Can a test for E6/E7 transcripts of human papillomavirus type 16 serve as a diagnostic tool for the detection of micrometastasis in cervical cancer?

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Abstract
Tissue from 11 cases of cervical cancer positive for human papillomavirus (HPV) type 16 DNA and 69 pelvic lymph nodes from the same patients were examined for HPV 16 DNA and mRNA from the E6/E7 genes. Five of the tumors were squamous, 3 adeno- and 3 adenosquamous carcinoma. From the primary tumors and the extirpated lymph nodes DNA and RNA or mRNA was subjected to PCR and RT-PCR. Three transcription profiles (only E6*1, E6*1 and E6*11 or full-length E6-E7 plus both of the spliced transcripts) were found in all of the 11 HPV 16 DNA-positive primary tumors. From the total of 69 lymph nodes analyzed 28 were positive for mRNA. HPV 16 DNA was found in 7 additional samples. Cytokeratin was found in 19 of these lymph nodes, indicating epithelial origin of tumor cells. Only 1 patient had 2 metastases evidenced by histology. These were both positive for HPV DNA and mRNA. The finding of HPV DNA, mRNA and cytokeratin in lymph nodes of patients with cervical cancer should be an indication of lymphogenically driven micrometastases of the tumor. The HPV mRNA assay should offer higher specificity than the DNA test since mRNA can be found in live cells only, while HPV DNA also can originate from dead cell material sequestered in the lymph nodes.