- The genomic polymorphism of high-risk human papillomavirus (HPV) for types other than 16 has not been extensively described. We describe here the genomic polymorphism of high-risk HPV type 31 in 79 women (62 HIV-seropositive, 17 HIV-seronegative) by PCR-sequencing of the long control region (LCR), E6 and E7. LCR polymorphism was generated by 25 (6.4%) single-nucleotide variations over 391 bases. Each variant compared to the prototype contained from 2 to 13 variations (mean of 9.4 +/- 3.3, median of 10). Considering the number of variation sites in each region of HPV genome, the LCR was more variable than E6 (13 over 496 nucleotide (nt), P=0.03) and E7 (9 over 296 nt, P=0.03). Non-synonymous nucleotide variations were found in 31 (75.6%) of 41 isolates and were observed at six positions in E6. Each of the 8 HPV-31 E7 variants contained from 2 to 5 mutations (mean of 4.29 +/- 1.11, median of 5) compared to the prototype. Three non-synonymous E6 and E7 variations were within cysteine arrays. The LCR prototype was significantly over-represented in Caucasian women (14 (25%) of 56) compared to women of African descent (0 (0%) of 15 women, P=0.03). Four (23.5%) of 17 women with persistent versus 6 (25.0%) of 24 women with transient infections were infected by the prototype (P=1.00). HPV-31 LCR was more polymorphic than oncogenes and was associated with ethnicity.