Abstract
Background/Aim: The optimal extent of neck dissection (ND) in oral squamous cell carcinoma (OSCC) is controversial, particularly regarding levels IV and V in cases with metastases in levels I-III. This study evaluated the probability of metastases in levels IV-V when levels I-III are pN+ in cN0 necks and analyzes prognostic factors influencing their occurrence.
Patients and Methods: A retrospective study was performed at the Department of Oral, Maxillofacial and Facial Plastic Surgery, Ludwigshafen Hospital, Germany, including 61 patients with primary OSCC treated surgically including ND. Patients underwent either supraomohyoid ND (SOND) of levels I-III with secondary extension to IV-V or modified radical ND (MRND) of levels I-V. Statistical analysis assessed the correlation between metastases in levels IV-V and extracapsular spread (ECS), number of positive lymph nodes, T-classification, bone infiltration, grading, lymphovascular invasion, vascular invasion, and perineural invasion.
Results: Among the 61 patients with metastases in levels I-III, 6 patients (9.8%) had metastases in levels IV-V. A significant correlation (p=0.042) indicated that pN+ in levels I-III is associated with >5% risk of level IV-V metastases. The presence of more than one metastasis in levels I-III significantly (p=0.027) predicted level IV-V involvement. A pN status of >pN2b significantly (p=0.002) increased the prevalence of metastases in levels IV-V. ECS showed a trend toward increased IV-V involvement, though not statistically significant (p=0.078).
Conclusion: The risk of level IV-V metastases in patients with pN+ in levels I-III exceeds 5% in cN0 necks. The number of affected nodes and pN classification were the strongest predictors. These findings support selective extension of ND beyond level III in specific patients and emphasize individualized treatment strategies.
Introduction
Oral squamous cell carcinoma (OSCC) accounts for over 90% of all malignancies in the oral cavity (1-4). Risk factors include tobacco and alcohol consumption, viral infections such as HPV, and genetic predisposition (1, 2, 5, 6). Common oral manifestations include leukoplakia, erythroplakia, erythroleukoplakia, proliferative verrucous leukoplakia, oral submucous fibrosis, oral lichenoid lesions and actinic cheilitis. Also, functional impairments like restriction of mouth opening or dysphagia can be seen (7-10). In late-stage cases systemic manifestations like fever, night sweats, weight loss and cervical lymphadenopathy are common (5).
Staging examinations using magnetic resonance and computed tomography imaging, as well as surgical biopsy, are essential for establishing the diagnosis (11, 12). Treatment options include surgical resection, radiation, chemotherapy or a combination of the above mentioned, depending on the tumor characteristics and the general condition and wishes of the patient (3).
OSCC frequently metastasizes to regional cervical lymph nodes, influencing treatment decisions and prognosis (13-16). At the time of initial diagnosis, approximately 20-40% of patients with oral squamous cell carcinoma present with clinically evident cervical lymph node involvement. However, despite a clinically negative lymph node status, in 20-30% of patients occult metastases can be pathologically detected (17, 18). The presence of occult metastases is also linked to a lower 5-year survival rate and a lower mean survival time (18).
Therefore, neck dissection (ND) plays a crucial role in staging and therapy of OSCC. Many studies have focused on metastasis patterns, yet the clinical decision-making process regarding ND extension remains variable across institutions (19, 20). While levels I-III are routinely dissected in OSCC, the necessity of including levels IV and V is controversial (13, 21, 22). The primary concern is balancing oncological control with the potential morbidity associated with more extensive surgical procedures. Understanding the nodal spread pattern and identifying reliable predictors of levels IV-V metastases are crucial for optimizing treatment strategies and improving patient outcomes.
The primary objective of this study was to investigate the statistical probability of cervical lymph node metastases occurring in levels IV and V in patients with oral squamous cell carcinoma who were staged with a N0 neck, to derive conclusions for therapeutic strategies. Additionally, tumor-related influencing factors that may promote the occurrence of metastases in levels IV and V were analyzed.
Patients and Methods
Study design. The study was conducted retrospectively and included patients diagnosed with OSCC who underwent primary surgical resection and ND at the Department of Oral, Maxillofacial and Facial Plastic Surgery, Ludwigshafen Hospital, between January 2013 and April 2024.
The study was submitted to the responsible Ethics Committee and was approved. The patients provided written consent for both the procedures and participation in the study. A comprehensive review of patient records was conducted to extract relevant clinical and pathological data.
Study population. The study population included a total of 61 patients with histologically confirmed OSCC with cN0 neck who underwent primary surgical treatment with either supraomohyoid ND (SOND) and subsequent extension to levels IV and V or modified radical ND (MRND). Patients with extraoral tumor manifestations, recurrent OSCC, undefined cervical lymph node levels, or prior radio- or chemotherapy were excluded. Additionally, those with incomplete follow-up data were not included in the final analysis to maintain data integrity.
