Study reveals new genetic risk factors for HPV infection

A research led by University of Maryland School of Medicine researchers and published in the journal The European Journal of Human Genetics has identified genetic variants that could raise a woman's risk of getting cervical cancer from a high-risk HPV infection.

Human papillomavirus (HPV) is the second most common cancer-causing virus, accounting for 690,000 cervical and other cancers each year worldwide. While the immune system usually clears HPV infections, those that persist can lead to cancer, and a new finding suggests that certain women may have a genetic susceptibility for persistent or frequent HPV infections.

In the study, researchers conducted a genome-wide association study of high-risk HPV infections in a cohort of over 10,000 women. 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 were in the control group.

The results revealed that the top variant associated with prevalent high-risk HPV infection was located 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.

"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,” said study leader Sally N. Adebamowo, MBBS, MSc, ScD, Associate Professor of Epidemiology & Public Health at UMSOM

Reference:Adebamowo, S.N., Adeyemo, A., Adebayo, A. et al. Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections. Eur J Hum Genet (2024). https://doi.org/10.1038/s41431-023-01521-7