Equine Papillomavirus: Warts, Sarcoids, and Cancer

Equine papillomaviruses are a diverse group of DNA viruses that cause a surprising range of problems in horses, from harmless warts in young animals to aggressive cancers in older ones. The term covers at least seven recognized types specific to horses (designated EcPV1 through EcPV7), each with its own tissue preferences and disease potential. On top of that, bovine papillomavirus types 1 and 2 routinely jump from cattle to horses, causing equine sarcoids, the single most common skin tumor in horses worldwide. Understanding which virus does what, how they spread, and what can be done about them matters for anyone managing horse health.

A Family With Many Members

Papillomaviruses are highly species-adapted. The ones that infect horses are genetically distinct from each other to a degree that surprises even virologists. The first three equine types identified, EcPV1, EcPV2, and EcPV3, share less than 60 percent of their DNA in the gene most commonly used for classification, meaning they each belong to entirely different genera within the broader papillomavirus family.¹ That level of divergence is roughly comparable to the difference between human papillomaviruses that cause common warts and those linked to cervical cancer. Newer types keep being discovered: EcPV4 through EcPV7 have been identified in recent years, and a 2025 study described yet another candidate virus with only about 52 percent similarity to its closest known relatives, potentially representing a new genus altogether.²

This genetic diversity matters because it means different equine papillomaviruses behave differently. EcPV1 causes the familiar warts on young horses’ muzzles. EcPV2 is implicated in genital and oral cancers. EcPV4 has been linked to ear plaques. Each type has its own tissue tropism and its own potential for harm, so lumping them all together as “horse warts” misses the picture entirely.

Classical Warts in Young Horses

The condition most horse owners recognize as papillomavirus is cutaneous papillomatosis: clusters of small, rough, cauliflower-like growths that appear on the muzzle, lips, and around the nostrils of young horses, typically between one and three years old. These are caused by EcPV1 and are almost always benign. The warts develop after direct contact with an infected horse or a contaminated surface like shared tack, feed buckets, or fencing. An incubation period of several weeks to months means a horse can pick up the virus long before any growths appear.

In most cases, the immune system handles these warts on its own. Histological studies show that as papillomas begin to regress, immune cells called Langerhans cells flood the junction between the outer skin and the deeper tissue, becoming highly active and recruiting T lymphocytes to mount a targeted attack on infected cells.³ This immune clearance typically resolves the warts within a few months, and the horse is left with lasting immunity. Veterinary intervention is rarely needed unless warts interfere with eating, bridling, or are cosmetically unacceptable for show purposes.

Congenital papillomas, present at birth, are rarer and more puzzling. At least one documented case in a foal showed bovine papillomavirus type 1 infection rather than an equine type, suggesting that some neonatal lesions involve cross-species transmission during pregnancy or birth rather than classical EcPV1.⁴

Equine Sarcoids and the Bovine Papillomavirus Connection

Sarcoids are the most common skin tumor in horses, and they are not caused by an equine virus at all. Bovine papillomavirus types 1 and, less often, type 2 are the primary drivers.⁵ These viruses jump from cattle to horses, where they behave differently than in their natural host. In cattle, BPV1 and BPV2 cause benign warts that typically regress. In horses, the virus cannot complete its full lifecycle but still transforms cells into tumor tissue, producing locally aggressive masses that come in several clinical forms: flat, verrucous (warty), nodular, fibroblastic (fleshy and ulcerated), and mixed.

Genomic analysis of BPV strains found in horse sarcoids supports the idea that these viruses originated in cattle and crossed into horses through multiple separate transmission events, likely relatively recently in evolutionary terms. One particular sequence variant appears overrepresented in equine sarcoids, suggesting it may have a fitness advantage in horse tissue.⁶ Complete genome analysis of BPV1 and BPV2 strains from both cattle warts and horse sarcoids further confirms this ongoing cross-species relationship.⁷

Sarcoids can appear anywhere on the body but favor the head, ventral abdomen, limbs, and areas around wounds or scars. They are notorious for recurring after removal, which makes them a persistent management challenge.

How Sarcoid-Causing Virus Hijacks Horse Cells

The reason BPV causes persistent tumors in horses rather than self-limiting warts has to do with the virus’s oncoproteins, particularly E5. In sarcoid tissue, the BPV E5 protein binds to a receptor on the surface of horse cells called the platelet-derived growth factor beta receptor, forcing it into an activated state.⁸ This receptor normally responds to growth signals, so its hijacking effectively tells the cell to keep dividing. The activated receptor then triggers downstream signaling cascades that promote cell survival and proliferation.⁹ Compared to normal equine skin, sarcoid tissue shows significantly higher levels of this receptor activation.¹⁰

BPV E5 also helps the tumor hide from the immune system. In equine cells expressing E5, the molecular tags that flag cells for immune surveillance get trapped inside the cell instead of reaching the surface where immune cells could detect them.¹¹ The result is a tumor that grows unchecked and avoids immune clearance, explaining why sarcoids can persist for years and resist the same immune response that clears classical EcPV1 warts relatively quickly.

