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 infectio n is considered to be a marker for progressive cervical intra-epithelial ne oplasia (CIN). However, most high risk, HPV-infected, pre-cancerous lesions will not progress to invasion. Several reports suggest that specific HPV 1 6 E6 and/or E7 sequence variations may be associated with a high risk for p rogression. No data from German patients have so far been reported. Therefo re, we analyzed intra-type variations of these oncogenes in women with norm al histology or CIN 1 (less than or equal to CIN 1), CIN 2/3 or ICC, Cervic al 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 fra mes of oncogenes HPV 16 E6 and E7 were amplified by nested PCR followed by primer cycle sequencing. From each cervical scrape, 2 independent PCR ampli cons were generated and sequenced from both orientations. The prototype seq uence of HPV 16 E6 and E7 was identified in 33% and 87% of less than or equ al to CIN 1, in 62% and 69% of CIN 2/3 and in 43% and 86% of ICC, respectiv ely (not significant). Of all variants identified, the E6 variant 350G (L83 V) and the E7 variant 822G were most frequently detected irrespective of hi stology and showed prevalence rates of 27% to 43% and 7% to 20%, respective ly. No statistically significant differences in the prevalence of the E6 or E7 prototype sequences, any variants or multivariants in German women with less than or equal to CIN 1, CIN 2/3 or ICC were found. (C) 1999 Wiley-Lis s, Inc.