Association of Elective Neck Dissection With Survival in cT1N0M0 Floor of Mouth Squamous Cell Carcinoma: A Population-Based Propensity Score Matching Analysis

Abstract

Background

Studies on neck management of early-stage floor of mouth (FOM) squamous cell carcinoma (SCC) are very few and controversial. We aimed to study whether elective neck dissection (END) for patients with clinically stage T1N0M0 (cT1N0M0) FOM SCC is beneficial for survival.

Methods

Information on patients diagnosed with cT1N0M0 FOM SCC between 2004 and 2015 was collected from the Surveillance, Epidemiology and End Results (SEER) database. Cox proportional risk models and Kaplan–Meier curves were used for survival analysis and log-rank tests were performed to compare whether overall survival (OS) and cancer-specific survival (CSS) differed. Propensity score matching (PSM) was performed to eliminate the effect of confounding variables.

Results

There were 1014 patients with cT1N0M0 FOM SCC. Among them, END group: 455 cases; observation group: 559 cases. COX regression analysis before PSM demonstrated hazard ratio (HR) in the observation group compared to END (OS: 1.108 (.926–1.326), P = .262; CSS: 1.033 (.772–1.382), P = .827). There was no survival difference between END and observation survival before PSM (5-year OS: 71.8% vs. 67.8%, P = .180; 5-year CSS: 84.5% vs. 84.8%, P = .930); the matched results were the same as before PSM.

Conclusion

Observation may be a more appropriate option compared with END in cT1N0M0 FOM SCC.

Keywords

neck dissection floor of mouth propensity score matching cT1N0MO

Introduction

Oral cancer is the seventh most common cancer worldwide.¹ Recent global estimates have indicated that there will be 377713 new cases and 177757 deaths from oral cancer in 2022.^2,3 Among them, squamous cell carcinoma (SCC) comprises more than 90% of all oral malignancies.^4,5 As one of the common sites for oral cancer, the floor of mouth (FOM) accounts for about 27.2% of it.⁶ Although treatment modalities are improving, the prognosis for FOM SCC remains poor, with 5-year overall survival (OS) rate of 39% and cancer-specific survival (CSS) rate of 59%.⁷ This is mainly due to the abundant lymphatic drainage in the oral cavity and the early onset and duration of local lymph node metastases in oral SCC.⁸ It has been reported in several publications that lymph node metastases can reduce patient survival by 50% compared to lymph node negativity.^9,10,11

Management of the neck in patients with negative clinical lymph nodes has been controversial, considering the presence of occult neck metastases that are clinically and imaging undetectable. Among others, proponents of elective neck dissection (END) have argued that the procedure reduces recurrence rates and improves survival in patients.¹² However, pro-observation scholars have evidenced that in cT1-2N0 patients, the OS and disease-free survival of patients were not statistically different between END and observation.¹³ Hongshi Cai et al. have reported that there was no statistical difference in cervical lymph node recurrence in FOM between the END and observation groups. However, considering the small number of patients with cT1-T2N0 FOM SCC, it remains to be determined whether END treatment is superior to the observation group.¹³

The tongue and FOM are common sites from which early nodal metastasis develop in the oral cavity, and many research have demonstrated that END in early-stage tongue cancer is associated with reduced regional recurrence and prolonging OS.^14–16 However, the incidence of FOM SCC is small, and most studies were single-center, therefore the debate on whether END for early-stage FOM SCC is beneficial for survival is still inconclusive. Surveillance, Epidemiology and End Results (SEER) is a publicly available oncology database that collects information from nearly 30% of the US population. Here the purpose of our study was to use the data from SEER to quantify the value of END for clinically staged T1N0M0 (cT1N0M0) FOM SCC.

