Equine papillomavirus is a virus that infects horses, leading to the development of benign growths known as papillomas or warts, typically on the skin or mucous membranes. These viruses belong to the Papillomaviridae family and are species-specific, with several types identified in horses. Papillomavirus infections are generally self-limiting, but in some cases, they can persist or lead to more severe conditions such as sarcoids, which are locally invasive skin tumors. This page compiles peer-reviewed research studies and scholarly articles that explore the biology, transmission, clinical presentation, and potential treatments of papillomavirus infections in horses.
Yamashita-Kawanishi N, Ito S, Chambers JK, Uchida K, Sato M, Chang HW, Knight C, van der Meer F, Haga T.Equus caballus papillomavirus type 2 (EcPV2) infection has been associated with genital squamous cell carcinoma (SCC) development in horses. However, very few reports on EcPV2-associated disease in Asia exist. Our study characterizes pathological and virological features of an EcPV2-associated vulvar SCC from a Japanese mare. Conventional PCR, in situ hybridization, reverse-transcriptase PCR and immunohistochemistry confirmed the presence and distribution of EcPV2 within the lesion and suggested that p53 degradation may not be the mechanism by which this virus induces neoplastic transformation...
Ramsauer AS, Wachoski-Dark GL, Fraefel C, Ackermann M, Brandt S, Grest P, Knight CG, Favrot C, Tobler K.There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is etiologically associated with the development of genital squamous cell carcinoma (SCC) and precursor lesions in equids. However, the precise mechanisms underlying neoplastic progression remain unknown. To allow the study of EcPV2-induced carcinogenesis, we aimed to establish a primary equine cell culture model of EcPV2 infection. Three-dimensional (3D) raft cultures were generated from equine penile perilesional skin, plaques and SCCs. Using histological, molecular biological and immunohistochemical methods, rafts...
Porcellato I, Mecocci S, Brachelente C, Cappelli K, Armando F, Tognoloni A, Chiaradia E, Stefanetti V, Mechelli L, Pepe M, Gialletti R, Passeri B....In horses, penile squamous cell carcinomas (epSCCs) are among the most common cutaneous neoplastic lesions. These tumors usually arise in benign lesions such as viral plaques and papillomas frequently induced by papillomavirus type 2 (EcPV2) infection. In the last decade, the introduction of immune checkpoint inhibitors (ICI) for the treatment of human cancers has demonstrated promising results. Among the most commonly targeted pathways, there is PD-1/PD-L1 and CTLA-4. The aim of this study is to investigate the expression of the PD-1/PD-L1 pathway and CTLA-4 in the tumor microenvironment of ...
Wenker C, Hoby S, Steck BL, Ramsauer AS, Blatter S, Tobler K.Equine sarcoids (ES) were diagnosed in 12 Somali wild asses (SWA) () from 10 different institutions of the SWA European Endangered Species Programme from 1976 to 2019. Samples of surgically excised masses, biopsies, or necropsy samples were submitted for histologic and virologic analysis. In addition, tissue samples from one onager (), one kulan (), and two Hartmann's mountain zebras (HMZ) () were examined. Histology confirmed the diagnosis of ES exhibiting the typical microscopic features. Polymerase chain reaction detected bovine papillomavirus type 1 (BPV1) DNA in eight SWA samples and bovi...
Mecocci S, Porcellato I, Armando F, Mechelli L, Brachelente C, Pepe M, Gialletti R, Passeri B, Modesto P, Ghelardi A, Cappelli K, Razzuoli E.Equine genital squamous cell carcinomas (egSCCs) are among the most common equine tumors after sarcoids, severely impairing animal health and welfare. papillomavirus type 2 (EcPV2) infection is often related to these tumors. The aim of this study was to clarify the molecular mechanisms behind egSCCs associated with EcPV2 infection, investigating receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in NF-kB pathway, together with the Wnt and IL17 signaling pathways. We analyzed the innate immune response through gene expression evaluation of key cytokines and transcription fac...
Armando F, Godizzi F, Razzuoli E, Leonardi F, Angelone M, Corradi A, Meloni D, Ferrari L, Passeri B.Squamous cell carcinoma (SCC) is one of the most frequent tumors of skin and muco-cutaneous junctions in the horse. Equine papillomavirus type 2 (EcPV2) has been detected in equine SCC of the oral tract and genitals, and recently also in the larynx. As human squamous cell carcinoma of the larynx (SCCL), it is strongly etiologically associated with high-risk papillomavirus (h-HPV) infection. This study focuses on tumor cells behavior in a naturally occurring tumor that can undergo the so-called epithelial to mesenchymal transition (EMT). A SCCL in a horse was investigated by immunohistochemistr...
Kaynarcalidan O, Oğuzoğlu TÇ.Papillomaviruses are oncogenic DNA viruses and induce hyperplastic benign lesions of both cutaneous and mucosal tissues in their various hosts, including many domestic and wild animals as well as humans. There are some Papillomavirus genotypes that can infect hosts different from their own, such as BPV 1 and BPV 2 originated from cattle, which can also infect horses and are responsible for fibroblastic tumours in horses. This review article summarizes the origin and evolution of papillomaviruses as an etiological agent in the historical process. The main focus in this review is the evaluation ...
