Infection with human papilloma virus (HPV) is the primary cause of cervical cancer and a subset of head and neck cancers worldwide. A University of Colorado Cancer Center paper describes a fascinating mechanism that links these two conditions – viral infection and cancer. The link, basically, is a family of enzymes called APOBEC3. These APOBEC3 enzymes are an essential piece of the immune system’s response to viral infection, attacking viral DNA to cause disabling mutations. Unfortunately, as the paper shows, especially the action of family member APOBEC3A can spill over from its attack against viruses to induce DNA mutations and damage in the host genome as well. In other words, this facet of the immune system designed to scramble viral DNA can scramble human DNA as well, sometimes in ways that cause cancer.
Infection with human papilloma virus (HPV) is the primary cause of cervical cancer and a subset of head and neck cancers worldwide. A University of Colorado Cancer Center paper describes a fascinating mechanism that links these two conditions – viral infection and cancer. The link, basically, is a family of enzymes called APOBEC3. These APOBEC3 enzymes are an essential piece of the immune system’s response to viral infection, attacking viral DNA to cause disabling mutations. Unfortunately, as the paper shows, especially the action of family member APOBEC3A can spill over from its attack against viruses to induce DNA mutations and damage in the host genome as well. In other words, this facet of the immune system designed to scramble viral DNA can scramble human DNA as well, sometimes in ways that cause cancer.
“We know that the majority of cancers are caused by genetic mutations. And we know some of the mechanisms that cause these mutations, for example UV radiation can cause mutations that lead to skin cancer and smoking can cause mutations that lead to lung cancer. But there are many more cancers in which we don’t know the source of the mutations. The APOBEC3 family can explain how some of these mutations are created. In fact, APOBEC3A can be activated in many ways – not just with HPV infection – and its action may drive a percentage of oncogenic mutations across many cancer types,” says Dohun Pyeon, PhD, investigator at the CU Cancer Center and associate professor in the Department of Immunology and Microbiology at the CU School of Medicine.
Specifically, data from the Cancer Genome Atlas showed signatures of APOBEC3-mediated mutations in the PIK3CA gene of about 40 percent of HPV-positive head and neck cancers, but only about 10 percent of HPV-negative head and neck cancers. Adding to this storyline of APOBEC3A-mediated oncogenesis was the fact that expression of APOBEC3A was much higher in HPV-positive cancers.
Read more at University of Colorado Anschutz Medical Campus
Image: Dohun Pyeon, PhD, and colleagues describe the mechanism linking HPV and cancer. (Credit: University of Colorado Cancer Center)
