-bearing animals64 and inoculation of fibroblasts from turtle fibropapillomas has produced fibromas in immunodeficient mice68. However, to date this new turtle virus has not been cultured and Koch's postulates have not yet been demonstrated. Limited experiments on two cultured sea turtle herpesviruses, lung–eye–trachea disease virus and HV2245, have established that both can persist and retain their infectivity outside the host in the marine environment for up to 120 hours69. If fibropapilloma-associated turtle herpesvirus behaves similarly, environmental persistence could be important in natural disease transmission, especially in areas of high turtle density. Other factors that could contribute to viral persistence and spread include mechanical vectors, such as leeches, which have been shown to carry sufficient viral loads (up to 10 million copies) to be a potential vector70.

Virus-associated papillomas and carcinomas are also described in several marine cetacean and sirenian species in free-ranging and managed populations (Table 1). In wildlife, tumours of the genital tract are important if they interfere with successful breeding, pregnancy or parturition. In one study, benign genital papillomas were present in 66.7% of dusky dolphins and 48.5% of Burmeister's porpoises71, and were considered important enough to interfere with copulation in 10% of Burmeister's porpoises71,72.

Table 1 Examples of oncogenic viruses in humans and wildlife

Genital tract carcinoma is an emerging disease in California sea lions. Before the early 1980s, malignant tumours of any type were only rarely reported in pinnipeds41,73,74. However, from 1979 to 1994, 18% of sexually mature sea lions that were found stranded along the Californian coast and died during rehabilitation had histologically aggressive, widely metastatic genital transitional cell carcinomas75. In a subsequent report, 6.3% of California sea lions that died during a series of unusual mortality events caused by harmful algal blooms from May to October, 1998, had benign or malignant genital tumours53.

Otarine herpesvirus-1 is the putative cause of genital carcinoma in California sea lions76,77. This virus is consistently found in tumours examined by electron microscopy or immunohistochemical staining and by PCR of the viral DNA polymerase and terminase genes76,77,78. Otarine herpesvirus-1 is a gammaherpesvirus in the genus Rhadinovirus and is closely related to human herpesvirus-8 (Ref. 76), the causative agent of Kaposi's sarcoma79,80. Interestingly, papillomaviruses cause cervical cancer in women, and human papillomaviruses 16 and 18 are considered to be high risk for the development of malignant cancer81,82. Surprisingly, no papillomaviruses have been detected in sea lion or other marine mammal genital tract carcinomas78,77.

The high prevalence of genital tract carcinomas in California sea lions is unprecedented in any pinniped species. Despite apparently increasing cancer prevalence, tumours have not been associated with changes in population growth, which from 1975 to 2005 has been increasing at an annual rate of approximately 5.6% per year83. Continued monitoring will be essential to determine long-term population effects, identify causes for high prevalence and establish potential environmental cofactors that initiate or promote tumour development.

Cancer is a multifactorial disease. In the domestic cow infection with bovine papillomavirus 4 (the cause of oesophageal and rumenal papillomas) and exposure to ptaquiloside (a natural carcinogen in bracken fern) results in the malignant transformation of papillomas to squamous cell carcinoma84. A similar interplay may occur between viruses and chemical cofactors in sea turtle fibropapillomatosis (that is, increased incidence of fibropapillomatosis in sea turtles in polluted bodies of water)59,85 or sea lion genital cancer: an 85% higher level of polychlorinated biphenyls is found in the blubber of sea lions with genital carcinoma relative to those without genital carcinoma86. Systematic studies assessing the potential direct or indirect roles of these contaminants in tumour development have not been performed. However, the above examples suggest that in some wild populations, carcinogenesis reflects the combined effects of multiple factors, potentially including those from the local environment.

Environmental effects

High cancer incidence is reported in wildlife populations in environments that are heavily contaminated with anthropogenic chemicals. Fish living in industrialized waterways suffer epizootics of liver and skin cancer87,88,89,90. In the population of beluga whales living in the SLE, an environment that receives effluent from aluminium smelting facilities91, cancer is the second leading cause of death9. Although several industrial and agricultural pollutants have been recovered from the estuary, polycyclic aromatic hydrocarbons (PAHs) are a major concern, as they are recognized occupational hazards and human carcinogens92,93,94,95. Causal relationships between wildlife cancers and contaminant exposure are receiving increased attention owing to risks for both wildlife and humans.

Cancer epizootics have been recognized in many species of fresh water, marine and estuarine fish. The most intensively studied epizootics have occurred in industrialized areas of the United States and Canada, such as the Great Lakes tributaries, including locations considered to be areas of concern (Box 2), Puget Sound harbours and bays of the East coast of the United States. These environments are all contaminated by PAHs released from steel mills, creosote production plants and petroleum facilities87,88,96,97. Epizootic tumours reported in these areas include hepatocellular adenomas, hepatocellular carcinomas, cholangiomas and cholangiocellular carcinomas in brown bullhead catfish (Ictalurus nebulosus)98 and English sole (Parophrys vetulus)87,88, epidermal and oral papillomas in brown bullheads and white sucker fish (Catostomus commersoni)89, and (rarely) squamous cell carcinomas and melanomas in brown bullhead catfish90,99. Most affected species are bottom feeders, which suggests that a benthic lifestyle contributes to high cancer incidence through chronic exposure to contaminated sediment and consumption of contaminated invertebrates. PAH profiles from species experiencing epizootic cancer support this theory, as they reflect the PAH compounds found in the food items and compound profiles of the sediment in their habitats87,88,100.

Support for causal relationships between environmental pollutant exposure and cancer in fish has been experimental and observational. Fish laboratory models have demonstrated that dietary and intraperitoneal exposure to the PAH benzo[a]pyrene (BaP) produces hepatocellular or biliary tumours101. Additionally, skin and liver tumours have been induced by exposure to extracts prepared from PAH-contaminated sediment. In one experiment, extracts from environmental sediment samples were painted onto the skin of brown bullhead catfish and this resulted in a 38% increased incidence of skin tumours over 2 years102. In a similar study with the same extract, dietary exposure resulted in both biliary and hepatocellular tumours102. Striking causal associations have also been made when environmental contamination decreased following closure of industrial facilities along affected waterways. For example, the prevalence of hepatocellular carcinoma in adult brown bullhead catfish living in the Black River, Ohio, United States, ranged from 22% to 39% in the early 1980s103. At that time, age-selective mortality owing to the high cancer prevalence nearly eliminated fish older than 5 years from the population104. Following a downturn in the steel industry, the coking facility located along the river closed in 1983. PAH levels in the sediment declined from 1,000 μg per g in 1980 to 4 μg per g in 1987. During that time, the incidence of liver cancer in brown bullhead catfish decreased by 75% and the percentage of 5-year-old fish in the population tripled103.

