Outcome and Predictor Variables

The outcome of interest was pN metastasis. This outcome was defined as a clinically node-negative tumor that was identified in the lymph nodes after END or development of biopsy-confirmed regional metastatic disease within 2 years in patients whose necks were observed.

Variables of interest were clinical (age, sex, race and ethnicity, body mass index [calculated as weight in kilograms divided by height in meters squared], smoking history, and anatomic tumor site) and pathological (largest tumor dimension, DOI, muscle invasion, submucosal invasion, dysplasia, histological grade, involvement of margins, perineural invasion [PNI], and lymphovascular invasion [LVI]) variables. Race and ethnicity data were reported in the electronic health records of the participating institutions. The race and ethnic categories included Asian, Black, Hispanic, Native American, and White.

Pathologists at the participating institutions currently measure tumor DOI from the plumb line that is perpendicular to the horizon established by the basement membrane of the nearest normal squamous mucosa, which is consistent with the incorporation of DOI into the eighth edition of the American Joint Committee on Cancer staging manual.^20,21 However, measurement of this variable was not standardized throughout the study period. Although DOI and thickness are not interchangeable, thickness is generally used preoperatively because DOI is assessed using the surgical specimen. However, both DOI and thickness are associated with lymph node metastases.²² For the purpose of this study, DOI and thickness were both collected, and DOI was used when available.