Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical cancer. Most women naturally clear HPV infections; however, the biological mechanisms related to HPV pathogenesis have not been clearly elucidated. Dr. Sadeep Shrestha, associate professor in the department of epidemiology at the University of Alabama at Birmingham, and his doctoral student Ms. Staci Sudenga (now a post-doctoral fellow at the H. Lee Moffitt Cancer Center, in Tampa, Florida), along with department colleague Dr. Howard W. Wiener, statistician II and collaborator of the HIV Epidemiology Research Study (HERS), analyzed whether host genetic factors that specifically regulate immune response could play an important role.
All HIV-positive women in the multisite, prospective cohort HERS with a HR-HPV infection and at least one follow-up biannual visit were included in this study. Cervicovaginal lavage samples were tested for HPV using type-specific HPV hybridization assays. Type-specific HPV clearance was defined as two consecutive HPV-negative tests after a positive test. DNA from participants was genotyped for 196,524 variants within 186 known immune related loci using the custom ImmunoChip microarray.
Overall, three single-nucleotide polymorphisms, or SNPs (rs1112085, rs11102637, and rs12030900), in the MAGI-3 gene and one SNP (rs8031627) in the SMAD3 gene were associated with HR-HPV clearance. A variant (rs1633038) in HLA-G were also significantly associated in African Americans. The researchers concluded that results from this study support associations of immune-related genes, having potential biological mechanism, with differential cervical HR-HPV infection outcomes. “Dense Genotyping of Immune-Related Loci Identifies Variants Associated with Clearance of HPV among HIV-Positive Women in the HIV Epidemiology Research Study (HERS)” was published in the June issue of PLOS One.