Keywords
Anatomical distribution - demographic pattern - head and neck squamous cell carcinoma
- histopathological grade - risk factors
Introduction
Head and neck cancers (HNCs) are the sixth most common malignancy in the world. Majority
of HNCs are squamous cell carcinoma (HNSCC), and among these, oral cancers account
for up to 40% of all malignancies.[1] France, India, and Brazil have the highest age-adjusted rates of HNC and Indian
females account for the highest age-adjusted rates of HNC in the world.[2],[3] Anatomical sites affected by HNC varies worldwide. In India, the most common site
is oral cavity, whereas pharynx accounts for majority of cases in France,[4] reflecting the influence of exposure to different risk factors in the population.[2],[5] Because of indigenous practice of chewing pan and betel leaf with tobacco, cancers
of tongue as well as buccal mucosa are frequent.[6] Prognosis of oral squamous cell carcinoma (OSCC) is influenced by tumor primary
site, nodal involvement, tumor thickness, and status of the surgical margins and is
greatly influenced by the stage of the disease, especially pathological TNM (pTNM).[7]
A literature search revealed that data regarding distribution in different age groups
and sex, anatomic distribution, and clinicopathologic profile of HNSCC are scarce
in the eastern region of India. The present study aims to report these features from
a series of HNSCC from a referral center in Kolkata, West Bengal.
Materials and Methods
The duration of the present study was 2 years. All patients presented with HNC were
screened for histologically proven SCC. These cases were evaluated for inclusion in
the present study. Patients having other variants of malignancy, recurrence, metastatic
carcinoma from unknown primary site, and lesions diagnosed only by cytological methods
were excluded from the study group.
Data regarding sex, age, duration of illness, risk factors, clinical presentation
of the lesion, location, and size were obtained. Clinical presentation of the lesions
was classified in three groups: ulcers (including plain ulcers, and exophytic ulcerated
masses), leukoerythroplakias, and tumors presenting both ulcers and leukoerythroplakic
areas.[8] Anatomic location of tumor in the oral cavity was subclassified based on the following
sites: buccal mucosa (including buccal sulcus/mucobuccal fold), alveolar mucosa and
gingiva (including retromolar area), border of tongue, floor of mouth (with extension
to ventral tongue), upper and lower lips, soft palate, and tonsil areas. Histological
slides were reviewed for the classification of tumors according to the following grade:
well-differentiated (WD), moderately differentiated (MD), and poorly differentiated
(PD) tumors according to the WHO criteria.[9] In cases where the tumor was excised by radical surgery, pTNM was performed. Standard
statistical methods were applied to analyze these data.
Results
A total of 123 cases were initially evaluated for inclusion in the study. After applying
the exclusion criteria, 108 cases were selected as the study population. The anatomic
distribution of cases is shown in [Table 1]. Buccal mucosa is the most common region (36 cases, 33.33%) followed by dorsal surface
of tongue (26 cases, 24.07%) [Table 1].
Table 1
Distribution of cases according to anatomic location
|
Location
|
Number of cases (%)
|
|
Buccal mucosa
|
36 (33.33)
|
|
Dorsal surface of tongue
|
26 (24.07)
|
|
Alveolar mucosa/gingiva/retromolar area
|
16 (14.81)
|
|
Larynx
|
13 (12.04)
|
|
Pharynx
|
9 (8.33)
|
|
Floor of mouth
|
3 (2.78)
|
|
Ventral surface of tongue
|
1 (0.93)
|
|
Palate
|
1 (0.93)
|
|
Nasal cavity
|
2 (1.85)
|
|
Lower lip
|
1 (0.93)
|
|
Total
|
108 (100.00)
|
Male accounted for 79 cases (73.15%) while 29 cases (26.85%) occurred in female (M:F
- 2.7:1) [Table 2]. Majority of anatomic locations had a sex ratio in favor of males, the highest being
buccal mucosa (M:F - 8:1). Exceptionally, cases of neoplasms arising from alveolar
mucosa/gingiva/retromolar area had a sex ratio in favor of females (M:F - 0.45:1).
