The association between equine Papillomavirus type 2 and equine Squamous cell carcinomas : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Palmerston North, New Zealand
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Squamous cell carcinomas (SCCs) are malignant epithelial neoplasms affecting most species. Equine SCCs are most common on the penis, where they result in significant welfare and economic costs and frequently necessitate euthanasia. In humans, half of penile SCCs are caused by infection with papillomaviruses (PVs). The research described in this thesis investigated whether PVs similarly cause equine penile SCCs (EPSCCs). Testing of equine penile samples using conventional PCR and consensus primers amplified PV DNA significantly more frequently from SCCs than from nonRSCC lesions. Sequencing of the amplified DNA showed that there was just one PV type present, and that it was a newlyRdiscovered PV called equine papillomavirus type 2 (EcPVR2). In#situ hybridization and immunohistochemistry localized PV DNA and antigen to neoplastic cells but not to adjacent tissue. These results suggested that EcPVR2 could influence the development of EPSCCs. A quantitative PCR assay was then developed to test for EcPVR2 presence and load in a large number of equine samples from the penis and from other SCCRprone body sites. This showed that EcPVR2 is present significantly more frequently, and at significantly higher loads, in EPSCCs than in nonRSCC tissues. Furthermore, some equine pharyngeal SCCs contained low EcPVR2 loads. However, as EcPVR2 was also sometimes present in grossly normal pharyngeal samples, the significance of this was uncertain. EcPVR2 DNA was only rarely detectible in grossly normal vulvovestibular mucosal samples and never in nictitating membrane samples. To help determine whether EcPVR2 causes cancer or is an incidental bystander, immunostaining for three cellular regulatory proteins (transformationRrelated protein 53 (p53), retinoblastoma protein (pRb), and cyclinRdependent kinase inhibitor 2A) was performed. This showed that, unlike highRrisk human PVs, the presence of EcPVR2 DNA within a SCC was not associated with degradation of the tumor suppressor proteins p53 or pRb. While these results do not support a causative association between EcPVR2 and equine SCCs, the possibility that EcPVR2 causes cancer by changing other cell regulatory proteins cannot be excluded. Overall, evidence from our and others’ research strongly suggests that EcPVR2 is involved in EPSCCs, but does not prove unequivocally that it causes these neoplasms.
Appendix A removed due to copyright restriction.
Research Subject Categories::VETERINARY MEDICINE