Investigators with The Cancer Genome Atlas Research Network, including a researcher from the UAB School of Public Health, have identified novel genomic and molecular characteristics of cervical cancer that will aid in the subclassification of the disease and may help target therapies that are most appropriate for each individual patient.
[Photo: Dr. Akinyemi Ojesina]
The new study, published this week, conducted a comprehensive analysis of the genomes of 178 primary cervical cancers, and found that more than 70 percent of the tumors had genomic alterations in either one or both of two important cell signaling pathways. The researchers also found that a subset of tumors did not show evidence of human papillomavirus infection.
Dr. Akinyemi Ojesina, assistant professor in the department of epidemiology in the UAB School of Public Health, has been involved with the study for the past three years and is a corresponding author on this paper. “Essentially, we performed comprehensive genomic analyses of cervical cancers, and identified genetic mutations that are novel drivers of the disease. This is extremely exciting because we can now develop targeted therapies.”
According to Dr. Ojesina, an associate scientist at the UAB Comprehensive Cancer Center and adjunct faculty investigator at the HudsonAlpha Institute for Biotechnology, many aspects of this study are intriguing. Researchers found that a unique set of eight cervical cancers showed molecular similarities to endometrial cancers. Most of these endometrial-like cancers were HPV-negative, and they had strikingly high frequencies of mutations in the PTEN, ARID1A and KRAS genes.
It has been thought that virtually all cases of cervical cancer are caused by HPV, and just two HPV types are responsible for about 70 percent of all cases. “Basically, this study confirms some of our previous work, also published in Nature in 2014, that HPV infection may not be involved in all cases of cervical cancer,” said Ojesina, who is a major contributor to the TCGA Cervical Cancer Analysis Working Group.
“In the last few decades, immunotherapy has emerged as one of the most promising areas of cancer therapy,” Dr. Ojesina said. “Some treatments boost the body’s immune system in a general way, and others help train the immune system to attack cancer cells specifically. We have now found evidence of mutations in genes that normally put ‘brakes’ on the immune system, suggesting treatment with drugs that take those brakes off may be effective against cervical cancer cells.”
In terms of next steps, Ojesina and the other authors hope to determine whether HPV-positive and HPV-negative tumors will respond differently to targeted therapies.