Porcellato I, Mecocci S, Mechelli L, Cappelli K, Brachelente C, Pepe M, Orlandi M, Gialletti R, Passeri B, Ferrari A, Modesto P, Ghelardi A....Penile squamous cell carcinomas (SCCs) are common tumors in older horses, with poor prognosis mostly due to local invasion and recurrence. These tumors are thought to be mainly caused by papillomavirus type 2 (EcPV-2). The aim of this study is to characterize the tumor immune environment (TIME) in equine penile tumors. Equine penile epithelial tumors (17 epSCCs; 2 carcinomas , CIS; 1 papilloma, P) were retrospectively selected; immune infiltrate was assessed by histology and immunohistochemistry; RT-qPCR tested the expression of selected chemokines and EcPV-2 DNA and RNA. The results confirme...
Munday JS, Hardcastle MR, Sim M.A 10-year-old horse presented with two 3-cm diameter exophytic masses over the fetlock. Histology was consistent with a hyperplastic squamous papilloma and numerous cell changes consistent with papillomavirus (PV) infection were visible. Partial sequences of PV L1 and E1 ORFs were amplified using consensus PCR primers. The sequences were most similar to Equus caballus type 1 (EcPV1). However, as the sequences were only around 73% similar to EcPV1, they appear to be from a novel PV type that is likely to be within the genus. The papillomas were treated with topical imiquimod and resolved withi...
Greenwood S, Chow-Lockerbie B, Ramsauer S, Wachoski-Dark G, Knight C, Wobeser B. papillomavirus type 2 (EcPV-2) has been recognized as a potential cause of a subset of genital squamous cell carcinomas (SCCs) in horses. In the current study, we measured EcPV-2 seropositivity in 50 healthy horses from Western Canada, and these were compared to a herd of horses with known EcPV-2 exposure. Second, the presence of EcPV-2 DNA was measured using EcPV-2-specific PCR (polymerase chain reaction), performed on a variety of tissues collected at necropsy from 70 horses that lacked any history, gross, or histologic evidence of neoplasia or papillomavirus-associated disease. EcPV-2-spec...
Greenwood S, Chow-Lockerbie B, Epp T, Knight C, Wachoski-Dark G, MacDonald-Dickinson V, Wobeser B.Equus caballus papillomavirus type-2 (EcPV-2) has been proposed as a causal factor in equine genital squamous cell carcinoma (SCC). This study had 2 objectives: first, calculate the frequency of papillomavirus (PV) and EcPV-2 infection in papillomas, carcinomas in situ (CIS), and SCCs in Western Canadian horses; and second, determine if EcPV-2 status of equine SCCs is associated with overall survival (OS). EcPV-2 status of 115 archived tissue samples, spanning 6 years, was determined using broad spectrum (MY09/11) and EcPV-2-specific polymerase chain reaction (PCR) assays, EcPV-2-E6/E7 chromog...
Peters-Kennedy J, Lange CE, Ortved K.Aural plaques are associated with and thought to be caused by one or more Equus caballus papillomaviruses (EcPV). Aural plaques have not previously been reported to be associated with squamous cell carcinoma (SCC). Objective: To describe a horse with aural plaques and squamous cell carcinoma (SCC) on the right pinna. Methods: A 28-year-old thoroughbred gelding presented for multiple plaques and a mass on the right pinna. Methods: Pinnal resection, histopathological investigation, multiple conventional PCRs for papillomavirus DNA and Sanger sequencing were performed. Results: Multiple, raised, ...
Porcellato I, Modesto P, Cappelli K, Varello K, Peletto S, Brachelente C, Martini I, Mechelli L, Ferrari A, Ghelardi A, Razzuoli E.In horses, squamous cell carcinomas (SCCs) are the most common malignant tumors developing on non-pigmented skin, muco-cutaneous areas, like external genitalia, and, less frequently, in the stomach. Growing evidence suggests Equus caballus papillomavirus type 2 (EcPV2) as causative agent of genital SCCs. Our case report describes a 20-year-old, female, mixed-breed pony with co-occurring vulvar papilloma and in situ carcinoma and gastric SCC. Both lesions were positive for the same EcPV2, as confirmed by DNA sequencing. E6 mRNA expression was observed both in vulvar lesions and gastric SCC, whi...
Arthurs C, Suarez-Bonnet A, Willis C, Xie B, Machulla N, Mair TS, Cao K, Millar M, Thrasivoulou C, Priestnall SL, Ahmed A.Equine penile squamous cell carcinoma (EpSCC) is a relatively common cutaneous neoplasm with a poor prognosis. In this study, we aimed to determine the protein expression and colocalisation of FRA1, c-Myc, Cyclin D1, and MMP7 in normal (NT), tumour (T), hyperplastic epidermis and/or squamous papilloma (Hyp/Pap), poorly-differentiated (PDSCC), or well-differentiated (WDSCC) EpSCC using a tissue array approach. Further objectives were to correlate protein expression to (i) levels of inflammation, using a convolutional neural network (ii) equine papillomavirus 2 (EcPV2) infection, detected using ...