Materials and Methods

Data Acquisition

Data of patients with FOM SCC which diagnosed as 6th American Joint Committee on Cancer (AJCC) N0 stage were obtained from the SEER database through the SEER*Stat software (version 8.4.0; www.seer.cancer.gov). Inclusion criteria were displayed in Figure 1: (1) International Classification of Disease for Oncology third edition (ICD-O3) site codes (“C04.0-Anterior floor of mouth,” “C04.1-Lateral floor of mouth,” “C04.8-Overlapping lesion of floor of mouth,” “C04.9-Floor of mouth, NOS”). Morphology codes were: 8070/3-8076/3; (2) SCC was confirmed by pathology; (3) FOM SCC was the only cancer or the first primary tumor diagnosed; (4) year of diagnosis was from 2004 to 2015. Exclusion criteria were (1) non-T1N0M0 patients; (2) OS less than one month; (3) unknown race and cause of death information; (4) lymph node surgery as a biopsy, unknown; (5) radiotherapy information as a radioactive transplant; (6) the code of tumor size was unknown. As the SEER database is a public database, institutional review of patient informed consent is not required. OS was defined as the interval between the date of surgery and the date of death from any cause or the date of the last follow-up visit. CSS was measured as the interval from the date of surgery to the date of death due to the FOM SCC.

Figure 1.

The flowchart of this study. Abbreviations: SEER, Surveillance, Epidemiology and End Results.

Statistical Analysis

The Cox proportional risk model was used to determine prognostic factors for survival in cT1N0M0 FOM SCC, and survival curves were graphed by the Kaplan–Meier method, with log-rank tests comparing END group with observation group patients for differences in OS and CSS. In additional, to minimize the effect of confounding factors, we performed propensity score matching (PSM) with a 1:1 ratio of END to observation patients, and then used a logistic regression model to calculate the propensity score for each patient. The model included the following variables: age, sex, race, year of diagnosis, tumor grade, tumor size, marital status, and radiotherapy and chemotherapy. Matching was performed using a non-replacement caliper matching method. The caliper value was set at .01. The standardized mean difference (SMD) was used to evaluate whether variables were balanced between the observation and END groups before and after matching, with SMD value <.10 as the criterion for adequate balance.^17,18 All statistical analyses were performed using R statistical software (version 4.0.3). The test was P < .05.

Results

Baseline Characteristics

As indicated in the flowchart (Figure 1), we downloaded data on 2237 patients with 6th AJCC N0 stage FOM SCC from the SEER database, and finally, 1014 patients with cT1N0M0 who met the criterion were included in our study. Table 1 summarized the baseline characteristics of the patients, END group: 455 cases; observation group: 559 cases; it can be noted that nearly 70% of patients with cT1N0M0 FOM SCC were male, and the patients were largely white. Age (SMD value = .192), tumor size (SMD value = .377), tumor grade (SMD value = .270), and marital status (SMD value = .145), variables that were uneven before matching, were balanced after PSM (SMD value <.1), as shown in Table 1 and Figure 3C.

Table 1.

Clinical Characteristics of cT1N0M0 FOM SCC Patients before and after Matching.

Variables	Patient Baseline Characteristics before PSM			Patient Baseline Characteristics after PSM
Variables	Observation (n = 559)	END (n = 455)	SMD	Observation (n = 346)	END (n = 346)	SMD
Age			.192			.018
<65 years	336 (60.1%)	315 (69.2%)		230 (66.5%)	227 (65.6%)
≥65 years	223 (39.9%)	140 (30.8%)		116 (33.5%)	119 (34.4%)
Sex			.013			.070
Male	396 (70.8%)	325 (71.4%)		241 (69.7%)	252 (72.8%)
Female	163 (29.2%)	130 (28.6%)		105 (30.3%)	94 (27.2%)
Race			.028			.025
White	506 (90.5%)	410 (90.1%)		323 (93.4%)	321 (92.8%)
Black	37 (6.6%)	33 (7.3%)		18 (5.2%)	20 (5.8%)
Others	16 (2.9%)	12 (2.6%)		5 (1.4%)	5 (1.4%)
Year of diagnosis			.017			.035
2004–2009	279 (49.9%)	231 (50.8%)		169 (48.8%)	175 (50.6%)
2010–2015	280 (50.1%)	224 (49.2%)		177 (51.2%)	171 (49.4%)
Tumor size			.377			.012
1–10 mm	321 (57.4%)	177 (38.9%)		170 (49.1%)	168 (48.6%)
11–20 mm	238 (42.6%)	278 (61.1%)		176 (50.9%)	178 (51.4%)
Grade			.270			.037
Grade I–II	410 (73.3%)	372 (81.8%)		290 (83.8%)	291 (84.1%)
Grade III–IV	63 (11.3%)	51 (11.2%)		28 (8.1%)	30 (8.7%)
Unknown	86 (15.4%)	32 (7.0%)		28 (8.1%)	25 (7.2%)
Radiation			.040			<.001
Yes	78 (14.0%)	70 (15.4%)		40 (11.6%)	40 (11.6%)
None/unknown	481 (86.0%)	385 (84.6%)		306 (88.4%)	306 (88.4%)
Chemotherapy			.002			.038
Yes	17 (3.0%)	14 (3.1%)		7 (2.0%)	9 (2.6%)
No/unknown	542 (97.0%)	441 (96.9%)		339 (98.0%)	337 (97.4%)
Marital status			.145			.039
Married	398 (71.2%)	351 (77.1%)		267 (77.2%)	262 (75.7%)
Unmarried	107 (19.1%)	74 (16.3%)		56 (16.2%)	58 (16.8%)
Unknown	54 (9.7%)	30 (6.6%)		23 (6.6%)	26 (7.5%)

