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Veterinary medicine and science2024; 10(1); e1342; doi: 10.1002/vms3.1342

Equus caballus papillomavirus type 2 (EcPV2)-associated benign penile lesions and squamous cell carcinomas.

Abstract: Squamous cell carcinoma is the most common genital, ocular and gastric tumour in horses. Equus caballus papillomavirus type 2 (EcPV2) DNA has been detected in several studies in equine penile squamous cell carcinomas (SCCs) and precursor lesions providing evidence of a causal role of EcPV2 in equine genital SCCs. Recently, EcPV2 E6/E7 nucleic acids were also detected in equine gastric SCCs, but further studies are required to determine the role of EcPV2 infection in the pathogenesis of gastric SCC. EcPV2 nucleic acids have been rarely described in ocular SCCs and precursor lesions. To investigate the presence of EcPV2 nucleic acids with polymerase chain reaction (PCR) and in situ hybridisation (ISH) in penile hyperplasias, papillomas and SCCs in horses and to determine whether EcPV2 nucleic acids can be detected in SCCs affecting other locations, including the stomach, ocular tissues and larynx. Twenty-one archival formalin-fixed paraffin embedded (FFPE) tissue samples, including 12 genital lesions comprising penile hyperplasias, papillomas and SCCs, 6 ocular SCCs, 2 gastric SCCs and 1 laryngeal SCC, were screened by PCR and ISH for EcPV2 E6/E7 DNA and mRNA. Archival FFPE tissue samples (eyelid and penile mucosa and preputium) from six horses without a diagnosis or history of neoplastic or papillomavirus-associated disease were included as controls. EcPV2 nucleic acids were detected by PCR and ISH in all genital lesions (12/12) and gastric SCCs (2/2), in two ocular SCCs (2/6) and in one laryngeal SCC (1/1). In control horses, one eyelid sample was positive in PCR but not in ISH. The remaining control samples were negative for EcPV2 E6/E7 nucleic acids in PCR and ISH. These results further support the role of EcPV2 infection in the development of equine genital SCCs and suggest that EcPV2 infection may also act as a predisposing factor for other SCCs in horses, including gastric, ocular and laryngeal SCCs.
© 2024 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.
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Publication Date: 2024-01-16 PubMed ID: 38227707PubMed Central: PMC10790322DOI: 10.1002/vms3.1342Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Research Overview

  • This study investigates the presence and potential role of Equus caballus papillomavirus type 2 (EcPV2) in benign and malignant squamous cell lesions, specifically in genital, gastric, ocular, and laryngeal tumors in horses.
  • It aims to clarify whether EcPV2 is involved in the pathogenesis of squamous cell carcinomas (SCCs) beyond the genital area, supporting its causal relationship with equine genital SCCs and possible involvement in other locations.

Background and Purpose

  • Squamous cell carcinoma (SCC) is identified as the most common tumor affecting the genital, ocular, and gastric regions in horses.
  • Previous studies detected EcPV2 DNA in equine penile SCCs and precursor lesions, indicating its possible causal role in genital SCC development.
  • EcPV2 E6/E7 nucleic acids have also been recently found in equine gastric SCCs, but their role there remains less clear and warrants further investigation.
  • EcPV2 DNA and RNAs have been rarely reported in ocular SCCs and precursor lesions, needing more clarity on the viral contribution.
  • This study’s main aim was to assess EcPV2 nucleic acids presence through polymerase chain reaction (PCR) and in situ hybridisation (ISH) in penile hyperplasias, papillomas, SCCs, and SCCs of other locations including stomach, eye, and larynx in horses.

Methods

  • The study analyzed 21 archived formalin-fixed paraffin-embedded (FFPE) tissue samples from horses, including:
    • 12 genital lesions: penile hyperplasias, papillomas, and SCCs
    • 6 ocular SCCs
    • 2 gastric SCCs
    • 1 laryngeal SCC
  • PCR and ISH were used to detect EcPV2 E6/E7 DNA and mRNA within these samples.
  • Control tissues included eyelid and penile mucosa/preputium from six horses without known neoplastic or papillomavirus-associated diseases.