The age range of cases in the study group noted was between 31 and 81 years. Most
cases occurred in the age group of 40–59 years (58 cases, 53.70%) [Chart 1]. Mean age of all cases was 53.21 (±12.17) years [Table 2]. However, cases of SCC arising from pharynx had a mean age of 63.22 (±7.40) years.
Table 2
Demographic data of the study group according to anatomical site
|
Site
|
Average age
|
Male:female
|
|
Buccal mucosa
|
50.08±11.39
|
8:1
|
|
Dorsal surface of tongue
|
50.62±13.20
|
1.6:1
|
|
Alveolar mucosa/gingiva/retromolar area
|
54.31±11.97
|
0.45:1
|
|
Larynx
|
53.69±12.76
|
All male
|
|
Pharynx
|
63.22±7.40
|
3.5:1
|
|
Others
|
61.75±7.40
|
2:1
|
|
Total
|
53.23±12.17
|
2.7:1
|
Chart 1 Distribution of cases according to age range
History of smoking was obtained in 63 (58.33%) cases and tobacco/beetle nut chewing
in 41 (37.96%) cases. Consumption of alcohol was noted in 45 (41.67%) cases. No addition
of these substances was noted in 21 cases (19.44%). Clinically, the most common presentation
was ulcerated lesion (51 cases, 47.22%) followed by whitish lesion or mass (28 cases,
25.93%) and hoarseness of voice (11 cases, 10.19%). On examination, anemia was noted
in 29 (26.85%) cases and palpable regional lymph node was detected in 18 (16.67%)
cases.
Clinically, duration of symptoms in most cases (60.19%) was <6 months and only 10.19%
cases had duration of >1 year [Table 3]. Most common clinical appearance of tumors was ulcer with leukoerythroplakia (39.81%)
followed by ulcerated lesions (27.78%).
Table 3
Clinical characteristics of cases in the study group (n=108)
|
Parameters
|
Number of cases (%)
|
|
Duration of symptoms
|
|
|
<6 months
|
65 (60.19)
|
|
6-12 months
|
32 (29.63)
|
|
>12 months
|
11 (10.19)
|
|
Predominant clinical appearance of tumors Ulcer
|
30 (27.78)
|
|
Ulcer with leukoerythroplakia
|
43 (39.81)
|
|
Exophytic mass
|
28 (25.93)
|
|
Leukoerythroplakia
|
7 (6.51)
|
Specimen of radical surgery was obtained in 45 cases (41.67%) and biopsy of the tumor
was available in 63 cases (58.33%) for pathological study [Table 4]. Microscopically, Grade I (WD) were the most common (67 cases, 62.04%) followed
by Grade II (MD) tumors (38 cases, 35.19%), while Grade III (PD) tumors were the least
common.
Table 4
Histological characteristics of tumors
|
Number of cases (%)
|
|
Tumor differentiation (n=108)
|
|
|
Grade I well differentiated
|
67 (62.04)
|
|
Grade II moderately differentiated
|
38 (35.19)
|
|
Grade III poorly differentiated
|
3 (2.78)
|
|
Specimens of radical surgery (n=45)
|
|
|
Greatest dimension of tumor
|
|
|
2 cm or less
|
12 (26.67)
|
|
2-4 cm
|
18 (40.00)
|
|
>2 cm
|
15 (33.33)
|
|
Tumor depth
|
|
|
<1 cm
|
17 (37.78)
|
|
1-2 cm
|
16 (35.56)
|
|
>2 cm
|
12 (26.67)
|
|
Status of surgical resection margins
|
|
|
Involved
|
16 (35.56)
|
|
Uninvolved
|
29 (64.44)
|
|
Lymph node metastasis
|
|
|
Involved
|
10 (22.22)
|
|
Not involved
|
35 (77.78)
|
|
Lymphovascular invasion
|
7 (15.56)
|
|
Perineural invasion
|
5 (11.11)
|
|
Bone/cartilage invasion
|
2 (4.44)
|
|
Dysplasia at margin
|
12 (26.67)
|
Additional pathological observation was documented in specimens of radical surgeries
(n = 45). Most tumors had the greatest dimension between 2 and 4 cm (18 cases, 40.00%).