Cancer is rarely reported in wild or captive cetaceans, and the literature consists predominantly of single cases of lymphoma, leukaemias and a wide range of other neoplasms (for example, granulosa cell tumours, seminomas, and cholangio, renal, squamous and anaplastic carcinomas)9,105,106. However, beluga whales in the SLE exhibit a high rate of cancer. Small intestinal adenocarcinoma is the most frequent malignancy seen in SLE belugas, in contrast to that observed in other cetaceans9,107,108. Additionally, among marine mammals, mammary carcinoma has been reported only in SLE beluga whales9,109. Industrial and agricultural environmental contaminants have been identified in the SLE110,111,112,113,114. High concentrations of BaP have also been documented in SLE tissue samples, and the concentrations of polychlorinated biphenyls, dichlorodiphenyl trichloroethane, mirex, mercury and lead are much higher in beluga whales from the SLE than those living in the Arctic107,111,112. After a decline in the population owing to hunting pressures, the SLE beluga whales received endangered species status from the Canadian government in 1980, but since that time there has been no evidence of population recovery9,115. Comparative mortality data from the isolated SLE beluga whales and a population of beluga whales in a less contaminated environment in northwest Alaska indicate that beluga whales from the SLE die at an earlier age, in part owing to the high rate of cancer9,116.

High environmental levels of BaP are proposed as an important factor in tumorigenesis in SLE beluga whales; however, this idea is contentious and the role of these agents is under active investigation. BaP is a potent procarcinogen, and the site of metabolism and carcinogenesis depends on the route of exposure117,118,119. Mice chronically exposed to oral BaP develop small intestinal adenocarcinomas, gastric carcinoma and papillomas of the squamous portion of the stomach120,121. High environmental levels of BaP in the SLE, known human carcinogenicity and evidence from animal models has led to the theory that oral BaP exposure in beluga whales has a role in their high incidence of intestinal cancer.

The proposed source of exposure to BaP in SLE beluga whales is ingestion. Beluga whales dredge the sediment, feeding on large numbers of invertebrates, animals known to bioaccumulate BaP122,123. Blue mussels in the Saguenay River portion of the SLE beluga whale habitat contain BaP levels that are 200 times higher than in blue mussels in adjacent habitats124. PAH exposure induces cytochrome P450 1A1 (CYP1A1) expression in hepatic and extrahepatic tissues and CYP1A1 can serve as a biomarker for PAH exposure. SLE beluga whales show increased CYP1A1 expression in multiple organs (including the liver, lung, urinary bladder and testis), which is consistent with systemic PAH exposure and metabolism117,125. CYP1A1 activates PAHs into carcinogenic metabolites, and in animal models the proximal small intestine contains the highest concentrations of CYP1A1 (Ref. 126). Therefore, in SLE beluga whales it has been suggested that ingested BaP induces small intestinal enzyme activity, resulting in the high incidence of intestinal neoplasia observed9 (Fig. 1).

Figure 1: Proposed mechanism of BaP small intestinal carcinogenesis in beluga whales.

Environmental exposure to the procarcinogen benzo[a]pyrene (BaP) is thought to have a role in the high incidence of small intestinal neoplasia in beluga whales in the St Lawrence River Estuary. The proposed mechanism involves intestinal exposure through ingestion of contaminated prey items and sediment followed by induction of cytochrome P450 1A1 (CYP1A1) in small intestinal epithelial cells. CYP1A1 is responsible for oxidation and metabolism of BaP to the carcinogen (BaP 7,8 diol 9,10 epoxide). The activated carcinogen preferentially binds DNA at the exocyclic nitrogen of the guanine residue, which is required for base pairing, resulting in the potential for G → T transversion during DNA replication and disruption of tumour suppressors or proto-oncogenes.

Relationships between tumour development and environmental contamination are strongly suggested by scientific data and circumstantial evidence from wildlife studies. Tumour epizootics in fish and the high cancer rate in the SLE beluga whale population are important indicators of ecosystem health. Care and caution must be applied to the selection of tumours used as environmental indicators. Some epizootic cancers are solely viral (Table 1) or genetic in origin and therefore would not serve as appropriate indicators of environmental contamination. For example, spontaneous nephroblastomas of Japanese eels (Anguilla japonica) contain a mutant gene with a high level of homology to the human Wilm's tumour suppressor (WT1) gene127. Therefore, only certain tumours can be indicators of environmental contamination and ecosystem health. Similarities of high cancer incidence and tumour type between species support the conclusion of common risk factors in shared environments and show the value of wildlife populations as important indicators of environmental discord.

Conclusion and future directions

Wildlife cancer reveals itself as a series of challenges and opportunities for conservation. The above examples include cases in which cancer has limited population growth or has caused population declines through the novel mechanism of allograft transmission, viral oncogenesis and the effects of carcinogenic environmental contaminants. However, the list of examples is short and a more complete understanding of the role of tumours in wildlife population dynamics and the individual and interactive factors that drive tumorigenesis across a wide range of wildlife species is lacking but necessary.

Health monitoring, disease surveillance and scientific inquiry focused on understanding basic biology and interactive factors in wildlife cancer are crucial to our understanding of wildlife health, the role of cancer in wildlife populations and our ability to identify, assess and mitigate the risks for disease development in wildlife populations. Key elements for improving current limitations that exist in each of these key activities include identifying, coordinating and expanding existing surveillance networks; increasing and developing capacity for disease diagnostics and epidemiology; securing increased funding for multi-disciplinary scientific research and training aimed at identifying the complex mechanisms involved in wildlife tumorigenesis; integrating human and animal health surveillance systems; creating a unified animal and environmental health database; and improving current relationships, as well as establishing new collaborative relationships with stakeholders and policy makers. Expanding the range and scope of each of these activities will have broad and direct benefits for wildlife and also potentially for the environment and humans. Early recognition of cancer epizootics in wildlife has the potential to drive timely environmental mitigation and influence environmental policy. Building capacity and leveraging expertise across disciplines will result in expanded opportunities for advancing our understanding of normal cellular processes and mechanisms of carcinogenesis as has occurred historically in investigations of wildlife cancer. As we look to the future, there is tremendous opportunity for achieving imagined advances in our understanding of wildlife health, contributing to the protection and conservation of wildlife and creating a healthier planet.

Change history

  • 30 June 2009

    In the version of this article initially published online and in print, table 1 on page 521 mistakenly indicated papillomavirus as the associated virus for flatback turtle (Natator depressus), olive ridley turtle (Lepidochelys olivacea), loggerhead turtle (Caretta caretta), leatherback turtle (Dermochelys coriacea), Kemp’s ridley turtle (L. kempii) and hawksbill turtle (Eretmochelys imbricata). These entries have therefore been removed from the table. Reference 154 has also been removed from the article because other references in the main text discuss the virus association in specific turtle species. Accordingly, references 155–162 have been renumbered as references 154–161. These errors have been corrected for the HTML and PDF versions of the article.


