Is the Depth of Invasion a Marker for Elective Neck Dissection in Early Oral Squamous Cell Carcinoma? Yassine Aaboubout 1,2 , Quincy M. van der Toom 2 , Maria A. J. de Ridder 3 , Maria J. De Herdt 2 , Berdine van der Steen 2 , Cornelia G. F. van Lanschot 2 , Elisa M. Barroso 1,4,5 , Maria R. Nunes Soares 1,5 , Ivo ten Hove 4 , Hetty Mast 4 , Roeland W. H. Smits 2 , Aniel Sewnaik 2 , Dominiek A. Monserez 2 , Stijn Keereweer 2 , Peter J. Caspers 5 , Robert J. Baatenburg de Jong 2 , Tom C. Bakker Schut 5 , Gerwin J. Puppels 5 , Jose ´ A. Hardillo 2 and Senada Koljenovic ´ 1 * 1 Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands, 2 Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands, 3 Department of Medical informatics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands, 4 Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands, 5 Department of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands Objective: The depth of invasion (DOI) is considered an independent risk factor for occult lymph node metastasis in oral cavity squamous cell carcinoma (OCSCC). It is used to decide whether an elective neck dissection (END) is indicated in the case of a clinically negative neck for early stage carcinoma (pT1/pT2). However, there is no consensus on the cut-off value of the DOI for performing an END. The aim of this study was to determine a cut-off value for clinical decision making on END, by assessing the association of the DOI and the risk of occult lymph node metastasis in early OCSCC. Methods: A retrospective cohort study was conducted at the Erasmus MC, University Medical Centre Rotterdam, The Netherlands. Patients surgically treated for pT1/pT2 OCSCC between 2006 and 2012 were included. For all cases, the DOI was measured according to the 8 th edition of the American Joint Committee on Cancer guideline. Patient characteristics, tumor characteristics (pTN, differentiation grade, perineural invasion, and lymphovascular invasion), treatment modality (END or watchful waiting), and 5-year follow-up (local recurrence, regional recurrence, and distant metastasis) were obtained from patient files. Results: A total of 222 patients were included, 117 pT1 and 105 pT2. Occult lymph node metastasis was found in 39 of the 166 patients who received END. Univariate logistic regression analysis showed DOI to be a significant predictor for occult lymph node metastasis (odds ratio (OR) = 1.3 per mm DOI; 95% CI: 1.1–1.5, p = 0.001). At a DOI of 4.3 mm the risk of occult lymph node metastasis was >20% (all subsites combined). Conclusion: The DOI is a significant predictor for occult lymph node metastasis in early stage oral carcinoma. A NPV of 81% was found at a DOI cut-off value of 4 mm. Therefore, an END should be performed if the DOI is >4 mm. Keywords: oral cancer, squamous cell carcinoma of head and neck, depth of invasion, occult metastasis, elective neck dissection Frontiers in Oncology | www.frontiersin.org March 2021 | Volume 11 | Article 628320 1 Edited by: Paolo Bossi, University of Brescia, Italy Reviewed by: Jonathan Michael Bernstein, Imperial College London, United Kingdom Thomas Gander, University Hospital Zürich, Switzerland *Correspondence: Senada Koljenovic ´ s.koljenovic@erasmusmc.nl Specialty section: This article was submitted to Head and Neck Cancer, a section of the journal Frontiers in Oncology Received: 11 November 2020 Accepted: 01 February 2021 Published: 12 March 2021 Citation: Aaboubout Y, van der Toom QM, de Ridder MAJ, De Herdt MJ, van der Steen B, van Lanschot CGF, Barroso EM, Nunes Soares MR, ten Hove I, Mast H, Smits RWH, Sewnaik A, Monserez DA, Keereweer S, Caspers PJ, Baatenburg de Jong RJ, Bakker Schut TC, Puppels GJ, Hardillo JA and Koljenovic ´ S (2021) Is the Depth of Invasion a Marker for Elective Neck Dissection in Early Oral Squamous Cell Carcinoma? Front. Oncol. 11:628320. doi: 10.3389/fonc.2021.628320 ORIGINAL RESEARCH published: 12 March 2021 doi: 10.3389/fonc.2021.628320