Key Findings

  • EcPV2 nucleic acids (DNA and RNA) were detected using PCR and ISH in:
    • All genital lesions (12/12 samples)
    • Both gastric SCC samples (2/2)
    • Two out of six ocular SCC samples (2/6)
    • The single laryngeal SCC sample (1/1)
  • Among control horses, one eyelid sample was PCR positive but negative by ISH, suggesting low or non-pathogenic viral presence. The rest of the control samples were negative for EcPV2 nucleic acids.

Conclusions and Implications

  • The study strengthens the evidence that EcPV2 infection plays a significant causal role in the development of equine genital SCCs and their precursor lesions.
  • The consistent detection of EcPV2 in gastric SCCs supports the hypothesis that EcPV2 may also contribute to carcinogenesis in the equine stomach.
  • Detection of EcPV2 in some ocular and laryngeal SCCs suggests the virus might act as a predisposing or risk factor in SCC development outside the genital tract, but further research is needed to confirm this association and understand the mechanisms involved.
  • Control samples largely tested negative, indicating that EcPV2 presence is associated with neoplastic lesions rather than normal tissue, further underscoring its potential oncogenic role.

Overall Significance

  • The findings illuminate the broader oncogenic potential of EcPV2 in horses, linking it not only to genital tumors but also possibly to SCCs in other tissues.
  • These results may guide future diagnostic, preventive, and therapeutic strategies by targeting EcPV2 to reduce the burden of SCC in horses.
  • Moreover, understanding the virus’s role could stimulate the development of vaccines or antiviral treatments tailored to equine papillomavirus-associated cancers.

Cite This Article

APA
Tuomisto L, Virtanen J, Kegler K, Levanov L, Sukura A, Sironen T, Kareskoski M. (2024). Equus caballus papillomavirus type 2 (EcPV2)-associated benign penile lesions and squamous cell carcinomas. Vet Med Sci, 10(1), e1342. https://doi.org/10.1002/vms3.1342

Publication

Veterinary medicine and science
ISSN: 2053-1095
NlmUniqueID: 101678837
Country: England
Language: English
Volume: 10
Issue: 1
Pages: e1342
PII: e1342

Researcher Affiliations

Tuomisto, Laura
  • Faculty of Veterinary Medicine, Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
Virtanen, Jenni
  • Faculty of Veterinary Medicine, Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
  • Faculty of Medicine, Department of Virology, University of Helsinki, Helsinki, Finland.
Kegler, Kristel
  • Faculty of Veterinary Medicine, Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
Levanov, Lev
  • Faculty of Medicine, Department of Virology, University of Helsinki, Helsinki, Finland.
Sukura, Antti
  • Faculty of Veterinary Medicine, Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
Sironen, Tarja
  • Faculty of Veterinary Medicine, Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
  • Faculty of Medicine, Department of Virology, University of Helsinki, Helsinki, Finland.
Kareskoski, Maria
  • Faculty of Veterinary Medicine, Department of Production Animal Medicine, University of Helsinki, Helsinki, Finland.

MeSH Terms

  • Horses
  • Animals
  • DNA, Viral / analysis
  • Hyperplasia / veterinary
  • Horse Diseases / pathology
  • Papillomavirus Infections / veterinary
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / pathology
  • Carcinoma, Squamous Cell / veterinary
  • Carcinoma, Squamous Cell / pathology
  • Papillomaviridae / genetics
  • Papilloma / veterinary