  1. 1

    Rous, P. A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J. Exp. Med. 13, 397–411 (1911).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. 2

    Malumbres, M. & Barbacid, M. RAS oncogenes: the first 30 years. Nature Rev. Cancer 3, 459–465 (2003).

    CAS  Article  Google Scholar 

  3. 3

    Klaus, A. & Birchmeier, W. Wnt signalling and its impact on development and cancer. Nature Rev. Cancer 8, 387–398 (2008).

    CAS  Article  Google Scholar 

  4. 4

    Karesh, W. & Cook, R. One world — one health. Clin. Med. 9, 5–7 (2009).

    Article  Google Scholar 

  5. 5

    Centers for Disease Control and Prevention. The burden of chronic diseases and their risk factors: national and state perspectives 2004. US Department of Health and Human Services [online], (2004).

  6. 6

    Aguirre, A. A. et al. Pathology of fibropapillomatosis in olive ridley turtles Lepidochelys olivacea nesting in Costa Rica. J. Aquat. Anim. Health 11, 283–289 (1999).

    Article  Google Scholar 

  7. 7

    Stroud, R. K. & Roffe, T. J. Causes of death in marine mammals stranded along the Oregon coast. J. Wildl. Dis. 15, 91–97 (1979).

    CAS  PubMed  Article  Google Scholar 

  8. 8

    Crooks, K. R., Scott, C. A. & Van Vuren, D. H. Exotic disease and an insular endemic carnivore, the island fox. Biol. Conserv. 98, 55–60 (2001).

    Article  Google Scholar 

  9. 9

    Martineau, D. et al. Cancer in wildlife, a case study: beluga from the St. Lawrence estuary, Québec, Canada. Environ. Health Perspect. 110, 285–292 (2002).

    PubMed  PubMed Central  Article  Google Scholar 

  10. 10

    Hamede, R. K., McCallum, H. & Jones, M. Seasonal, demographic and density-related patterns of contact between Tasmanian devils (Sarcophilus harrisii): implications for transmission of devil facial tumour disease. Austral. Ecol. 33, 614–622 (2008).

    Article  Google Scholar 

  11. 11

    McCallum, H. et al. Distribution and impacts of Tasmanian devil facial tumor disease. EcoHealth 4, 318–325 (2007).

    Article  Google Scholar 

  12. 12

    Hawkins, C. et al. Emerging disease and population decline of an island endemic, the Tasmanian devil Sarcophilus harrisii. Biol. Cons. 131, 307–324 (2006).

    Article  Google Scholar 

  13. 13

    Pyecroft, S. et al. Towards a case definition for devil facial tumour disease: what is it? EcoHealth 4, 346–351 (2007).

    Article  Google Scholar 

  14. 14

    Loh, R. et al. The pathology of devil facial tumor disease (DFTD) in Tasmanian devils (Sarcophilus harrisii). Vet. Pathol. 43, 890–895 (2006).

    CAS  PubMed  Article  Google Scholar 

  15. 15

    Loh, R. et al. The immunohistochemical characterization of devil facial tumor disease (DFTD) in the Tasmanian devil (Sarcophilus harrisii). Vet. Pathol. 43, 896–903 (2006).

    CAS  PubMed  Article  Google Scholar 

  16. 16

    McCallum, H., Barlow, N. & Hone, J. How should pathogen transmission be modelled? Trends Ecol. Evol. 16, 295–300 (2001).

    CAS  PubMed  Article  Google Scholar 

  17. 17

    Lachish, S., Jones, M. & McCallum, H. The impact of disease on the survival and population growth rate of the Tasmanian devil. J. Anim. Ecol. 76, 926–936 (2007).

    PubMed  Article  Google Scholar 

  18. 18

    Pyecroft, S. Transmission trials: devil facial tumor disease. Devil Facial Tumour Diseases: Senior Scientist's Scientific Forum 18 [online], (2007).

    Google Scholar 

  19. 19

    Pearse, A. & Swift, K. Allograft theory: transmission of devil facial-tumour disease. Nature 439, 549 (2006).

    CAS  PubMed  Article  Google Scholar 

  20. 20

    Siddle, H. V. et al. Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proc. Natl Acad. Sci. USA 104, 16221–16226 (2007).

    CAS  PubMed  Article  Google Scholar 

  21. 21

    Kreiss, A. et al. Assessment of cellular immune responses of healthy and diseased Tasmanian devils (Sarcophilus harrisii). Dev. Comp. Immunol. 32, 544–553 (2008).

    CAS  PubMed  Article  Google Scholar 

  22. 22

    Kreiss, A., Wells, B. & Woods, G. M. The humoral immune response of the Tasmanian devil (Sarcophilus harrisii) against horse red blood cells. Vet. Immunol. Immunopathol. (in the press).

  23. 23

    Woods, G. et al. The immune response of the Tasmanian devil (Sarcophilus harrisii) and devil facial tumour disease. EcoHealth 4, 338–345 (2007).

    Article  Google Scholar 

  24. 24

    Murgia, C. et al. Clonal origin and evolution of a transmissible cancer. Cell 126, 477–487 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25

    Gandhi, M. J. & Strong, D. M. Donor derived malignancy following transplantation: a review. Cell Tissue Bank 8, 267–286 (2007).

    PubMed  Article  Google Scholar 

  26. 26

    Aguirre-Ghiso, J. A. Models, mechanisms and clinical evidence for cancer dormancy. Nature Rev. Cancer 7, 834–846 (2007).

    CAS  Article  Google Scholar 

  27. 27

    Ajithkumar, T. V. et al. Management of solid tumours in organ-transplant recipients. Lancet Oncol. 8, 921–932 (2007).

    PubMed  Article  Google Scholar 

  28. 28

    Mozos, E. et al. Immunohistochemical characterization of canine transmissible venereal tumor. Vet. Pathol. 33, 257–263 (1996).

    CAS  PubMed  Article  Google Scholar 

  29. 29

    Das, U. & Das, A. K. Review of canine transmissible venereal sarcoma. Vet. Res. Commun. 24, 545–556 (2000).

    CAS  PubMed  Article  Google Scholar 

  30. 30

    Mukaratirwa, S. & Gruys, E. Canine transmissible venereal tumour: cytogenetic origin, immunophenotype, and immunobiology. A review. Vet. Q. 25, 101–111 (2003).

    CAS  PubMed  Article  Google Scholar 

  31. 31

    VonHoldt, B. M. & Ostrander, E. A. The singular history of a canine transmissible tumor. Cell 126, 445–447 (2006).

