Uniform distribution of HPV 16 E6 and E7 variants in patients with normal histology, cervical intra-epithelial neoplasia and cervical cancer.

High-risk human papillomaviruses (HPV), particularly HPV 16, are associated with invasive cervical cancer (ICC), and persistent high-risk HPV infection is considered to be a marker for progressive cervical intra-epithelial neoplasia (CIN). However, most high-risk, HPV-infected, pre-cancerous lesions will not progress to invasion. Several reports suggest that specific HPV 16 E6 and/or E7 sequence variations may be associated with a high risk for progression. No data from German patients have so far been reported. Therefore, we analyzed intra-type variations of these oncogenes in women with normal histology or CIN 1 (< or = CIN 1), CIN 2/3 or ICC. Cervical scrapes from 75 patients with normal histology or CIN and biopsies from 37 ICC patients all positive for HPV 16 were analyzed. The open reading frames of oncogenes HPV 16 E6 and E7 were amplified by nested PCR followed by primer cycle sequencing. From each cervical scrape, 2 independent PCR amplicons were generated and sequenced from both orientations. The prototype sequence of HPV 16 E6 and E7 was identified in 33% and 87% of < or = CIN 1, in 62% and 69% of CIN 2/3 and in 43% and 86% of ICC, respectively (not significant). Of all variants identified, the E6 variant 350G (L83V) and the E7 variant 822G were most frequently detected irrespective of histology and showed prevalence rates of 27% to 43% and 7% to 20%, respectively. No statistically significant differences in the prevalence of the E6 or E7 prototype sequences, any variants or multivariants in German women with < or = CIN 1, CIN 2/3 or ICC were found.