Human papillomavirus 16 E6 polymorphisms in cervical lesions from different European populations and their correlation with human leukocyte antigen class II haplotypes

Infection with high-risk human papillomavirus (HPV) is necessary for the de velopment of a cervical lesion, but only a fraction of precursor lesions pr ogress to cancer. Additional factors, other than HPV type per se, are likel y to increase the probability for progression. Intratype genome variations have been reported to be associated with viral persistence and the developm ent of a major cervical disease. We have recently shown that the prevalence of specific HPV16-E6 variants in invasive cervical cancer (ICC) varies bet ween Italian and Swedish women. To extend our initial study we have analyze d E6 variants in cervical lesions from Czech women, ranging from low-grade cervical intraepithelial neoplasia (LCIN) to ICC and scaled up the sample s ize of our initial study of Swedish and Italian women. In addition, we have correlated the cases of cancers with human leukocyte antigen (HLA) class I I haplotypes. In line with our earlier observation, the distribution of spe cific HPVI6-E6 genotypes in CIN and ICC varied in the 3 cohorts. For instan ce, the HPV16-E6 L83V variant, which has been found to be positively associ ated with ICC in Swedish women (p=0.002), was more prevalent in LCIN than i n ICC in Italian and Czech women (p=0.01 and = 0.03, respectively). These d ata indicate that host genetic factors, such as HLA polymorphism, may deter mine the potential oncogenicity of the HPVI6-E6 L83V variant. Indeed, the D R04-DQ03 haplotype, which is approximately 3-fold more abundant in the norm al Swedish population than in those in Italy and the Czech Republic, was fo und to be positively associated with HPVI6-E6 L83V in the 3 cohorts investi gated (p=0.01). This observation may explain why L83V is a risk factor more in Sweden than in the other 2 countries. (C) 2001 Wiley-Liss, Inc.