Patient screening. Codes from the ninth edition of the ICD-CM diagnostic manual (“International Statistical Classification of Diseases and Related Health Problems”) were utilized to identify patients with ND of more than three levels. The assigned patient case numbers were then used to retrieve the corresponding electronic medical records from the digital patient information system (SAP®, SAP GUI 7.70, Walldorf, Germany). Data collection was based on clinical and radiological findings from the Department of Oral, Maxillofacial and Facial Plastic Surgery, Klinikum Ludwigshafen. The collected data was recorded in an Excel spreadsheet (Excel for Microsoft 365, version 16.89.1).
Protocol for surgical management. Our treatment strategy included elective lymph node dissection of levels I-III of the ipsilateral lymph nodes in cases of cN0 situations in addition to tumor resection and reconstruction. For carcinomas crossing the midline, bilateral lymph node dissection of levels I-III was conducted. If pathohistological examination confirmed lymph node metastases in levels I-III, an extension of the ND to include levels IV-V on the affected side, as well as dissection of levels I-III on the contralateral side, was performed. In the case of intraoperatively suspicious lymph nodes, frozen section biopsies were performed, and if the findings were positive, a MRND was carried out immediately. In some cases, however, a MRND was performed immediately due to the primary extent of the tumor or reconstructive requirements, e.g., pedicled distant flaps like pectoralis major or latissimus dorsi.
Data collection and statistical analysis. Patient demographics, tumor characteristics, surgical treatment details, and histopathological findings were documented (Table I). To evaluate the risk of occurrence of metastases in levels IV-V and the correlation between those and various prognostic factors, statistical analyses were conducted. The prognostic factors were extracapsular spread (ECS), the number of affected lymph nodes, T-classification, bone infiltration, grading, lymphovascular invasion, vascular invasion, and perineural invasion. Pearson’s Chi-squared test and Fisher’s exact tests were used to analyze categorical variables. The Mann-Whitney U Test was used for the comparison of two independent groups when parametric assumptions were not met. Statistical analysis was performed using IBM SPSS Statistics (Version 29.0, Armonk, NY, USA).
Demographic and clinical characteristics of the study cohort (n=61).
Results
Demographic distribution. A total of 61 patients enrolled in the study with 32 being male and 29 being female. The mean age was 65.77 and the age range was 25 to 93 years. Further demographic and clinical characteristics are shown in Table I.
Metastatic involvement. From 61 patients with pN+ status in levels I-III, 6 patients (9.8%) were found to have metastases in levels IV-V (Table II). There was a statistical significance (p=0.042) that in a (pN+) situation in levels I-III, lymph node metastases in level IV-V were more than 5% likely to occur.
Metastatic involvement in the study cohort (n=61).
Factors influencing metastatic behavior. Further statistical analysis identified key predictors of levels IV-V metastases. The pN status of levels I-III influenced the occurrence of metastases in levels IV-V statistically significant (p=0.002). The presence of more than one metastasis in levels I-III increased the probability of metastases in levels IV-V significantly (p=0.027), especially a pN status > pN2b was associated with a statistically significant higher occurrence of metastases in levels IV-V (p=0.002).
Although ECS and the presence of perineural invasion demonstrated a trend towards significance (p=0.078; p=0.067), it did not reach the threshold for statistical significance. Other factors, including pT status, bone infiltration, grading, lymphovascular invasion, and vascular invasion, did not exhibit a statistically significant association with levels IV-V metastases (Table III).
Clinicopathological characteristics of the study group stratified according to the metastatic involvement in levels IV-V (n=61).
Discussion
The presence of a positive nodal status is one of the strongest independent negative prognostic factors for disease-specific survival (23). This highlights the high clinical relevance of early diagnosis and close follow-up of the cervical lymph node region in patients with oral squamous cell carcinoma.
The results of the study indicate that the probability of metastases in levels IV-V among OSCC patients with (pN+) status in levels I-III exceeds the commonly assumed 5% threshold. This suggests that selective extension of ND to these levels may be justified, particularly in high-risk cases.
In the systematic review and meta-analysis by Yu et al. (2025), the frequencies of lymph node metastases OSCC across different neck levels were investigated. The occurrence of metastases in levels IV and V was reported as 2% and 1%, respectively. However, the included studies showed low heterogeneity. In addition, no specific distinction was made between clinical N0 and N1 stages (24).
Varying prevalence rates for metastases in levels IV-V were reported in a systematic review carried out by Altuwaijri et al. (2021), with findings ranging from 1.8% to 66%, depending on the study design, inclusion criteria, and tumor localization (25).