Onen EA.The aim of this study was to evaluate formalin-inactivated autovaccination to treat cutaneous papillomatosis and to perform molecular typing of the papillomavirus in four horses (two foals, one 3-year-old filly and a 5-year-old stallion). Methods: Histopathological slides of lesions were prepared and stained with haematoxylin and eosin (H&E) to establish a diagnosis that was based on observation koilocytosis, which is a pathognomonic cytopathic change that is associated with papillomatosis, using light microscopy. Polymerase chain reaction (PCR) and DNA sequencing were performed using the ...
Apprich V, Licka T, Freiler S, Gabriel C.Impaired keratinocyte differentiation has recently been suggested as a key event in equine hoof canker development. Koilocytotic appearance of keratinocytes, one of the most characteristic morphological alterations in hoof canker tissue, is also a common marker for papillomavirus (PV) infection, and bovine PV-1 and/or -2 (BPV-1/2) has previously been detected in equine canker patients. Therefore, the present study aimed to correlate the frequency and severity of koilocytotic keratinocytes with BPV detection in hoof canker samples. Hoof tissue of 5/18 canker-affected horses and 2/6 control hors...
Alloway E, Linder K, May S, Rose T, DeLay J, Bender S, Tucker A, Luff J.Squamous cell carcinoma (SCC) is the most common neoplasm of the equine stomach. However, the mechanisms underlying malignant transformation are unknown. As papillomavirus-2 (EcPV-2) is a likely cause of some genital SCCs, we hypothesized that EcPV-2 is associated with a subset of equine gastric SCCs. To this aim, we performed polymerase chain reaction (PCR) and in situ hybridization (ISH) for EcPV-2 E6/ E7 oncogenes on 11 gastric SCCs and on gastric samples from 15 control horses with no SCC. PCR for EcPV-2 was positive in 7/11 (64%) gastric SCCs; non-SCC gastric samples were all negative. I...
Ramsauer AS, Wachoski-Dark GL, Fraefel C, Tobler K, Brandt S, Knight CG, Favrot C, Grest P.There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is causally associated with the development of equine genital squamous cell carcinomas (SCCs). Early stages of disease present clinically as plaques or wart-like lesions which can gradually progress to tumoural lesions. Histologically these lesions are inconsistently described as benign hyperplasia, papilloma, penile intraepithelial neoplasia (PIN), carcinoma in situ (CIS) or SCC. Guidelines for histological classification of early SCC precursor lesions are not precisely defined, leading to potential misdiagnosis. Th...
Li CX, Chang WS, Mitsakos K, Rodger J, Holmes EC, Hudson BJ.Papillomaviruses (PVs) have been identified in a wide range of animal species and are associated with a variety of disease syndromes including classical papillomatosis, aural plaques, and genital papillomas. In horses, 13 PVs have been described to date, falling into six genera. Using total RNA sequencing (meta-transcriptomics) we identified a novel equine papillomavirus in semen taken from a thoroughbred stallion suffering a genital lesion, which was confirmed by nested RT-PCR. We designate this novel virus (EcPV9). The complete 7656 bp genome of EcPV9 exhibited similar characteristics to th...
Hibi H, Hatama S, Obata A, Shibahara T, Kadota K.A case of laryngeal squamous cell carcinoma (SCC) and squamous papilloma in a 19-year-old Thoroughbred stallion is described. The animal exhibited severe wheezing caused by laryngopharyngeal stenosis. Histological examination identified laryngeal, laryngotracheal, and guttural pouch tumor masses consisting of areas of SCC. In the epiglottic lesion, the overlying epithelium was replaced by papilloma cells, and superficial cells frequently had nuclear inclusion bodies that expressed oncoprotein E6, which is characteristic of high risk human papillomaviruses. The papillomatous epithelium was cont...
Ramsauer AS, Kubacki J, Favrot C, Ackermann M, Fraefel C, Tobler K.Equine papillomavirus type 2 (EcPV2) was discovered only recently, but it is found consistently in the context of genital squamous cell carcinomas (SCCs). Since neither cell cultures nor animal models exist, the characterization of this potential disease agent relies on the analysis of patient materials. To analyse the host and viral transcriptome in EcPV2-affected horses, genital tissue samples were collected from horses with EcPV2-positive lesions as well as from healthy EcPV2-negative horses. It was determined by RNA-seq analysis that there were 1957 differentially expressed (DE) host genes...
Peters-Kennedy J, Lange CE, Rine SL, Hackett RP.Equus caballus papillomavirus 8, a recently discovered virus, has been reported to cause generalised papillomavirus in horses. Objective: To describe a case in which multiple viral plaques, viral papillomas, squamous cell carcinoma (SCC) in situ and invasive squamous cell carcinoma (ISCC) were associated with EcPV8 in a horse. Methods: Case report. Methods: A 16-year-old mixed breed horse presented with dozens of raised crusted papular to nodular lesions over a course of 4 years. Masses had been surgically excised four times and cisplatin beads and emulsion were implanted on three different ...
