Clinical Spectrum, Pattern, and Level-Wise Nodal Involvement Among Oral Squamous Cell Carcinoma Patients – Audit of 945 Oral Cancer Patient Data

Abstract

Oral Squamous cell carcinoma (OSCC) is a locoregionally aggressive malignancy. Timely management of neck node dissemination, an important prognostic factor, impacts survival. The aim of the current study was to obtain comprehensive data on patterns or level-wise involvement of neck nodes to optimize neck management in OSCC. It was a retrospective analysis of a prospectively maintained database in a hospital-based setting. The current study evaluated patterns of spread to neck nodes in 945 pathologically proven OSCC patients who underwent neck dissection between 1995 and 2013. Clinical, surgical, pathological, level-wise information of neck nodes was available, and records of these patients were analyzed in relation to the pattern of involvement. Absolute/relative frequency distribution was used to describe the distribution of categorical variables. Continuous measures were organized as mean (standard deviation) and/or median (range). Buccal mucosa (28.78%) was the most common, whereas lip (5.08%) was the least common oral subsite. Modified neck dissection (69.75%) was the most common type of neck dissection. Pathological node positivity was documented in 39.8% patients and Level I(62.54%) and level II(57.33%) are the most common neck levels for nodal involvement. Involvement of Level III to V was seen less often (7.17%). There was no significant association between node positivity among different subsites of oral cancer. Neck level I and II are the most commonly involved levels. Sensitivity and specificity of clinical assessment are 83.51% and 30.05%, respectively. In view of this void in clinical assessment and a predictable nodal spread, alternate node assessment methodology must be explored.

Introduction

Oral squamous cell carcinoma (OSCC), the most common cancer in Southeast Asia, disseminates to cervical nodes which strongly influences survival and prognosis [1–6]. Clinically, N0 necks’ harbor occult metastasis in up to 34% of cases, whereas only 40% clinically suspected neck nodes are metastatic on final histopathology based on the subsite [7–14].

Surgery, the standard of care for nodal metastasis in neck, has evolved from radical to selective neck dissection(SND), but it still remains sub-optimal [7–9, 13, 14]. Tailoring surgery based on pattern of spread might help balance morbidity and oncological outcomes [15]. The objective of this study was to find out the pattern of nodal involvement in different subsets of oral SCC.

Materials and Methods

A retrospective analysis of the prospectively maintained database on oral cancer patients available in our institute was performed resembling other such studies [7, 16]. This data base was custom designed for oral cancer patients in a structured and comprehensive fashion encompassing all clinical, surgical, histopathological, adjuvant therapy, and follow-up details. All the data was captured prospectively. Histopathologically proven oral squamous cell carcinoma (OSCC) patients who underwent surgery including neck dissection between 1995 and 2013 were included for analysis. All patients were managed by a multidisciplinary head and neck team, and standard protocol-based treatment was offered as per prevailing international management guidelines. Standard internationally accepted neck compartment classification and neck dissection nomenclature was utilized in this study.

A total of 945 patients fulfilled the abovementioned inclusion criteria. Clinical, surgical, pathological, level-wise information of neck nodes of these patients was analyzed in relation to the pattern of involvement. Absolute/relative frequency distribution was used to describe the distribution of categorical variables. Continuous measures were organized as mean (standard deviation) and/or median (range).

Results

Out of 945 OSCC patients, 733 (77.57%) were male and 212 (22.43%) female. The average age of the patients was 50.73 years (SD-12.46). Majority of them were between 40 and 60 years old.

Clinical Features

Majority of patients presented with oral ulcer or growth (96.3%) and pain were present in 44.87% of the cases. Around 70% of these patients were tobacco chewers and 37% were smokers. Clinically, skin was involved in around 24% and bone in 27% of the patients. Details of the clinical observations are tabulated in (Table 1).

Table 1.

Clinical observations in the present study

Oral subsite	Frequency	Percentage
Buccal mucosa	272	28.78
Tongue	200	21.16
Alveolo-buccal	177	18.73
Alveolus	104	11.01
Central arch and FOM	90	9.52
RMT	54	5.71
Lip	48	5.08
T Stage clinical
T1	80	8.47
T2	252	26.67
T3	99	10.48
T4	514	54.39
Neck node clinical
Yes	712	75.34
No	233	24.66

Surgical and Histopathological Information

Buccal mucosa (28.78%) and tongue (21.16%) were the most common oral sub-types and lip (5.08%) was the least common subsite (Table 1).

Modified neck dissection was the most common type of neck dissection performed (69.75 %). Supra-omohyoid neck dissection (SOHND) was done in 145 (15.34 %) patients, and bilateral neck dissection was done in 178 (18.84%) of the patients (Table 2). Well-differentiated tumors were seen in 70% of the cases. Margin positive resections accounted for 8% and postoperative radiation therapy was given in 67% patients.

