Genetic variants that may be associated with prevalent or persistent HPV infection are identified

Researchers have discovered genetic mutations that may make certain women more susceptible to widespread or persistent human papillomavirus (HPV) infection and increase their risk of developing cervical cancer. According to a recent study published by Adebamowo et al. European Journal of Human Genetics.

background

HPV, the second most common cancer-causing virus, causes approximately 690,000 cases of cervical cancer and other types of cancer each year worldwide. The immune system is usually able to clear HPV infections, but if the infection persists it can cause cancer.

Although the incidence of cervical cancer has been on the decline over the past 50 years as a result of early detection through Pap tests and HPV screening, the incidence of cervical cancer among patients aged 30 to 44 increased by 2012. It has increased by nearly 2% annually between 2019 and 2019. This is a report from the American Cancer Society. Additionally, the incidence of cervical cancer has steadily declined among young women who first benefited from the HPV vaccine, which was approved for use in 2006.

In the United States, more than 50% of patients diagnosed with cervical cancer have never been tested or have not been tested in the past 5 years. In Nigeria, only a small number of female patients have access to the HPV vaccine.

Research methods and results

Researchers conducted a genome-wide association study of high-risk HPV infections in more than 10,000 female patients using data from the African Collaborating Center for Microbiome and Genomics Research Cohort Study. They found that 903 of the patients had a high-risk HPV infection at the beginning of the study period, of which 224 had resolved HPV infection and 679 had persistent HPV infection; It noted that more than 9,800 patients were HPV negative and receiving treatment. Control.

Researchers found that the rs116471799 variant is located near chromosome 4. LDB2 Protein-encoding genes were significantly associated with prevalent high-risk HPV infection. They found that the variants were concentrated around it. TPTE2 Genes associated with gallbladder cancer were associated with persistent HPV infection.gene SMAD2 and CDH12 It was also correlated with persistent high-risk HPV infection and a significant polygenic risk score.

conclusion

“While certain genetic variants are associated with high-risk HPV infection, other variants and the human leukocyte antigen gene are associated with persistent infection, which has been shown to increase the risk of developing cervical cancer. ” emphasized the study's lead author. Sally N. Adebamowo, MBBS, M.A., Ph.D., Associate Professor of Epidemiology and Public Health, University of Maryland School of Medicine. “This is an important finding that suggests a genetic basis for cervical cancer risk. This is the first fully powered genome-wide association study of cervical high-risk HPV infection. “The polygenic risk score model should also be evaluated in other populations,” she stressed.

This discovery led researchers to create a polygenic risk score to determine whether a particular genetic profile increases the likelihood of experiencing prevalent or persistent HPV infection, and which patients develop cervical cancer. It is now possible to show whether there is a high risk of developing the disease.

“Our findings can be used to risk stratify persistent high-risk HPV infections to accurately prevent or personalize cervical cancer. I would like to conduct research. [polygenic risk scores] “Genomic risk factors play a role in sustained cervical cancer prevention,” the lead study author emphasized. Clement A. Adebamowo, BM, ChB, ScDProfessor of Epidemiology and Public Health, University of Maryland School of Medicine.

“These 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. Reducing the burden of high-risk HPV-associated diseases on global health “Confirmatory studies are critical to verify these important findings in other populations, with the aim of further research.” Dr. Mark T. GladwinJohn Z. Bowers and Akiko K. Bowers are Distinguished Professor and Dean of the University of Maryland School of Medicine and Vice President for Medical Affairs at the University of Maryland.

Disclosure: Research for this study was supported by the African Microbiome and Genomics Research Grant, the UM-Capacity Development for Research in AIDS Associated Malignancy Grant, and the Polygenic Risk Score Methodology and Analysis for Diverse Ancestry Populations. For full study author disclosure, please visit: nature.com.