Contents lists available at ScienceDirect Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology Postoperative staging of the neck dissection using extracapsular spread and lymph node ratio as prognostic factors in HPV-negative head and neck squamous cell carcinoma patients Katarina Majercakova a , Cristina Valero b , Montserrat López b , Jacinto García b , Nuria Farré a , Miquel Quer b , Xavier León b,c, ⁎ a Radiotherapy Oncology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain b Otorhinolaryngology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain c Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain ARTICLE INFO Keywords: Extracapsular spread Lymph node ratio pN TNM classification Head and neck cancer HPV-negative ABSTRACT Objectives: The presence of nodes with extracapsular spread (ECS) and the lymph node ratio (LNR) have prognostic competence in the pathologic evaluation of patients with a head and neck squamous cell carcinoma (HNSCC) treated with a neck dissection. The purpose of this study is to assess the effect of ECS & LNR on prognosis of HPV negative HNSCC patients treated with neck dissection and to compare to 8th edition TNM/ AJCC classification. Materials and methods: We carried out a retrospective study of 1383 patients with HNSCC treated with a neck dissection between 1985 and 2013. We developed a classification of the patients according to the presence of nodes with ECS and the LNR value with a recursive partitioning analysis (RPA) model. Results: We obtained a classification tree with four terminal nodes: for patients without ECS (including patients pN0) the cut-off point for LNR was 1.6%, while for patients with lymph nodes with ECS it was 11.4%. The 5-year disease-specific survival for patients without ECS/LNR < 1.6% was 83.3%; for patients without ECS/ LNR ≥ 1.6% it was 61.5%; for patients with ECS/LNR < 11.4% it was 33.7%; and for patients with ECS/ LNR ≥ 11.4% it was 18.5%. The classification obtained with RPA had better discrimination between categories than the 8th edition of the TNM/AJCC classification. Conclusion: ECS status and LNR value proved high prognostic capacity in the pathological evaluation of the neck dissection. The combination of ECS and LNR improved the predictive capacity of the 8th edition of the TNM/ AJCC classification in HPV-negative HNSCC patients. Introduction Lymph node status is one of the most important clinical predictors of survival for head and neck squamous cell carcinoma (HNSCC) pa- tients. The standard pathological nodal staging (pN) of a neck dissec- tion considers the number, size and location of positive lymph nodes. Several studies and meta-analysis show that the presence of lymph nodes with extracapsular spread (ECS), defined as extension of the tumor outside the lymph node capsule, negatively affects prognosis in HPV-negative HNSCC patients [1–4]. Interestingly, ECS did not affect survival in patients with HPV-positive oropharyngeal tumors [5,6]. These studies have led to the inclusion of the ECS into the pathological classification criteria in the 8th edition of the TNM/AJCC classification of HPV-negative patients [7,8]. The 8th edition TNM/AJCC classification improves the differentiation in survival among the pN categories as well as the distribution of the number of patients per category in HNSCC HPV-negative patients when compared with the 7th edition TNM/AJCC [9]. To further improve the classification of nodal disease, several au- thors have analyzed the lymph node ratio (LNR). LNR is defined as the proportion of metastatic lymph nodes related to the total number of examined neck nodes. LNR has proved a very high prognostic capacity in neck dissection evaluation. High LNR values have consistently re- lated to a worse overall and specific survival in most series (Supplementary material, Table 1). The objective of this study is to assess the prognostic competence of the pathological classification of the neck dissection obtained from evaluating ECS and LNR together and to compare this classification https://doi.org/10.1016/j.oraloncology.2017.12.010 Received 9 August 2017; Received in revised form 8 November 2017; Accepted 15 December 2017 ⁎ Corresponding author at: Otorhinolaryngology Department, Hospital de la Santa Creu i Sant Pau, C/ Mas Casanovas, 90, 08041 Barcelona, Spain. E-mail address: xleon@santpau.cat (X. León). Oral Oncology 77 (2018) 37–42 1368-8375/ © 2017 Elsevier Ltd. All rights reserved. T