# Prognostic Value of Lymph Node Density in Lingual Squamous Cell Carcinoma  
[PERSON]  
1 Maxilofacial Surgery Department, Hospital General Universitario [PERSON], C/[PERSON] 46, 28007 Madrid, Spain 1  
[PERSON]  
1 Maxilofacial Surgery Department, Hospital General Universitario [PERSON], C/[PERSON] 46, 28007 Madrid, Spain 1  
[PERSON]  
1 Maxilofacial Surgery Department, Hospital General Universitario [PERSON], C/[PERSON] 46, 28007 Madrid, Spain 1  
[PERSON]  
1 Maxilofacial Surgery Department, Hospital General Universitario [PERSON], C/[PERSON] 46, 28007 Madrid, Spain 1  
[PERSON].  
clinically or radiologically diagnosed, a therapeutic complete lymphadenectomy of levels I-V should be performed. If, on the other hand, the neck is negative (N0), either a selective neck dissection of levels I-III or I-IV or a selective sentinel lymph node biopsy can be performed. The need for a bilateral lymphadenectomy depends on whether or not the contralateral neck is positive and on the proximity of the tumor to the midline of the tongue [1].  
Prognostic staging based exclusively on AJCC classification may not predict survival in oral cavity squamous cell carcinoma (OSCC) with absolute reliability [2; 4; 5; 6; 7]. Therefore, attempts have been made to study other additional prognostic factors that provide a high enough risk to recommend the use of adjuvant radiotherapy or intensification of the adjuvant treatment approach (radiotherapy associated with chemotherapy), which in turn is associated with a risk of acute toxicity and late complications that can substantially affect the quality of life of the patients [8; 9; 10; 11]. It is therefore mandatory to find reliable prognostic factors that may lead us to identify high-risk patients who can benefit from a more aggressive treatment approach.  
One of the most widespread criticisms of the AJCC pathologic staging system applied to N stage is that it is limited by the quality of the neck dissection--interoperator reliability--and the anatomopathologic sampling procedure. In this context, the lymph node density (LND)--defined as the proportion of positive nodes among the total number of nodes removed from the dissection--has emerged as an independent prognostic factor that is able to compensate for the potential bias derived from the technique used by taking into account three factors [12; 13]:  
* The regional spread of the disease (number of positive lymph nodes);
* The surgical treatment (total number of nodes removed during surgery);
* The accuracy of the histopathological analysis.  
LND has been shown to be a reliable predictor of survival in some solid tumors, including breast cancer, colon cancer and pancreatic cancer, in addition to head and neck cancer [12; 14]. Specifically, high LND values have been associated with worse outcomes in terms of overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) in squamous cell carcinoma of the oral cavity, and specifically in LSCC [12; 15; 16].  
The present study aims to validate the concept of LND in lingual squamous cell carcinoma (LSCC) and its prognostic significance. Different potentially optimal cut-off values of LND have been proposed in several retrospective studies and in two systematic reviews [12; 17]. In this study, following the recommendations of different studies, the cut-off point is an LND value of 0.04.  
The hypothesis formulated by the investigators was that LND \(\geq\) 0.04 worsens the prognosis of patients undergoing surgery for LSCC. The primary objective of the study was to assess the correlation between the LND value and OS and DFS.  
The secondary objectives were: (1) to assess the relationship between LND and other poor prognostic factors in LSCC such as pathological margin status, DOI and perineural infiltration; (2) to analyze the correlation with tumor staging according to the 8 th edition of the AJCC.