Lee SK, Lee JK, Lee I.Equus caballus papillomavirus type 2 (EcPV-2) is implicated in genital neoplasms in horses, including equine penile papillomas, penile intraepithelial neoplasia, and squamous cell carcinoma (SCC). This virus seldom regresses spontaneously and can result in the development of SCC, which may result in significant clinical damage and economic cost. However, the prevalence of this virus is unknown in clinically unaffected horses. The aim of this study was to determine the prevalence of EcPV-2 DNA in genital swabs from healthy horses in the Republic of Korea and to investigate genetic variability w...
Mira J, Herman M, Zakia LS, Olivo G, Araújo JP, Borges AS, Oliveira-Filho JP.Despite the reported association between aural plaques and the presence of Equus caballus papillomavirus (EcPV), there are few data regarding the distribution of viral types in different geographic regions or possible correlations for different papillomaviruses and lesion characteristics. We detected the presence and frequency of EcPV (1-7) DNA in aural plaque biopsies of horses from different regions of Brazil and identified the patterns of these infections or coinfections and their possible association with lesion severity. A total of 108 aural plaque biopsies from horses in the 5 geopolitic...
Dong J, Zhu W, Yamashita N, Chambers JK, Uchida K, Kuwano A, Haga T.Although many studies have been conducted worldwide for Equus caballus papillomavirus (EcPV), limited information is available on the virus in Japan. We recently collected one classical viral papillomatosis sample (E150904) from a racing horse in Japan. Papillomavirus infection was confirmed by histopathology, immunohistochemistry and PCR assays, and the sample was diagnosed as epithelial papilloma. Full-length genome of the virus was cloned and sequenced. It was 7,613 bp in length and had the same genome organization with reported EcPV-1. Moreover, phylogenetic analysis based on L1 gene revea...
Linder KE, Bizikova P, Luff J, Zhou D, Yuan H, Breuhaus B, Nelson E, Mackay R.Currently, seven equine papillomaviruses (PV) are known and are associated with one of three different and distinct clinical presentations. Objective: To report the clinical, histopathological and immunohistochemical findings in horses with generalized papillomatosis associated with a novel equine PV, Equus caballus papillomavirus 8 (EcPV8). Methods: Three client-owned quarter horses. Methods: Case report, retrospective. Results: Dozens to thousands of papillomas involved the axilla, inguinal area and proximal limbs as well as the ventral and lateral neck, thorax and abdomen. Lesions were some...
Sykora S, Brandt S.Squamous cell carcinoma (SCC) is a common disease that seriously impairs the health and welfare of affected horses and other equids. In humans, almost all cervical carcinomas, a high percentage of anogenital SCCs and a subset of SCCs of the head and neck are caused by high-risk human papillomavirus (hrHPV) infection. Since hrHPV-induced human cancers and equine SCC have similar cytological and histopathological features, it has been hypothesised that equine SCCs could also be induced by papillomaviruses. This review provides an overview of the current evidence for an aetiological association b...
Sykora S, Jindra C, Hofer M, Steinborn R, Brandt S.In horses, squamous cell carcinomas (SCC) commonly affect the external genitals. There is growing evidence that equine papillomavirus type 2 (EcPV2) infection promotes disease development. To assess the possible association of EcPV2 with equine SCCs of the head (HSCC), 15 HSCC DNA samples were screened by E6/E7, E2, and LCR PCR and amplicons were analysed for sequence variations. The physical form of EcPV2 in HSCC, genital lesions, and smegma from horses with SCC was then addressed using EcPV2 immunocapture PCR (IC/PCR) for detection of virion, and E6 vs. E2 qPCR to investigate possible integr...
Hainisch EK, Abel-Reichwald H, Shafti-Keramat S, Pratscher B, Corteggio A, Borzacchiello G, Wetzig M, Jindra C, Tichy A, Kirnbauer R, Brandt S.We have previously shown that immunization of horses with bovine papillomavirus type 1 (BPV1) L1 virus-like particles (VLPs) is safe and highly immunogenic and that BPV1 and bovine papillomavirus type 2 (BPV2) are closely related serotypes. Here we evaluated the protective potential of a BPV1 L1 VLP vaccine against experimental BPV1 and BPV2 challenge and studied the safety and immunogenicity of a bivalent equine papillomavirus type 2 (EcPV2)/BPV1 L1 VLP vaccine. Fourteen healthy horses were immunized with BPV1 L1 VLPs (100 µg per injection) plus adjuvant on days 0 and 28, while seven remai...
