The HPV 16 Genome Induces Carcinomas and T-cell Lymphomas in Transgenic Mice

Human papillomavirus type 16 is highly associated with cervical carcinoma. Here we report families of transgenic mice produced by the microinjection of a dimer repeat sequence of the human papillomavirus type 16 genome. Thirty-two transgenic animals in four families developed multiple organ malignancies that appeared in middle age without other intervention. The tumor phenotype of poorly differentiated carcinomas or malignant lymphomas and the transgene cosegregate in these lineages. The tumors arise in the subcutaneous compartment, thoracic cavity, or abdomen; are widely metastatic; and grow rapidly in nude mice. No cervical lesions were identified in six females examined. No rearrangements in transgene E6/E7, E2, and E1 regions were found in tumor tissues, and the truncated E2 region, which was thought to play an important role in human cervical carcinogenesis, was not needed for tumorigenesis in these animals. The transgenic mice produce RNA from the E6/E7 open reading frames, which has been identified in both the carcinomas and the lymphomas, but RNA from the E2 open reading frame is present only in malignant T-cell lymphomas and not in carcinomas, hyperplastic lymphoid tissue, or normal lymphoid tissue.