February 19, 2016
Smoking and infection with human papillomavirus (HPV) are two risk factors for an increasingly common type of throat cancer. In a new study, University of North Carolina’s Lineberger Comprehensive Cancer Center researchers have found that distinct genetic mutation patterns emerge in people with HPV-positive oropharyngeal squamous cell carcinoma who are heavy smokers.
UNC Gillings School of Global Public Health co-authors include Jose P. Zevallos, MD, MPH, FACS, adjunct assistant professor; Andrew Olshan, PhD, Barbara Sorenson Hulka Distinguished Professor in Cancer Epidemiology and chair; and Angela L. Mazul, doctoral student, all in the Gillings School’s Department of Epidemiology.
Preliminary findings, presented Feb. 18 at the 2016 Multidisciplinary Head and Neck Cancer Symposium in Scottsdale, Ariz., could help inform treatment decisions for people with HPV-positive oropharyngeal squamous cell carcinoma and a history of smoking.
“Our major finding was that basically not all HPV-positive oropharyngeal cancers are created equal at a genetic level,” said Zevallos, who is an associate member of UNC Lineberger and assistant professor and director of oncologic research in the UNC School of Medicine’s Department of Otolaryngology/Head and Neck Surgery. “When we stratify patients with HPV-positive cancer by how much they smoke, we notice that patients who smoke less than 10 years have different mutations than patients who smoke more.”
Studies have shown that patients with HPV-linked oropharyngeal squamous cell carcinoma respond better to treatments than do patients with HPV-negative cancer. The finding has led researchers to investigate whether they can still achieve a cure for HPV-positive oropharyngeal cancer patients while lowering the intensity of their radiation and chemotherapy treatment.
Zevallos and his team want to establish mutational profiles of HPV-positive oropharyngeal cancer that could be used to better stratify patients’ risk and inform treatment decisions.
“We know that HPV-positive oropharyngeal cancer patients have excellent prognoses,” Zevallos said. “Because of that excellent prognosis, there has been a lot of work around the country to create treatment protocols that are less intensive. Our study aimed to come up with molecular criteria based on genomic mutations to better stratify their risk.”
The researchers used next-generation sequencing to analyze genetic mutations in 66 HPV-positive oropharyngeal cancer patients who also were categorized into groups according to smoking history. Patients were stratified based upon whether they had smoked more or less than 10 pack-years, i.e., the equivalent to one pack of cigarettes each day for 10 years.
They found a higher likelihood of being disease-free and overall survival in the group that had smoked less than 10 pack-years. Difference in mutations between the two groups were based on smoking history.
According to the study abstract, mutations in genes such as TP53, CDKN2A, KRAS and NOTCH1 appeared almost exclusively in the group that had smoked more than 10 pack-years, while HLA-A mutations were almost exclusively in the group of people who smoked less.
“What we notice is that there is a series of mutations that are found exclusively in patients who are heavy smokers, and a unique mutation in the HPV-positive non-heavy-smokers,” Zevallos said.
Zevallos said that the findings indicate that physicians could be taking more into account than HPV status when considering whether to reduce the intensity of treatment for patients with this cancer type.
“Our goal should be, when we see an HPV-positive patient in the clinic, that we don’t assume automatically that patients will do very well,” Zevallos said. “We should use other criteria beyond HPV status to more effectively personalize their treatments.”
Other co-authors included E. Yim, of the UNC Department of Otolaryngology/Head and Neck Surgery; P. Brennan, of the International Agency for Research on Cancer in Lyon, France; J.M. Taylor, of the UNC Department of Otolaryngology/Head and Neck Surgery; M. Weissler, of UNC Hospitals; D. Anantharaman, of the International Agency for Research on Cancer in Lyon; B. Abedi-Ardekani, of the International Agency for Research on Cancer in Lyon; and N.N. Hayes, of the UNC School of Medicine.
The Multidisciplinary Head and Neck Cancer Symposium is sponsored by the American Society for Radiation Oncology, the American Society of Clinical Oncology, and the American Head and Neck Society.
One of only 45 National Cancer Institute (NCI)-designated comprehensive cancer centers, UNC Lineberger brings together exceptional physicians and scientists to investigate and improve the prevention, early detection and treatment of cancer.