We investigated the role of human papillomavirus (HPV) type 52 polymorphism in the persistence of HPV infection, which is a predictor for cervical lesions. Cervical samples obtained at 6-month intervals were tested for HPV-52 in 1055 women; 41, 12, and 58 women had persistent, transient, and unclassified HPV-52 infections, respectively. HPV-52 isolates were analyzed by polymerase chain-reaction sequencing of the long control region (LCR), E6, and E7 genes. Although age (odds ratio [OR], 0.90 [95% confidence interval [CI], 0.81-0.99]), nonprototypic LCR (OR, 9.26 [95% CI, 2.1-41.7]), and E6 variant (OR, 7.04 [95% CI, 1.4-37]) were associated, in univariate analysis, with the persistence of HPV-52 infection, a nonprototypic LCR variant was the only independent predictor of it (OR, 14.1 [95% CI, 1.1-200]). In the latter variants, the loss of a binding site for a repressor of HPV expression was associated with the persistence of HPV infection (OR, 7.25 [95% CI, 1.67-31.25]).