First Genome Wide Association Study Finds Variants Linked to Susceptibility of Cervical Cancer-Causing Virus

A research team conducted a genome-wide association study of high-risk HPV infections in a cohort of over 10,000 women, whose data were collected as part of the African Collaborative Center for Microbiome and Genomics Research (ACCME) cohort study. A total of 903 of the participants had high-risk HPV infections when the study began, with 224 participants having HPV infections that resolved, and 679 having persistent HPV infections. More than 9,800 HPV-negative women from the ACCME study served as controls.

Study leader Sally N. Adebamowo, MBBS, MSc, ScD, Associate Professor of Epidemiology & Public Health at UMSOM said, “We found certain genetic variants were associated with having high-risk HPV infections, while other variants and human leukocyte antigen (HLA) genes were associated with persistent infections, which increase the risk of developing cervical cancer,”

“This is a critical finding that suggests genetic underpinnings for cervical cancer risk. It is the first sufficiently powered genome-wide association study of cervical high-risk HPV infections. Our polygenic risk score models should be evaluated in other populations.”

Specifically, she and her colleagues found that the top variant associated with prevalent high-risk HPV infection was rs116471799, on the fourth chromosome near the LDB2 gene, which encodes for proteins. They found persistent HPV was associated with variants clustered around the TPTE2, a protein encoding gene associated with gallbladder cancer. The genes SMAD2 and CDH12 were also associated with persistent high risk HPV infections, and significant polygenic risk scores. Together the findings enabled the research team to develop polygenic risk scores to determine the likelihood that a certain genetic profile would increase the risk of having prevalent or persistent HPV infections.

“Our findings can be used for risk stratification of persistent high-risk HPV infections for precision or personalized cervical cancer prevention. We hope to conduct long-term studies on the integration of PRS and genomic risk factors into the continuum of cervical cancer prevention,” said study corresponding author Clement A. Adebamowo, BM, ChB, ScD, Professor of Epidemiology & Public Health at UMSOM.

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