Equine sarcoids develop upon bovine papillomavirus type 1 or 2 (BPV1, BPV2) infection in conjunction with trauma and represent the most common tumour disease in horses and other equids, including donkeys. In face of a sarcoid outbreak involving 12 of 111 donkeys and mules at the 'Rifugio degli Asinelli', a subsidiary charity organization of The Donkey Sanctuary, non-invasively collected sample material including crusts, dandruff, swabs and hair roots was collected from sarcoid-affected and 26 healthy donkeys, as well as dandruff from a grooming kit and tabanids caught from or in the vicinity o...
Pascoe RR, Summers PM.The results of a retrospective survey of tumours and tumour-like lesions encountered in horses in a veterinary practice in south east Queensland between 1956 and 1978 are presented. Forty-two per cent of the lesions were examined histologically. The most commonly occurring neoplasms were the equine sarcoid, papilloma and squamous cell carcinoma of the eye and external genitalia. Neurofibroma was an important problem in the eyelid region. Intra-abdominal tumours were rarely encountered in this series.
Ghim SJ, Rector A, Delius H, Sundberg JP, Jenson AB, Van Ranst M.Equus caballus papillomavirus type 1 (EcPV-1) was isolated from a cutaneous papilloma, the most common neoplasm in horses. The complete EcPV-1 nucleotide sequence and genomic organization were determined. Phylogenetic analysis showed that EcPV-1 is a close-to-root papillomavirus, with only distant relationships to the fibropapillomaviruses and the benign cutaneous papillomaviruses. To produce EcPV-1 virus-like particles (VLPs), the EcPV-1 L1 major capsid protein was expressed in insect cells using a recombinant baculovirus vector. The self-assembled EcPV-1 VLPs were morphologically indistingui...
Bogaert L, Willemsen A, Vanderstraeten E, Bracho MA, De Baere C, Bravo IG, Martens A.Squamous cell carcinoma (SCC) represents the most common genital malignant tumor in horses. Similar to humans, papillomaviruses (PVs) have been proposed as etiological agents and recently Equine papillomavirus type 2 (EcPV2) has been identified in a subset of genital SCCs. The goals of this study were (1) to determine the prevalence of EcPV2 DNA in tissue samples from equine genital SCCs, penile intraepithelial neoplasia (PIN) and penile papillomas, using EcPV2-specific PCR, (2) to examine the prevalence of latent EcPV2 infection in healthy genital mucosa and (3) to determine genetic variabili...
Munday JS, Knight CG, Luff JA.Papillomaviruses (PVs) cause disease in humans, dogs, cats, and horses. While there are some differences, many aspects of the pathogenesis, presentation, and treatment of these diseases are similar between the four species. In this review, the PV-induced diseases of humans are compared to the similar diseases that develop in the companion animal species. By comparing with the human diseases, it is possible to make assumptions about some of the less common and less well-studied diseases in the veterinary species. In the first part of this review, the PV lifecycle is discussed along with the cla...
Armando F, Mecocci S, Orlandi V, Porcellato I, Cappelli K, Mechelli L, Brachelente C, Pepe M, Gialletti R, Ghelardi A, Passeri B, Razzuoli E.Equine penile squamous cell carcinoma (epSCC) is the most frequent tumor of the external male genitalia, representing 67.5% of equine genital cancers. epSCC is associated with papilloma virus (PV) infection and has been recently proposed as a model for human PV-induced squamous cell carcinomas. It has already been suggested that epSCC might undergo epithelial-to-mesenchymal transition (EMT). This work aims to investigate in detail this process and the possible role of PV oncoproteins in epSCC. For this purpose, 18 penile SCCs were retrospectively selected and tested for both EcPV2 presence and...
Yuan Z, Gallagher A, Gault EA, Campo MS, Nasir L.Bovine papillomavirus (BPV) type 2 is involved in carcinogenesis of the urinary bladder in cattle, while BPV-1 is commonly associated with equine sarcoid tumours. In both cases the early viral proteins are expressed, but virion is not produced. Given the similarities in BPV biology between the tumours in cattle and horses, bovine bladder cancers and equine sarcoids were compared with respect to physical status, load of viral DNA and variability of the E5 open reading frame (ORF). Rolling circle amplification demonstrated that BPV-1 and BPV-2 genomes exist as double stranded, episomal, circular...
Torres SM, Koch SN.This article reviews various aspects of 3 clinical disorders associated with papillomavirus in horses commonly known as classical viral papillomatosis, genital papillomas/papillomatosis, and aural plaques. Classical papillomatosis is usually asymptomatic and spontaneously resolves within 1 to 9 months; therefore, treatment is often not required. Genital papillomas/papillomatosis have not been reported to spontaneously resolve, and there is increasing evidence that genital papillomas may evolve to in situ or invasive squamous cell carcinomas. Horses with aural plaques may be asymptomatic or may...
Théon AP, Pascoe JR, Carlson GP, Krag DN.Twenty horses with 30 lesions were studied to evaluate the effects of intratumoral chemotherapy with cisplatin in sesame oil on equine sarcoids (n = 19), squamous cell carcinomas (n = 7), and squamous cell papillomas (n = 4). Treatment consisted of 4 sessions of intratumoral cisplatin chemotherapy at 2-week intervals. A controlled-release formulation of cisplatin in sesame oil was used to limit drug egress from the injection site. Mean dosage per session was 0.97 (+/- 0.17, SEM) mg of cisplatin/cm3 of tumor tissue treated for tumor volumes ranging from 10 to 20 cm3. Dosage tended to be slightl...
