Human Papillomavirus Type 33 Polymorphisms and High‐Grade Squamous Intraepithelial Lesions of the Uterine Cervix

Background. We investigated the association between polymorphisms of human papillomavirus (HPV)-33 and squamous intraepithelial lesions (SILs). Methods. Endocervical specimens from 89 women infected with HPV-33, out of a total of 5347 recruited for 2 case-control and 2 cohort studies, were further analyzed by polymerase chain reaction sequencing of the long control region (LCR), E6, and E7. Results. Of the 89 samples, 64 were normal, 7 had low-grade SILs (including 3 determined by histopathologic analysis), 15 had high-grade SILs (HSILs, including 14 determined by histopathologic analysis), and 3 had an unknown diagnosis. Non-prototype-like LCR variants were significantly associated with HSILs (age- and study site-adjusted odds ratio [OR], 9.2 [95% confidence interval {CI}, 1.8-45.9]). The C7732G variation, which results in the loss of a putative binding site for the cellular upstream stimulatory factor, was associated with HSILs (age-and site-adjusted OR, 8.0 [95% CI, 1.5-42.8]). E6 and E7 polymorphisms were not associated with HSILs. Samples collected at 6-month intervals from 14 participants contained the same variant. The HPV-33 MT 1-0-0 variant carrying the G7584A variation was detected more frequently in women from Brazil (7/20 [35%]) than in women from Canada (1/65 [1.5%]; P = .001). Conclusion. Intratypic LCR variants of HPV-33 seem to vary geographically and to differ with respect to their oncogenic potential.