Note: Others = American Indian/Alaska Native or Asian or Pacific Islander.

Abbreviations: END, elective neck dissection; PSM, propensity score matching; SMD, standardized mean difference.

COX Regression Analysis

Before matching, we included factors that were statistically different in the univariate analysis in a multivariate COX regression analysis, which revealed that age, gender, tumor size, and radiotherapy were all independent prognostic factors for OS and CSS in cT1N0M0 FOM SCC (P < .05). In contrast, the univariate analysis pointed out that END was not a prognostic factor for OS (P = .262) nor CSS (P = .827) (Table 2). Furthermore, in Table 3, it can be seen that in the post-matching cohort, age, tumor size, and radiotherapy remained independent factors for OS and CSS in cT1N0M0 FOM SCC except for gender, while END remained the same as before matching, and it was still not an influential factor for OS (P = .965) and CSS (P = .688).

Table 2.

COX Regression Analysis of OS and CSS in Patients with cT1N0M0 FOM SCC before Matching.

Variables	OS				CSS
	Univariate Analysis	P	Multivariate Analysis	P	Univariate Analysis	P	Multivariate Analysis	P
	HR (95 CI)	P	HR (95 CI)	P	HR (95 CI)	P	HR (95 CI)	P
Age
<65 years	Ref		Ref		Ref		Ref
≥65 years	1.908 (1.595–2.283)	<.001	1.994 (1.665–2.388)	<.001	1.751(1.299–2.362)	<.001	2.093 (1.544–2.836)	<.001
Sex
Male	Ref		Ref		Ref		Ref
Female	.732 (.595–.900)	.003	.697 (.566–.858)	.001	.701 (.501–.981)	.038	.702 (.500–.986)	.041
Race
White	Ref				Ref
Black	1.151 (.829–1.598)	.400			1.433 (.881–2.332)	.148
Others	.580 (.288–1.168)	.127			.363 (.090–1.464)	.155
Year of diagnosis
2004–2009	Ref				Ref		Ref
2010–2015	.871 (.718–1.061)	.172			.703 (.515–.960)	.026	.689 (.503–.943)	.020
Grade
Grade I–II	Ref				Ref
Grade III–IV	1.259 (.968–1.636)	.085			1.451 (.967–2.180)	.073
Unknown	.781 (.579–1.052)	.103			.671 (.400–1.125)	.130
Tumor size
1–10 mm	Ref		Ref		Ref		Ref
11–20 mm	1.424 (1.190–1.704)	<.001	1.360 (1.131–1.635)	.001	2.217 (1.630–3.015)	<.001	2.090 (1.525–2.862)	<.001
Marital status
Married	Ref				Ref
Unmarried	1.034 (.818–1.308)	.780			1.133 (.784–1.638)	.506
Unknown	.779 (.543–1.118)	.176			.838 (.483–1.454)	.529
Radiation
Yes	Ref		Ref		Ref		Ref
None/unknown	.597 (.476–.749)	<.001	.679(.531–.868)	.002	.432 (.306–.610)	<.001	.505 (.347–.736)	<.001
Chemotherapy
Yes	Ref		Ref		Ref		Ref
No/unknown	.528 (.341–.818)	.004	.747 (.466–1.195)	.223	.366 (.199–.673)	.001	.816 (.419–1.589)	.550
END
Yes	Ref				Ref
No	1.108(.926–1.326)	.262			1.033 (.772–1.382)	.827

Note: Others = American Indian/Alaska Native or Asian or Pacific Islander.