Li CX, Chang WS, Mitsakos K, Rodger J, Holmes EC, Hudson BJ.Papillomaviruses (PVs) have been identified in a wide range of animal species and are associated with a variety of disease syndromes including classical papillomatosis, aural plaques, and genital papillomas. In horses, 13 PVs have been described to date, falling into six genera. Using total RNA sequencing (meta-transcriptomics) we identified a novel equine papillomavirus in semen taken from a thoroughbred stallion suffering a genital lesion, which was confirmed by nested RT-PCR. We designate this novel virus (EcPV9). The complete 7656 bp genome of EcPV9 exhibited similar characteristics to th...
Newkirk KM, Hendrix DV, Anis EA, Rohrbach BW, Ehrhart EJ, Lyons JA, Kania SA.Squamous cell carcinoma (SCC) is the most common tumor arising in the periocular and penile areas of horses. Both ultraviolet radiation and papillomaviruses have been implicated in the pathogenesis of SCC in various species, including the horse. This retrospective study used polymerase chain reaction (PCR) to detect papillomavirus DNA in archival biopsy samples from equine periocular and penile SCC from 3 different geographic areas (northeast, southeast, and central United States). Forty-two periocular SCCs were tested; none contained papillomavirus DNA. Twenty-two penile SCCs were tested, and...
Angelos JA, Marti E, Lazary S, Carmichael LE.The DNA from equine sarcoid samples from New York State and Switzerland was isolated and probed with bovine papillomavirus type 1 (BPV-1) to determine if BPV genomes were present. Twelve of 13 sarcoids from New York State and 17/20 sarcoids from Switzerland contained DNA that hybridized to the BPV-1 probe. Restriction enzyme analysis of the positive samples demonstrated restriction fragment profiles characteristic of BPV-1 in 22 sarcoids and restriction fragment profiles characteristic of bovine papillomavirus type 2 (BPV-2) in 7 sarcoids. In addition, three tissues histologically diagnosed as...
Yuan Z, Gobeil PA, Campo MS, Nasir L.Papillomaviruses are DNA viruses that cause tumours of the skin in humans and animals. The natural host of bovine papillomavirus is cattle, but also equids, resulting in tumours termed sarcoids. Matrix metalloproteinase 1 (MMP-1) expression is up-regulated in sarcoid fibroblasts and tumours. We extended our observation to other MMPs and determined whether MMPs induced invasion of sarcoid fibroblasts. Collagenase (MMP-1) and Gelatinase (MMP-2, MMP-9) were over-expressed in sarcoid fibroblasts and tumours. The fibroblasts were invasive in a 3D/matrigel invasion assay system. Inhibition of MMP by...
Bloch N, Breen M, Spradbrow PB.Seventy six formalin-fixed paraffin-embedded sarcoids from 62 Australian horses, collected over a ten year period, were examined for the presence of genomic sequences from bovine papillomavirus 1 and 2 (BPV1, BPV2) with the polymerase chain reaction (PCR). Sequences that could be amplified by primers specific for BPV1 and BPV2 were present in 56 of the 76 sarcoids (73%). A restriction site present in BPV1 and absent from BPV2 was detected in 28 of 34 amplified products that were treated with endonuclease.
Armando F, Godizzi F, Razzuoli E, Leonardi F, Angelone M, Corradi A, Meloni D, Ferrari L, Passeri B.Squamous cell carcinoma (SCC) is one of the most frequent tumors of skin and muco-cutaneous junctions in the horse. Equine papillomavirus type 2 (EcPV2) has been detected in equine SCC of the oral tract and genitals, and recently also in the larynx. As human squamous cell carcinoma of the larynx (SCCL), it is strongly etiologically associated with high-risk papillomavirus (h-HPV) infection. This study focuses on tumor cells behavior in a naturally occurring tumor that can undergo the so-called epithelial to mesenchymal transition (EMT). A SCCL in a horse was investigated by immunohistochemistr...
Borzacchiello G, Mogavero S, De Vita G, Roperto S, Della Salda L, Roperto F.The equine sarcoid is the most common dermatologic neoplasm reported in horses. Bovine papillomavirus (BPV) types 1 and 2 are associated with sarcoids, in which the expression of the major transforming oncoprotein (E5) is often recorded. The transformation activity of the virus is due to the binding of the E5 to the platelet-derived growth factor beta receptor (PDGFbeta-r). In the present study, we show by Western blot in 4 sarcoid samples and 3 normal equine skin samples that the PDGFbeta-r is more phosphorylated in sarcoid tissue than in normal skin (P < .001). Furthermore, the physical i...