    CAS  PubMed  Article  Google Scholar 

  32. 32

    Cohen, D. The canine transmissible venereal tumor: a unique result of tumor progression. Adv. Cancer Res. 43, 75–112 (1985).

    CAS  PubMed  Article  Google Scholar 

  33. 33

    Epstein, R. B. & Bennett, B. T. Histocompatibility typing and course of canine venereal tumors transplanted into unmodified random dogs. Cancer Res. 34, 788–793 (1974).

    CAS  PubMed  Google Scholar 

  34. 34

    Liu, C. et al. Transient downregulation of monocyte-derived dendritic-cell differentiation, function, and survival during tumoral progression and regression in an in vivo canine model of transmissible venereal tumor. Cancer Immunol. Immunother. 57, 479–491 (2008).

    CAS  PubMed  Article  Google Scholar 

  35. 35

    Hsiao, Y. et al. Interactions of host IL-6 and IFN-γ and cancer-derived TGF-β1 on MHC molecule expression during tumor spontaneous regression. Cancer Immunol. Immunother. 57, 1091–1104 (2008).

    CAS  PubMed  Article  Google Scholar 

  36. 36

    Evermann, J. F. et al. Comparative features of a coronavirus isolated from a cheetah with feline infectious peritonitis. Virus Res. 13, 15–27 (1989).

    CAS  PubMed  Article  Google Scholar 

  37. 37

    O'Brien, S. J. et al. Genetic basis for species vulnerability in the cheetah. Science 227, 1428–1434 (1985).

    CAS  PubMed  Article  Google Scholar 

  38. 38

    Lachish, S., Jones, M. & McCallum, H. The impact of disease on the survival and population growth rate of the Tasmanian devil. J. Anim. Ecol. 76, 926–936 (2007).

    PubMed  Article  Google Scholar 

  39. 39

    McCallum, H. Tasmanian devil facial tumour disease: lessons for conservation biology. Trends Ecol. Evol. 23, 631–637 (2008).

    PubMed  Article  Google Scholar 

  40. 40

    Lloyd-Smith, J. O., Getz, W. M. & Westerhoff, H. V. Frequency-dependent incidence in models of sexually transmitted diseases: portrayal of pair-based transmission and effects of illness on contact behaviour. Proc. Biol. Sci. 271, 625–634 (2004).

    PubMed  PubMed Central  Article  Google Scholar 

  41. 41

    Gulland, F. M., Lowenstine, L. J. & Spraker, T. R. in Marine Mammal Medicine 2nd edn (eds Dierauf, L. A. & Gulland, F. M.) 521–550 (CRC, Boca Raton, 2001).

    Google Scholar 

  42. 42

    Hilker, F. M., Langlais, M. & Malchow, H. The Allee effect and infectious diseases: extinction, multistability, and the (dis-)appearance of oscillations. Am. Nat. 173, 72–88 (2009).

    PubMed  Article  Google Scholar 

  43. 43

    Angulo, E. et al. Double Allee effects and extinction in the island fox. Conserv. Biol. 21, 1082–1091 (2007).

    PubMed  Article  Google Scholar 

  44. 44

    Jones, M. et al. Conservation management of Tasmanian devils in the context of an emerging, extinction-threatening disease: devil facial tumor disease. EcoHealth 4, 326–337 (2007).

    Article  Google Scholar 

  45. 45

    Peterson, M. J. & Silvy, N. J. Reproductive stages limiting productivity of the endangered Attwater's prairie chicken. Conserv. Biol. 10, 1264–1276 (1996).

    Article  Google Scholar 

  46. 46

    Bennett, M. D. Western barred bandicoots in health and disease. Thesis, Murdoch Univ. (2008).

    Google Scholar 

  47. 47

    Drew, M. L. et al. Reticuloendotheliosis in captive greater and Attwater's prairie chickens. J. Wildl. Dis. 34, 783–791 (1998).

    CAS  PubMed  Article  Google Scholar 

  48. 48

    Bennett, M. D. et al. Hematologic characteristics of captive western barred bandicoots (Perameles bougainville) from Western Australia. Vet. Clin. Pathol. 36, 348–353 (2007).

    PubMed  Article  Google Scholar 

  49. 49

    Barbosa, T. et al. Pathogenicity and transmission of reticuloendotheliosis virus isolated from endangered prairie chickens. Avian Dis. 51, 33–39 (2007).

    PubMed  Article  Google Scholar 

  50. 50

    Drechsler, Y. et al. An avian, oncogenic retrovirus replicates in vivo in more than 50% of CD4+ and CD8+ T lymphocytes from an endangered grouse. Virology 386, 380–386 (2009).

    CAS  PubMed  Article  Google Scholar 

  51. 51

    Bennett, M. D. et al. In situ hybridization to detect bandicoot papillomatosis carcinomatosis virus type 1 in biopsies from endangered western barred bandicoots (Perameles bougainville). J. Gen. Virol. 89, 419–423 (2008).

    CAS  PubMed  Article  Google Scholar 

  52. 52

    Woolford, L. et al. Cutaneous papillomatosis and carcinomatosis in the Western barred bandicoot (Perameles bougainville). Vet. Pathol. 45, 95–103 (2008).

    CAS  PubMed  Article  Google Scholar 

  53. 53

    Gulland, F. Domoic acid toxicity in California sea lions (Zalophus californianus) stranded along the central California coast, May–October 1998. National Oceanic and Atmospheric Administration [online], (2000).

    Google Scholar 

  54. 54

    Adnyana, W., Ladds, P. W. & Blair, D. Observations of fibropapillomatosis in green turtles (Chelonia mydas) in Indonesia. Aust. Vet. J. 75, 736–742 (1997).

    CAS  PubMed  Google Scholar 

  55. 55

    Herbst, L. H. Fibropapillomatosis of marine turtles. Annu. Rev. Fish. Dis. 4, 389–425 (1994).

    Article  Google Scholar 

  56. 56

    Balazs, G. H. Research plan for marine turtle fibropapilloma. NOAA Technical Memorandum NMFS [online], (1991).

    Google Scholar 

  57. 57

    Work, T. M. et al. Retrospective pathology survey of green turtles Chelonia mydas with fibropapillomatosis in the Hawaiian Islands, 1993–2003. Dis. Aquat. Organ. 62, 163–176 (2004).

    PubMed  Article  Google Scholar 

  58. 58

    Williams, E. et al. An epizootic of cutaneous fibropapillomas in green turtles Chelonia mydas of the Caribbean: part of a panzootic? J. Aquat. Anim. Health 6, 70–78 (1994).

    Article  Google Scholar 

  59. 59

    Herbst, L. H. & Klein, P. A. Green turtle fibropapillomatosis: challenges to assessing the role of environmental cofactors. Environ. Health Perspect. 103 Suppl. 4, 27–30 (1995).