Abbreviations: OS, overall survival; CSS, cancer-specific survival; Ref, reference. HR, hazard ratio; CI, confidence interval. END, elective neck dissection.

Table 3.

COX Regression Analysis of OS and CSS in Patients with cT1N0M0 FOM SCC after Matching.

Variables	OS				CSS
	Univariate Analysis	P	Multivariate Analysis	P	Univariate Analysis	P	Multivariate Analysis	P
	HR (95 CI)	P	HR (95 CI)	P	HR (95 CI)	P	HR (95 CI)	P
Age
<65 years	Ref		Ref		Ref		Ref
≥65 years	1.772 (1.422–2.207)	<.001	1.794 (1.437–2.240)	<.001	1.508(1.038–2.190)	.031	1.560 (1.073–2.268)	.020
Sex
Male	Ref		Ref		Ref
Female	.771(.601–.989)	.040	.740 (.576.951)	.018	.676 (.443–1.030)	.069
Race
White	Ref				Ref
Black	1.318 (.868–2.002)	.195			1.742 (.937–3.236)	.079
Others	.198 (.0278–1.410)	.106			<.001 (.000–)	.994
Year of diagnosis
2004–2009	Ref				Ref
2010–2015	.893(.703–1.135)	.354			.687(.470–1.004)	.053
Grade
Grade I–II	Ref				Ref
Grade III–IV	1.359 (.955–1.934)	.088			1.548 (.899–2.665)	.115
Unknown	.813 (.526–1.255)	.350			.681 (.317–1.466)	.326
Tumor size
1–10 mm	Ref		Ref		Ref		Ref
11–20 mm	1.516 (1.216–1.891)	.000	1.453 (1.161–1.819)	.001	2.368 (1.619–3.462)	.000	2.243 (1.526–3.297)	<.001
Marital status
Married	Ref				Ref
Unmarried	.940 (.692–1.276)	.689			1.072 (.673–1.708)	.769
Unknown	.970 (.622–1.514)	.894			1.060 (.534–2.101)	.869
Radiation
Yes	Ref		Ref		Ref		Ref
None/unknown	.628 (.462–.854)	.003	.736 (.536–1.006)	.055	.401 (.258–.622)	<.001	.477 (.305–.744)	.001
Chemotherapy
Yes	Ref				Ref
No/unknown	.661 (.341–1.283)	.221			.561 (.207–1.521)	.256
END
Yes	Ref				Ref
No	1.005 (.8087–1.249)	.965			.930 (.653–1.325)	.688

Note: Others = American Indian/Alaska Native or Asian or Pacific Islander.

Abbreviations: OS, overall survival; CSS, cancer-specific survival; Ref, reference; HR, hazard ratio; CI, confidence interval; END, elective neck dissection.

Comparison of Survival Between END and Observation Groups

Kaplan–Meier survival curves for OS and CSS before PSM were exhibited in Figure 2A-B, where it can be observed that there was no statistical difference in survival in the END compared to the observation group (5-year OS: 71.8% vs. 67.8%, P = .180; 5-year CSS: 84.5% vs. 84.8%, P = .930). Moreover, there was still no significant difference in survival in the END group compared with the observation group after PSM (Figure 2C-D). To further assess whether survival differed between the END group and the observation group on various clinical characteristics, we performed subgroup survival analysis on the matched cohort. As presented in Figure 3A-B, the hazard ratio (HR) values for the observation group were close to 1 compared to the END on each subgroup and were not statistically different (P > .05).

Figure 2.

