Study Identifies Genetic Variants Potentially Linked to Prevalent or Persistent HPV Infections

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Investigators have uncovered genetic variants that may predispose certain female patients to prevalent or persistent human papillomavirus (HPV) infections and increase their risk of developing cervical cancer, according to a recent study published by Adebamowo et al in the European Journal of Human Genetics.


HPV—the second most common cancer-causing virus—accounts for about 690,000 cases of cervical cancer and other types of cancers across the world each year. Although the immune system is typically capable of clearing HPV infections, those that persist can lead to cancer.

Despite a downward trend in cervical cancer rates over the past 50 years as a result of early detection from Papanicolaou tests and HPV screening, the incidence of cervical cancer in patients aged 30 to 44 years rose nearly 2% per year between 2012 and 2019, according to a report from the American Cancer Society. In addition, rates of cervical cancer have steadily declined among younger female patients who were among the first to benefit from HPV vaccines approved for use in 2006.

In the United States, over 50% of patients diagnosed with cervical cancer have never been screened or were not screened in the last 5 years. In Nigeria, only a small percentage of female patients have access to HPV vaccines.

Study Methods and Results

The investigators used data from the African Collaborative Center for Microbiome and Genomics Research cohort study to conduct a genome-wide association study of high-risk HPV infections in over 10,000 female patients. They noted that 903 of the patients had high-risk HPV infections at the start of the study period—224 of whom saw their HPV infections resolve and 679 of whom experienced persistent HPV infections—and more than 9,800 patients were HPV-negative and served as controls.

The investigators discovered that the rs116471799 variant, located on the fourth chromosome near the LDB2 gene that encodes for proteins, was significantly associated with prevalent high-risk HPV infections. They found that variants clustered around the TPTE2 gene, associated with gallbladder cancer, was associated with persistent HPV infections. The genes SMAD2 and CDH12 also correlated with persistent high-risk HPV infections and significant polygenic risk scores.


“We found certain genetic variants were associated with having high-risk HPV infections, while other variants and human leukocyte antigen genes were associated with persistent infections—which increase the risk of developing cervical cancer,” stressed lead study author Sally N. Adebamowo, MBBS, MSc, ScD, Associate Professor of Epidemiology & Public Health at the University of Maryland School of Medicine. “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,” she emphasized.

The findings enabled the investigators to develop polygenic risk scores to determine whether certain genetic profiles would increase the likelihood of experiencing prevalent or persistent HPV infections as well as indicate which patients may be at an increased risk of developing cervical cancer.

“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 [polygenic risk scores] and genomic risk factors into the continuum of cervical cancer prevention,” underscored senior study author Clement A. Adebamowo, BM, ChB, ScD, Professor of Epidemiology & Public Health at the University of Maryland School of Medicine.

“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. 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,” concluded Mark T. Gladwin, MD, the John Z. and Akiko K. Bowers Distinguished Professor and Dean of the University of Maryland School of Medicine and Vice President for Medical Affairs at the University of Maryland.

Disclosure: The research in this study was supported by the African Collaborative Center for Microbiome and Genomics Research Grant, UM–Capacity Development for Research in AIDS Associated Malignancy Grant, and Polygenic Risk Score Methods and Analysis for Populations of Diverse Ancestry–Study Sites. For full disclosures of the study authors, visit

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