Specific rearrangements of human papillomavirus DNA provide molecular evidence for genetic heterogeneity of primary cervical cancers, recurrencies, and lymph node metastases in two patients.

Two different characteristic patterns of human papilloma virus (HPV) type 16 DNA were found by Southern blot hybridization in four pelvic and paraaortic lymph node metastases in a patient with FIGO stage IIIb cervical cancer. Both patterns added up to give the HPV 16 DNA pattern of the primary tumor. This strongly suggests that the tumor was composed of two distinct compartments, each spawning its own lymph node metastases. A second patient presented with a vaginal tumor 4 years after stage IIb cervical cancer had been treated with hysterectomy only. The vaginal tumor was removed and pelvic lymphadenectomy performed. Integrated HPV 16 DNA was found in the vaginal tumor whereas one involved and one free lymph node contained episomal HPV 16 DNA with a characteristic deletion. The apparent heterogeneity of the cancer cell population may indicate that the metastasis is not related to the vaginal tumor but that it is a late sequel of the cervical cancer. Alternatively the metastasis could have originated from an unsampled portion of the vaginal tumor.