Canine papillomavirus types 1 and 2 in classical papillomas: High abundance, different morphological associations and frequent co-infections.

Canine papillomatosis is mainly attributed to papillomavirus infections. Papillomavirus DNA is also frequently identified in healthy skin, and evidence of high papillomavirus diversity complicates this simplistic view of causality. The aim of this study was to determine how frequently canine papillomas contain papillomavirus DNA and express viral protein, and how these factors correlate to the histology and anatomic location. Fifty-three archived, formalin-fixed samples of canine papillomas and eight samples of other proliferative skin lesions from dogs were included. Samples were re-evaluated histologically, tested for papillomavirus L1-antigen using immunohistochemistry, and for papillomavirus DNA with PCR assays and molecular sequencing. Most papillomas from haired skin contained papillomavirus DNA (96%) and antigen (92%). Of oral papillomas, 88% were positive for both papillomavirus DNA and antigen. Approximately 50% of non-papilloma proliferations and papillomas from eyelid/conjunctiva specimens contained viral DNA, but antigen was present in only 12% of eyelid/conjunctiva papillomas and in none of the non-papilloma proliferations. The presence of viral antigen was highly correlated with histological indicators of viral infection, including intranuclear inclusions, koilocytes, cytoplasmatic vacuolation and dysplasia. The viruses found were mainly CPV1 and CPV2. CPV1 dominated in oral infections, while CPV2 dominated in cutaneous endophytic papillomas. Co-infections with CPV1 and CPV2 accounted for about 20% of all detected infections. These results support a role for papillomaviruses in canine cutaneous and oral, exophytic and endophytic papillomas and support previously raised doubts about their role in squamous papillomas from eyelid/conjunctiva specimens.