    PubMed  PubMed Central  Google Scholar 

  60. 60

    Huerta, P. et al. First confirmed case of fibropapilloma in a leatherback turtle (Dermochelys coriacea). Proceedings of the Twentieth Annual Symposium on Sea Turtle Biology and Conservation [online], (2000).

    Google Scholar 

  61. 61

    Guillen, L. & Villalobos, J. P. Papillomas in Kemp's ridley turtles. Proceedings of the Nineteenth Annual Symposium on Sea Turtle Conservation and Biology [online], (1999).

    Google Scholar 

  62. 62

    D'Amato, A. F. & Moraes-Neto, M. First documentation of fibropapillomas verified by histology in Eretmochelys imbricata. Marine Turtle Newsletter [online], (2000).

    Google Scholar 

  63. 63

    Herbst, L. H. et al. Comparative pathology and pathogenesis of spontaneous and experimentally induced fibropapillomas of green turtles (Chelonia mydas). Vet. Pathol. 36, 551–564 (1999).

    CAS  PubMed  Article  Google Scholar 

  64. 64

    Lu, Y. et al. Detection of herpesviral sequences in tissues of green turtles with fibropapilloma by polymerase chain reaction. Arch. Virol. 145, 1885–1893 (2000).

    CAS  PubMed  Article  Google Scholar 

  65. 65

    Greenblatt, R. J. et al. Genomic variation of the fibropapilloma-associated marine turtle herpesvirus across seven geographic areas and three host species. J. Virol. 79, 1125–1132 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. 66

    Herbst, L. H. Experimental transmission of green turtle fibropapillomatosis using cell-free tumor extracts. Dis. Aquat. Org. 22, 1–12 (1995).

    Article  Google Scholar 

  67. 67

    Yu, Q. et al. Amplification and analysis of DNA flanking known sequences of a novel herpesvirus from green turtles with fibropapilloma. Arch. Virol. 145, 2669–2676 (2000).

    CAS  PubMed  Article  Google Scholar 

  68. 68

    Herbst, L. H. et al. Differential gene expression associated with tumorigenicity of cultured green turtle fibropapilloma-derived fibroblasts. Cancer Genet. Cytogenet. 129, 35–39 (2001).

    CAS  PubMed  Article  Google Scholar 

  69. 69

    Curry, S. S. et al. Persistent infectivity of a disease-associated herpesvirus in green turtles after exposure to seawater. J. Wildl. Dis. 36, 792–797 (2000).

    CAS  PubMed  Article  Google Scholar 

  70. 70

    Greenblatt, R. J. et al. The Ozobranchus leech is a candidate mechanical vector for the fibropapilloma-associated turtle herpesvirus found latently infecting skin tumors on Hawaiian green turtles (Chelonia mydas). Virology 321, 101–110 (2004).

    CAS  PubMed  Article  Google Scholar 

  71. 71

    Van Bressem, M. F. et al. Genital and lingual warts in small cetaceans from coastal Peru. Dis. Aquat. Org. 26, 1–10 (1996).

    Article  Google Scholar 

  72. 72

    Van Bressem, M. F., Van Waerebeek, K. & Raga, J. A. A review of virus infections of cetaceans and the potential impact of morbilliviruses, poxviruses and papillomaviruses on host population dynamics. Dis. Aquat. Org. 38, 53–65 (1999).

    CAS  PubMed  Article  Google Scholar 

  73. 73

    Sweeney, J. C. & Gilmartin, W. G. Survey of diseases in free-living California sea lions. J. Wildl. Dis. 10, 370–376 (1974).

    CAS  PubMed  Article  Google Scholar 

  74. 74

    Newman, S. J. & Smith, S. A. Marine mammal neoplasia: a review. Vet. Pathol. 43, 865–880 (2006).

    CAS  PubMed  Article  Google Scholar 

  75. 75

    Gulland, F. M. et al. Metastatic carcinoma of probable transitional cell origin in 66 free-living California sea lions (Zalophus californianus), 1979 to 1994. J. Wildl. Dis. 32, 250–258 (1996).

    CAS  PubMed  Article  Google Scholar 

  76. 76

    King, D. P. et al. Otarine herpesvirus-1: a novel gammaherpesvirus associated with urogenital carcinoma in California sea lions (Zalophus californianus). Vet. Microbiol. 86, 131–137 (2002).

    CAS  PubMed  Article  Google Scholar 

  77. 77

    Buckles, E. L. et al. Otarine herpesvirus-1, not papillomavirus, is associated with endemic tumours in California sea lions (Zalophus californianus). J. Comp. Pathol. 135, 183–189 (2006).

    CAS  PubMed  Article  Google Scholar 

  78. 78

    Lipscomb, T. P. et al. Common metastatic carcinoma of California sea lions (Zalophus californianus): evidence of genital origin and association with novel gammaherpesvirus. Vet. Pathol. 37, 609–617 (2000).

    CAS  PubMed  Article  Google Scholar 

  79. 79

    Chang, Y. et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266, 1865–1869 (1994).

    CAS  Article  PubMed  Google Scholar 

  80. 80

    Ambroziak, J. A. et al. Herpes-like sequences in HIV-infected and uninfected Kaposi's sarcoma patients. Science 268, 582–583 (1995).

    CAS  PubMed  Article  Google Scholar 

  81. 81

    Nelson, J. H., Averette, H. E. & Richart, R. M. Cervical intraepithelial neoplasia (dysplasia and carcinoma in situ) and early invasive cervical carcinoma. CA Cancer J. Clin. 39, 157–178 (1989).

    PubMed  Article  Google Scholar 

  82. 82

    Smith, J. S. et al. Age-specific prevalence of infection with human papillomavirus in females: a global review. J. Adolesc. Health 43 (Suppl. 1), S5.e1–S5.eb2 (2008).

    Google Scholar 

  83. 83

    NOAA Fisheries Service, California sea lion (Zalophus californianus californianus): US stock. National Marine Fisheries Service [online], (2007).

  84. 84

    Jarrett, W. F. H. et al. High incidence area of cattle cancer with a possible interaction between an environmental carcinogen and a papilloma virus. Nature 274, 215–217 (1978).

    CAS  PubMed  Article  Google Scholar 

  85. 85

    Foley, A. M. et al. Fibropapillomatosis in stranded green turtles (Chelonia mydas) from the eastern United States (1980–1998): trends and associations with environmental factors. J. Wildl. Dis. 41, 29–41 (2005).

    PubMed  Article  Google Scholar 

  86. 86

    Ylitalo, G. M. et al. The role of organochlorines in cancer-associated mortality in California sea lions (Zalophus californianus). Mar. Pollut. Bull. 50, 30–39 (2005).

