Improving Margin Assessment during Transoral Robotic Surgery for p16+ Oropharyngeal Squamous Cell Carcinoma with Utilization of Intraoperative Positive Controls

Presentation: A106
Topic: Oropharynx / HPV Related Disease
Type: Poster
Authors: Alice C Yu, BA1; Jeffrey D Goldstein, MD2; Elliot Abemayor, MD, PhD1; Abie H Mendelsohn, MD1
Institution(s): 1Department of Head and Neck Surgery, University of California Los Angeles; 2Department of Pathology, University of California Los Angeles


The purpose of this study was to ascertain rates and clinical features predictive of non-diagnostic intraoperative frozen margins in patients undergoing transoral robotic surgical (TORS) for p16+ oropharyngeal squamous cell carcinoma (OPSCC). Additionally, we aimed to determine the effects of using intraoperative positive controls on the accuracy of frozen margin sampling and the subsequent impact on use of operating room resources.

Hypothesis: Our hypothesis was that the use of an intraoperative positive control would further aid pathologists in determining frozen margin status thereby resulting in shorter procedure times.

Study Design: Retrospective cohort review

Methods: All patients receiving curative-intent TORS for biopsy-proven p16+ OPSCC performed by a single attending surgeon from 2017 to 2021 were included. Exclusion criteria included HPV-negative status, participation in a clinical trial of neoadjuvant chemoradiotherapy, and tumors of unknown primary origin. Three patients presented with multiple synchronous primary OPSCC cancers; each tumor was analyzed independently. Clinical, histopathologic, and resource usage data were collected and analyzed. Statistical analysis was performed with student’s t-test and chi-square testing.

Results: Of 170 OPSCC tumors matching inclusion criteria, 50% (85 of 170) received intraoperative positive control sampling. Eleven percent (18 of 170) of tumors exhibited at least one non-diagnostic frozen margin necessitating additional intraoperative rounds of frozen margin sampling. Margin reversal from positive on frozen sections to negative on final evaluation occurred in 7% (12 of 170) of tumors, whereas reversal from negative to positive occurred in 3% (6 of 170) of cases.

Patients with non-diagnostic intraoperative margins were more likely to experience margin reversal of positive on frozen to negative on fixed (p < 0.001). Salvage TORS for tumors with prior head and neck radiation was also associated with positive-to-negative margin reversal (p = 0.042).  However, no clinical characteristics including tumor site, size, TNM staging, prior head and neck radiation, or non-diagnostic intraoperative margins were associated with negative-to-positive margin reversal.

Use of positive control biopsies was significantly associated with negative frozen margin status upon case conclusion (p=0.023) but was not associated with higher rates of negative margin status on fixed sections. In patients with non-diagnostic margins requiring additional intraoperative sampling, use of a positive control biopsy significantly reduced time spent in the operating room (p=0.028). This relationship persisted after controlling for surgery type, prior head and neck cancer, or presence of multiple primary tumors (p = 0.042).

Conclusions: Frozen intraoperative margins in robotic resections of OPSCC are diagnostically challenging as they are susceptible to uncertainty. Margin status reversal from positive on frozen to negative on fixed is associated with prior head and neck irradiation and the presence of non-diagnostic intraoperative frozen margins. Margin reversal from negative to positive is not associated with any clinical features and appears stochastic. Intraoperative positive control biopsy can provide clarity in cases with non-diagnostic margins, reducing the need for additional sampling and time spent in the operating room.