HPV16 variants and HLA alleles are associated with cervical carcinoma in Korean women

Abstract

Background: Persistent human papillomavirus type 16 (HPV16) is the major risk factor for cervical cancer. HPV16 intratypic variants differ in their geographical distribution and oncogenic potential. In addition, the susceptibility to cervical cancer is also known to be affected by ethnicity. This study aimed to analyze the distribution of HPV16 variants and human leukocyte antigen (HLA) polymorphism and their association with cervical lesion histopathology in Korean women. Methods: In total, 133 HPV16-positive cervical samples from women admitted to Seoul National University Boramae Hospital were analyzed by sequencing E6, E7, and L1 genes and the long control region (LCR), and the variant distribution according to cervical lesion grade was determined. Among them, the samples from invasive cancer patients were tested for the determination of allele frequencies of HLA-B, -DRB1, -DQA1 and -DQB1 of host cells. The association between the HLA allele frequency and HPV 16 variant specific invasive cancer was analyzed. Results: Isolates were grouped into a phylogenetic lineage, and A1-3, A4, C, and D sublineages were detected in 54.1, 37.8, 0.7, and 7.4% of samples, respectively. The most commonly observed LCR variations were 7521G>A (91.5%), 7730A>C (59.6%), and 7842G>A (59.6%). Furthermore, A4 or D sublineage-positive women had a higher risk for invasive cancer than women who were positive for A1–3. Among HPV phylogenetic clusters, A1–3 was the predominant sublineage, and within A1–3, the 350G polymorphism was highly frequent. Although limited number of samples were included, HLA-B*13, B*51, DRB1*07, DRB1*09, DRB1*11, DQA1*2 and DQA1*4 were risk factor of invasive cancer for A4 infected patients. HLA-DRB1*15 was risk factor for cervical cancer for A1-3 and D infected patients. Conclusions: The results differed from those of previous studies in Korea and other Asian countries. The findings suggest that cervical neoplasia incidence in HPV16-infected patients could be affected by the distribution of HPV16 variants and HLA type in the population.