Variation in the E2-binding domain of HPV 16 is associated with high-gradesquamous intraepithelial lesions of the cervix

Human papillomaviruses (HPV) are strongly associated with cervical intraepi thelial neoplasia (CIN) and invasive cancer mainly through the action of th e E6 and E7 viral proteins, transcription of which is down-regulated by the E2 protein. To test the hypothesis that HPV 16 E2 variation is important i n the development of high-grade squamous neoplasia of the cervix, we carrie d out a cross-sectional analysis of low-grade and high-grade squamous intra epithelial lesions (SILs) for specific mutations in the HPV 16 E2 gene and for E2 gene disruption in these regions. Isolates were also analysed for th e HPV 16 350T-G variant. 22 of 178 low-grade SILs and 43 of 61 high-grade S ILs examined, contained HPV 16. No relationship was found between the E6 35 0T-G variant, or the E2 hinge region 3410C-T variant, and lesion grade. How ever, disruption of the regions of E2 analysed was significantly more frequ ent in high-grade lesions, and there was a significant association between the 3684C-A variant in the E2 DNA binding domain and high-grade histology s uggesting that this variant may be important in progression to high-grade i ntraepithelial disease. (C) 2001 Cancer Research Campaign.