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Pathogens (Basel, Switzerland)2024; 13(7); 597; doi: 10.3390/pathogens13070597

Histopathological and Virological Findings of a Penile Papilloma in a Japanese Stallion with Equus Caballus Papillomavirus 2 (EcPV2).

Abstract: Equus caballus papillomavirus 2 (EcPV2) is known to cause genital neoplasms in horses. However, reports on EcPV2 in Japan and Asia are limited. Herein, we present the histopathological and virological findings of the first reported case of an EcPV2-associated penile mass in Japan. The patient was a 22-year-old stallion with a history of breeding in Japan and abroad. Histopathological examination contained RNA in situ hybridization targeting the E6/E7 region and an immunohistochemical approach, and whole-genome sequencing was conducted within the viral examination. Proliferating epidermal cells were observed, and EcPV2 E6/E7 mRNA was detected within the epidermis, which was interpreted as viral papilloma. The detected EcPV2 virus was genetically close to foreign strains and different from the strain previously reported from a Japanese mare. This suggests that various types of EcPV2 might already exist among horses in Japan. Although the mass reported herein was not malignant based on histopathological findings and the absence of recurrence, its presence on the penis would be an obstacle to breeding. These results provide a better understanding of the pathogenesis and diversity of EcPV2.
Publication Date: 2024-07-19 PubMed ID: 39057823PubMed Central: PMC11279536DOI: 10.3390/pathogens13070597Google Scholar: Lookup
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Summary

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Overview

  • This study reports the first case in Japan of a penile papilloma in a stallion caused by Equus caballus papillomavirus 2 (EcPV2), providing detailed histopathological and virological analysis.
  • The research highlights the genetic diversity of EcPV2 strains in Japan and discusses the clinical implications of these viral-induced neoplasms in horses.

Background

  • Equus caballus papillomavirus 2 (EcPV2) is a virus known to cause genital tumors in horses.
  • While EcPV2 infections have been documented in various regions, cases in Japan and broader Asia are scarcely reported.
  • Understanding the characteristics and diversity of EcPV2 in Japan is important for equine health management, especially breeding practices.

Case Description

  • The subject was a 22-year-old stallion with a history of breeding both in Japan and overseas.
  • A penile mass was identified, raising concerns due to its potential impact on reproduction and horse health.

Methods and Analysis

  • Histopathological examination: Tissue samples from the penile mass showed proliferating epidermal (skin) cells suggestive of a papilloma rather than malignancy.
  • Virological investigation:
    • RNA in situ hybridization targeting the E6/E7 region of the viral genome was used to detect viral mRNA within the tissue, confirming active viral infection.
    • Immunohistochemistry techniques were applied to further characterize the viral presence in the epidermis.
    • Whole-genome sequencing of the detected virus was performed to analyze the genetic makeup and compare it with known EcPV2 strains.

Key Findings

  • Active EcPV2 infection was confirmed in the penile papilloma through detection of viral E6/E7 mRNA within the proliferating epidermal cells.
  • The virus strain identified was genetically closer to foreign EcPV2 strains than to the strain previously reported in a Japanese mare, indicating the existence of multiple EcPV2 variants in Japan.
  • The histopathological features indicated a benign papilloma, as there was no evidence of malignancy or recurrence of the mass following treatment.
  • Despite its benign nature, the penile papilloma poses a complication for breeding due to its location on the reproductive organ.

Implications and Significance

  • Recognition of EcPV2’s role in causing genital papillomas enhances understanding of equine viral diseases in Japan.
  • The genetic diversity of EcPV2 strains suggests multiple viral introductions or endemic variants within the Japanese horse population.
  • Veterinarians and breeders should be aware of EcPV2 infections and their potential impact on horse breeding and health.
  • This case underscores the need for surveillance and further research on papillomavirus infections in horses across Asia.

