Equine genital and ocular squamous cell carcinomas: clinical, histopathological, molecular and viral characterization with proposed histopathological classification system

Equine squamous cell carcinomas (eSCCs) are common, and a proportion are likely induced by <i>Equus caballus</i> papillomavirus 2 (EcPV-2). Accurate prediction of clinical outcomes is challenging with no recognized prognostic criteria or consistent histopathological classification scheme for eSCC. The aims of this study were to histopathologically subtype a large case series of eSCCs (genital and ocular) and correlate them with p16 and HER-2 expression, equine papillomavirus infection status, and various clinical and histopathological parameters to predict tumour behavior and prognosis. One hundred and eighty-five samples were examined and subtyped histologically. HER-2 and p16 immunohistochemistry (IHC) and <i>in situ</i> hybridization (ISH) for the EcPV-2 E6/E7 oncogenes were performed on a subset of cases, and follow-up survival data were analyzed. The results were compared and correlated with published guidelines on the categorization of human SCC. Six histopathological subtypes of SCC, according to the WHO, were identified for the first time in horses: usual/invasive (most common), verrucous, pseudoglandular, papillary, warty, and basaloid, with different histological subtypes demonstrating prognostic significance. HER-2 and EcPV-2 statuses were not associated with prognosis in horses with SCC. p16 expression is not associated with EcPV-2 status but could be a potential prognostic factor. ISH demonstrated EcPV-2 genetic material in the majority of eSCCs, except for the papillary subtype, which includes mature, not just pre-cancerous, eSCCs. Widespread HER-2 expression in eSCCs could suggest a role for this cell receptor as a potential therapeutic target.