Genetic Markers Linked to Persistent HPV Infections

The human papillomavirus (HPV) stands as the second most prevalent cancer-causing virus globally, contributing to approximately 690,000 cases of cervical and other cancers annually. Though the immune system typically eradicates HPV infections, those that endure can escalate to cancer.

Recent research indicates that specific women may possess genetic predispositions to persistent or recurrent HPV infections. Uncovered in a study spearheaded by researchers from the University of Maryland School of Medicine, these genetic variations could elevate a woman’s susceptibility to developing cervical cancer following exposure to high-risk HPV strains. ()

Findings were recently published in The European Journal of Human Genetics.

The 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.

HPV Infections and Genetic Variants: Fresh Insights

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

A recent report from the American Cancer Society found that cervical cancer among women ages 30 to 44 rose almost 2 percent a year from 2012 to 2019. This is after a big decline in cervical cancer rates over the past half-century due to early detection from Pap smears and HPV screening tests. In addition, rates of cervical cancer, have steadily declined among younger women who were among the first to benefit from HPV vaccines, which were approved for use in 2006.

In the U.S., more than half of women diagnosed with cervical cancer have never been screened or were not screened in the last five years, according to the Centers for Disease Control and Prevention. In Nigeria, only a small percentage of women have access to the HPV vaccine, so those included in the study were largely unvaccinated.

“The results provide insight into the role of antigen processing and presentation, and HLA-DRB1 alleles in immune surveillance and persistence of high-risk HPV infections,” said Mark T. Gladwin, MD, who is the John Z. and Akiko K. Bowers Distinguished Professor and Dean, UMSOM, and Vice President for Medical Affairs, University of Maryland, Baltimore. “Confirmatory studies are crucial to validate these important findings in other populations, with the goal of reducing the burden of high-risk HPV related diseases on global health.”

Reference:

1. Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections – (https://www.nature.com/articles/s41431-023-01521-7)

Source-Eurekalert