UCLA scientists find link between gigaxonin protein and HPV-positive head and neck cancers

UCLA scientists have discovered for the first time that a protein usually linked to rare neurological disorders is also associated with human papilloma virus (HPV) positive head and neck cancers. The protein was also shown to help improve the effectiveness of chemotherapy treatments, laying the groundwork for the development of more specialized therapies.

Head and neck cancer is the sixth most common form of cancer worldwide, and represents five percent of all cancers diagnosed annually in the United States. Of the more than 42,000 head and neck cancer cases diagnosed each year, 12,000 will die from the disease. HPV is the most common sexually transmitted infection, and diagnoses are at epidemic proportions, with an estimate that nearly all sexually active men and women will get it at some point in their lives.

Led by Drs. Eri Srivatsan and Marilene Wang, UCLA Jonsson Comprehensive Cancer Center members and co-authors of the study, researchers found a link between the protein gigaxonin and head and neck cancer while investigating the chemotherapy drug cisplatin. The drug is successfully able to kill cancer cells by interacting with the protein p16 which is commonly produced in HPV positive cancers.

Though HPV has mostly been seen in cervical cancer, over the past several years there has been an increase in p16-positive HPV-related head and neck cancers. These cancers often affect non-smoking younger adults, who previously were not considered to be at high risk for head and neck cancer.

"We studied the interaction of p16 in the nucleus of the cancer cell after treatment with cisplatin, and observed how the protein interacted with gigaxonin," said Dr. Wang, professor-in-residence of head and neck surgery. "We found it stops the cell cycle, allowing chemotherapy treatment to prevent the cell from growing and killing the cancer cell."

For the study, Drs. Wang and Srivatsan as well as eight other colleagues at UCLA also analyzed 103 archival clinical samples from head and neck cancer patients to identify the relationship between p16 nuclear expression and cancer free survival. They found that patients with cancers with p16 expression had better survival rates than without p16 expression.

They hope the new findings will lead to an enhanced form of personalized targeted therapy for head and neck cancer patients, ultimately reducing the harsh side effects of chemotherapy and radiation.

"This discovery opens new possibilities in the diagnosis and treatment of HPV positive head and neck cancers," said Dr. Srivatsan, professor of general surgery.
The study was recently published online in the Journal of Biological Chemistry.