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Personalizing Treatment for HPV-Related Head and Neck Cancer

By Eric M. Genden, MD, Brett Miles, MD, DDS, Marshall Posner, MD, and Andrew G. Sikora, MD, PhD
Published Online: Monday, July 22, 2013
The Tisch Cancer Institute
Dr. Eric M. Genden

Eric M. Genden, MD

Dr. Brett Miles

Brett Miles, MD, DDS

Dr. Marshall Posner

Marshall Posner, MD

Dr. Andrew G. Sikora

Andrew Sikora, MD, PhD

The Tisch Cancer Institute at The Mount Sinai Medical Center New York City
Strategic Partnership Program
Over the past decade, it has become apparent that head and neck squamous cell carcinoma (HNSCC)—including cancers of the mouth, throat, and larynx—is actually two separate diseases. As the incidence of “classic” tobacco/alcohol–induced HNSCC has declined, sharply increasing numbers of patients with HNSCC caused by the human papillomavirus (HPV) have forced us to rethink our approach to the diagnosis and treatment of patients with head and neck cancer.

HPV-related HNSCC most commonly occurs in the tonsils and base of the tongue, a region known as the oropharynx. Patients with HPV-related oropharyngeal cancer (HPVOPC) tend to present with advanced-stage disease due to spread to the lymph nodes of the neck, but paradoxically have a far better prognosis than patients with classic HNSCC. This creates a dilemma for treating physicians: how to personalize treatment of this unique patient population in an evidence-based fashion.

De-escalation of Nonsurgical Therapy

Since surgical approaches to OPC prior to the advent of robot-assisted surgery involved splitting the mandible, chemoradiation has become the standard-of-care treatment for OPC at most centers. While HPVOPC generally has an excellent response to chemoradiation, with a >80% cure rate for patients with stage III-IV disease at many institutions, the side effects of combination therapy regimens can be severe and leave a significant minority of patients with lifelong speaking and swallowing dysfunction. In the minds of many practitioners this raises the question: Are we overtreating the majority of patients with HPV-related head and neck cancer?

At the Icahn School of Medicine at Mount Sinai (ISMMS), we feel that this question is best answered in the context of well-designed clinical trials, rather than ad hoc treatment de-escalation. One such trial is the ongoing Quarterback Trial (principal investigator [PI]: Marshall Posner, MD), designed to determine the comparative rates of progressionfree survival and locoregional control in HPVOPC patients treated with standard or reduced-dose chemoradiotherapy.

In this trial, stage III-IV HPVOPC patients who responded to induction chemotherapy are randomized to treatment with reduced-dose radiation, carboplatin, and Erbitux, versus standard-dose radiation plus carboplatin alone. The results of this study, conducted at ISMMS and several other participating centers, will determine whether deescalation can be performed safely in the HPVOPC patient population and guide design of further trials in this population.

Robot-Assisted Surgery as a Tool for Risk-Based Adjuvant Treatment

While all patients with cancer are clinically staged prior to initial therapy, only surgical treatment allows pathological information about negative prognostic factors (number of cancer-containing lymph nodes, extracapsular nodal extension, margin status, and presence of lymphovascular or perineural tumor extension) to risk-stratify patients and identify those who require adjuvant chemoradiation. The advent of transoral laser microsurgery (TLM) and transoral robotic surgery (TORS), which avoids the morbid lip- and jaw-splitting open surgical approaches of prior eras, has renewed interest in surgery for HPVOPC.

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