Equine and feline oronasal papillomavirus-positive and -negative squamous cell carcinoma: a comparative study based on diagnostic imaging, pathomorphologic and molecular methods

Oral or head and neck squamous cell carcinoma (OSCC, HNSCC) are highly local aggressive neoplasms, most commonly affecting cats and horses among companion animals. At the time of diagnosis this tumor is challenging for owners and veterinarians as the prognosis is poor. Little is known about risk factors, pathogenesis and morphological characteristics of this tumor in veterinary medicine. Therefore, the main goal of this PhD project is to better characterize OSCC and HNSCC in cats and horses with diagnostic imaging, pathomorphologic and molecular methods to improve diagnosis and potentially reveal biomarkers that can act as future targets for therapeutic methods. Thus, we first investigated the morphological character of OSCC in cats and HNSCC in horses by computed tomography and histopathology. To gain insights in the molecular characteristics of this tumor as a second goal all feline OSCC and equine HNSCC samples were analyzed for the presence of species-specific papillomavirus types. To further investigate molecular characteristics papillomavirus positive and negative samples of horses were compared for the expression of selected epithelial, mesenchymal, endothelial and stem-cell markers. As a last step we conducted a pilot project to evaluate the use of cell culture lines of feline OSCC and equine HNSCC for future theranostic approaches by combining a magnetic resonance imaging contrast agent (Gadolinium) with a potential therapeutic agent (Salinomycin) and monitoring the effects on cells. Our results in terms of computed tomographic images displayed different osseous phenotypic tendencies, with more osseous aggressive features in cats. Histopathology showed variable features of keratinization and number of mitotic cells as well as extensive and deep osseous invasion in both cats and horses, which fits to the known infiltrative nature of this tumor. Regarding concurrent papillomavirus infection, 22 % of all equine sample screened positive for equine papillomavirus type 2 and less than 10 % for feline papillomaviruses distributed throughout feline papillomavirus type 1-3. The findings of the immunohistochemical analyzes suggest partial epithelial mesenchymal transition by expression of vimentin, a mesenchymal marker and cytokeratin, an epithelial marker in all papillomavirus-positive and negative equine HNSCC as well as cancer stem-cell markers, CD44 and CD271 as possible malignancy markers. As a result of the cell culture experiments, a dose-dependent response of the theranostic agent (Salinomycin and Gadolinium) on the cell viability could be detected and indicate further investigations. In conclusion, the findings of this work add diagnostic imaging, pathomorphologic and molecular features of feline OSCC and equine HNSCC to the knowledge of this little investigated tumor to contribute to the advancement of forthcoming diagnosis and treatment.