Human papillomavirus DNA in genital cancers, metastases, and lymph nodes

To evaluate the utility of human papillomavirus (HPV) DNA as molecular marker for diagnostic screening of lymph nodes for cancer metastases, we examined 16 involved and 124 histologically cancer-free nodes of 34 patients with cervical, vulval, or vaginal carcinomas associated with HPV 6, 16, 18, 31, 33, 45, or X. All metastases of HPV-positive tumors contained viral DNA of the same type as the primary cancer but in one case the copy number of viral genomes was dramatically reduced. In a varying proportion of histologically normal nodes of 7 of 23 patients with HPV 16-positive cancers HPV 16 DNA was revealed by Southern blot hybridization and/or PCR. Histologic reevaluation showed a metastasis in one case. Three examples of tumor heterogeneity regarding physical state or copy number of viral DNA are presented. Tumor heterogeneity is discussed as possible explanation for apparently inconsistent results such as HPV-negative metastases of HPV-positive tumors.