Mean tumor thickness was 0.98 (±69) cm. Tumor depth was <1 cm in 17 cases (37.78%)
and 1–2 cm in 16 cases (35.56%). Surgical resection margin was involved by the tumor
in 16 (35.56%) cases, while metastatic deposit in the lymph nodes was seen in 10 (22.22%)
patients. Other notable findings were lymphovascular invasion (7 cases, 15.56%), perineurial
invasion (5 cases, 11.11%), and bone or cartilage invasion (2 cases, 4.44%).
In 62 cases (57.41%) documented, macroscopic appearance of tumors was available (as
noted either in resected specimens or by imaging) [Table 5]. While exophytic lesions were most common in the buccal mucosa (9 out of 23, 39.13%),
ulceroproliferative lesions were most common in the tongue (9 out of 17, 52.04%).
However, microscopic examination revealed that Grade I SCC is the most common histological
grade in both locations (72.22% and 65.38%).
Table 5
Macroscopic appearance and microscopic grade of tumors according to site of the lesion
|
Tumor features
|
Buccal mucosa
|
Dorsal surface of Tongue
|
Alveolar mucosa/gingiva/retromolar area/lower lip
|
Larynx
|
Pharynx
|
Others
|
Total
|
|
Macroscopic appearance (n=62)
|
23
|
17
|
10
|
7
|
3
|
2
|
62
|
|
Ulcer
|
6
|
3
|
5
|
1
|
1
|
2
|
18
|
|
Ulceroproliferative
|
7
|
9
|
0
|
6
|
2
|
0
|
24
|
|
Exophytic
|
9
|
3
|
4
|
0
|
0
|
0
|
16
|
|
Infiltrative
|
1
|
2
|
1
|
0
|
0
|
0
|
4
|
|
Total
|
|
|
|
|
|
|
|
|
Microscopic grade (n=108)
|
36
|
26
|
16
|
13
|
9
|
8
|
108
|
|
Grade I
|
26
|
17
|
11
|
3
|
5
|
5
|
67
|
|
Grade II
|
10
|
9
|
5
|
9
|
3
|
2
|
38
|
|
Grade III
|
0
|
0
|
1
|
1
|
1
|
0
|
3
|
Chi-square test was used to find a correlation between sets of two variables, i.e.,
microscopic grade of tumor to age of patient, site of tumor, duration in months, and
macroscopic appearance of lesion. The correlation between microscopic grade and anatomic
site of tumor was found to be statistically significant [Table 6].
Table 6
Correlation between histopathological grade with clinical features. Chi-square test
is significant in the correlation of grade and anatomic site (P<0.05)
|
Parameter
|
Microscopic grade
|
P
|
|
Grade I (n=67)
|
Grade II (n=38)
|
Grade III (n=3)
|
|
Age (years)
|
|
|
|
|
|
<50
|
27
|
13
|
1
|
0.814778
|
|
50 or more
|
40
|
25
|
2
|
|
|
Anatomic site
|
|
|
|
|
|
Oral cavity
|
56
|
25
|
1
|
0.026487
|
|
Other sites
|
11
|
13
|
2
|
|
|
Duration (months)
|
|
|
|
|
|
<6
|
41
|
23
|
1
|
0.627198.
|
|
>6
|
26
|
15
|
2
|
|
|
Macroscopic appearance
|
|
|
|
|
|
Ulcer/ulcer with leukoerythroplakia
|
46
|
25
|
2
|
0.954941
|
|
Other lesions
|
21
|
13
|
1
|
|
Discussion
OSCC is the major bulk of tumor constituting HNSCC as well as oral cancers. There
is a wide variation in the incidence of OSCC in different regions of the world. However,
high proportion of occurrence of OSCC among these groups represents the exposure to
different carcinogenic substances and their genetic predisposition.
