Med student Wesley Stepp takes on cancer diagnostics gap
The fourth-year medical student wants to better predict the aggressiveness of head and neck cancers and help physicians plan ideal treatment regimens.
Wesley Stepp was a Ph.D. student working at the NIH Clinical Center when he entered a patient’s room and saw a shy 13-year-old girl covered in warts caused by human papillomavirus (HPV). She burst into tears.
“I was just there to do my work and collect some samples,” Stepp said. “But that experience really made clear that there is a very human side to everything we do in the lab.”
Stepp applied for an NIH Ph.D. to MD training grant, which led him to the UNC School of Medicine.
His background in HPV-related research and the increase in HPV-driven head and neck cancers sparked his interest in otolaryngology. When he had an idea for a particular research project, he approached Harold Pillsbury chair of the department of otolaryngology/head and neck surgery, who suggested he work with Jose Zevallos, a head and neck surgeon.
“I began speaking to Jose about my idea and because of my Ph.D. background in HPV research, he sort of gave me the reins,” Stepp said.
After Zevallos left Carolina to join the faculty at Washington University in St. Louis, Stepp began working with Trevor Hackman, associate professor of otolaryngology/head and neck surgery, who remains Stepp’s primary research advisor.
“Dr. Hackman has provided great guidance on how the science fits with the actual medicine,” Stepp said. “He’s been a great clinical shepherd for this work.”
Stepp focuses on HPV-driven head and neck cancers. Presently, head and neck cancers are grouped into two categories based on the presence of p16, a tumor suppressor protein. Tumors found positive for p16 are less aggressive than those without it, and they are treated accordingly, often with clinical trials using lower doses of radiotherapy.
“I thought there must actually be many smaller buckets because our testing was not sensitive enough,” Stepp Said. He set out to test his idea.
Tumor testing has traditionally been done using specific kinds of stains. In Stepp’s study, tumors were tested using a method that looks at RNA gene expression in a high throughput manner pioneered at Carolina by Chuck Perou to study how certain breast cancers might respond to treatment. Stepp found a wide range of genetic expressions for tumors falling within the p16 positive bucket.
“At the genetic level, we found that although these tumors were p16 positive, they all had different ‘microexpressions’ that differentiated them from each other,” Stepp said.
Stepp used these results to determine the relative aggressiveness of a tumor based on certain genetic markers. With a more specific tumor phenotype, physicians can better determine a course of treatment.
Stepp was first author of a study on this work, published in JAMA Otolaryngology-Head & Neck Surgery.
“Ultimately, we’d like to be able to say which treatment modality a patient will best respond to and the likelihood of recurrence,” Stepp said. “We’re trying to individualize the treatment of head and neck cancers. That’s the big picture.”
This proof of concept study was conducted in 21 patients and Stepp is working now on an expanded study to validate these results.
As Stepp thinks about this work and what might come next, he remembers back to when he first decided to apply to medical school and the questions he got about changing the course of his career. During his time at UNC School of Medicine, those answers have gained even greater clarity.
“Every day I have the opportunity to see patients and hopefully make an impact on their lives,” Stepp said. “I’m as much of a lab body. What I enjoy about medicine is getting to meet people and learn about them.”
As he continues this line of research, he hopes to expand the use of his testing method to maximize the effectiveness of treatments for head and neck cancers.
“The home run will be when we can prove this test shows what sort of treatment a patient needs to have the best shot at remission or of not having cancer anymore,” Stepp said.
