Persistent HPV Infection Is Associated With Genetic Variations

(CTN News) – Human papillomavirus HPV infections with persistent mutations have been identified by researchers at the University of Maryland.

Sally Adebamowo, associate professor of epidemiology & public health at the University of Maryland School of Medicine, said certain genetic variants were associated with HPV infections that were high risk, and other variants and HLA genes were associated with persistent infections, which increased cervical cancer risk. It’s a critical finding that suggests genetics is involved in cervical cancer risk.

It’s the first genome-wide association study of HPV infections in cervical high-risk women.”

Almost 690,000 cervical cancers are caused each year by HPV, the second most common cancer-causing virus. HPV infects more than 80% of women at some point in their lives, but 90% are cleared by the immune system within two years.

According to Adebamowo, even though HPV vaccines are highly effective at preventing cervical cancer, “accessibility remains limited, particularly in low-resource settings, where distribution, affordability, and education need to improve. Additionally, these vaccines don’t cover all carcinogenic HPV types.”

It’s been suggested that genetic factors play a role in HPV prevalence, but exact genetic variants that underlie susceptibility to cervical high-risk HPV infections are largely unknown, say researchers.

“Identifying genetic factors associated with HPV provides valuable insight into the biological pathways of HPV infection and carcinogenic progression,” Adebamowo said.

As part of the African Collaborative Center for Microbiome and Genomics Research (ACCME) cohort study, Adebamowo and his team did genome-wide association studies and HLA allele studies of prevalence and persistence of cervical high-risk HPV infections in a cohort of over 10,000 women.

Nine hundred three participants had high-risk HPV infections at the start of the study. Six79 of these infections persisted after nine months, while 224 cleared up.

Researchers found that those with a prevalent infection at baseline were more likely to carry a variant in the LDB2 gene, a protein coding gene expressed mostly in the uterus and cervix, compared to 9846 women who remained HPV-negative.

Also associated with persistent high-risk HPV were variants near TPTE2, SMAD2, and CDH12, which all code for proteins that are highly expressed in the endocervix.

According to the researchers, HLA molecules are involved in the processing and presentation of antigen, which is the first step in activating the immune system.

Adebamowo stated: “Our results can be used to develop polygenic risk score models in diverse populations, which can be used to predict an individual’s risk of developing a disease. The results of such investigations could pave the way for more effective prevention and monitoring strategies, including the identification of novel therapeutic targets and personalized medicine approaches for women at high risk of cervical cancer.

Currently, the team is conducting replication studies in other populations and developing and testing polygenic risk score models using various statistical and computational techniques.

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