Papillomas and cancer in cattle.

Papillomaviruses induce hyperproliferation of epithelial cells of the skin or mucosa (papillomas), and certain types can also infect fibroblasts. They are a very heterogeneous group of viruses, and individual types are associated with specific lesions. The papillomas are mostly benign but some tumours may eventually undergo malignant conversion when genetic or environmental factors are involved. In cattle, bovine papillomavirus type 4 (BPV-4) is the causative agent of papillomas of the alimentary canal, which can become the focus for the development of carcinomas in animals feeding on the bracken fern. These animals are immunosuppressed and are often affected also by adenocarcinomas of the lower bowel and by carcinomas and haemangiosarcomas of the urinary bladder. Persistent, widespread papillomatosis and cancers of both the alimentary tract and the urinary bladder have been experimentally reproduced in animals either kept on a diet of bracken or immunosuppressed with azathioprine. As is the case for the naturally occurring cancers, no viral DNA was detected in the experimental cancers of the upper alimentary canal or of the lower bowel, indicating that the viral genome is not required for the maintenance of the malignant state. On the contrary, BPV-2 DNA was detected in several bladder cancers, both natural and experimental, suggesting that this virus can be present in a latent form and can be involved in malignant transformation. Further evidence of latent infection was provided by the onset of BPV-1 or BPV-2 skin warts in papillomatosis-free animals. These findings are obviously relevant to the human disease.