Head-and-neck cancers, which begin in the cells lining the moist surfaces of the mouth, throat, larynx, and sinuses, are commonly caused by tobacco use, alcohol use, and human papillomavirus (HPV) infection. Oddly, HPV-positive head-and-neck cancers — meaning, infection with HPV preceded development of cancer — have a better prognosis than cancers that are HPV-negative. Now, a new study has identified four proteins that play a crucial role in drug-resistant HPV-negative head-and-neck squamous cell cancers, bringing hope to Dr. Ranee Mehra, a medical oncologist, and her co-researchers who seek better treatment targets in order to create more effective drugs.
Even if HPV-positive head-and-neck cancers may have better outcomes than their HPV-negative counterparts, it is no joke being diagnosed with cancer. According to Johns Hopkins Medicine, up to 80 percent of all oropharyngeal cancers in the U.S. may be due to infection with the HPV virus, especially HPV-16. (The most common of all the sexually transmitted infections, HPV is believed to infect more than half of all active people during their lives.) Many HPV infections go away on their own within two years, and even high-risk HPVs do not result in cancer most of the time. Still, the number of cases of oropharyngeal cancers, which involve the base of the tongue and the tonsils, directly caused by HPV infection are on the rise in the U.S. In fact, doctors believe infections lasting many years increase a person’s risk of developing cancer.
Mehra and her colleagues began their new study by looking at tissue samples from 101 cases of head-and-neck cancer banked between the years of 1990 and 2002 at the Fox Chase tissue repository. These samples were chosen by the team of researchers because they are cross-referenced with both patient treatment information and survival data. The team then used tissue microarrays (an intensive form of clinical analysis) to examine samples one at a time. Specifically, the team searched for expression of ERCC1, a DNA repair protein; survivin, a protein that inhibits apoptosis or programmed cell death; and two proteins active during cell division, Aurora A and phospho-Aurora A. The team focused on this quartet of proteins because past research has suggested they might prove to be significant.
The researchers discovered that expression of the repair protein ERCC1 was positively associated with each of the cell-division proteins, AuroraA and phospho-Aurora, while both Aurora proteins also appeared to be related. The researchers also linked survivin to both Aurora A and ERCC1.
What does all this mean?
According to Mehra, the level of expression of aptly-named survivin may be related to survival rates, especially in patients who have been treated with surgery plus radiation. Tumors with less-than-average levels of survivin were linked to improved patient survival rates compared to tumors with more-than-average levels. And verifying previous work, Mehra also found that lower levels of ERCC1 predicted improved survival rates among patients treated with radiation. "The ultimate goal would be to better understand a tumor's protein signature and underlying biology so that, in the future, we can better understand treatments are more likely to be beneficial to our patients with head and neck cancer," said Mehra, who has presented her findings at the American Association for Cancer Research annual meeting today in San Diego.