    CAS  PubMed  Article  Google Scholar 

  87. 87

    Malins, D. C. et al. Toxic chemicals in marine sediment and biota from Mukilteo, Washington: relationships with hepatic neoplasms and other hepatic lesions in English sole (Parophrys vetulus). J. Natl Cancer Inst. 74, 487–494 (1985).

    CAS  PubMed  Google Scholar 

  88. 88

    Malins, D. C. et al. Toxic chemicals in sediments and biota from a creosote-polluted harbor: relationships with hepatic neoplasms and other hepatic lesions in English sole (Parophrys vetulus). Carcinogenesis 6, 1463–1469 (1985).

    CAS  PubMed  Article  Google Scholar 

  89. 89

    Smith, I., Ferguson, H. & Hayes, M. Histopathology and prevalence of epidermal papillomas epidemic in brown bullhead, Ictalurus nebulosus (Lesueur) and white sucker, Catostomus commersoni (Laceped) populations from Ontario, Canada. J. Fish. Dis. 12, 373–388 (1989).

    Article  Google Scholar 

  90. 90

    Baumann, P. C., Smith, I. R. & Metcalfe, C. D. Linkages between chemical contaminants and tumors in benthic Great lakes fish. J. Great Lakes Res. 22, 131–152 (1996).

    CAS  Article  Google Scholar 

  91. 91

    Martel, L. et al. Polycyclic aromatic hydrocarbons in sediments from the Saguenay Fjord, Canada. Bull. Environ. Contam. Toxicol. 37, 133–140 (1986).

    CAS  PubMed  Article  Google Scholar 

  92. 92

    World Health OrganizationInternational Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42. Suppl. 7. [online], (1998).

  93. 93

    International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. IARC Monographs Vol. 32 (World Health Organization, 1983).

  94. 94

    Bosetti, C., Boffetta, P. & La Vecchia, C. Occupational exposures to polycyclic aromatic hydrocarbons, and respiratory and urinary tract cancers: a quantitative review to 2005. Ann. Oncol. 18, 431–446 (2007).

    CAS  PubMed  Article  Google Scholar 

  95. 95

    Boffetta, P., Jourenkova, N. & Gustavsson, P. Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons. Cancer Causes Control 8, 444–472 (1997).

    CAS  PubMed  Article  Google Scholar 

  96. 96

    Malins, D. C. et al. Field and laboratory studies of the etiology of liver neoplasms in marine fish from Puget Sound. Environ. Health Perspect. 71, 5–16 (1987).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  97. 97

    Black, J. J. & Baumann, P. C. Carcinogens and cancers in freshwater fishes. Environ. Health Perspect. 90, 27–33 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. 98

    Blazer, V. S. et al. Diagnostic criteria for proliferative hepatic lesions in brown bullhead Ameiurus nebulosus. Dis. Aquat. Org. 72, 19–30 (2006).

    PubMed  Article  Google Scholar 

  99. 99

    Sakamoto, K. & White, M. Dermal melanoma with schwannoma-like differentiation in a brown bullhead catfish (Ictalurus nebulosus). J. Vet. Diagn. Invest. 14, 247–250 (2002).

    PubMed  Article  Google Scholar 

  100. 100

    Maccubbin, A. E. et al. Evidence for polynuclear aromatic hydrocarbons in the diet of bottom-feeding fish. Bull. Environ. Contam. Toxicol. 34, 876–882 (1985).

    CAS  PubMed  Article  Google Scholar 

  101. 101

    Hendricks, J. D. et al. Hepatocarcinogenicity of benzo[a]pyrene to rainbow trout by dietary exposure and intraperitoneal injection. J. Natl Cancer Inst. 74, 839–851 (1985).

    CAS  PubMed  Google Scholar 

  102. 102

    Black, J. J. et al. in Water Chlorination Chemistry, Environmental Impact and Health Effects (eds Jolley, R. L et al.) 415–427 (Plenum, New York, 1984).

    Google Scholar 

  103. 103

    Baumann, P. C. & Harshbarger, J. C. Decline in liver neoplasms in wild brown bullhead catfish after coking plant closes and environmental PAHs plummet. Environ. Health Perspect. 103, 168–170 (1995).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  104. 104

    Baumann, P. C., Harshbarger, J. C. & Hartman, K. J. Relationship between liver tumors and age in brown bullhead populations from two Lake Erie tributaries. Sci. Total Environ. 94, 71–87 (1990).

    CAS  PubMed  Article  Google Scholar 

  105. 105

    Landy, R. B. in The Comparative Pathology of Zoo Animals (eds Montali, R. G. & Migaki, G.) 579–584 (Smithsonian Institution Press, Washington DC, 1980).

    Google Scholar 

  106. 106

    Newman, S. J. & Smith, S. A. Marine mammal neoplasia: a review. Vet. Pathol. 43, 865–880 (2006).

    CAS  PubMed  Article  Google Scholar 

  107. 107

    De Guise, S., Lagacé, A. & Béland, P. Tumors in St. Lawrence beluga whales (Delphinapterus leucas). Vet. Pathol. 31, 444–449 (1994).

    CAS  PubMed  Article  Google Scholar 

  108. 108

    Martineau, D. et al. Intestinal adenocarcinomas in two beluga whales (Delphinapterus leucas) from the estuary of the St. Lawrence River. Can. Vet. J. 36, 563–565 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. 109

    Mikaelian, I. et al. Metastatic mammary adenocarcinomas in two beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary, Canada. Vet. Rec. 145, 738–739 (1999).

    CAS  PubMed  Article  Google Scholar 

  110. 110

    Martineau, D. et al. Pathology of stranded beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary, Québec, Canada. J. Comp. Pathol. 98, 287–311 (1988).

    CAS  PubMed  Article  Google Scholar 

  111. 111

    Muir, D. C. G. et al. Persistent organochlorines in beluga whales (Delphinapterus leucas) from the St. Lawrence River estuary-I. Concentrations and patterns of specific PCBs, chlorinated pesticides and polychlorinated dibenzo-p-dioxins and dibenzofurans. Environ. Pollut. 93, 219–234 (1996).

    CAS  PubMed  Article  Google Scholar 

  112. 112

    Muir, D. C. G. et al. Persistent organochlorines in beluga whales (Delphinapterus leucas) from the St. Lawrence River estuary—II. Temporal trends, 1982–1994. Environ. Pollut. 93, 235–245 (1996).

    CAS  PubMed  Article  Google Scholar 

  113. 113

    Hobbs, K. E. et al. PCBs and organochlorine pesticides in blubber biopsies from free-ranging St. Lawrence River Estuary beluga whales (Delphinapterus leucas), 1994–1998. Environ. Pollut. 122, 291–302 (2003).

    CAS  PubMed  Article  Google Scholar 

  114. 114

    Martineau, D. et al. Pathology and toxicology of beluga whales from the St. Lawrence Estuary, Quebec, Canada. Past, present and future. Sci. Total Environ. 154, 201–215 (1994).