Cite This Article

APA
Uchida-Fujii E, Kato Y, Ueno T, Numasawa Y, Yusa S, Haga T. (2024). Histopathological and Virological Findings of a Penile Papilloma in a Japanese Stallion with Equus Caballus Papillomavirus 2 (EcPV2). Pathogens, 13(7), 597. https://doi.org/10.3390/pathogens13070597

Publication

ISSN: 2076-0817
NlmUniqueID: 101596317
Country: Switzerland
Language: English
Volume: 13
Issue: 7
PII: 597

Researcher Affiliations

Uchida-Fujii, Eri
  • Division of Infection Control and Disease Prevention, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Kato, Yusei
  • Division of Infection Control and Disease Prevention, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Ueno, Takanori
  • Microbiology Division, Equine Research Institute, Japan Racing Association, 1400-4 Shiba, Shimotsuke 329-0412, Tochigi, Japan.
Numasawa, Yasuko
  • Division of Infection Control and Disease Prevention, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Yusa, Shigeki
  • The Japan Bloodhorse Breeders' Association Shizunai Stallion Station, 517 Shizunaitahara, Shinhidaka-cho 056-0144, Hokkaido, Japan.
Haga, Takeshi
  • Division of Infection Control and Disease Prevention, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
  • Laboratory of OSG Veterinary Science for Global Disease Management, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

MeSH Terms

  • Animals
  • Male
  • Horse Diseases / virology
  • Horse Diseases / pathology
  • Horses
  • Japan
  • Papilloma / virology
  • Papilloma / veterinary
  • Papilloma / pathology
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / veterinary
  • Papillomavirus Infections / virology
  • Papillomavirus Infections / pathology
  • Penile Neoplasms / virology
  • Penile Neoplasms / veterinary
  • Penile Neoplasms / pathology
  • Penis / virology
  • Penis / pathology

Grant Funding

  • JPJ009417 / Ministry of Agriculture, Forestry and Fisheries

Conflict of Interest Statement

Takanori Ueno was employed by Japan Racing Association as a Department Manager, and Shigeki Yusa was employed by the Japan Bloodhorse Breeder’s Association as a Farm Manager. Takeshi Haga was appointed as Project Professor of Laboratory of OSG Veterinary Science for Global Disease Management, an endowment laboratory from OSG Corporation. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

