Head and neck cancers have repeatedly been linked to infection with human papillomavirus (HPV), with more than half of oropharyngeal squamous cell carcinomas (HNSCCs) positive for HPV. Interestingly, HPV-positive HNSCCs respond better to radiation therapy and have a better prognosis than HPV-negative tumors. But the molecular pathways responsible for their different sensitivities are unclear.
In the March 1 issue of Clinical Cancer Research, Natalia Issaeva, research assistant professor of otolaryngology, and colleagues report that an enzyme called SMG-1 (which participates in sensing DNA damage and is thought to be a tumor suppressor) may play a key role. They found that HPV-positive HNSCC cells and tumors have reduced expression of SMG-1 – and that low SMG-1 expression correlates with positive HPV status and improved patient survival. Depleting SMG-1 in HPV-negative cells increased their sensitivity to radiation, whereas overexpressing the protein in HPV-positive cells protected them from radiation therapy.
The results suggest that assessing SMG-1 levels in tumor biopsies may help to predict how likely a patient’s tumor is to respond to radiation therapy.
The work was supported by an endowment provided to the Barry Baker Laboratory for Head and Neck Oncology at Vanderbilt University.
