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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
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
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.