Sequence variation in the E7 gene of human papillomavirus type 18 in tumor and non-tumor patients and antibody response to a conserved seroreactive epitope.

ABSTRACT

We have determined nucleotide sequences of the E7 open reading frame (ORF) of human papillomavirus type 18 (HPV-18) isolates obtained from 18 cervical carcinomas from Tanzanian and German patients and 8 cervical scrapings from Tanzanian non-tumor patients. The HPV-18 prototype sequence was detected in only 3 out of 26 isolates. Silent mutations were found at nt positions 640 and 751, whereas the mutations observed at nt positions 770, 806, 864 and 865 all change the respectively encoded amino acid. The HPV-18 isolates of 3 German carcinomas showed the same mutations (at position 751) as those of 2 established cervical carcinoma cell lines (HeLa and C4-1), whereas different mutations were found in 16/23 African isolates (at positions 640 and 864), to which the isolate of cell line SW756 was similar (changes at positions 640 and 865). Seven out of 15 HPV-18-positive Tanzanian tumor patients (46.7%) reacted in a peptide ELISA against a recently described seroreactive epitope of the HPV-18 E7 ORF (nt positions 704-769). Mutational changes of the E7 ORF were excluded as a possible explanation for the lack of antibody response, because there was no correlation with the serological results. The seroreactive region appears to be well conserved despite geographically varying mutations within the E7 ORF of HPV-18.