Table 2.

Surgical details of type of neck dissection

Type of neck dissection	No. of cases	Percentage
Ipsilateral
RND	79	8.36
MND1	546	57.78
MND2	113	11.96
MND3	62	6.56
SOHND	145	15.34
Contralateral, n = 178
MND1	4	0.42
MND2	12	1.27
MND3	33	3.49
SOHND	129	13.65
Not done	767	81.16

Pattern of Nodal Involvement

All the 945 patients underwent surgery including neck dissection. Clinically nodes were palpable in 712 (75.34%), whereas pathologically nodes were positive in only 376 (39.79%) patients. In clinically positive neck, 314 patients were also pathologically positive, i.e., sensitivity of clinical observation was 83.51%. However, the specificity of the clinical examination for nodal involvement was quite low (30.05%).

The median number of dissected nodes was 16 (1–58). In pathologically node positive patients (pN +), the median number of positive nodes was 2 (1–24). Among them, only 1 node was positive in 39.63%, 2–4 nodes were positive in 43.08%, and more than 4 nodes were positive in 17.29% of the patients (Table 3).

Table 3.

Table showing post-op histopathological detail

Variables	Frequency	Percentage
Overall histopathological node status
Positive	376	39.79
Negative	569	60.21
Oral subsite wise pathological node positivity
Buccal mucosa	97	35.7
Tongue	90	45.0
Alveolo-buccal	77	43.5
Alveolus	45	43.3
Floor of mouth	28	31.1
Retromolar trigone	17	31.5
Lip	22	45.8
Median number of nodes dissected	16(range 1–58)
Median node positivity	2(range 1–24)
Groups of nodes involved
0	569	60.21
1	149	15.77
2–4	162	17.14
> 4	65	9.31
Skip metastasis
Level III	16	5
Level IV	7	2
Level V	2	0.5

FOM floor of mouth; RTM retromolar trigone; RND radical neck dissection; MND modified radical neck dissection; SOHND supra-omohyoid neck dissection

Overall, level-wise distribution of nodes was available for 746 patients and included 307 pathologically positive patients. Out of 307 cases, contra-lateral neck dissection was done in 55 patients and bilateral SOHND was done in only 6 cases. Level I and II are the most common neck levels for nodal involvement (62.54% and 57.33%, respectively) in pathologically node-positive group where level-wise data was available and together they cover 92.83% of the nodal involvement. On the contrary, at levels III, IV, and V, nodal involvement was 17.26%, 8.79%, and 5.32%, respectively (Table 4). Skip metastasis at level III was seen in 5% cases, at level IV in 2% cases, and at level V only in 0.5% cases (Table 3).

Table 4.

Level-wise nodal involvement pattern

Variables	Ipsilateral neck (n = 307) Frequency (%)	Contralateral Neck(n = 55) Frequency (%)	Total (n = 307) Frequency (%)
Level I
Positive	187 (60.91)	16 (29.09)	192 (62.54)a
Negative	120 (39.09)	39 (70.91)	115 (37.46)
Level II
Positive	161 (52.44)	24 (43.64)	176 (57.33)b
Negative	146 (47.56)	31 (56.36)	131 (42.67)
Level III
Positive	51 (16.61)	2 (03.64)	53 (17.26)
Negative	256 (83.39)	53 (96.36)	254 (82.74)
Level IV c
Positive	26 (08.64)	1 (02.04)	27 (08.97)
Negative	275 (91.36)	48 (97.96)	274(91.03)
Level V c
Positive	14 (04.65)	2 (04.08)	16 (05.32)
Negative	287 (95.35)	47 (95.92)	285(94.68)

^aOne patient had bilateral dissection

^bNine patients were treated bilaterally

^cSOHND cases were excluded from the denominator

Discussion

Oral squamous cell carcinoma is a locoregionally aggressive malignancy. Further, nodal involvement is a very important prognostic factor, and its management has always been a point of debate. Over time, the understanding of anatomy, biology, and surgical approach to neck management has evolved significantly. There is a paradigm shift in surgical management of neck nodes from traditional radical neck dissection, to more conservative, functional, and less morbid procedures like modified neck dissection and supra-omohyoid neck dissection [9, 17]. Despite these advancements, there are gray zones in the assessment, prediction, and optimal management of neck nodes in oral cancer patients. Deo et al. reported a significant overtreatment of neck nodes among oral cancer patients [9]. Although the recent randomized trial by d’Cruz et al. has largely settled the debate on elective vs therapeutic neck dissection, the results do suggest that 70% of clinical N0 necks are overtreated with attendant morbidity [18].

