Bioinformatics Study Explains Why Some Tumors Have Better Outcomes

University of Illinois Cancer Center researchers uncovered molecular differences between two subtypes of a common head and neck cancer that may help explain why patients with tumors related to human papilloma virus (HPV) infection have significantly better outcomes than patients with HPV-negative tumors.

The research team, led by Xiaowei Wang, professor of pharmacology and regenerative medicine at the UIC College of Medicine, conducted a comprehensive study of 315 tumors from patients with oropharyngeal squamous cell carcinoma, commonly referred to as throat or tonsil cancer.  This cancer is broadly divided into two categories – those associated with HPV infection and those that are mostly tied to tobacco and alcohol consumption.

By focusing on the types of cells and genes present in and around the tumor – known as the tumor microenvironment–the researchers confirmed that tumor subtype dictates prognosis for patients and identified potential treatment targets to improve survival rates for those with non-HPV-associated tumors.

The presence of HPV promotes the body’s own immune response and suppresses activities in the extracellular matrix, Wang said. The cancer is more aggressive and harder to treat when HPV is not present.

“We found that what happens around the cancer, in the tumor microenvironment, explains the poorer prognosis for patients with non-HPV-associated disease,” Wang explained. “The body’s immune system doesn’t attack the tumor like it does when HPV is present. Instead, fibroblasts form and help the cancer grow and spread.”

Patients with HPV-positive throat cancer have a five-year survival rate of 85-90%. The survival rate for those with HPV-negative tumors have a far lower five-year survival rate of 25-40%. In both subtypes, the cancer is far more common in men.

An immune checkpoint gene, CD276, was identified as a potential target for treating HPV-negative throat cancer. Blocking CD276 has been shown to decrease tumor growth in pancreatic cancer models. The gene is also correlated with worse clinical outcomes in ovarian cancer.

The authors acknowledged that there were some limitations to the study: none of the tumors analyzed were treated with immunotherapy and the majority of samples were HPV-positive. Notable strengths include the large number of samples analyzed, the use of molecular biology techniques and bioinformatics, and the use of two sets of cases for discovery and validation.

Findings from the comprehensive bioinformatics study were published in the International Journal of Cancer.  

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