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 32 references
  1. Alloway E, Linder K, May S, Rose T, DeLay J, Bender S, Tucker A, Luff J. A subset of equine gastric squamous cell carcinomas is associated with papillomavirus–2 infection. Veterinary Pathology 57(3), 427–431.
    pmc: PMC7335262pubmed: 32180540
  2. Bogaert L, Willemsen A, Vanderstraeten E, Bracho MA, Baere CD, Bravo IG, Martens A. EcPV2 DNA in equine genital squamous cell carcinomas and normal genital mucosa. Veterinary Microbiology 158(1–2), 33–41.
    pubmed: 22397936
  3. Cappelli K, Ciucis CGD, Mecocci S, Nervo T, Crescio MI, Pepe M, Gialletti R, Pietrucci D, Migone LF, Turco S, Mechelli L, Passamonti F, Drago C, Donato GG, Varello K, Modesto P, Chillemi G, Ghelardi A, Razzuoli E. Detection of papillomavirus type‐2 in asymptomatic Italian horses. Viruses 14(8), 1696.
    pmc: PMC9412442pubmed: 36016317
  4. Fischer NM, Favrot C, Birkmann K, Jackson M, Schwarzwald CC, Müller M, Tobler K, Geisseler M, Lange CE. Serum antibodies and DNA indicate a high prevalence of equine papillomavirus 2 (EcPV2) among horses in Switzerland. Veterinary Dermatology 25(3), 210–e54.
    pubmed: 24840327
  5. Gheit T. Mucosal and cutaneous human papillomavirus infections and cancer biology. Frontiers in Oncology 9, 355.
    pmc: PMC6517478pubmed: 31134154
  6. Greenwood S, Chow‐Lockerbie B, Epp T, Knight C, Wachoski‐Dark G, MacDonald‐Dickinson V, Wobeser B. Prevalence and prognostic impact of papillomavirus type 2 infection in equine squamous cell carcinomas in Western Canadian horses. Veterinary Pathology 57(5), 623–631.
    pubmed: 32812522
  7. Greenwood S, Chow‐Lockerbie B, Ramsauer S, Wachoski‐Dark G, Knight C, Wobeser B. Prevalence of papillomavirus type‐2 infection and seropositivity in asymptomatic Western Canadian horses. Veterinary Pathology 57(5), 623–631.
    pubmed: 32812517
  8. Hendrix DVH. Equine ocular squamous cell carcinoma. Clinical Techniques In Equine Practice 4(1), 87–94.
  9. Hibi H, Hatama S, Obata A, Shibahara T, Kadota K. Laryngeal squamous cell carcinoma and papilloma associated with papillomavirus 2 in a horse. Journal of Veterinary Medical Science 81(7), 1029–1033.
    pmc: PMC6656819pubmed: 31167980
  10. Jones SE. Papillomaviruses in equids: A decade of discovery and more to come?. Equine Veterinary Education 34(5), 236–240.
  11. Kainzbauer C, Rushton J, Tober R, Scase T, Nell B, Sykora S, Brandt S. Bovine papillomavirus type 1 and papillomavirus 2 in equine squamous cell carcinoma of the head and neck in a Connemara mare. Equine Veterinary Journal 44(1), 112–115.
    pubmed: 21668491
  12. Knight CG, Munday JS, Peters J, Dunowska M. Equine penile squamous cell carcinomas are associated with the presence of equine papillomavirus type 2 DNA sequences. Veterinary Pathology 48(6), 1190–1194.
    pubmed: 21282669
  13. Lale D, Geyer A, Jindra C, Cavalleri JMV, Ramsauer AS. Equine papillomavirus type 2‐associated, carcinomatous lesions of the penis and laryngopharynx of an elderly Icelandic horse gelding. Veterinary Record Case Reports 11(1), e508.
  14. Lange CE, Tobler K, Lehner A, Grest P, Welle MM, Schwarzwald CC, Favrot C. EcPV2 DNA in equine papillomas and in situ and invasive squamous cell carcinomas supports papillomavirus etiology. Veterinary Pathology 50(4), 686–692.
    pubmed: 23064881
  15. Li CX, Chang WS, Mitsakos K, Rodger J, Holmes EC, Hudson BJ. Identification of a novel equine papillomavirus in semen from a thoroughbred stallion with a penile lesion. Viruses 11(8), 713.
    pmc: PMC6723834pubmed: 31382657
  16. Linder KE, Bizikova P, Luff J, Zhou D, Yuan H, Breuhaus B, Nelson E, Mackay R. Generalized papillomatosis in three horses associated with a novel equine papillomavirus (EcPV8). Veterinary Dermatology 29(1), 72–e30.
    pubmed: 28833761
