Genome-wide study identifies genetic risk factors for HPV infection

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Human papillomavirus (HPV) is the second most common cancer-causing virus, causing 690,000 cases of cervical and other cancers worldwide each year. While the immune system usually clears HPV infections, persistent HPV infections can lead to cancer, and a new finding suggests that some women may be genetically susceptible to persistent or frequent HPV infections. A study led by researchers at the University of Maryland School of Medicine found that these genetic variants may increase a woman’s risk of cervical cancer due to high-risk HPV infection.

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

The research team conducted a genome-wide association study of high-risk HPV infection in more than 10,000 women, with data collected as part of the African Collaborating Center for Microbiome and Genome Research (ACCME) cohort study. A total of 903 participants had high-risk HPV infections at the start of the study, 224 of whom had their HPV infections in remission, and 679 of whom had persistent HPV infections. More than 9,800 HPV-negative women in the ACCME study served as controls.

We found that certain genetic variants are associated with high-risk HPV infection, while other variants and human leukocyte antigen (HLA) genes are associated with persistent infection, thereby increasing the risk of cervical cancer. said study leader Sally N. Adebamowo, MBBS, MSc, ScD, associate professor of epidemiology and public health at UMSOM. This is an important finding showing a genetic basis for cervical cancer risk. This is the first adequate and powered genome-wide association study of cervical high-risk HPV infection. Our polygenic risk score model should be evaluated in other ethnic groups.

Specifically, she and her colleagues found that the most important variant associated with prevalent high-risk HPV infections is rs116471799, located on the fourth chromosome near the LDB2 gene, which encodes a protein. They found that persistent HPV was associated with mutations surrounding TPTE2, a protein-coding gene associated with gallbladder cancer. The SMAD2 and CDH12 genes were also associated with persistent high-risk HPV infection and a significant polygenic risk score. These findings allowed the research team to develop a polygenic risk score to determine the likelihood that a certain genetic profile increases the risk of widespread or persistent HPV infection.

Our findings can be used for risk stratification of persistent high-risk HPV infection to achieve precise or personalized cervical cancer prevention. We hope to conduct long-term studies integrating 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 and public health at UMSOM.

A recent report from the American Cancer Society found that cervical cancer rates increased by nearly 2% annually in women ages 30 to 44 from 2012 to 2019. The incidence rate dropped significantly. In addition, cervical cancer rates have steadily declined among young women, who were the first to benefit from the HPV vaccine, which was approved for use in 2006.

In the United States, more than half of women diagnosed with cervical cancer have never been screened or have not been screened within the past five years, according to the Centers for Disease Control and Prevention. In Nigeria, only a small proportion of women have access to the HPV vaccine, so most of the women in the study were not vaccinated.

These results provide insight into antigen processing and presentation and the role of HLA-DRB1 alleles in immune surveillance and persistence of high-risk HPV infection. said Mark T. Gladwin, MD, John Z. Bowers and Akiko K. Bowers Distinguished Professor, UMSOM Dean, Vice Chancellor for Medical Affairs, University of Maryland, Baltimore. Confirmatory studies are critical to validate these important findings in other ethnic groups, with the goal of reducing the global health burden of high-risk HPV-related diseases.

refer to: Adebamowo SN, Adeyemo A, Adebayo A, et al. Genomic, HLA, and polygenic risk score analysis for prevalent and persistent cervical human papillomavirus (HPV) infection. European Journal of Human Genetics. 2024. Doe: 10.1038/s41431-023-01521-7

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