Biology of Head and Neck Cancer

Transcript:

Ezra Cohen, MD: Thank you for joining this OncLive Peer Exchange^® entitled, “Advanced Head and Neck Cancers: Looking Forward.” We have entered a new era in the treatment of squamous cell carcinoma of the head and neck, owing to improved insight surrounding the underlying biology of this disease and new advances in therapeutic targeting of the immune system. This expert panel discussion will focus on strategies for refining treatment of advanced disease and improving outcomes after recurrence. We’ll provide perspective on the latest research findings and their application to clinical practice.

I am Dr. Ezra Cohen, and I am a professor of medicine for the Division of Hematology/Oncology, Department of Medicine at UC San Diego, and the co-director of the Center for Precision Immunotherapy. Joining me for this discussion are Dr. Joshua Bauml, assistant professor of medicine at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia; Dr. Barbara Burtness, professor of medicine at the Yale University of Medicine and co-leader of the Developmental Therapeutics Research Program at Yale Cancer Center in New Haven, Connecticut; and Dr. Jared Weiss, an assistant professor of medicine and section chief of Thoracic and Head/Neck Oncology at UNC in Chapel Hill, North Carolina. Thank you for joining us.

Let’s first start by talking about the biology and the stratification for patients with head and neck squamous cell carcinoma. Josh, take us through a little bit about the underlying biology of this disease.

Joshua M. Bauml, MD: Absolutely. Thanks so much, Ezra. Head and neck cancer used to be a relatively homogenous disease. It was caused largely by exposure to tobacco and alcohol. But now we’re seeing more and more subgroups for head and neck cancer. The one that is affecting most Americans is human papillomavirus, or HPV. At this point, it is the leading cause of oropharyngeal head and neck cancer, and patients with HPV-associated head and neck cancers have a different epidemiology. They tend to be younger, they tend to be healthier, and they have a much better prognosis.

At this point, though, HPV—or, as it’s measured by its surrogate marker, P16 positivity—is only a prognostic marker; it’s not used as a predictive marker to choose the treatment. But still, it harkens to the idea that maybe we should be treating these patients differently, given their underlying biology. And some emerging data are finding that there are different molecular profiles for patients who have HPV-positive versus HPV-negative head and neck cancers, with differential mutations in those 2 subgroups.

Ezra Cohen, MD: We know now that there are, as you alluded to, potentially different genetic drivers of these 2 subsets, and, in fact, of individual head and neck cancers. Jared, can you talk a little bit about the genetic drivers of this disease? And are any of them actionable? Are they things that we should be paying attention to?

Jared Weiss, MD: Well, there’s a definite answer to that of “maybe.” So, traditionally, in terms of trying to decide what to do, we look to stage: the T stage of the size and invasiveness of the tumor, the N stage, and the number of nodes. This told us if we were going to do definitive radiation and whether or not to add chemotherapy to that. Postoperatively, we looked at pathologic features such as extracapsular extension and margins, perhaps some other things, to decide for whom we were going to add chemotherapy to radiation.

We now live in a world where we have multiple good modalities to treat head and neck cancer. So, for example, in oropharyngeal cancer, we have all of these wonderful advances in radiation, such as IMRT, perhaps protons, and better systemic agents to consider adding. In the world of surgery, we have these new transoral surgeries that, as a theme, have less morbidity, fewer functional and cosmetic defects, blood loss on par with a blood draw, and less hospital time. We find ourselves in this world saying, “OK, with all of these pathologic features, these stage-based features, and these biologic features, what, as clinicians, can we really drill down on and use to decide what we’re going to do?” That’s what we care about at the end of the day, what should we do?

And there’s really not a lot of absolute definition. There’s a ton of conversation about HPV as a prognostic biomarker. It is clear that no matter what you do, the HPV-positive patient does better than the HPV-negative patient. At ASCO this year, there was an interesting abstract looking at biologic characteristics and clinical characteristics of oropharynx patients, trying to ask, “Can any of these predictors alone—the stage, the biology, or perhaps a combined score—better predict who should be treated radiotherapeutically and who might benefit from escalation to inclusion of surgery?”

There was a suggestion that patients with a combined score of p16 high-risk HPV DNA, survivin, and tumor-infiltrating lymphocytes might predict a population of oropharynx patients that would perhaps do better with surgery. It’s important to remember that not all of these measures are clinically available. There isn’t a test you can order that gives you all of this at once. So, I see this as an introduction to a story, not the end of the story. As a suggestion, we may 1 day be dividing patients between surgery and radiotherapeutic approaches, not necessarily by stage or just by expected functional deficit, but perhaps biology might eventually empower us in the clinic to know who really needs surgery and who really needs radiation.

Transcript Edited for Clarity