Researchers Discover New Genomic Characteristics of Cervical Cancer

Some cases of cervical cancer resemble endometrial cancer, while others were not caused by HPV infection.

The genomic and molecular characteristics of cervical cancer were recently discovered by The Cancer Genome Atlas (TCGA) Research Network, the National Institutes of Health reported in a press release.

These new findings will help classify the subtypes of the disease, and could even lead to targeted treatments for cervical cancer.

In the study, the authors analyzed the genomes of 178 different types of cervical cancer. They discovered that more than 70% of tumors had alterations in 1 or 2 important signaling pathways.

Additionally, the researchers found certain tumors did not have evidence of a human papillomavirus (HPV) infection, according to a study published in Nature.

There are more than 500,000 new cases of cervical cancer, and more than 250,000 deaths per year.

“The vast majority of cases of cervical cancer are caused by persistent infection with oncogenic types of HPV,” said National Cancer Institute (NCI) Acting Director Douglas Lowy, MD. “Effective preventive vaccines against the most oncogenic forms of HPV have been available for a number of years, with vaccination having the long-term potential to reduce the number of cases of cervical cancer.”

Unfortunately, many women have not received the vaccine, and cannot be protected from HPV-related cancers.

“However, most women who will develop cervical cancer in the next couple of decades are already beyond the recommended age for vaccination and will not be protected by the vaccine,” Dr Lowy said. “Therefore, cervical cancer is still a disease in need of effective therapies, and this latest TCGA analysis could help advance efforts to find drugs that target important elements of cervical cancer genomes in addition to the HPV genes.”

Interestingly, the investigators also discovered that a subset of 8 cervical cancers were highly similar to endometrial cancers. This subset of cancers are typically HPV-negative, and carry mutations in the KRAS, ARID1A, and PTEN genes.

“The identification of HPV-negative endometrial-like tumors confirms that not all cervical cancers are related to HPV infection and that a small percentage of cervical tumors may be due to strictly genetic or other factors,” said Jean-Claude Zenklusen, PhD, director of NCI’s TCGA program office. “This aspect of the research is one of the most intriguing findings to come out of the TCGA program, which has been looking at more than 30 tumor types over the past decade.”

Since immunotherapy options are becoming prevalent in cancer care, the authors evaluated genes that code for immune targets to determine if any were high, according to the study. They discovered several genes were amplified, which may impact the efficacy of immunotherapy.

The genes CD274—encoding the PD-L1 immune checkpoint protein— and PDCD1LG2—encoding PD-L2—were both amplified in these cancers. Additionally, the researchers identified new mutations in MED1, ERBB3, CASP8, HLA-A, and TGFBR2 genes.

The investigators found multiple cases of gene fusions that involved the BCAR4 gene, which created RNA that responded to treatment with lapatinib, according to the study. Treatment with that drug could be an effective targeted treatment for certain cancers, the authors noted.

Nearly three-quarters of cervical cancers had alterations in 1 or both of the PI3K/MAPK and TGF-beta signaling pathways, which may present another potential treatment.

These findings further characterize cervical cancer, and its subtypes, which may create targeted treatments for these cancers. The most important question raised was whether HPV-positive or negative tumors would react differently to treatments, the study concluded.