Survival curves for patients with cT1N0M0 FOM SCC receiving END versus observation group. A: OS before PSM; B: CSS before PSM; C: OS after PSM; D: CSS after PSM. Abbreviations: FOM, floor of mouth; SCC, squamous cell carcinoma; END, elective neck dissection; OS, overall survival; CSS, cancer-specific survival; PSM, propensity score matching.

Figure 3.

Forest plots for subgroup analysis of OS (A) and CSS (B) after matching C: Plot of differences between variables before and after matching, (SMD) less than .1 is the criterion for balance. Abbreviations: OS, overall survival; CSS, cancer-specific survival; SMD, standardized mean difference. Note: Others = American Indian/Alaska Native or Asian or Pacific Islander.

Discussion

The FOM, as one of the common sites of oral cancer, has been studied by most scholars in combination with malignancies in other subsites of oral due to the risk factors for recurrence and survival that are similar to those of the oral cancer population.¹⁹ It has been suggested that when the risk of occult metastases exceeds 15-20%, END can be performed to avoid the spread of occult metastases.^20,21 However, most studies on lymph node dissection grouped T1 and T2 together. This could lead to bias and error in the analysis of patients with T1 staging due to the differences in clinical presentation between the two. For instance, Conner Massey et al had noted that in oral cancer patients the rate of occult lymph node metastasis in T1 patients was 11.5%, while the rate of occult metastasis in patients with T2 tumor was more than twice that of T1 (24.5%), so they recommended the use of END in the T2N0M0 group, which was observed in the T1N0M0 OSCC group.⁸ Similar results have also been made with FOM SCC, where Paolo Cariati et al. discovered occult lymph node metastases in 12.9% and 30.7% of patients with T1 and T2 stage, respectively.²² This suggests that the value of END should be evaluated separately for the T1 and T2 groups.

We collected data on 1014 patients with cT1N0M0 FOM SCC through the SEER database to assess the value of END. The results showed that END was not a prognostic factor for it. Moreover, there was no significant difference in OS and CSS in the observation group compared to the END group (P > .05). Considering the possible bias from confounding factors, we implemented PSM for the END group and observation. After matching, with 346 patients in each of the END and Observation groups, we found that there was still no difference in OS and CSS between the two groups, which was essentially the same as before matching (P > .05). This indicated that the END group had no survival advantage in terms of OS and CSS compared with the observation groups. Given that there is insufficient data to support the need for lymph node dissection in early-stage FOM SCC, many academics have focused on the utility of sentinel lymph node biopsy (SNB). SNB is a new diagnostic tool that detects microscopic tumor deposits in the lymph nodes of the neck. The advantage of this approach is that treatment is tailored to the individual patient and only those patients with positive anterior lymph nodes can undergo therapeutic neck dissection. Alvarez J et al found that biopsy was not harmful to the survival of patients with floor of mouth cancer and prevented 65% of patients from undertaking END.²³ However, it has a 14% false negative,²³ so further research is needed on its application in FOM cancer. Furthermore, our study demonstrated that age, tumor size and radiotherapy were independent prognostic factors for T1N0M0 mouth floor cancer before and after matching. It has been widely established that age and tumor size are risk factors for survival in cancer patients.²⁴ However, it was surprising that our analysis found a lower risk of death in patients without radiotherapy compared to radiotherapy in cT1N0M0 FOM SCC. Satvir Saggi et al. have also reported negative effects of radiotherapy on CSS in the early-stage FOM cancer.¹⁹ These findings may be related to inadequate treatment or severe complications.²⁵

In conclusion, observation may be a more appropriate option for patients with cT1N0M0 FOM SCC. Despite these findings, there are limitations to our study. First, in the 8th edition of AJCC staging,²⁶ T1 has been updated as tumor size of ≤ 2 cm and depth of infiltration (DOI) ≤ 5 mm. It has been found that DOI is also closely related to survival, with a 5-year OS rate of 93.3% for patients with tumor thickness < 4 mm. In contrast, the OS rate was only 33.3% in cases with DOI >4 mm.²² And the National Comprehensive Cancer Network (NCCN) guidelines strongly recommend END for patients with tumor thickness greater than 4 mm.²⁷ However, this information was not provided in SEER database. In addition, possible coding errors of the SEER database and the absence of specific information on the extent of lymph node dissection, side effects and complications of surgery, chemotherapy and radiotherapy had limited our interpretation of the results. Finally, PSM eliminated the effect of confounding factors, but itself may introduce potential selection bias and the level of evidence remains lower than in randomized controlled clinical trials.²⁸ With these limitations in mind, multicenter, prospective, randomized controlled trials are required to minimize confusion and confirm these findings.

