# Prognostic Value of Lymph Node Density in Lingual Squamous Cell Carcinoma
## 2 Materials and Methods  
### Population and Study Variables  
To address the research purpose, the investigators implemented a retrospective longitudinal study of patients diagnosed with lingual squamous cell carcinoma (LSSC) and operated on by the Maxillofacial Surgery Department at Gregorio Maranon Hospital between 1 September 2016 and 1 September 2021. This study has been approved by the Ethics and Research Committee of the Hospital General Gregorio Maranon and in accordance with the principles of the Declaration of Helsinki.  
All the patients in the study were operated on by the same surgeons in charge of head and neck oncological surgery in the Department of Maxillofacial Surgery at the Gregorio Maranon Hospital. The histopathological study was performed by the same pathologist in charge of head and neck histological studies at the hospital.  
Information on each patient was obtained from patient records from the Department of Oral and Maxillofacial Surgery's operating room report file and histopathology reports. The following parameters were studied:  
* Demographic variables: gender, age, stratified age, smoker, drinker;
* Clinical variables: clinical size of the tumor, location of the tumor, diagnostic CT, diagnostic MRI, size and radiological DOI of the tumor, clinical staging, reconstruction, type of dissection, radiotherapy (RT) and postoperative chemotherapy (QT);
* Histological variables: degree of tumor differentiation, perineural invasion, lymphovascular invasion, TNM and pathological staging according to the 8 th edition of the AJCC, LND, neck positivity, ENE and tumor budding;
* Control variables: loco-regional recurrence, distant recurrence and mortality. In order to be included in the study, patients had to fulfill the following inclusion criteria:  
1. Histological confirmation of the diagnosis of primary lingual squamous cell carcinoma;
2. Patients operated on by the Oral and Maxillofacial Surgery Department at Gregorio Maranon General Hospital between 9 January 2016 and 9 January 2021;
3. Patients for whom surgery was the treatment of choice and whose intervention consisted of tumor resection and associated cervical lymphadenectomy;
4. Negative resection surgical margins for tumor involvement. The exclusion criteria were:  
1. Disease that exceeds the anterior 2/3 of the tongue (involvement of the base of the tongue);
2. Patients previously treated for carcinoma of the oral cavity (surgery, radiotherapy or chemotherapy);
3. Patients whose medical records did not identify the variables under study.  
Once the inclusion and exclusion criteria were established, a sample size of 62 patients was obtained (Figure 1).  
Figure 1: Flowchart. Sample size.  
Receiver operating characteristic (ROC) curve and area under the curve (AUC), sensitivity, specificity and 95% confidence interval (CI) were used to determine the LND values that best defined both risk groups. According to the authors' estimates, subjects were divided into binary subgroups using the best LND value as the cut-off point. Figure 2 shows cut-off values for predicting overall survival (OS) by ROC curve analysis. Results reported that the best cut-off value for LND was 0.04 (AUC, 0.689; sensitivity, 33%; specificity, 87%; \(p\) = 0.029). Figure 2.