How the Viruses Spread

Transmission routes vary by virus type. For BPV and sarcoid formation, biting flies appear to play a meaningful role. BPV1 DNA has been detected in flies trapped near sarcoid-affected horses, and the viral sequences found in those flies match the variants commonly seen in equine sarcoids.¹² Experimental work showed that the stable fly Stomoxys calcitrans can pick up BPV from infected tissue, though the viral load rises and then drops off within days, meaning transmission is most likely to happen shortly after a fly has fed on an infected lesion.¹³ Flies that had fed on bovine papillomas carried higher viral loads for longer than those exposed to equine sarcoid tissue, suggesting that cattle with active warts are a more potent source of virus than sarcoid-bearing horses.

For EcPV2, the virus most closely linked to genital cancers, sexual transmission is the most obvious route. A case report from Japan described a breeding stallion with an EcPV2-positive penile papilloma whose viral strain was genetically closer to foreign isolates than to previously reported Japanese strains, consistent with the virus spreading through international breeding activities.¹⁴ Direct contact during mating, shared grooming equipment, and contaminated surfaces are all plausible routes, though the relative importance of each has not been pinned down precisely.

EcPV2 and Genital Cancer

The most medically serious equine papillomavirus is EcPV2, which is strongly associated with squamous cell carcinoma of the penis, prepuce, and, less commonly, the vulva and anus in horses. Studies consistently find EcPV2 DNA in the vast majority of these tumors. One investigation detected EcPV2 DNA in 90 percent of penile squamous cell carcinoma samples.¹⁵ Another found EcPV2 in all but one of sixteen penile cancers tested, as well as in all precancerous lesions and papillomas from the same sites. The virus was also found in lymph node metastases and even a contact metastasis in the mouth, confirming that EcPV2-associated cancer can spread beyond the primary site.¹⁶

Importantly, a proportion of genital squamous cell carcinomas appear to arise without EcPV2 involvement, instead being linked to chronic sun damage. In situ hybridization, which can localize viral genetic material directly within tumor cells, has helped distinguish these two subsets. One study using this technique found abundant virus inside the cancer cells in about half of penile tumors, while the other half showed evidence of solar damage instead.¹⁷ This dual-pathway model parallels what is seen in humans, where some head and neck cancers are HPV-driven and others arise from other risk factors like tobacco or UV exposure.

EcPV2 has also been detected in up to 40 percent of oronasal squamous cell carcinomas, and emerging evidence indicates that genetic variants of the virus’s key oncogenes exist, though how these variants affect disease severity is still under investigation.¹⁸ More recently, EcPV7 was identified in a small number of penile cancers, but its tumors looked clinically and histologically identical to those caused by EcPV2, so there is no way to tell them apart by appearance alone.¹⁹

Aural Plaques and Ocular Tumors

Aural plaques are flat, white, crusty patches that form inside the ear flap of horses. They are common and mostly cosmetic, though they can make horses head-shy when their ears are handled. Despite containing papillomavirus antigen, early studies found that aural plaques did not carry EcPV1 DNA, leading researchers to hypothesize that a different, then-unidentified papillomavirus was responsible.²⁰ Subsequent work identified EcPV3, EcPV4, EcPV5, and EcPV6 in aural plaque tissue. In at least one documented case, aural plaques progressed to squamous cell carcinoma, with EcPV4 detected in the tumor by PCR.²¹ While this progression appears rare, it complicates the traditional view that aural plaques are entirely benign.

Ocular and periocular squamous cell carcinomas are another common cancer in horses, particularly in breeds with light-colored skin and minimal pigment around the eyes. However, the viral story here diverges from what happens in genital tumors. One study testing 42 periocular cancers found no papillomavirus DNA in any of them, a statistically significant difference from the high positivity rate in penile cancers.²² This suggests that eye-area cancers in horses are driven primarily by UV exposure and pigmentation rather than viral infection. A more recent and broader study did find EcPV2 genetic material in the majority of equine squamous cell carcinomas across body sites, though the papillary subtype (which includes some ocular tumors) was a notable exception.²³ The relationship between papillomavirus and ocular tumors remains an area where researchers have not reached consensus.