Conclusion

In conclusion, in this study population of cT1N0M0 FOM SCC, there was no significant difference in OS and CSS in the observation group compared with END. Observation may be an appropriate option but further study is warranted.

Footnotes

Acknowledgements

Thanks to the creators of the SEER database and all the staff for providing us with a public database.

Author Contributions

TL conceived the project, designed the research and drafted the manuscript. CC, YW directed this research. CJ, YW, and XX revised the manuscript. All authors reviewed the manuscript.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Central University Basic Research Fund of China (No. WK9110000146).

Ethical Approval

As the SEER database is a public database, ethics and patient consent are not applicable in our study.

Informed Consent

There is no need for institutional review of patient informed consent for the SEER database is a public database.

ORCID iD

Tao Li

References

Amit

Yen

Liao

, et al. Improvement in survival of patients with oral cavity squamous cell carcinoma: An international collaborative study. Cancer. 2013;119(24):4242-4248. doi:10.1002/cncr.28357.

Sung

Ferlay

Siegel

, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660.

Nocini

Vianini

Girolami

, et al. PD-L1 in oral squamous cell carcinoma: A key biomarker from the laboratory to the bedside. Clin Exp Dent Res. 2022;8(3):690-698. doi:10.1002/cre2.590.

Chi

Day

Neville

. Oral cavity and oropharyngeal squamous cell carcinoma--an update. CA Cancer J Clin. 2015;65(5):401-421. doi:10.3322/caac.21293.

Cerbelli

Girolami

Eccher

, et al. Evaluating programmed death-ligand 1 (PD-L1) in head and neck squamous cell carcinoma: concordance between the 22C3 PharmDx assay and the SP263 assay on whole sections from a multicentre study. Histopathology. 2022;80(2):397-406. doi:10.1111/his.14562.

Fakhry

Koch

Gourin

. The Effect of tumor subsite on short-term outcomes and costs of care after oral cancer surgery. Laryngoscope. 2013;123(7):1652-1659. doi:10.1002/lary.23952.

Moro

JDS

Maroneze

Ardenghi

Barin

Danesi

. Oral and oropharyngeal cancer: epidemiology and survival analysis. Einstein 2018;16(2):eAO4248. Published 2018 Jun 7. doi:10.1590/S1679-45082018AO4248.

Massey

Dharmarajan

Bannuru

Rebeiz

. Management of N0 neck in early oral squamous cell carcinoma: A systematic review and meta-analysis. Laryngoscope. 2019;129(8):E284-E298. doi:10.1002/lary.27627.

Amit

Yen

Liao

, et al. Clinical nodal stage is a significant predictor of outcome in patients with oral cavity squamous cell carcinoma and pathologically negative neck metastases: results of the international consortium for outcome research. Ann Surg Oncol. 2013;20(11):3575-3581. doi:10.1245/s10434-013-3044-0.

10.

Peters

Senft

Hoekstra

, et al. Pretreatment screening on distant metastases and head and neck cancer patients: Validation of risk factors and influence on survival. Oral Oncol. 2015;51(3):267-271. doi:10.1016/j.oraloncology.2014.12.006.

11.

Feng

Cheng

Alzahrani

Han

Ward

. Elective neck dissection in T1N0M0 oral squamous cell carcinoma: When is it necessary? J Oral Maxillofac Surg. 2020;78(12):2306-2315. doi:10.1016/j.joms.2020.06.037.

12.

D'Cruz

Vaish

Kapre

, et al. Elective versus therapeutic meck dissection in node-negative oral cancer. N Engl J Med. 2015;373(6):521-529. doi:10.1056/NEJMoa1506007.

13.

Cai

Zhu

Wang

Zhang

Hou

. Neck nodal recurrence and survival of clinical T1-2 N0 oral squamous cell carcinoma in comparison of elective neck dissection versus observation: A meta-analysis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2020;129(4):296-310. doi:10.1016/j.oooo.2019.10.012.

