Cervical Cancer Classified Into Two Distinct Molecular Subgroups

Cervical cancer is a significant cause of cancer-related deaths in women, accounting for 266,000 deaths worldwide each year. To further understand how this cancer develops in the body, researchers from the University College London (UCL) and the University of Southampton discovered that cervical cancer could be divided into two distinct molecular subgroups, C1 and C2.

The researchers began by utilizing publicly available US data on 236 cervical squamous cell carcinoma (CSCC) cases, which is the most common form of cervical cancer. The team could distinguish between these two subtypes using a multi-omics approach, which includes complex analyses identifying molecular markers and characteristics with biological processes, such as DNA, RNA, proteins, metabolites, and more. 

Recently published in Nature Communications, the work uncovers that C1 tumors have a might higher number of cytotoxic T cells, or specialized white blood cells known to kill tumors. These findings suggest that patients with C1 tumors may have a more robust immune response within the tumor microenvironment.  

To see if this pattern of results holds up in a larger sample, the team included molecular profiles to be examined by researchers from the University of Kent, the University of Cambridge, Oslo University Hospital, the University of Bergen, and the University of Innsbruck. This added an additional 313 CSCC clinical cases in Norway and Austria, with much more detailed patient follow-up data available to the researchers.

After this integrated analysis, the scientists found that, in the US cohort, nearly a quarter of the patients could be classified into the C2 subtype, which was shown to be far more clinically aggressive than C1. Additionally, they confirmed that C1 tumors contained far more specialized T cells than C2 tumors. The difference in outcomes between patients with C1 and C2 tumors was very similar across US and European cohorts.

“Despite major steps forward in preventing cervical cancer, many women still die from the disease,” says co-corresponding author Tim Fenton, associate professor in cancer biology at the School of Cancer Sciences Center for Cancer Immunology at the University of Southampton. “Our findings suggest that determining whether a patient has a C1 or a C2 cervical cancer could help in planning their treatment, since it appears to provide additional prognostic information beyond that gained from clinical staging (examining the size and degree to which the tumour has spread beyond the cervix at the time of diagnosis).”

“This collaborative multi-disciplinary research is a major step forward in our understanding of cervical cancer,” states co-corresponding author Kerry Chester, professor of molecular medicine at UCL Cancer Institute. “Through careful molecular profiling and genetic analysis of cervical cancer tumours we have gained valuable new insight into the tumour microenvironment and factors potentially making the cancer less aggressive in some patients.”