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Tumour virus research2021; 12; 200226; doi: 10.1016/j.tvr.2021.200226

Vulvar squamous cell carcinoma associated with Equus caballus papillomavirus type 2 infection in a Japanese mare.

Abstract: 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. The complete viral sequence in this Japanese case shows near perfect sequence homology with European reference strains of EcPV2, which may be useful when considering the target for future EcPV2 vaccine development. This report also serves to highlight the importance of EcPV2 in female (vulvar) neoplasia, which is less commonly recognized than EcPV2-induced male (penile or preputial) neoplasia. Finally, the SCC described in this mare was an unusual acantholytic variant that has not been reported previously in horses. It is the first report of EcPV2 identified from genital SCC in Asia and underscores the likely worldwide distribution of this virus and its consistent association with equine genital neoplasia.
Publication Date: 2021-09-17 PubMed ID: 34543774PubMed Central: PMC8496317DOI: 10.1016/j.tvr.2021.200226Google Scholar: Lookup
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  • Journal Article

Summary

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The research article explores a case of vulvar squamous cell carcinoma (SCC) connected to Equus caballus papillomavirus type 2 (EcPV2) in a Japanese mare, marking the first instance of EcPV2-related genital SCC in Asia. The study delves into the pathological and virological aspects, documents the virus sequence, and highlights the lesser-known impact of EcPV2 on female equine neoplasia.

Association of EcPV2 and Squamous Cell Carcinoma

  • The research focuses on the connection between EcPV2 infection and the development of squamous cell carcinoma (SCC) in horses. Notably, the study examines a case of vulvar SCC, linked to EcPV2 infection, found in a Japanese mare.
  • An established correlation exists between EcPV2 and genital SCC development in horses but very few studies exist in Asia. The current research helps fill this knowledge gap.

Pathological and Virological Features

  • The study defines the pathological and virological traits of the EcPV2-related vulvar SCC. Various techniques such as Conventional PCR, in situ hybridization, reverse-transcriptase PCR and immunohistochemistry were used to confirm the presence and distribution of EcPV2 within the lesion.
  • The research suggests that the degradation of the protein p53 may not be the mechanism through which the virus induces neoplastic transformation, implying the involvement of other processes in the development of the cancer.

Study of the Virus Sequence

  • Researchers also studied and recorded the complete viral sequence in this Japanese case, noting its near perfect sequence homology with European strains of EcPV2. This is valuable information to consider when developing a future EcPV2 vaccine.

Highlighting the Impact of EcPV2 on Female Equine Neoplasia

  • This research stresses the significance of EcPV2 in female neoplasia, specifically vulvar neoplasia, which is often less recognized than EcPV2-induced male neoplasia.
  • The SCC described in this Japanese mare was an unusual acantholytic variant, which provides extra insights for future research. It’s an unreported variant in horses and could lead to more comprehensive understanding of the disease.

Underlining the Worldwide Distribution of EcPV2

  • The detection of EcPV2 in genital SCC in Asia, paired with the sequence resemblance to European strains, underscores the possible worldwide distribution of the virus. The report emphasizes that the virus is likely consistently associated with equine genital neoplasia, underscoring the need for broad-based awareness and research.

Cite This Article

APA
Yamashita-Kawanishi N, Ito S, Chambers JK, Uchida K, Sato M, Chang HW, Knight C, van der Meer F, Haga T. (2021). Vulvar squamous cell carcinoma associated with Equus caballus papillomavirus type 2 infection in a Japanese mare. Tumour Virus Res, 12, 200226. https://doi.org/10.1016/j.tvr.2021.200226

Publication

ISSN: 2666-6790
NlmUniqueID: 101775149
Country: Netherlands
Language: English
Volume: 12
Pages: 200226
PII: 200226

Researcher Affiliations

Yamashita-Kawanishi, Nanako
  • 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.
Ito, Soma
  • Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Chambers, James K
  • Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Uchida, Kazuyuki
  • Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Sato, Masato
  • Mitsuishi Animal Medical Center, Hokkaido South Agricultural Mutual Aid Association, Hokkaido, Japan.
Chang, Hui Wen
  • Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei 106, Taiwan.
Knight, Cameron
  • Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
van der Meer, Frank
  • Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
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. Electronic address: ahaga@g.ecc.u-tokyo.ac.jp.

