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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.
Publication Date: 2024-01-16 PubMed ID: 38227707PubMed Central: PMC10790322DOI: 10.1002/vms3.1342Google Scholar: Lookup
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  • Journal Article

Summary

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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

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.

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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