Two Discoveries With Cervical Cancer: Novel Regulatory Genes and the True Mortality Rate

Investigators with The Cancer Genome Atlas Research Network have identified 8 new genes following molecular characterization of 228 primary cervical cancers, which can help subclassification of the disease and develop more personalized targeted therapies.

The study, published in Nature,¹ conducted a comprehensive analysis of the genomes of 178 primary cervical cancers, and found that more than 70% of the tumors had genomic alterations in either one or both of 2 important cell signaling pathways. Surprisingly, a subset of the tumors was not positive for the human papillomavirus, which is the most common cause of cervical cancer. The analysis showed that SHKBP1, ERBB3, CASP8, HLA-A, and TGFBR2 were significantly mutated in the tumor samples, while D274/PD-L1, PDCD1LG2/PD-L2, and the BCAR4 lncRNA were significantly amplified.

Akinyemi Ojesina, MD, PhD, assistant professor in the Department of Epidemiology, School of Public Health at the University of Alabama at Birmingham, who’s one of the corresponding authors on the study is excited with the prospect of developing novel targeted therapies for cervical cancer.

Another exciting finding is the mutations in genes that express PD-L1 and PD-L2, which are targets of immunotherapies that are already approved in other cancer types like melanoma and lung cancer.

This study was published on the same day as another study published in the journal Cancer,² which found that the death rate from the disease is much higher than was previously thought. More importantly, the racial disparity is much wider, the study found. After correcting for the prevalence of hysterectomy, the authors estimated the deaths due to cervical cancer for both white and black women after stratifying based on age, state, and age.

The results were surprising. The mortality rate nearly doubled for black women: from 5.7 per 100,000 (95% CI, 5.5-6.0) to 10.1 per 100,000 (95% CI, 9.6-10.6). The death rate for white women after correction increased from 3.2 per 100,000 (95% CI, 3.1-3.2) to 4.7 per 100,000 (95% CI, 4.6-4.8). The highest mortality was observed in women older than 85 years: 37.2 deaths per 100,000.

The authors noted a need to improve screening efforts while simultaneously raising public awareness on the importance of screening.

References

1. The Cancer Genome Atlas Research Network. Integrated genomic and molecular characterization of cervical cancer [published online January 23, 2017]. Nature. doi:10.1038/nature21386.

2. Beavis AL, Gravitt PE, Rositch AF. Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States [published online January 23, 2017]. Cancer. doi: 10.1002/cncr.30507.