Study provides new understanding of molecular mechanisms of HPV-induced tumors

The incidence of human papillomavirus (HPV)-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) of the oropharynx has dramatically increased over the last decade and is now more frequently diagnosed than uterine cervical cancer in the United States. To better understand the disease, a Yale Cancer Center team analyzed HNSCC data from The Cancer Genome Atlas to identify molecular characteristics of HPV+ HNSCC and correlated them with patient outcomes.

In their review, the team identified a subset of HPV+ HNSCCs with mutations in the genes TRAF3 (tumor necrosis factor receptor-associated factor 3) and CYLD (cylindromatosis lysine 63 deubiquitinase). The mutations in the TRAF3 and CYLD genes correlated with improved patient survival. Their findings are published in the journal Cancer.

The Yale Cancer Center team's findings suggest that the TRAF3 and CYLD mutations may support an alternative mechanism through which HPV causes cancer. New knowledge of this previously undescribed subtype of HPV+ HNSCC and a new understanding of the molecular mechanisms of HPV-induced tumors could lead to new therapeutic strategies for treatment of patients.

"This is a seminal study for head and neck cancers that suggests a new method of tumor development for HPV that does not rely on integration of the HPV genome, but instead relies on mutations that allow the cell to carry the HPV viral genome," Wendell Yarbrough, MD, MMHC, FACS, Professor of Surgery (Otolaryngology) and of Pathology, Section Chief of Otolaryngology and Director of the Head & Neck Cancers Program at Smilow Cancer Hospital, commented.

"Having markers for tumors with improved survival will allow us to identify which patients may be treated with less aggressive therapy to avoid long-term side effects, and conversely, will identify patients that may need new or more aggressive therapy."