Genetics and HPV Infections: A Critical Finding
Researchers at the University of Maryland have made an important discovery regarding human papillomavirus (HPV) infections. Sally Adebamowo, an associate professor of epidemiology & public health at the University of Maryland School of Medicine, explains that certain genetic variants are associated with high-risk HPV infections, while other variants and HLA genes are linked to persistent infections, which increase the risk of cervical cancer. This finding suggests that genetics play a role in determining cervical cancer risk.
HPV is the second most common cancer-causing virus, causing approximately 690,000 cervical cancers each year. It infects more than 80% of women at some point in their lives, but fortunately, 90% of these infections are cleared by the immune system within two years.
While HPV vaccines are highly effective in preventing cervical cancer, accessibility remains limited, particularly in low-resource settings. Distribution, affordability, and education need improvement, and it’s worth noting that these vaccines don’t cover all carcinogenic types of HPV.
The Role of Genetics in HPV Prevalence
While it has been suggested that genetic factors contribute to HPV prevalence, the specific genetic variants associated with susceptibility to high-risk HPV infections are mostly unknown. Adebamowo and his team aimed to fill this knowledge gap by conducting the first genome-wide association study of HPV infections in cervical high-risk women.
As part of the African Collaborative Center for Microbiome and Genomics Research (ACCME) cohort study, the researchers performed genome-wide association studies and HLA allele studies on over 10,000 women. Of the participants, 903 had high-risk HPV infections at the beginning of the study. After nine months, 679 of these infections persisted, while 224 cleared up.
Insights from the Study
The researchers discovered that women with a prevalent infection at baseline were more likely to carry a variant in the LDB2 gene, which is primarily expressed in the uterus and cervix, compared to the 9,846 women who remained HPV-negative. Additionally, variants near TPTE2, SMAD2, and CDH12 were associated with persistent high-risk HPV infections. These genes code for proteins that are highly expressed in the endocervix.
The Role of HLA Molecules
The researchers also found that HLA molecules play a role in processing and presenting antigens, which is the first step in activating the immune system. This further highlights the importance of genetic factors in HPV infections.
Implications for Prevention and Treatment
Adebamowo believes that the results of this study can be used to develop polygenic risk score models that predict an individual’s risk of developing cervical cancer. This could lead to more effective prevention and monitoring strategies, as well as the identification of novel therapeutic targets and personalized medicine approaches for women at high risk.
Future Studies
The research team is currently conducting replication studies in other populations to validate their findings. They are also developing and testing polygenic risk score models using various statistical and computational techniques.
In conclusion, this groundbreaking study sheds light on the genetic factors associated with HPV infections. It provides valuable insight into the biological pathways of HPV infection and carcinogenic progression. With further research and application of these findings, we can improve prevention and treatment strategies for women at high risk of cervical cancer.