Two uncommon tumors of the head and neck first revealed primary roles for two classes of cancer genes (oncogenes, tumor suppressor genes) in the origin of human cancer. In Burkitt's lymphoma the initiating event is a chromosomal translocation that leads to unregulated expression of an oncogene (MYCC), whereas retinoblastoma involves loss of function of both copies of a tumor suppressor gene (RB1). In osteosarcoma the RB1 gene is often affected, as is the gene (TP53) that codes for the p53 protein. TP53 is frequently mutated in carcinomas of the head and neck, as in one of the ras oncogenes. Multiple genetic changes typify carcinomas. Some carcinomas of the head and neck contain one of the human papilloma viruses that produce proteins that combine with and inactivate p53 and pRB proteins, rendering mutations in these genes unnecessary.