    CAS  PubMed  Article  Google Scholar 

  115. 115

    De Guise, S. et al. Possible mechanisms of action of environmental contaminants on St. Lawrence beluga whales (Delphinapterus leucas). Environ. Health Perspect. 103 (Suppl. 4), 73–77 (1995).

    PubMed  PubMed Central  Google Scholar 

  116. 116

    Martineau, D. et al. St. Lawrence beluga whales, the river sweepers? Environ. Health Perspect. 110, A562–A564 (2002).

    PubMed  PubMed Central  Google Scholar 

  117. 117

    Klaunig, J. E. & Kamendulis, L. M. in Casarett & Doull's Toxicology: The Basic Science of Poisons 329–379 (McGraw-Hill Medical, New York, 2008).

    Google Scholar 

  118. 118

    Kane, A. B. & Kumar, V. in Robbins and Cotran Pathologic Basis of Disease 270 (Elsevier Saunders, Philadelphia, 2005).

    Google Scholar 

  119. 119

    Timbrell, J. A. in Principles of Biochemical Toxicology 295–297 (CRC, London, 2008).

    Book  Google Scholar 

  120. 120

    Culp, S. J. et al. A comparison of the tumors induced by coal tar and benzo[a]pyrene in a 2-year bioassay. Carcinogenesis 19, 117–124 (1998).

    CAS  PubMed  Article  Google Scholar 

  121. 121

    Culp, S. J. et al. DNA adduct measurements, cell proliferation and tumor mutation induction in relation to tumor formation in B6C3F1 mice fed coal tar or benzo[a]pyrene. Carcinogenesis 21, 1433–1440 (2000).

    CAS  PubMed  Google Scholar 

  122. 122

    Rust, A. J. et al. Relationship between metabolism and bioaccumulation of benzo[a]pyrene in benthic invertebrates. Environ. Toxicol. Chem. 23, 2587–2593 (2004).

    CAS  PubMed  Article  Google Scholar 

  123. 123

    Rocher, B. et al. Genotoxicant accumulation and cellular defence activation in bivalves chronically exposed to waterborne contaminants from the Seine River. Aquat. Toxicol. 79, 65–77 (2006).

    CAS  PubMed  Article  Google Scholar 

  124. 124

    Cossa, D., Picard-Bérubé, M. & Gouygou, J. P. Polynuclear aromatic hydrocarbons in mussels from the Estuary and Northwestern Gulf of St. Lawrence, Canada. Bull. Environ. Contam. Toxicol. 31, 41–47 (1983).

    CAS  PubMed  Article  Google Scholar 

  125. 125

    Wilson, J. Y. et al. Systemic effects of arctic pollutants in beluga whales indicated by CYP1A1 expression. Environ. Health Perspect. 113, 1594–1599 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  126. 126

    Zhang, Q. Y. et al. Characterization of rat small intestinal cytochrome P450 composition and inducibility. Drug Metab. Dispos. 24, 322–328 (1996).

    CAS  PubMed  Google Scholar 

  127. 127

    Harshbarger, J. C. & Slatick, M. S. Lesser known aquarium fish tumor models. Mar. Biotechnol. 3, S115–S129 (2001).

    CAS  PubMed  Article  Google Scholar 

  128. 128

    Lombard, L. S. & Witte, E. J. Frequency and types of tumors in mammals and birds of the Philadelphia Zoological Garden. Cancer Res. 19, 127–141 (1959).

    CAS  PubMed  Google Scholar 

  129. 129

    Effron, M., Griner, L. & Benirschke, K. Nature and rate of neoplasia found in captive wild mammals, birds, and reptiles at necropsy. J. Natl Cancer Inst. 59, 185–198 (1977).

    CAS  PubMed  Article  Google Scholar 

  130. 130

    Ryan, M. J., Hill, D. L. & Whitney, G. D. Malignant chromatophoroma in a gopher snake. Vet. Pathol. 18, 827–829 (1981).

    CAS  PubMed  Article  Google Scholar 

  131. 131

    Suedmeyer, W. K. et al. Diagnosis and clinical management of multiple chromatophoromas in an eastern yellowbelly racer (Coluber constrictor flaviventris). J. Zoo Wildl. Med. 38, 127–130 (2007).

    PubMed  Article  Google Scholar 

  132. 132

    Montali, R. J., Hoopes, P. J. & Bush, M. Extrahepatic biliary carcinomas in Asiatic bears. J. Natl Cancer Inst. 66, 603–608 (1981).

    CAS  PubMed  Google Scholar 

  133. 133

    Miller, R. E. et al. Hepatic neoplasia in two polar bears. J. Am. Vet. Med. Assoc. 187, 1256–1258 (1985).

    CAS  PubMed  Google Scholar 

  134. 134

    Lair, S. et al. Epidemiology of neoplasia in captive black-footed ferrets (Mustela nigripes), 1986–1996. J. Zoo Wildl. Med. 33, 204–213 (2002).

    PubMed  Article  Google Scholar 

  135. 135

    Le Calvez, S., Perron-Lepage, M. & Burnett, R. Subcutaneous microchip-associated tumours in B6C3F1 mice: a retrospective study to attempt to determine their histogenesis. Exp. Toxicol. Pathol. 57, 255–265 (2006).

    PubMed  Article  Google Scholar 

  136. 136

    Tillmann, T. et al. Subcutaneous soft tissue tumours at the site of implanted microchips in mice. Exp. Toxicol. Pathol. 49, 197–200 (1997).

    CAS  PubMed  Article  Google Scholar 

  137. 137

    Elcock, L. E. et al. Tumors in long-term rat studies associated with microchip animal identification devices. Exp. Toxicol. Pathol. 52, 483–491 (2001).

    CAS  PubMed  Article  Google Scholar 

  138. 138

    Pessier, A. et al. Soft tissue sarcomas associated with identification of microchip implants in two small zoo mammals. Proc. Am. Assoc. Zoo Vet. 139 (1999).

  139. 139

    Siegal-Willott, J. et al. Microchip-associated leiomyosarcoma in an Egyptian fruit bat (Rousettus aegyptiacus). J. Zoo Wildl. Med. 38, 352–356 (2007).

    PubMed  Article  Google Scholar 

  140. 140

    McAloose, D., Munson, L. & Naydan, D. K. Histologic features of mammary carcinomas in zoo felids treated with melengestrol acetate (MGA) contraceptives. Vet. Pathol. 44, 320–326 (2007).

    CAS  PubMed  Article  Google Scholar 

  141. 141

    Harrenstien, L. A., Munson, L. & Seal, U. S. Mammary cancer in captive wild felids and risk factors for its development: a retrospective study of the clinical behavior of 31 cases. J. Zoo Wildl. Med. 27, 468–476 (1996).

