Human Papillomavirus in Clinically and Histologically Normal Tissue of Patients with Genital Cancer

To study the association of human papillomavirus (HPV) and herpes simplex virus (HSV) with genital cancer, we collected specimens of cervical, vulvar, endometrial, and vaginal tumors at the time of operation in patients with cancer. In some patients, matched internalcontrol (histologically normal) tissue was also collected. DNA extracted from the tissue was probed with Radio-labeled HPV type 16 DNA, HPV type 18 DNA, and cloned fragments of HSV type 2 DNA. Hybridization to the Hind IIIa clone of HSV-2 was detected in only 1 cervical tumor and 1 vulvar tumor (9 percent) among the 22 tumors tested. However, DNA sequences hybridizing to HPV-16 were detected in 21 of 25 tumors (84 percent) and in 8 of 11 (73 percent) of the DNA samples from clinically and histologically normal, paired, internal-control tissues from the patients with cancer. HPV-16 DNA was found in one of nine normal cervixes (11 percent) of women without genital neoplastic disease or abnormal cytology. HPV-18 DNA was detected in only 2 of 24 tumors (8 percent), 1 cervical and 1 vulvar. Our results show a strong association between the presence of HPV-16 genomes and genital tumors and between HPV-16 genomes and histologically normal tissue within 2 to 5 cm of the tumors. The implications of these findings remain to be explored. (N Engl J Med 1986; 315:1052–8.) An interesting and well-documented study by Ferenczy et al. 1 showed clearly that papillomavirus may be present in histologically normal tissue near the site of both anogenital condylomata and intraepithelial neoplasia. As part of a large study of human papillomavirus (HPV) and herpes simplex virus (HSV) genomes in persons with genital cancers in western Scotland and northeastern England, we conducted a small investigation to determine whether HPV genomes were present in clinically and histologically normal paired, matched control tissues from patients with cancer. We found that the cloned HPV-16 DNA probe hybridized to sequences in 8 of 11 clinically and histologically . . .