Human papillomavirus type 18 E6* mRNA in primary tumors and pelvic lymph nodes of Hungarian patients with squamous cervical cancer.

Seven biopsy specimens from squamous-cell carcinomas of the uterine cervix were examined by RT-PCR for human-papilloma-virus(HPV)-specific transcripts. With our HPV18-transcription-specific primer pair (5' nts 127-149; 3' nts 587-607), all 7 were shown to contain one strong viral mRNA signal from the early 6/early 7 open reading frames (E6/E7 ORFs). Sequence analysis of the cloned PCR product proved that the transcript was generated by splicing out an intron in E6 from nucleotides 233 to 416, thereby corresponding to the HPV18 E6* spliced mRNA. Nine out of 9 metastatic and 5 of 7 histologically negative lymph nodes from the same patients were also found to be positive for the same mRNA transcript. However, 4 HPV18 unrelated primary tumors and the connected regional pelvic lymph nodes (3 metastatic, 7 histologically negative) were negative for the HPV18 E6* mRNA. Cytokeratin signals indicating tumor cells of epithelial origin were detected in 7 out of the 9 transcript-positive lymph nodes with histological signs of metastasis and in 2 out of the 5 transcript-positive histologically negative lymph nodes. This suggests that the dispersion of the epithelial monoclonal tumor cells was lymphogenic in origin.