Molecular margins in head and neck cancer: Current techniques and future directions

Complete tumor extirpation with clear surgical margins remains a central tenet of oncologic head and neck surgery. Rates of locoregional recurrence and survival are both significantly worse when clear margins are unable to be obtained. Current clinical practice relies on the use of frozen sections intra-operatively, followed by traditional histopathologic analysis post-operatively to assess the surgical margin. However, with improved understanding of tumor biology and advances in technology, new techniques have emerged to analyze margins at a molecular level. Such molecular margin analysis interrogates tissue for genetic, epigenetic, or proteomic changes that may belie tumor presence or aggressive features not captured by standard histopathologic techniques. Intra-operatively, this information may be used to guide resection, while post-operatively, it may help to stratify patients for adjuvant treatment. In this review, we summarize the current state of molecular margin analysis and describe directions for future research.