14.

Abu-Ghanem

Yehuda

Carmel

, et al. Elective Neck Dissection vs Observation in Early-Stage Squamous Cell Carcinoma of the Oral Tongue With No Clinically Apparent Lymph Node Metastasis in the Neck: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg. 2016;142(9):857-865. doi:10.1001/jamaoto.2016.1281.

15.

Xie

Shen

. Association of neck dissection with survival for early stage N0 tongue cancer: A SEER population-based study. Medicine (Baltimore). 2018;97(51):e13633. doi:10.1097/MD.0000000000013633.

16.

Peng

Chu

Lai

, et al. Is there a role for neck dissection in T1 oral tongue squamous cell carcinoma? The UCLA experience. Am J Otolaryngol. 2014;35(6):741-746. doi:10.1016/j.amjoto.2014.06.019.

17.

Leng

Wang

Sun

Chen

. Survival comparison of Three histological subtypes of lung squamous cell carcinoma: A population-based propensity score matching analysis. Lung Cancer. 2020;142:13-19. doi:10.1016/j.lungcan.2020.01.020.

18.

Austin

. The relative ability of different propensity score methods to balance measured covariates between treated and untreated subjects in observational studies. Med Decis Making. 2009;29(6):661-677. doi:10.1177/0272989X09341755.

19.

Saggi

Badran

Han

Kuan

St John

. Clinicopathologic characteristics and survival outcomes in floor of mouth squamous cell carcinoma: A population-based study. Otolaryngol Head Neck Surg. 2018;159(1):51-58. doi:10.1177/0194599818756815.

20.

Weiss

Harrison

Isaacs

. Use of decision analysis in planning a management strategy for the stage N0 neck. Arch Otolaryngol Head Neck Surg. 1994;120(7):699-702. doi:10.1001/archotol.1994.01880310005001.

21.

Paleri

Urbano

Mehanna

, et al. Management of neck metastases in head and neck cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol. 2016;130(S2):S161-S169. doi:10.1017/S002221511600058X.

22.

Cariati

Cabello Serrano

Roman Ramos

Sanchez Lopez

Fernandez Solis

Martinez Lara

. Behavior of squamous cell carcinoma of the floor of the mouth. Is supraomohyoid neck dissection sufficiently safe to manage clinically N0 patients? Acta Otorrinolaringol Esp 2019;70(2):68-73. doi:10.1016/j.otorri.2018.02.007.

23.

Alvarez

Bidaguren

McGurk

, et al. Sentinel node biopsy in relation to survival in floor of the mouth carcinoma. Int J Oral Maxillofac Surg. 2014;43(3):269-273. doi:10.1016/j.ijom.2013.10.022.

24.

Menezes

Lehn

Gonçalves

. Epidemiological and histopathological data and E-cadherin-like prognostic factors in early carcinomas of the tongue and floor of mouth. Oral Oncol. 2007;43(7):656-661. doi:10.1016/j.oraloncology.2006.08.004.

25.

Smee

Broadley

Bridger

Williams

. Floor of mouth carcinoma: surgery still the dominant mode of treatment. J Med Imaging Radiat Oncol. 2012;56(3):338-346. doi:10.1111/j.1754-9485.2012.02387.x.

26.

Moeckelmann

Ebrahimi

Tou

, et al. Prognostic implications of the 8th edition American Joint Committee on Cancer (AJCC) staging system in oral cavity squamous cell carcinoma. Oral Oncol. 2018;85:82-86. doi:10.1016/j.oraloncology.2018.08.013.

27.

Colevas

Yom

Pfister

, et al. NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018. J Natl Compr Canc Netw. 2018;16(5):479-490. doi:10.6004/jnccn.2018.0026.

28.

Pan

Yang

Wen

Tong

Tang

. Does adenocarcinoma have a worse prognosis than squamous cell carcinoma in patients with cervical cancer? A real-world study with a propensity score matching analysis. J Gynecol Oncol. 2020;31(6):e80. doi:10.3802/jgo.2020.31.e80.