Wilson AD, Armstrong ELR, Gofton RG, Mason J, De Toit N, Day MJ.Sarcoids are common skin tumours of horses and donkeys that are characterised by persistent proliferation of dermal fibroblasts associated with the presence of bovine papillomavirus (BPV) DNA. Some early BPV proteins have been demonstrated within sarcoids and RNA containing both early and late transcripts is present, yet it remains unclear whether late replication of BPV, culminating in the production of infectious virus particles, can occur in equids. Here we report that BPV1 RNA isolated from equine sarcoids encodes a unique deletion of four residues within the L2 protein suggesting a novel ...
Hainisch EK, Abel-Reichwald H, Shafti-Keramat S, Pratscher B, Corteggio A, Borzacchiello G, Wetzig M, Jindra C, Tichy A, Kirnbauer R, Brandt S.We have previously shown that immunization of horses with bovine papillomavirus type 1 (BPV1) L1 virus-like particles (VLPs) is safe and highly immunogenic and that BPV1 and bovine papillomavirus type 2 (BPV2) are closely related serotypes. Here we evaluated the protective potential of a BPV1 L1 VLP vaccine against experimental BPV1 and BPV2 challenge and studied the safety and immunogenicity of a bivalent equine papillomavirus type 2 (EcPV2)/BPV1 L1 VLP vaccine. Fourteen healthy horses were immunized with BPV1 L1 VLPs (100 µg per injection) plus adjuvant on days 0 and 28, while seven remai...
Kainzbauer C, Rushton J, Tober R, Scase T, Nell B, Sykora S, Brandt S.In January 2010, 18 months after excision of an ocular squamous cell carcinoma (SCC), a Connemara mare presented with anorexia and periorbital/parotideal lesions. Post mortem examination revealed these lesions as forming one entity, with 2 additional growths in the retropharyngeal region and the left jugular groove, respectively. The lesions were confirmed histopathologically as SCCs. Using PCR, peripheral blood mononuclear cells (PBMCs) from 2008 and 2010, tumour tissue, intact skin and vulval mucosa were screened for Equus caballus papillomavirus type 2 (EcPV-2) and bovine papillomavirus typ...
Haralambus R, Burgstaller J, Klukowska-Rötzler J, Steinborn R, Buchinger S, Gerber V, Brandt S.Sarcoids are nonmetastasising, yet locally aggressive skin tumours that constitute the most frequent neoplasm in equids. Infection by bovine papillomaviruses types 1 and 2 (BPV-1, BPV-2) has been recognised as major causative factor in sarcoid pathogenesis, but a possible correlation of intralesional virus load with disease severity has not been established thus far. Objective: Given the pathogenic role of BPV-1 and BPV-2 in sarcoid disease, we suggest that intralesional viral DNA concentration may reflect the degree of affection. Methods: Severity of disease was addressed by recording the tum...
Greenwood S, Chow-Lockerbie B, Epp T, Knight C, Wachoski-Dark G, MacDonald-Dickinson V, Wobeser B.Equus caballus papillomavirus type-2 (EcPV-2) has been proposed as a causal factor in equine genital squamous cell carcinoma (SCC). This study had 2 objectives: first, calculate the frequency of papillomavirus (PV) and EcPV-2 infection in papillomas, carcinomas in situ (CIS), and SCCs in Western Canadian horses; and second, determine if EcPV-2 status of equine SCCs is associated with overall survival (OS). EcPV-2 status of 115 archived tissue samples, spanning 6 years, was determined using broad spectrum (MY09/11) and EcPV-2-specific polymerase chain reaction (PCR) assays, EcPV-2-E6/E7 chromog...
Lange CE, Tobler K, Ackermann M, Favrot C.The number of recognized papillomavirus (PV) species and potential PV genera has dramatically been increasing throughout the past decade. It seems that every host species might potentially harbour a large set of PVs, while the PVs of each species appear to belong to only a few genera. In horses at least three conditions beside the equine sarcoid have been described, being supposedly PV induced namely classical equine papillomas, genital papillomas and aural plaques. We were able to identify the DNA of novel equine PVs (EcPVs) in the two latter disorders where PV involvement had been predicted....
Strohmayer C, Klang A, Kummer S, Walter I, Jindra C, Weissenbacher-Lang C, Redmer T, Kneissl S, Brandt S.Squamous cell carcinoma of the head and neck (HNSCC) is a common malignant tumor in humans and animals. In humans, papillomavirus (PV)-induced HNSCCs have a better prognosis than papillomavirus-unrelated HNSCCs. The ability of tumor cells to switch from epithelial to mesenchymal, endothelial, or therapy-resistant stem-cell-like phenotypes promotes disease progression and metastasis. In equine HNSCC, PV-association and tumor cell phenotype switching are poorly understood. We screened 49 equine HNSCCs for equine PV (EcPV) type 2, 3 and 5 infection. Subsequently, PV-positive versus -negative lesi...
van den Top JG, Harkema L, Lange C, Ensink JM, van de Lest CH, Barneveld A, van Weeren PR, Gröne A, Martens A.Equine penile and preputial squamous cell carcinoma (SCC) is a potentially lethal disease of which little is known regarding the relationship between tumour characteristics and prognosis. Objective: To assess the relationship between tumour differentiation grade (tumour subtype), presence of papillomaviruses, expression of viral genes (E2, E6, L1), nuclear proteins p53 and Ki67 and metastasis in equine penile and preputial SCC and to assess the relationship of tumour subtype, presence of papillomavirus type 2, p53 and Ki67 with survival. Methods: Retrospective case-control study using archived...