Silent Carriers

One of the more unsettling findings in recent research is how common EcPV2 infection is in horses with no visible disease. A study of apparently healthy horses in western Canada found that about 29 percent were positive for EcPV2 when tested across multiple anatomic sites. The virus was detected most frequently on the penis (35 percent of males tested), followed by vulvar tissue, eyelids, oral mucosa, and even muzzle skin.²⁴ Over a third of horses tested showed antibodies against EcPV2, indicating prior exposure. A smaller study in Brazil detected EcPV2 DNA in the genital mucosa of a clinically normal horse with no visible lesions, the first such report from that country.²⁵

The existence of asymptomatic carriers complicates both disease management and diagnosis. Since EcPV2 DNA can be picked up by PCR from normal genital skin, simply finding the virus on a swab does not mean the horse has or will develop cancer. This is exactly why more targeted techniques like in situ hybridization, which shows the virus actually active inside tumor cells rather than just sitting on a surface, have become important for distinguishing incidental infection from true viral disease.

Treatment Options for Sarcoids

Sarcoids have a reputation for being frustratingly difficult to treat. The recurrence rates vary enormously depending on the method used, the type and location of the sarcoid, and how aggressively the margins are cleared. A recent study of diode laser excision, one of the more common modern approaches, reported a per-lesion recurrence rate of about 6 percent over a median follow-up of 32 months, which is encouragingly low. When calculated per horse (did any sarcoid come back, anywhere), the rate was about 21 percent. Achieving tumor-free margins at surgery made a significant difference: none of the lesions with clean margins recurred at the original site, compared to roughly 12 percent of those where margins were not clear.²⁶

Autologous vaccination, where tumor tissue from the horse itself is processed and reinjected to stimulate an immune response, has also shown promise. In a case series, owners reported a decrease in the number of lesions in 75 percent of cases and a decrease in size in about 94 percent. Clinical regression was noted in about 69 percent of treated horses. However, complications occurred in over 40 percent of cases, and not all owners were satisfied.²⁷ Other approaches used in practice include cryotherapy, topical chemotherapy agents like cisplatin or 5-fluorouracil, and intralesional injection of immune-stimulating compounds. No single treatment works for every sarcoid, and veterinary dermatologists often combine methods.

Toward a Preventive Vaccine

The success of HPV vaccines in humans has naturally raised the question of whether horses could benefit from similar protection. Research here has focused on two fronts: preventing EcPV1 warts and preventing BPV-associated sarcoids.

For EcPV1, researchers have produced virus-like particles from the major capsid protein. These VLPs look identical to real virus particles under an electron microscope but contain no viral DNA, so they cannot cause infection. They provoke strong immune responses and carry the type-specific surface features needed to generate neutralizing antibodies.²⁸

For sarcoid prevention, a BPV1 VLP vaccine has advanced further. A dose-escalation safety trial in horses showed no significant adverse reactions beyond mild, transient swelling at the injection site. All vaccinated horses developed strong neutralizing antibody levels, and most maintained protective titers for at least two years after the last dose.²⁹ A follow-up virus challenge study was even more compelling: when vaccinated and unvaccinated horses were injected with live BPV1, all seven control horses developed pseudo-sarcoids at every inoculation site, while 13 of 14 vaccinated horses were completely protected. The one vaccinated horse that developed any lesions grew only tiny tumors that regressed within five weeks.³⁰

Despite these results, no equine papillomavirus vaccine has reached the commercial market as of mid-2025. The path from experimental challenge studies to a licensed product is long, requiring large-scale field trials, regulatory approval, and a manufacturer willing to invest in a veterinary-specific product. Sarcoids remain common enough and expensive enough to treat that there would be clear demand if a vaccine became available, but the timeline is uncertain.

What EcPV2 Research Means for Human Oncology

An unexpected dimension of equine papillomavirus research is its relevance to human medicine. Human papillomavirus causes a large fraction of cervical, anal, and oropharyngeal cancers, and the parallels between EcPV2-driven equine genital cancers and HPV-driven human genital cancers are striking enough that researchers have explicitly proposed horses as a natural-disease model for studying HPV-associated cancer.³¹ Both species develop squamous cell carcinomas driven by viral oncoproteins at mucosal sites. Both show a spectrum from benign papilloma through precancerous change to invasive carcinoma. Both have a subset of cancers at the same sites that arise independently of viral infection. And in both species, the virus can be found asymptomatically in healthy individuals who never develop disease. Studying the tumor immune microenvironment in equine cancers could offer insights that would be difficult or unethical to obtain from human patients, particularly around natural immune evasion and the factors that tip asymptomatic infection toward malignancy.