Vaccination against human papillomavirus (HPV) can protect against many forms of the virus, which can cause cervical cancer. But not everyone gets vaccinated, and there’s still a risk of becoming infected with an HPV type that the vaccination doesn’t cover. Early epigenetic events associated with HPV infection are still mysterious, so researchers in the United Kingdom decided to investigate. They found that two types of HPV changed DNA methylation patterns in nonrandom ways, and these changes could have implications for cervical cancer.
The researchers knew that two oncoproteins of HPV16 increase the expression and activity of DNMT1, a DNA methyltransferase, but they wondered whether HPV caused epigenetic changes early on in the infection—changes that could lead to cancer.
They used genome-wide promoter arrays to detect HPV16- and HPV18-associated methylation changes using primary human foreskin fibroblasts, which can support viral episome replication (unlike models used in previous studies). Here are a few of the highlights:
- Transfection with either HPV virus changed the methylation patterns of thousands of genes; those with increased methylation were often reported in other studies as being differentially methylated in cervical cancers as well.
- The changes were clustered in DNA methylation “hotspots”.
- Hypermethylation hotspots were often in sites where HPV integrates into the genome, suggesting that the changes might be involved in cancer.
- Bivalently marked genes (those associated with cancer) in embryonic stem cells were more likely to have increased methylation after HPV transfection.
- They found an association between infection onset in a cohort of young women and an increase in methylated forms of certain genes.
“Our findings suggest that further investigation of the distribution and determinants of early virus induced epigenetic reprogramming will provide important insights into the pathogenesis of virus associated malignancy,” say the paper’s authors.
Get the latest on HPV and DNA methylation at Carcinogenesis, May 2012.