  17. Miglinci L, Reicher P, Nell B, Koch M, Jindra C, Brandt S. Detection of equine papillomaviruses and gamma‐herpesviruses in equine squamous cell carcinoma. Pathogens 12(2), 179.
    pmc: PMC9958655pubmed: 36839451
  18. Münger K, Phelps WC, Bubb V, Howley PM, Schlegel R. The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. Journal of Virology 63(10), 4417–4421.
    pmc: PMC251060pubmed: 2476573
  19. Newkirk KM, Hendrix DVH, Anis EA, Rohrbach BW, Ehrhart EJ, Lyons JA, Kania SA. Detection of papillomavirus in equine periocular and penile squamous cell carcinoma. Journal of Veterinary Diagnostic Investigation 26(1), 131–135.
    pubmed: 24323055
  20. Peters‐Kennedy J, Lange CE, Rine SL, Hackett RP. papillomavirus 8 (EcPV8) associated with multiple viral plaques, viral papillomas, and squamous cell carcinoma in a horse. Equine Veterinary Journal 51(4), 470–474.
    pubmed: 30456819
  21. Porcellato I, Modesto P, Cappelli K, Varello K, Peletto S, Brachelente C, Martini I, Mechelli L, Ferrari A, Ghelardi A, Razzuoli E. papillomavirus type 2 (EcPV2) in co‐occurring vulvar and gastric lesions of a pony. Research in Veterinary Science 132, 167–171.
    pubmed: 32590224
  22. Ramsauer AS, Wachoski‐Dark GL, Fraefel C, Tobler K, Brandt S, Knight CG, Favrot C, Grest P. Paving the way for more precise diagnosis of EcPV2‐associated equine penile lesions. BMC Veterinary Research 15(1), 356.
    pmc: PMC6805557pubmed: 31640696
  23. Scase T, Brandt S, Kainzbauer C, Sykora S, Bijmholt S, Hughes K, Sharpe S, Foote A. papillomavirus‐2 (EcPV‐2): An infectious cause for equine genital cancer. Equine Veterinary Journal 42(8), 738–745.
    pubmed: 21039805
  24. Straticò P, Razzuoli E, Hattab J, Guerri G, Celani G, Palozzo A, Bonanni D, Fruscione F, Varasano V, Petrizzi L, Marruchella G. Equine gastric squamous cell carcinoma in a Friesian stallion. Journal of Equine Veterinary Science 117, 104087.
    pubmed: 35908598
  25. Strohmayer C, Klang A, Kummer S, Walter I, Jindra C, Weissenbacher‐Lang C, Redmer T, Kneissl S, Brandt S. Tumor cell plasticity in equine papillomavirus‐positive versus‐negative squamous cell carcinoma of the head and neck. Pathogens 11(2), 266.
    pmc: PMC8875230pubmed: 35215208
  26. Sykora S, Brandt S. Papillomavirus infection and squamous cell carcinoma in horses. Veterinary Journal 223, 48–54.
    pubmed: 28671071
  27. Sykora S, Jindra C, Hofer M, Steinborn R, Brandt S. Equine papillomavirus type 2: An equine equivalent to human papillomavirus 16?. Journal of Veterinary 225, 3–8.
    pubmed: 28720295
  28. Tamura K, Stecher G, Kumar S. MEGA11: Molecular evolutionary genetics analysis version 11. Molecular Biology and Evolution 32(7), 3022–3027.
    pmc: PMC8233496pubmed: 33892491
  29. Van Den Top JGB, De Heer N, Klein WR, Ensink JM. Penile and preputial tumours in the horse: A retrospective study of 114 affected horses. Equine Veterinary Journal 40(6), 528–532.
    pubmed: 18487101
  30. Torres SMF, Koch SN. Papillomavirus‐associated diseases. Veterinary Clinics of North America: Equine Practice 29, 643–655.
    pubmed: 24267681
  31. Zaravinos A. An updated overview of HPV‐associated head and neck carcinomas. Oncotarget 5(12), 3956–3969.
    pmc: PMC4147298pubmed: 24970795
  32. Zhu KW, Affolter VK, Gaynor AM, Dela Cruz FN, Pesavento PA. Equine genital squamous cell carcinoma: in situ hybridization identifies a distinct subset containing papillomavirus 2. Veterinary Pathology 52(6), 1067–1072.
    pubmed: 25967135

Citations

This article has been cited 1 times.
  1. Quatember H, Nell B, Richter B, Rigler D, Dolezal M, Sykora S, Wallner B. Studying the Impact of the DDB2 T338M Missense Mutation on the Development of Equine Squamous Cell Carcinoma and Sarcoid. Animals (Basel) 2025 Mar 22;15(7).
    doi: 10.3390/ani15070911pubmed: 40218305google scholar: lookup
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