MeSH Terms

  • Animals
  • Carcinoma, Squamous Cell / veterinary
  • Female
  • Horse Diseases
  • Horses
  • Japan
  • Male
  • Papillomaviridae / genetics
  • Papillomavirus Infections / veterinary
  • Vaccine Development

References

This article includes 48 references
  1. de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses.. Virology 2004 Jun 20;324(1):17-27.
    doi: 10.1016/j.virol.2004.03.033pubmed: 15183049google scholar: lookup
  2. Ghim SJ, Rector A, Delius H, Sundberg JP, Jenson AB, Van Ranst M. Equine papillomavirus type 1: complete nucleotide sequence and characterization of recombinant virus-like particles composed of the EcPV-1 L1 major capsid protein.. Biochem Biophys Res Commun 2004 Nov 19;324(3):1108-15.
    doi: 10.1016/j.bbrc.2004.09.154pubmed: 15485669google scholar: lookup
  3. Lange CE, Vetsch E, Ackermann M, Favrot C, Tobler K. Four novel papillomavirus sequences support a broad diversity among equine papillomaviruses.. J Gen Virol 2013 Jun;94(Pt 6):1365-1372.
    doi: 10.1099/vir.0.052092-0pubmed: 23486670google scholar: lookup
  4. 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 2019 Aug 4;11(8).
    doi: 10.3390/v11080713pmc: PMC6723834pubmed: 31382657google scholar: lookup
  5. 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).. Vet Dermatol 2018 Feb;29(1):72-e30.
    doi: 10.1111/vde.12481pubmed: 28833761google scholar: lookup
  6. 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 Nov;42(8):738-45.
  7. Dong J, Zhu W, Yamashita N, Chambers JK, Uchida K, Kuwano A, Haga T. Isolation of equine papillomavirus type 1 from racing horse in Japan.. J Vet Med Sci 2017 Dec 6;79(12):1957-1959.
    doi: 10.1292/jvms.17-0322pmc: PMC5745171pubmed: 28993549google scholar: lookup
  8. O'Banion MK, Reichmann ME, Sundberg JP. Cloning and characterization of an equine cutaneous papillomavirus.. Virology 1986 Jul 15;152(1):100-9.
    doi: 10.1016/0042-6822(86)90375-2pubmed: 3012863google scholar: lookup
  9. 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 Oct 22;15(1):356.
    doi: 10.1186/s12917-019-2097-0pmc: PMC6805557pubmed: 31640696google scholar: lookup
  10. Sykora S, Brandt S. Papillomavirus infection and squamous cell carcinoma in horses.. Vet J 2017 May;223:48-54.
    doi: 10.1016/j.tvjl.2017.05.007pubmed: 28671071google scholar: lookup
  11. van den Top JG, Harkema L, Lange C, Ensink JM, van de Lest CH, Barneveld A, van Weeren PR, Gröne A, Martens A. Expression of p53, Ki67, EcPV2- and EcPV3 DNA, and viral genes in relation to metastasis and outcome in equine penile and preputial squamous cell carcinoma.. Equine Vet J 2015 Mar;47(2):188-95.
    doi: 10.1111/evj.12245pubmed: 24898479google scholar: lookup
  12. Yamashita-Kawanishi N, Haga T. Anogenital-Associated Papillomaviruses in Animals: Focusing on Bos taurus Papillomaviruses.. Pathogens 2020 Nov 27;9(12).
    doi: 10.3390/pathogens9120993pmc: PMC7760238pubmed: 33260814google scholar: lookup
  13. Peters-Kennedy J, Lange CE, Rine SL, Hackett RP. Equus caballus papillomavirus 8 (EcPV8) associated with multiple viral plaques, viral papillomas, and squamous cell carcinoma in a horse.. Equine Vet J 2019 Jul;51(4):470-474.
    doi: 10.1111/evj.13046pubmed: 30456819google scholar: lookup
  14. 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 Sep;57(5):632-641.
    doi: 10.1177/0300985820941270pubmed: 32812517google scholar: lookup
  15. 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 Sep 27;166(1-2):257-62.
    doi: 10.1016/j.vetmic.2013.06.004pubmed: 23845733google scholar: lookup