References

This article includes 21 references
  1. Turco S, Gabbianelli F, Mavian CN, Pietrucci D, De Paolis L, Gialletti R, Mechelli L, De Ciucis CG, Cappelli K, Dell’Anno F. Genetic Characterization of a Novel Equus Caballus Papillomavirus Isolated from a Thoroughbred Mare. Viruses 2023;15:650.
    doi: 10.3390/v15030650pmc: PMC10059215pubmed: 36992359google scholar: lookup
  2. Scase T, Brandt S, Kainzbauer C, Sykora S, Bijmholt S, Hughes K, Sharpe S, Foote A. Equus Caballus Papillomavirus-2 (EcPV-2): An Infectious Cause for Equine Genital Cancer?. Equine Vet. J. 2010;42:738–745.
  3. Bogaert L, Willemsen A, Vanderstraeten E, Bracho MA, De Baere C, Bravo IG, Martens A. EcPV2 DNA in Equine Genital Squamous Cell Carcinomas and Normal Genital Mucosa. Vet. Microbiol. 2012;158:33–41.
    doi: 10.1016/j.vetmic.2012.02.005pubmed: 22397936google scholar: lookup
  4. Munday JS, Knight CG, Luff JA. Papillomaviral Skin Diseases of Humans, Dogs, Cats and Horses: A Comparative Review. Part 2: Pre-Neoplastic and Neoplastic Diseases. Vet. J. 2022;288:105898.
    doi: 10.1016/j.tvjl.2022.105898pmc: PMC11459685pubmed: 36152994google scholar: lookup
  5. Sykora S, Brandt S. Papillomavirus Infection and Squamous Cell Carcinoma in Horses. Vet. J. 2017;223:48–54.
    doi: 10.1016/j.tvjl.2017.05.007pubmed: 28671071google scholar: lookup
  6. Greenwood S, Chow-Lockerbie B, Epp T, Knight C, Wachoski-Dark G, MacDonald-Dickinson V, Wobeser B. Prevalence and Prognostic Impact of Equus Caballus Papillomavirus Type 2 Infection in Equine Squamous Cell Carcinomas in Western Canadian Horses. Vet. Pathol. 2020;57:623–631.
    doi: 10.1177/0300985820941266pubmed: 32812522google scholar: lookup
  7. Greenwood S, Chow-Lockerbie B, Ramsauer S, Wachoski-Dark G, Knight C, Wobeser B. Prevalence of Equus Caballus Papillomavirus Type-2 Infection and Seropositivity in Asymptomatic Western Canadian Horses. Vet. Pathol. 2020;57:632–641.
    doi: 10.1177/0300985820941270pubmed: 32812517google scholar: lookup
  8. 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. Vet. Pathol. 2011;48:1190–1194.
    doi: 10.1177/0300985810396516pubmed: 21282669google scholar: lookup
  9. Knight CG, Dunowska M, Munday JS, Peters-Kennedy J, Rosa BV. Comparison of the Levels of Equus Caballus Papillomavirus Type 2 (EcPV-2) DNA in Equine Squamous Cell Carcinomas and Non-Cancerous Tissues Using Quantitative PCR. Vet. Microbiol. 2013;166:257–262.
    doi: 10.1016/j.vetmic.2013.06.004pubmed: 23845733google scholar: lookup
  10. Vichi G, Porcellato I, Mechelli L, Fantauzzo G, Razzuoli E, Modesto P, Mecocci S, Brachelente C. Co-Occurrence of Papillomas Related to Equus Caballus Papillomavirus Type 2 and Cutaneous Habronemiasis. Equine Vet. Educ. 2022;34:e193–e197.
    doi: 10.1111/eve.13479google scholar: lookup
  11. 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 Equus Caballus Papillomavirus-2 Infection. Vet. Pathol. 2020;57:427–431.
    doi: 10.1177/0300985820908797pmc: PMC7335262pubmed: 32180540google scholar: lookup
  12. Knight CG, Munday JS, Rosa BV, Kiupel M. Persistent, Widespread Papilloma Formation on the Penis of a Horse: A Novel Presentation of Equine Papillomavirus Type 2 Infection. Vet. Dermatol. 2011;22:570–574.
  13. Yamashita-Kawanishi N, Haga T. Anogenital-Associated Papillomaviruses in Animals: Focusing on Bos Taurus Papillomaviruses. Pathogens 2020;9:993.
    doi: 10.3390/pathogens9120993pmc: PMC7760238pubmed: 33260814google scholar: lookup
  14. Lee S-K, Yoon J, Kim Y, Lee I. Penile Neoplasm Associated with Equus Caballus Papillomavirus Type 2 Infection in a Miniature Appaloosa. Korean J. Vet. Res. 2024;64:e8.
    doi: 10.14405/kjvr.20240011google scholar: lookup
  15. Yamashita-Kawanishi N, Ito S, Chambers JK, Uchida K, Sato M, Chang HW, Knight C, van der Meer F, Haga T. Vulvar Squamous Cell Carcinoma Associated with Equus Caballus Papillomavirus Type 2 Infection in a Japanese Mare. Tumour Virus Res. 2021;12:200226.
    doi: 10.1016/j.tvr.2021.200226pmc: PMC8496317pubmed: 34543774google scholar: lookup
  16. Lee S-K, Lee JK, Lee I. Molecular Detection of Equus Caballus Papillomavirus Type 2 in Genital Swabs From Healthy Horses in the Republic of Korea. J. Equine Vet. Sci. 2019;72:97–100.
    doi: 10.1016/j.jevs.2018.10.015pubmed: 30929791google scholar: lookup
  17. Hibi H, Hatama S, Obata A, Shibahara T, Kadota K. Laryngeal Squamous Cell Carcinoma and Papilloma Associated with Equus Caballus Papillomavirus 2 in a Horse. J. Vet. Med. Sci. 2019;81:1029–1033.
    doi: 10.1292/jvms.18-0461pmc: PMC6656819pubmed: 31167980google scholar: lookup
  18. Tamura K, Stecher G, Kumar S. MEGA11: Molecular Evolutionary Genetics Analysis Version 11. Mol. Biol. Evol. 2021;38:3022–3027.
    doi: 10.1093/molbev/msab120pmc: PMC8233496pubmed: 33892491google scholar: lookup
  19. 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 Vet. Res. 2019;15:356.
    doi: 10.1186/s12917-019-2097-0pmc: PMC6805557pubmed: 31640696google scholar: lookup
  20. Evans MF, Peng Z, Clark KM, Adamson CS-C, Ma X-J, Wu X, Wang H, Luo Y, Cooper K. HPV E6/E7 RNA In Situ Hybridization Signal Patterns as Biomarkers of Three-Tier Cervical Intraepithelial Neoplasia Grade. PLoS ONE 2014;9:e91142.
  21. Yamashita-Kawanishi N, Chambers JK, Uchida K, Tobari Y, Yoshimura H, Yamamoto M, Yumoto N, Aoki H, Sugiura K, Higuchi T. Genomic Characterisation of Bovine Papillomavirus Types 1 and 2 Identified in Equine Sarcoids in Japan. Equine Vet. J. 2021;53:1199–1209.
    doi: 10.1111/evj.13398pubmed: 33300145google scholar: lookup

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