Squamous cell carcinoma of the head and neck (
HNSCC) is a common malignant
tumor in humans and animals. In humans, papillomavirus (PV)-induced HNSCCs have a better prognosis than papillomavirus-unrelated HNSCCs. The ability of
tumor cells to switch from epithelial to mesenchymal, endothelial, or
therapy-resistant stem-cell-like phenotypes promotes
disease progression and
metastasis. In equine
HNSCC, PV-association and
tumor cell phenotype switching are poorly understood. We screened 49 equine HNSCCs for equine PV (EcPV) type 2, 3 and 5
infection. Subsequently, PV-positive versus -negative lesions were analyzed for expression of selected epithelial (
keratins, β-
catenin), mesenchymal (
vimentin), endothelial (COX-2), and stem-cell markers (
CD271, CD44) by immunohistochemistry (IHC) and immunofluorescence (IF;
keratins/
vimentin, CD44/
CD271 double-staining) to address
tumor cell plasticity in relation to PV
infection. Only EcPV2 PCR scored positive for 11/49 equine HNSCCs. IHC and IF from 11 EcPV2-positive and 11 EcPV2-negative
tumors revealed epithelial-to-mesenchymal transition events, with
vimentin-positive cells ranging between <10 and >50%. CD44- and CD271-staining disclosed the intralesional presence of infiltrative
tumor cell fronts and double-positive
tumor cell subsets independently of the PV
infection status. Our findings are indicative of (partial) epithelial-mesenchymal transition events giving rise to hybrid epithelial/mesenchymal and stem-cell-like
tumor cell phenotypes in equine HNSCCs and suggest CD44 and
CD271 as potential
malignancy markers that merit to be further explored in the horse.