The Human Papillomavirus (HPV) is responsible for around 690,000 cases of cervical and other cancers annually worldwide, making it the second most common cancer-causing virus. While the body’s immune system typically clears HPV infections, persistent infections can lead to cancer. A recent discovery suggests that certain women may have a genetic predisposition to persistent or frequent HPV infections, which could increase their risk of developing cervical cancer from a high-risk HPV infection.The immune system can usually clear HPV infections, but if they persist, they can lead to cancer. A new discovery suggests that some women may have a genetic predisposition for persistent or frequent HPV infections, which could increase their risk of developing cervical cancer from a high-risk HPV infection. University of Maryland School of Medicine researchers identified these genetic variants in a study, and the 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.0 women were included in the study, which was part of the African Collaborative Center for Microbiome and Genomics Research (ACCME) cohort study. At the start of the study, 903 participants had high-risk HPV infections, with 224 of them seeing their infections resolved and 679 experiencing persistent HPV infections. The study also included more than 9,800 women without HPV infections, who served as controls for comparison.
The researchers discovered that certain genetic variants were linked to 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.The leader of the study, Sally N. Adebamowo, MBBS, MSc, ScD, Associate Professor of Epidemiology & Public Health at UMSOM, stated, “This discovery is crucial as it indicates the presence of genetic factors contributing to the risk of cervical cancer. This is the first genome-wide association study with enough statistical power to identify genetic links to high-risk HPV infections. Our models for polygenic risk scores should be tested in other groups.”
More specifically, Adebamowo and her team identified the primary variant linked to prevalent high-risk HPV infection as rs116471799, located on the fourth chromosome near the LDB2 gene, which is responsible for encoding proteins. They also found that persistent HPV infection was linked to The TPTE2 gene, associated with gallbladder cancer, was found to have various genetic variants. SMAD2 and CDH12 genes were also linked to persistent high-risk HPV infections and had significant polygenic risk scores. These findings allowed the researchers to create polygenic risk scores to predict the likelihood of a certain genetic profile increasing the risk of prevalent or persistent HPV infections. The research team believes that these findings can be utilized for precision or personalized cervical cancer prevention by stratifying the risk of persistent high-risk HPV infections. They also intend to carry out long-term studies on the integration of these findings.The study’s corresponding author, Clement A. Adebamowo, BM, ChB, ScD, who is a Professor of Epidemiology & Public Health at UMSOM, stated that the integration of PRS and genomic risk factors is an important part of cervical cancer prevention. According to a recent report from the American Cancer Society, there has been an almost 2 percent annual increase in cervical cancer among women aged 30 to 44 from 2012 to 2019. This rise comes after a significant decline in cervical cancer rates over the past fifty years, largely due to early detection through Pap smears and HPV screening tests. Furthermore, younger women who were among the first to receive HPV vaccines have seen a steady decline in cervical cancer rates.The HPV vaccine was approved for use in 2006. In the U.S., over half of women diagnosed with cervical cancer have either never been screened or have not been screened in the last five years, as reported by 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. Mark T. Gladwin, MD, commented that the results of the study provide insight into the role of antigen processing and presentation, and HLA-DRB1 alleles in immune surveillance and persistence of high-risk HPV infections.Distinguished Professor and Dean at UMSOM, and Vice President for Medical Affairs at the University of Maryland, Baltimore, emphasized the importance of confirmatory studies to validate the significant findings in other populations. The goal is to reduce the burden of high-risk HPV related diseases on global health.
Study co-authors were from the National Human Genome Research Institute in Bethesda, MD; Asokoro District Hospital in Abuja, Nigeria; Federal Medical Center in Keffi, Nigeria; Wuse General Hospital in Abuja, Nigeria; University College Hospital, University of Ibadan, Ibadan, Nigeria; Institute of Human Virology Nigeria, Abuja, Niger.Paraphrasing of the given text:
Garki Hospital Abuja, Abuja, Nigeria; University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria; National Hospital Abuja, Abuja, Nigeria; Kubwa General Hospital, Abuja, Nigeria. This research was funded by the African Collaborative Center for Microbiome and Genomics Research Grant (NIH/NHGRI 1U54HG006947), UM-Capacity Development for Research in AIDS Associated Malignancy Grant (NIH/NCI 1D43CA153792-01), and Polygenic Risk Score (PRS) Methods and Analysis for Populations of Diverse Ancestry — Study Sites (NIH/NHGRI 1U01HG011717).