  16. Porcellato I, Modesto P, Cappelli K, Varello K, Peletto S, Brachelente C, Martini I, Mechelli L, Ferrari A, Ghelardi A, Razzuoli E. Equus caballus papillomavirus type 2 (EcPV2) in co-occurring vulvar and gastric lesions of a pony.. Res Vet Sci 2020 Oct;132:167-171.
    doi: 10.1016/j.rvsc.2020.06.003pubmed: 32590224google 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 Jul 19;81(7):1029-1033.
    doi: 10.1292/jvms.18-0461pmc: PMC6656819pubmed: 31167980google scholar: lookup
  18. Yu M, Chambers JK, Tsuzuki M, Yamashita N, Ushigusa T, Haga T, Nakayama H, Uchida K. Pigmented viral plaque and basal cell tumor associated with canine papillomavirus infection in Pug dogs.. J Vet Med Sci 2019 Nov 29;81(11):1643-1648.
    doi: 10.1292/jvms.19-0384pmc: PMC6895623pubmed: 31554746google scholar: lookup
  19. Yamashita-Kawanishi N, Chambers JK, Uchida K, Tobari Y, Yoshimura H, Yamamoto M, Yumoto N, Aoki H, Sugiura K, Higuchi T, Saito S, Haga T. Genomic characterisation of bovine papillomavirus types 1 and 2 identified in equine sarcoids in Japan.. Equine Vet J 2021 Nov;53(6):1199-1209.
    doi: 10.1111/evj.13398pubmed: 33300145google scholar: lookup
  20. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.. Mol Biol Evol 2018 Jun 1;35(6):1547-1549.
    doi: 10.1093/molbev/msy096pmc: PMC5967553pubmed: 29722887google scholar: lookup
  21. Needleman SB, Wunsch CD. A general method applicable to the search for similarities in the amino acid sequence of two proteins.. J Mol Biol 1970 Mar;48(3):443-53.
    doi: 10.1016/0022-2836(70)90057-4pubmed: 5420325google scholar: lookup
  22. Tamura K, Nei M, Kumar S. Prospects for inferring very large phylogenies by using the neighbor-joining method.. Proc Natl Acad Sci U S A 2004 Jul 27;101(30):11030-5.
    doi: 10.1073/pnas.0404206101pmc: PMC491989pubmed: 15258291google scholar: lookup
  23. Androphy EJ, Lowy DR, Schiller JT. Bovine papillomavirus E2 trans-activating gene product binds to specific sites in papillomavirus DNA.. Nature 1987 Jan 1-7;325(6099):70-3.
    doi: 10.1038/325070a0pubmed: 3025749google scholar: lookup
  24. 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 Jul 6;158(1-2):33-41.
    doi: 10.1016/j.vetmic.2012.02.005pubmed: 22397936google scholar: lookup
  25. Howarth S, Lucke VM, Pearson H. Squamous cell carcinoma of the equine external genitalia: a review and assessment of penile amputation and urethrostomy as a surgical treatment.. Equine Vet J 1991 Jan;23(1):53-8.
  26. van den Top JG, de Heer N, Klein WR, Ensink JM. Penile and preputial tumours in the horse: a retrospective study of 114 affected horses.. Equine Vet J 2008 Sep;40(6):528-32.
    doi: 10.2746/042516408X281180pubmed: 18487101google scholar: lookup
  27. 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: expression of biomarker proteins and EcPV2.. Sci Rep 2020 May 12;10(1):7863.
    doi: 10.1038/s41598-020-64014-3pmc: PMC7217868pubmed: 32398763google scholar: lookup
  28. 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 Sep;57(5):623-631.
    doi: 10.1177/0300985820941266pubmed: 32812522google scholar: lookup
  29. Smith MA, Levine DG, Getman LM, Parente EJ, Engiles JB. Vulvar squamous cell carcinoma in situ within viral papillomas in an aged Quarter Horse mare.. Equine Vet. Educ. 2009;21:11–16.
    doi: 10.2746/095777309X390551google scholar: lookup
  30. Van Den Top JGB, Ensink JM, Barneveld A, Van Weeren PR. Penile and Preputial Squamous Cell Carcinoma in the Horse and Proposal of a Classification System.. 2011.
  31. 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.. Vet Pathol 2013 Jul;50(4):686-92.
    doi: 10.1177/0300985812463403pubmed: 23064881google scholar: lookup
  32. Gross I, Walder A. Skin Diseases of the Dog and Cat.. second ed. Blackwell Publishing Ltd; 2005.
