Distinct Subtypes and Potential Treatment Options Found in Analysis of Head and Neck Cancers

Data published in the journal Cancer Cell presented possible new treatment options and elaborated on the contributions of key cancer-associated genes, phosphosites, and signaling pathways in human papillomavirus (HPV)­–negative head and neck squamous cell carcinomas (HNSCC).¹

The data systematically recorded information regarding the disease, with multi-omic analysis determining 3 distinct subtypes with high potential for treatment with respective available therapeutics.

“This study extends our biological understanding of HPV[-negative] HNSCC and generates therapeutic hypotheses that may serve as the basis for future preclinical studies and clinical trials toward molecularly guided precision treatment of this aggressive cancer type,” wrote the investigators.²

The first subtype, called CIN for “chromosome instability”, was determined to have the worst prognosis. It was associated with the larynx, a history of smoking, and increased instability of chromosomes. The research team suggested that this cancer type would respond best to CDK4/6 inhibitor treatment given its relation to aberrations of the CCND1 and CDKN2A genes as well as a high activity of the CDK4 and CDK6 enzymes.

The investigators analyzed a number of protein elevations of basal factors in the second subtype discovered, which was in turn called Basal. These represent the most basic proteins necessary for gene transcription activation. The subtype had both high activity in the EGFR signaling pathway and high expression of the AREG and TNFA molecules. This led the investigators to suggest that treatment with monoclonal antibodies targeting EGFR would best treat this subtype.

Immune, the final subtype, was discovered among patients who did not smoke and had high expression of multiple immune checkpoint proteins. The data suggest patients with this subtype would respond best to immune checkpoint inhibitors.

The overall data found high potential for treatment response in 32% of patients with the CIN subtype, 62% of those with the basal subtype, and 83% with the immune subtype.

“This study extends our biological understanding of HPV-negative HNSCCs and generates therapeutic hypotheses that may serve as the basis for future studies and clinical trials toward molecularly guided precision medicine treatment of this aggressive cancer type,” Daniel Chan, PhD, principal investigator on the trial and director of the Center for Biomarker Discovery and Translation at the Johns Hopkins University School of Medicine, said in a press release.

The team also determined that there were 2 modes of activation of EGFR. This determination suggests a potentially new way to stratify this cancer type based on the number of molecules bound to EGFR. Moreover, the investigators concluded that the loss of the ability to produce immune responses is credited to the widespread deletion of immune modulatory genes.

Investigators from both the United States and Poland analyzed 110 treatment-naïve primary HNSCC tumors and matched blood samples. A total of 66 tumors matched normal adjacent tissues.

“We have made the primary and processed datasets available in publicly accessible data repositories and portals, which will allow full investigation of this extensively characterized cohort by both the HNSCC and broader scientific communities. We also expect wide application of the demonstrated proteogenomics framework to future studies of HNSCC and other cancer types,” the investigators concluded

References:

1. Huang C, Chen L, Savage SR, et al. Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma. Cancer Cell. January 5, 2021. doi: 10.1016/j.ccell.2020.12.007

2. Researchers create comprehensive database of head and neck cancers. News release. Hopkins Medicine. January 7, 2021. Accessed January 25, 2021. https://www.hopkinsmedicine.org/news/newsroom/news-releases/researchers-create-comprehensive-database-of-head-and-neck-cancers