    Google Scholar 

  142. 142

    Pilotti, S. et al. Histologic evidence for an association of cervical intraepithelial neoplasia with human papilloma virus infection. Diagn. Gynecol. Obstet. 4, 357–362 (1982).

    CAS  PubMed  Google Scholar 

  143. 143

    Lambertsen, R. et al. Genital papillomatosis in sperm whale bulls. J. Wildl. Dis. 23, 361–367 (1987).

    CAS  PubMed  Article  Google Scholar 

  144. 144

    Van Bressem, M. et al. Genital warts in Burmeister's porpoises: characterization of Phocoena spinipinnis papillomavirus type 1 (PsPV-1) and evidence for a second, distantly related PsPV. J. Gen. Virol. 88, 1928–1933 (2007).

    CAS  PubMed  Article  Google Scholar 

  145. 145

    Van Bressem, M. F. et al. Genital diseases in the Peruvian dusky dolphin (Lagenorhynchus obscurus). J. Comp. Pathol. 122, 266–277 (2000).

    CAS  PubMed  Article  Google Scholar 

  146. 146

    Cassonnet, P. et al. in The World Marine Mammal Science Conference, Monaco 25 (1998).

    Google Scholar 

  147. 147

    Bossart, G. D. et al. Orogenital neoplasia in Atlantic bottlenose dolphins (Tursiops truncatus). Aquatic Mammals 31, 473–480 (2005).

    Article  Google Scholar 

  148. 148

    Geraci, J., Palmer, N. & St Aubin, D. Tumors in cetaceans: analysis and new findings. Can. J. Fish. Aquat. Sci. 44, 1289–1300 (1987).

    Article  Google Scholar 

  149. 149

    Rehtanz, M. et al. Isolation and characterization of the first American bottlenose dolphin papillomavirus: Tursiops truncatus papillomavirus type 2. J. Gen. Virol. 87, 3559–3565 (2006).

    CAS  PubMed  Article  Google Scholar 

  150. 150

    Van Bressem, M. F. et al. Cutaneous papillomavirus infection in a harbour porpoise (Phocoena phocoena) from the North Sea. Vet. Rec. 144, 592–593 (1999).

    CAS  PubMed  Article  Google Scholar 

  151. 151

    Bossart, G. D. et al. Cutaneous papillomaviral-like papillomatosis in a killer whale. Mar. Mam. Sci. 12, 274–281 (1996).

    Article  Google Scholar 

  152. 152

    Bossart, G. D. et al. Viral papillomatosis in Florida manatees (Trichechus manatus latirostris). Exp. Mol. Pathol. 72, 37–48 (2002).

    CAS  PubMed  Article  Google Scholar 

  153. 153

    De Guise, S., Lagacé, A. & Béland, P. Gastric papillomas in eight St. Lawrence beluga whales (Delphinapterus leucas). J. Vet. Diagn. Invest. 6, 385–388 (1994).

    CAS  PubMed  Article  Google Scholar 

  154. 154

    Memar, O. M., Rady, P. L. & Tyring, S. K. Human herpesvirus-8: detection of novel herpesvirus-like DNA sequences in Kaposi's sarcoma and other lesions. J. Mol. Med. 73, 603–609 (1995).

    CAS  PubMed  Article  Google Scholar 

  155. 155

    Gunvén, P. et al. Epstein–Barr virus in Burkitt's lymphoma and nasopharyngeal carcinoma. Antibodies to EBV associated membrane and viral capsid antigens in Burkitt lymphoma patients. Nature 228, 1053–1056 (1970).

    PubMed  Article  Google Scholar 

  156. 156

    Blumberg, B. S. et al. The relation of infection with the hepatitis B agent to primary hepatic carcinoma. Am. J. Pathol. 81, 669–682 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. 157

    Summers, J., Smolec, J. M. & Snyder, R. A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Proc. Natl Acad. Sci. USA 75, 4533–4537 (1978).

    CAS  PubMed  Article  Google Scholar 

  158. 158

    Granoff, A. Herpesvirus and the Lucké tumor. Cancer Res. 33, 1431–1433 (1973).

    CAS  PubMed  Google Scholar 

  159. 159

    Poiesz, B. J. et al. Isolation of a new type C retrovirus (HTLV) in primary uncultured cells of a patient with Sézary T-cell leukaemia. Nature 294, 268–271 (1981).

    CAS  PubMed  Article  Google Scholar 

  160. 160

    Martineau, D. et al. Molecular characterization of a unique retrovirus associated with a fish tumor. J. Virol. 66, 596–599 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. 161

    Paul, T. A. et al. Identification and characterization of an exogenous retrovirus from Atlantic salmon swim bladder sarcomas. J. Virol. 80, 2941–2948 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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The authors thank D. Lyden, W. Karesh and T. Chang, whose thoughtful suggestions, especially early on, helped shape the content of the manuscript. They also acknowledge D. Joly and the anonymous reviewers, whose critical reviews and comments markedly improved the final version.

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Correspondence to Denise McAloose.

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Allee effect

A decrease in population fitness, such as population decline, at low population density.


In the lowest ecological regions (such as the sediment surface) of a body of water.


An animal in the order Cetacea; includes, whales, dolphins and porpoises.


A benign tumour of the intrahepatic bile ducts.


Tumour of the pigment-producing, light-reflecting cells, xanthophores, erythrophores and iridiphores, in vertebrate and invertebrate species, such as amphibians, fish, reptiles, crustaceans and cepahalopods.


A condition characterized by the presence of proliferative neoplasms containing superficial epidermal and subjacent dermal tissue.


The International Union for Conservation of Nature and Natural Resources is a global environmental network created in 1948 consisting of government, non-governmental organizations and scientific members that works with United Nations agencies, companies and communities towards the development of best practices, policy and environmental laws.

Koch's postulates

Criteria established by Robert Koch and Friedrich Loeffler in 1884 that established a relationship between a pathogen and disease, including: detection of an organism in hosts suffering from the disease; isolation of the novel organism in pure culture from the original host; transmission of cultured organism causes disease development in the healthy naive experimental host and the isolation of the organism (confirmed identical to the original causative organism) from a lesion in an inoculated host.


An organochlorine insecticide that bioaccumulates in the environment and is carcinogenic.


An animal in the orders Carnivora or Odobenidae (walrus), Otariidae (fur seal and sea lion) or Phocidae (true seals).

Population dynamics

Marginal and long-term changes in birth, death, immigration, emigration and composition (such as, sex, age and class) of a population.


An animal in the families Trichechidae (manatees) or Dugongidae (dugongs and sea cows).

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McAloose, D., Newton, A. Wildlife cancer: a conservation perspective. Nat Rev Cancer 9, 517–526 (2009).

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