Human papillomavirus (HPV) is a common virus that can cause cancer, with 690,000 cases of cervical and other cancers being attributed to the virus each year globally. While the immune system typically clears HPV infections, some may persist and lead to cancer. A recent study led by researchers at the University of Maryland School of Medicine has identified genetic variants that may make certain women more susceptible to persistent or frequent HPV infections, increasing their risk of developing cervical cancer from a high-risk HPV infection. The findings, published in The European Journal of Human Genetics, suggest a genetic basis for cervical cancer risk and could have implications for personalized cancer prevention strategies.
The research team conducted a genome-wide association study of high-risk HPV infections in over 10,000 women as part of the African Collaborative Center for Microbiome and Genomics Research (ACCME) cohort study. The study found that specific genetic variants were associated with prevalent high-risk HPV infections, while other variants and human leukocyte antigen (HLA) genes were linked to persistent infections, which increase the risk of cervical cancer. By identifying genetic underpinnings for cervical cancer risk, the study has provided valuable insights that could be used for risk stratification and personalized prevention strategies for cervical cancer.
The study identified genetic variants associated with prevalent high-risk HPV infections, including a variant near the LDB2 gene on the fourth chromosome. Persistent HPV infections were associated with variants clustered around the TPTE2 gene, which is linked to gallbladder cancer. Other genes, such as SMAD2 and CDH12, were also associated with persistent high-risk HPV infections. These findings enabled the researchers to develop polygenic risk scores to assess the likelihood that a specific genetic profile would increase the risk of prevalent or persistent HPV infections, potentially aiding in personalized cancer prevention efforts.
Cervical cancer rates among women aged 30 to 44 have been on the rise in recent years, despite a significant decline in rates over the past 50 years due to early detection methods such as Pap smears and HPV screening tests. Rates of cervical cancer have fallen among younger women who were among the first to benefit from HPV vaccines, which were introduced in 2006. However, 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, highlighting the importance of regular screening and prevention efforts.
The study’s findings provide insights into the role of antigen processing and presentation, as well as HLA-DRB1 alleles in immune surveillance and persistence of high-risk HPV infections. The results could have implications for reducing the global burden of HPV-related diseases, such as cervical cancer. Confirmatory studies in other populations are needed to validate these important findings and further understand the genetic factors influencing HPV infections and cancer risk. This research was supported by grants from the NIH and emphasizes the importance of global collaboration in studying and addressing HPV-related diseases.
