Generalized papillomatosis in three horses associated with a novel equine papillomavirus (Ec<scp>PV</scp>8)

Linder, Keith E.; Bizikova, Petra; Luff, Jennifer; Zhou, Di; Yuan, Hang; Breuhaus, Babetta A.; Nelson, Elizabeth A.; MacKay, Robert J.

doi:10.1111/vde.12481

“…Since there are other papillomaviruses described to be associated with equine genital lesions, and co-infections with other PVs were reported [32][33][34], also broad-range PV PCR using CP4/5 [35] and Fap 59/64 [36] primer sets was done to detect other potentially involved PVs. These primers are designed to also detect the equine PVs type 3-8 [32][33][34]37] and the sarcoid associated bovine PVs type 1 and 2 [38]. Using these two broad-range PV primer sets, no other PVs were detectable, hence it is not likely that other PVs were involved in the development of the lesions assessed in this study.…”

Section: Aetiological Association Of Ecpv2 With Equine Penile Sccs Anmentioning

confidence: 98%

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

Ramsauer

¹

,

Wachoski-Dark

²

,

Fraefel

³

et al. 2019

Preprint

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Background 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. The aim of this study was to identify histologic criteria and diagnostic markers allowing for a more accurate diagnosis of EcPV2-associated equine penile lesions. Results A total of 61 archived equine penile lesions were histologically re-assessed and classified as benign hyperplasia, papilloma, CIS or SCC. From these, 19 representative lesions and adjacent normal skin were comparatively analysed for the presence of EcPV2 DNA and transcripts using PCR and RNA in situ hybridisation (RISH). All lesional samples were positive by EcPV2 PCR and RISH, while adjacent normal skin was negative. RISH analysis yielded signal distribution patterns that allowed distinction of early (hyperplasia, papilloma) from late stage lesions (CIS, SCC). Subsequently, the 19 lesions were further assessed for expression of p53, Ki67, MCM7 and MMP1 by immunohistochemistry (IHC). All four proteins were expressed in both normal and lesional tissue. However, p53 expression was up-regulated in basal keratinocyte layers of papillomas, CIS and SCCs, as well as in upper keratinocyte layers of CIS and SCCs. MCM7 expression was only up-regulated in upper proliferating keratinocyte layers of papillomas, CIS and SCCs. Conclusion This study proposes combining a refined histological protocol for analysis of equine penile lesions with PCR- and/or RISH based EcPV2-screening and p53/MCM7 IHC to more accurately determine the type of lesion. This may help to guide the choice of optimum treatment strategy, especially at early stages of disease.

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“…This virus has been reported only once before. Linder et al described three horses, aged 2, 2 and 10 years with histologically confirmed viral papillomas associated with EcPV8 [5]. None of these horses developed SCC.…”

Section: Discussionmentioning

confidence: 99%

“…Papillomavirus associated skin disorders are common in horses worldwide. Eight Equus caballus papillomaviruses (EcPV) and four distinct clinical presentations have been described; "classical viral papillomatosis" (EcPV1), "genital papillomas" (EcPV2), "aural plaques" (EcPV3-6) and newly described "generalised papillomatosis" (EcPV8) [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Equus caballus papillomavirus 8 (EcPV8) associated with multiple viral plaques, viral papillomas, and squamous cell carcinoma in a horse

Peters‐Kennedy

¹

,

Lange

²

,

Rine

³

et al. 2018

Equine Veterinary Journal

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Summary Background Equus caballus papillomavirus 8, a recently discovered virus, has been reported to cause generalised papillomavirus in horses. Objectives 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. Study design 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 occasions; however new masses continue to develop in sites of previous masses as well as new sites. Results Multiple viral plaques, viral papillomas, SCC in situ and ISCC, localised to the inguinal region, were diagnosed via histopathology. EcPV8 DNA was detected via PCR. Main limitations Since only a few cases have been reported, we do not know the incidence of EcPV8 nor how often it may be associated with SCC in situ or ISCC without further study. Conclusions This is the fourth reported case of viral papillomatosis in the context of an EcPV8 infection in a horse. This is the first case in which SCC has been associated with EcPV8.

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“…Since there are other papillomaviruses described to be associated with equine genital lesions, and co-infections with other PVs were reported [32][33][34], also broad-range PV PCR using CP4/5 [35] and Fap 59/64 [36] primer sets was done to detect other potentially involved PVs. These primers are designed to also detect the equine PVs type 3-8 [32][33][34]37] and the sarcoid associated bovine PVs type 1 and 2 [38]. Using these two broadrange PV primer sets, no other PVs were detectable, hence it is not likely that other PVs were involved in the development of the lesions assessed in this study.…”

Section: Aetiological Association Of Ecpv2 With Equine Penile Sccs Anmentioning

confidence: 98%

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

Ramsauer

¹

,

Wachoski-Dark

²

,

Fraefel

³

et al. 2019

Preprint

0

View full text Add to dashboard Cite

Background 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. The aim of this study was to identify histologic criteria and diagnostic markers allowing for a more accurate diagnosis of EcPV2-associated equine penile lesions. Results A total of 61 archived equine penile lesions were histologically re-assessed and classified as benign hyperplasia, papilloma, CIS or SCC. From these, 19 representative lesions and adjacent normal skin were comparatively analysed for the presence of EcPV2 DNA and transcripts using PCR and RNA in situ hybridisation (RISH). All lesional samples were positive by EcPV2 PCR and RISH, while adjacent normal skin was negative. RISH analysis yielded signal distribution patterns that allowed distinction of early (hyperplasia, papilloma) from late stage lesions (CIS, SCC). Subsequently, the 19 lesions were further assessed for expression of p53, Ki67, MCM7 and MMP1 by immunohistochemistry (IHC). All four proteins were expressed in both normal and lesional tissue. However, p53 expression was up-regulated in basal keratinocyte layers of papillomas, CIS and SCCs, as well as in upper keratinocyte layers of CIS and SCCs. MCM7 expression was only up-regulated in upper proliferating keratinocyte layers of papillomas, CIS and SCCs. Conclusion This study proposes combining a refined histological protocol for analysis of equine penile lesions with PCR- and/or RISH based EcPV2-screening and p53/MCM7 IHC to more accurately determine the type of lesion. This may help to guide the choice of optimum treatment strategy, especially at early stages of disease.

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Generalized papillomatosis in three horses associated with a novel equine papillomavirus (EcPV8)

Abstract: A novel equine papillomavirus (EcPV8) is associated with a distinct, plaque-type, generalized papillomatosis. Papillomas persisted for months to years, with or without treatment.

Cited by 26 publications

References 11 publications

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

Equus caballus papillomavirus 8 (EcPV8) associated with multiple viral plaques, viral papillomas, and squamous cell carcinoma in a horse

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

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