  33. Giordano G, D'Adda T, Merisio C, Gnetti L. Vulvar acantholytic squamous carcinoma: a case report with immunohistochemical and molecular study.. Int J Gynecol Pathol 2005 Jul;24(3):303-6.
  34. Lee SK, 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 Jan;72:97-100.
    doi: 10.1016/j.jevs.2018.10.015pubmed: 30929791google scholar: lookup
  35. Borvető F, Bravo IG, Willemsen A. Papillomaviruses infecting cetaceans exhibit signs of genome adaptation following a recombination event.. Virus Evol 2020 Jan;6(1):veaa038.
    doi: 10.1093/ve/veaa038pmc: PMC7326301pubmed: 32665861google scholar: lookup
  36. Rogers A, Waltke M, Angeletti PC. Evolutionary variation of papillomavirus E2 protein and E2 binding sites.. Virol J 2011 Aug 1;8:379.
    doi: 10.1186/1743-422X-8-379pmc: PMC3161962pubmed: 21806797google scholar: lookup
  37. Cullen AP, Reid R, Campion M, Lörincz AT. Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm.. J Virol 1991 Feb;65(2):606-12.
    doi: 10.1128/jvi.65.2.606-612.1991pmc: PMC239798pubmed: 1846186google scholar: lookup
  38. Dürst M, Kleinheinz A, Hotz M, Gissmann L. The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumours.. J Gen Virol 1985 Jul;66 ( Pt 7):1515-22.
    doi: 10.1099/0022-1317-66-7-1515pubmed: 2991428google scholar: lookup
  39. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application.. Nat Rev Cancer 2002 May;2(5):342-50.
    doi: 10.1038/nrc798pubmed: 12044010google scholar: lookup
  40. 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.. J Virol 1989 Oct;63(10):4417-21.
  41. McDougall JK. Immortalization and transformation of human cells by human papillomavirus.. Curr Top Microbiol Immunol 1994;186:101-19.
    doi: 10.1007/978-3-642-78487-3_6pubmed: 8205836google scholar: lookup
  42. Boyer SN, Wazer DE, Band V. E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway.. Cancer Res 1996 Oct 15;56(20):4620-4.
    pubmed: 8840974
  43. Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53.. Cell 1990 Dec 21;63(6):1129-36.
    doi: 10.1016/0092-8674(90)90409-8pubmed: 2175676google scholar: lookup
  44. Munday JS, Aberdein D. Loss of retinoblastoma protein, but not p53, is associated with the presence of papillomaviral DNA in feline viral plaques, Bowenoid in situ carcinomas, and squamous cell carcinomas.. Vet Pathol 2012 May;49(3):538-45.
    doi: 10.1177/0300985811419534pubmed: 21930804google scholar: lookup
  45. Lu DW, El-Mofty SK, Wang HL. Expression of p16, Rb, and p53 proteins in squamous cell carcinomas of the anorectal region harboring human papillomavirus DNA.. Mod Pathol 2003 Jul;16(7):692-9.
  46. Münger K, Howley PM. Human papillomavirus immortalization and transformation functions.. Virus Res 2002 Nov;89(2):213-28.
    doi: 10.1016/S0168-1702(02)00190-9pubmed: 12445661google scholar: lookup
  47. Wang J, Zhou D, Prabhu A, Schlegel R, Yuan H. The canine papillomavirus and gamma HPV E7 proteins use an alternative domain to bind and destabilize the retinoblastoma protein.. PLoS Pathog 2010 Sep 2;6(9):e1001089.
  48. Jeon S, Lambert PF. Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis.. Proc Natl Acad Sci U S A 1995 Feb 28;92(5):1654-8.
    doi: 10.1073/pnas.92.5.1654pmc: PMC42578pubmed: 7878034google scholar: lookup

Citations

This article has been cited 1 times.
  1. da Silva TRO, Gonçalves PNC, Marcus VB, Mucellini CI, Dos Santos IR, Kommers G, Driemeier D, Flores EF, Cargnelutti JF, Flores MM. Detection of Equus caballus papillomavirus-2 in equine penile/preputial papillomas and squamous cell carcinomas in southern Brazil.. Braz J Microbiol 2022 Sep;53(3):1707-1713.
    doi: 10.1007/s42770-022-00769-3pubmed: 35570259google scholar: lookup