Kaynarcalidan O, Oğuzoğlu TÇ.Papillomaviruses are oncogenic DNA viruses and induce hyperplastic benign lesions of both cutaneous and mucosal tissues in their various hosts, including many domestic and wild animals as well as humans. There are some Papillomavirus genotypes that can infect hosts different from their own, such as BPV 1 and BPV 2 originated from cattle, which can also infect horses and are responsible for fibroblastic tumours in horses. This review article summarizes the origin and evolution of papillomaviruses as an etiological agent in the historical process. The main focus in this review is the evaluation ...
Stadler S, Kainzbauer C, Haralambus R, Brehm W, Hainisch E, Brandt S.Based on the anecdotally reported eradication of a sarcoid using aciclovir cream, the curative potential of this ointment was investigated in 22 sarcoid-affected horses referred to the Equine Clinic Tillysburg, Austria, between 2006 and 2009. Sarcoid disease was diagnosed by clinical examination and bovine papillomavirus types 1 and 2 from intact skin and tumour tissue. As nine horses had more than one lesion, a total of 47 sarcoids were treated by daily topical application of aciclovir 5 per cent cream for a period of two to six months; in four horses, surgical tumour ablation was performed b...
Fischer NM, Favrot C, Birkmann K, Jackson M, Schwarzwald CC, Müller M, Tobler K, Geisseler M, Lange CE.The DNA of equine papillomavirus type 2 (EcPV2) is consistently found in equine papillomas and squamous cell carcinomas, indicating a causal association of EcPV2 in the pathogenesis of these tumours; however, little is known about the prevalence of this virus. Objective: The aim of this study was to determine the geno- and seroprevalence of EcPV2 in clinically healthy horses in Switzerland. Methods: Fifty horses presented to the equine department of the university clinic, displaying no skin or mucous membrane lesions or severe signs of other diseases, were sampled. Methods: Cytobrush samples ...
Mecocci S, Porcellato I, Armando F, Mechelli L, Brachelente C, Pepe M, Gialletti R, Passeri B, Modesto P, Ghelardi A, Cappelli K, Razzuoli E.Equine genital squamous cell carcinomas (egSCCs) are among the most common equine tumors after sarcoids, severely impairing animal health and welfare. papillomavirus type 2 (EcPV2) infection is often related to these tumors. The aim of this study was to clarify the molecular mechanisms behind egSCCs associated with EcPV2 infection, investigating receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in NF-kB pathway, together with the Wnt and IL17 signaling pathways. We analyzed the innate immune response through gene expression evaluation of key cytokines and transcription fac...
Knight CG, Munday JS, Rosa BV, Kiupel M.A 9-year-old gelding presented with approximately 100 papillomas that covered about 75% of the distal penis. Biopsy was performed, and histology showed evidence of viral cytopathic change and koilocytosis. Polymerase chain reaction using DNA extracted from biopsied tissue amplified equine papillomavirus type 2 (EcPV-2) DNA sequences. Sixteen months later, the horse was re-examined and the appearance of the papillomas was unchanged. Equine papillomavirus type 2 DNA sequences were again amplified from both biopsied tissue and swabs of the penis. Papillomavirus was localized to the lesions by imm...
Löhr CV, Juan-Sallés C, Rosas-Rosas A, Parás García A, Garner MM, Teifke JP.Sarcoids were diagnosed in two captive zebras from different facilities. Zebra 1 (Equus burchellii boehmi) was a 4.5-yr-old, captive-born male that presented with a 9- by 7-cm inguinal mass. Seven months after surgical excision of the inguinal mass, the zebra presented with a similar lesion in the right upper eyelid that has relapsed repeatedly and has not responded to treatment including local cisplatin injections and cryosurgery. Zebra 2 (of undetermined taxon) was housed at a private wild animal farm. The zebra presented with a single, raised, 2.5- by 2.0- by 2.0-cm, ulcerated mass on the n...
Nixon C, Chambers G, Ellsmore V, Campo MS, Burr P, Argyle DJ, Reid SW, Nasir L.Equine sarcoids are benign fibroblastic skin tumours affecting equids worldwide. Whilst the pathogenesis is not entirely understood, infection with Bovine Papillomavirus (BPV) types 1 and 2 has been implicated as a major factor in the disease process, however the mechanism by which BPV infection contributes to sarcoid pathology is not clear. In this study, we show that the majority of sarcoids express the BPV-1 major transforming gene E6. Further, we demonstrate that sarcoid lesions are not associated with high levels of cellular proliferation as assessed by Ki67 expression or with expression ...
