Papillomavirus infection in cattle: viral and chemical cofactors in naturally occurring and experimentally induced tumours.

Six different types of bovine papillomavirus (BPV-1 to BPV-6) have been identified and classified into two subgroups: subgroup A, which induce fibropapillomas, and subgroup B, which induce true epithelial papillomas. BPV-4, a member of subgroup B, is the aetiological agent of papillomas of the upper alimentary canal, which can become a focus for transformation to squamous-cell carcinomas in animals feeding on bracken fern. Strong circumstantial evidence suggests that the progression to malignancy is due to the interplay between BPV-4 and carcinogen(s) present in the fern. The carcinomas of the upper alimentary canal are often accompanied by adenomas and adenocarcinomas of the lower bowels, and by carcinomas and hemangiosarcomas of the urinary bladder. Bracken-grazing animals are also heavily immunosuppressed. Florid papillomatosis of the upper alimentary canal and cancers of the urinary bladder have been experimentally reproduced in animals either kept on a diet of bracken or immunosuppressed with azathioprine. Several bladder cancers contained multiple episomal copies of BPV-2 DNA, suggesting that this virus, or its genome, can be present in a latent form, and that it can be implicated in malignant transformation. Further indication of latent infection is provided by the onset of skin warts in papillomatosis-free animals. These warts developed at sites of damaged skin and harboured either BPV-1 or BPV-2. BPV-4 DNA has not been found in the naturally occurring cancers of the upper alimentary canal and of the lower bowels, except in one tongue carcinoma and one transforming papilloma, indicating that the viral genome is not required for the maintenance of the malignant state in the alimentary canal.