A Subset of Equine Gastric Squamous Cell Carcinomas Is Associated With Equus Caballus Papillomavirus–2 Infection

Abstract

Squamous cell carcinoma (SCC) is the most common neoplasm of the equine stomach. However, the mechanisms underlying malignant transformation are unknown. As Equus caballus papillomavirus–2 (EcPV-2) is a likely cause of some genital SCCs, we hypothesized that EcPV-2 is associated with a subset of equine gastric SCCs. To this aim, we performed polymerase chain reaction (PCR) and in situ hybridization (ISH) for EcPV-2 E6/ E7 oncogenes on 11 gastric SCCs and on gastric samples from 15 control horses with no SCC. PCR for EcPV-2 was positive in 7/11 (64%) gastric SCCs; non-SCC gastric samples were all negative. Intense hybridization signals for EcPV-2 E6/E7 nucleic acid were detected by ISH within tumor cells in 5/11 (45%) gastric SCCs, including distant metastases. No hybridization signals were detected within any of the non-SCC gastric cases. This study provides support for a potential association between EcPV-2 infection and a subset of equine gastric SCC.

Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL Pathway Correlated to Inflammation and Wnt Signaling Activation

“…The horse has been recently proposed as an animal model for human SCCs due to numerous histological similarities and the characteristic immune microenvironment of the genitalia tumors in the two species [ 4 , 33 ]. In both species, PV mucosal infections often induce cervical, oropharyngeal, penile, anal, vaginal, and vulvar cancer [ 34 , 35 ]; moreover, a case of equine gastric SCC has been linked with EcPV2 infection of the vulva [ 29 ]. The molecular mechanisms behind PV-induced tumor appears to be related to host local immune response by the tumor immune microenvironment (TIME) [ 36 , 37 ].…”

Epithelial to Mesenchymal Transition (EMT) in a Laryngeal Squamous Cell Carcinoma of a Horse: Future Perspectives

“…Particularly, h-HPV16 is the most common type (19.8%). Interestingly, equine papillomavirus type 2 (EcPV2) also has been recently associated with SCC of the penis, vulva, and stomach [7][8][9][10], as well as it has been recently detected in equine SCCL [11]. These data suggest that the horse is a good spontaneous animal model for studying the pathogenic mechanisms of this tumor in humans.…”

Cutaneous vs. Mucosal Tropism: The Papillomavirus Paradigm Comes to an “and”

“…Recent epidemiological and experimental data on β-HPVs are in line with this hypothesis, and this is evident also for genus α, which groups both cutaneous and mucosal HPVs (Minoni et al, 2020 ). Therefore, the characterization of biological properties, beyond the comparative analysis of genetic sequences, appears to be necessary for a comprehensive evaluation of viral tropism, as shown also by studies of animal PVs (Altamura et al, 2016 , 2018a ; Alloway et al, 2020 ; Minoni et al, 2020 ). Moreover, the search for each human and animal PV should be expanded across a wide spectrum of anatomical sites, regardless of which body region they were initially isolated from, because limiting to one site may lead to an underestimation of their oncogenic potential at additional locations, even those coated by different types of epithelium.…”

“…More precisely, EcPV-2 induced diseases develop preferentially at mucocutaneous junctions, suggesting a possible affinity for cells of both the skin and mucosal epithelia of genital region (Sykora and Brandt, 2017 ; Ramsauer et al, 2019 ). Interestingly, the presence of EcPV-2 has also been reported in a subset of equine head and neck cancers (HNCs), and recent work shows that EcPV-2 is detectable in neoplastic cells of equine gastric SCC (Knight et al, 2013 ; Sykora et al, 2017 ; Alloway et al, 2020 ).…”