The pattern of human papillomavirus type 16 (HPV-16) integration was studied in 23 invasive carcinomas of the cervix using subgenomic probes. Seventeen tumours contained integrated HPV-16 and in 13 of these there was evidence of disruption within the E1-E2 open reading frames (ORFs). In all cases the upstream regulatory region (URR)-E6-E7 ORFs was maintained intact. Two independently derived tumours were infected with episomal wild-type HPV-16 and an episomal variant of HPV-16 containing a 325 bp deletion within the URR (positions 7598 to 17) and a point mutation at position 20 (A to C). This is the first report of a variant HPV-16 which is likely to be both defective and transmissible. Loss of E2 expression and deletion of a large portion of the URR may be two of the mechanisms leading to altered HPV-16 early gene expression in cervical tumours.