The spectrum of cases in this study is more in line with places where oral cavity cancer is in epidemic proportions as a result of tobacco chewing. This contrasts with the Western populace wherein it’s a result of smoking and alcoholism. The traditional guidelines on neck management and their modifications come from retrospective analyses of lymphatic spread in this Western etiological subset and include hypopharyngeal and laryngeal carcinomas as well. There is paucity of literature from Asian subcontinent where oral cancer is very commonly seen.

The pattern of nodal metastasis has been described in literature as predictable pattern based on level wise involvement [15, 19]. Typically, the pattern of nodal involvement is in an orderly fashion from upper neck levels (I & II) to lower neck levels (III, IV & V) which was also found in our study [20]. In the present study, histopathological involvement of nodes in different levels of neck was observed, and accordingly, the patterns were reported. Histopathological involvement of nodes was seen in 39.79% of the patients. Level I and II are the most common neck levels for nodal involvement (62.54% and 57.33%, respectively) in pathologically node-positive group where level-wise data was available and together they cover 92.83% of the nodal involvement. In 2012, Deo et al. used data of buccal and alveolo-buccal cancer patients and have reported that level I was the most common level involved in pN + group (67.8%). Further, level II was involved in 17.5% of pN + patients. The overall involvement of level IV and V was only 9.4 and 4.7%, respectively [9].

Different studies reported different patterns and incidence of nodal involvement. Shah et al. in 1990 analyzed 501 previously untreated oral cancer patients and found that majority of metastatic nodes were in levels I to III. The prevalence of nodal metastasis in level IV was 3% for elective radical neck dissection, 15% for immediate radical neck dissection, and 16% subsequent radical neck dissection. Further, prevalence in level V was only 0.5% in elective radical neck dissection and 4% and 2%, respectively, in immediate radical neck dissection and subsequent radical neck dissection [17].

Jamsed et al. in 2007 analyzed 1056 cervical lymph nodes in T1-2 oral tongue cancer patients. The number of nodes in levels I, II, III, and IV was 261, 295, 230, and 250, respectively, and in level V, it was only 20. Further, positive nodes in neck were 40% in level I, 40% in level II, and 20% and 10% in level in III and IV. However, no nodes were found positive in level V [21].

In a publication by Gauri et al. evaluating 583 neck dissections in oral cancer patients, they found low incidence of metastases to levels IIB and V (3.8 and 3.3%, respectively). Whereas, the commonest levels involved being levels I to III (91%) [22].

Skip metastasis is one of the major challenges in the prediction of the pattern of nodal metastasis. This phenomenon of skip metastases in cancer of the mouth, especially in the tongue, was described by Rouvière in 1938 [23]. Without involvement of levels I and II, metastasis to inferior cervical nodes at levels III or IV has been also reported in cancers of the head and neck [24]. Byers et al. in 1997 analyzed 277 previously untreated tongue OSCC patients [25]. They reported that, 15.8% had either level III or IV metastatic LNs without involvement in levels I and II. Again, in 1997, Woolgar reported that incidence of skip metastasis in levels II and III was 10% [26]. These results were based on a series of neck dissections from 154 previously untreated patients with OSCC. In the present study, only 5% had skip metastasis in level III, while in level IV, it was seen in 2%, and in level V they were seen in only 0.5% cases.

Rao et al. reported nodal involvement in 181 cases of neck dissection of T3/T4 cancer of alveolo-buccal complex. The nodal involvement in level I was 85%, 51% in level II, 19% in level III, 18% in level IV, and 5% in level V. Further, chance of skip metastasis at levels IV and V was 4.4% [27].

The results of the current study showed that the overall node positivity rate was 39.79% and incidence of node positivity was relatively higher among locally advanced tongue and floor of mouth subsites in comparison to early stage oral cancers and subsites like alveolus, palate, and lip. Similar to previously reported studies, we also noted a predictable nodal spread with level I and II being the most involved levels. However, skip metastasis rate in levels IV and V was much lower.

The strengths of the current study are that it contains prospectively collected high-quality data and has a good sample size. However, it is limited by the retrospective nature of the analysis.

Most of the conventional guidelines based on Western data recommend a comprehensive neck dissection instead of a selective dissection in the presence of palpable nodes. The results of the current study suggest that clinical specificity of palpable nodes is quite poor and present a case for more conservative neck dissections leading to better functional outcomes. To improve staging accuracy of neck nodes, alternate methods like ultrasound-guided FNAC or SLNB should be used in the presence of clinically palpable nodes.

Conclusion

Among OSCC patients undergoing neck dissection pathologic node positivity is seen only in 39.79% of the patients. Neck level I and II are the most common neck levels for nodal involvement. Sensitivity and specificity of clinical assessment is 83.51% and 30.05%, respectively. In view of this void in clinical assessment for decision-making and a predictable nodal spread, alternate node assessment methodology like ultrasound-guided FNA and SLNB and super-selective neck dissection must be explored in future to optimize neck node management in oral cancer patients .