Hasegawa et al. (2017) described a prevalence of 7.9% of metastatic involvement in levels IV-V (26). In a study carried out by Liao et al. (2011) 8.2% of the patients showed metastases in levels IV-V (27). Our findings are consistent with those studies highlighting the presence of metastases beyond level III in a subset of OSCC patients. However, in the study of Agarwal et al. none of the patients with clinically negative necks showed metastatic involvement of level IV (28). This discrepancy with our findings may be attributed to differences in patient selection, as our study only focused on (pN+) cases of levels I-III, which inherently have a higher metastatic burden.
Several studies have examined the factors influencing the likelihood of levels IV-V metastases. The presence of multiple metastatic lymph nodes in levels I-III and a high pN classification correlated with an increased likelihood of level V involvement (29). Jayasuriya et al. (2021) demonstrated that a pN status >pN2b significantly influenced (p=0.001) the occurrence of metastases in level V (30). These findings reinforce our observation that especially a pN classification >2Nb is a strong significant predictor of nodal spread to the lower cervical levels.
The role of ECS in predicting nodal spread remains an area of debate. While our study did not establish a statistically significant association (p=0.078), trends observed in the data suggest a potential link that warrants further investigation. In previous studies, ECS was identified as a critical prognostic factor, associated with both locoregional recurrence and distant metastases (27, 29, 31). Given its established impact on survival outcomes, ECS should be considered when assessing the need for extension of the ND.
One of the primary concerns regarding the routine inclusion of levels IV-V in ND is the potential for increased surgical morbidity. Extensive ND is associated with a higher risk of complications, including accessory nerve injury, lymphedema, and impaired shoulder function. Therefore, a risk-benefit assessment must guide surgical decision-making. Advanced imaging techniques such as computed tomography and magnetic resonance imaging may help refine patient selection by improving the detection of subclinical metastases and guiding tailored surgical approaches (32).
This study had several limitations, including its retrospective nature and single-center design. Additionally, the relatively small sample size may have influenced the statistical power of certain analyses. Future prospective, multicenter studies with larger patient cohorts are needed to validate these findings and further clarify the indications for extended ND. While our study supports the ND of levels IV-V in certain patients with a (pN+) situation, further research is necessary to establish more definitive guidelines. For instance, in a study carried out by Obermeier et al. (2023) the risk of lymph node recurrence in levels IV-V after tumor resection and ND of level I-III or level I-V was investigated. There was no statistical significance (p=0.566) regarding the recurrence rate between the two study groups (33). There was also no statistically significant difference between patients with negative lymph nodes after primary level I-III ND and patients with positive lymph nodes after primary level I-III ND in terms of level IV and V recurrence (p=0.552).
Additional analyses focusing on postoperative disease progression, recurrence rates, and survival outcomes should be carried out to enable the identification of patterns that may further refine treatment recommendations for ND extension beyond level III.
Conclusion
Our results indicate that an extended ND encompassing levels IV-V is justified in patients presenting multiple lymph node metastases in levels I-III, especially in a pN classification greater than pN2b. Conversely, factors such as pT stage, tumor size, depth of invasion, bone infiltration, tumor differentiation, lymphovascular invasion, vascular invasion, and perineural sheath infiltration do not appear to significantly influence the decision-making process. In cases of pN1 status confined to levels I-III, the decision to extend the dissection should be made cautiously, particularly in elderly patients or those scheduled for postoperative radiotherapy.
Acknowledgements
We disclose any commercial associations that might pose a potential, perceived or real conflict of interest. These include grants, patent licensing arrangements, consultancies, stock or other equity ownership, donations, advisory board memberships, or payments for conducting or publicizing the study.
Footnotes
Authors’ Contributions
Haas, L.: Main project management, data acquisition and analysis, writing original draft, main investigator, conceptualization. Mischkowski, R. A.: General supervision, surgical treatment, methodology, conceptualization. Knape, U.: Patient treatment and surgical supervision. Król, K. M.: General patient management and data acquisition. Sakkas, A.: Methodology, review and data editing, conceptualization.
Conflicts of Interest
The Authors declare no conflicts of interest.
Artificial Intelligence (AI) Disclosure
During the preparation of this manuscript, a large language model (ChatGPT, OpenAI) was used solely for language editing and stylistic improvements in select paragraphs. No sections involving the generation, analysis, or interpretation of research data were produced by generative AI. All scientific content was created and verified by the authors. Furthermore, no figures or visual data were generated or modified using generative AI or machine learning-based image enhancement tools.
- Received August 28, 2025.
- Revision received September 14, 2025.
- Accepted September 23, 2025.
- Copyright © 2025 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
References
Jump to section
Related Articles
Cited By...
- No citing articles found.