Among the known risk factors, smoking, chewing tobacco, betel quid, areca nuts, and
drinking alcohols are significant. In a case–control study conducted in the US involving
1114 patients of oral and pharyngeal cancer, it was observed that risks of cancer
increased in a multiplicative manner in persons who are both smokers and drinkers.
There were similar relative risk patterns among different races and sexes.[10] Similarly, in a large study involving 5458 cases of HNC in Andhra Pradesh, India,
only 21.22% cases were free from such risk factors.[11] In the present study, only 19.44% cases had no addiction of these causative substances.
Other risk factors include ultraviolet radiation and poor oral hygiene.[12] Human papillomavirus is now emerging as a significant risk factor in nonsmokers
and in cancers involving tonsil, oropharyngeal region, and tongue.[13]
In worldwide, most studies had documented that HNSCC mostly occurred in males.[8],[10],[11] The male predominance is also apparent in all age groups and in all anatomic sites.[8],[11] A similar trend has been observed in the present study where M:F ratio was 2.7:1
with the highest ratio in buccal mucosa (M:F - 8:1). These patterns of sex ratio may
be explained by the fact that males are more commonly addicted to risk factors such
as alcohol, smoking, and chewing tobacco which are consumed concurrently.[8],[14]
Age groups that have been affected most commonly in the present study are 40–59 years
(58 cases, 53.70%) followed by 60–79 years (33 cases, 30.56%). No case has been detected
in persons below 30 years in the present study. The preponderance of such age distribution
may be explained by the fact that these persons are usually exposed to risk factors
for a sufficient duration, resulting in neoplastic changes. The occurrence of OSCC
below 40 years of age is uncommon and ranges from 0.4% to 6%.[8],[1]5]
In the present study, the most common site affected was buccal mucosa (33.33%) followed
by dorsal surface of tongue (24.07%). Addala et al. reported similar sites of affection among patients of HNC in Andhra Pradesh, India.[11] The predilection for buccal mucosa in patients from Southeast Asia has been attributed
to areca nut- and tobacco-chewing habits of people in this region.[16] In fact, the variations in the commonly affected sites in different geographic locations
are guided by the etiologic factors which are prominent in that particular zone. In
American and European countries, the most common site affected is the border of the
tongue, while the lower and upper gingiva have been reported to be commonly affected
in Nigeria.[8]
It was found in the current study that duration of symptoms in most cases (60.19%)
was <6 months. In only 10.19% of cases, the duration exceeded 1 year. A comparable
time span has been reported by Shenoi et al. in their study. They attributed the delay in diagnosis to low literacy rate, poor
financial status, and tendency of Indian patients to resort to home remedies before
seeking medical help.[17] Interestingly, Pires et al. observed that the mean time of complaint before diagnosis was longer in females than
in males.[8]
Many studies report that the site of predilection in HNC is apparently influenced
by gender though exact reasons justifying such distribution remain obscure. The palate,
alveolar mucosa, buccal mucosa, and gingiva are more commonly affected in females,
whereas in males, border of tongue, ventral surface of tongue, and floor of mouth
are the more common sites.[8],[14] In the present study, alveolar mucosa, gingiva, and retromolar area were found to
be the common sites of affection in females as compared to buccal mucosa and dorsal
surface of tongue, which showed a predilection for males.
Varied clinical appearances of tumors were appreciated in the present study, the most
common being ulcer with leukoerythroplakia (39.81%), followed by ulcerated lesions
(27.78%). Pires et al. however noted in their study that ulcers were the most common presentation (62%).
They reported ulcers with leukoerythroplakia in 21% cases only.[8]
In the present study, microscopically, Grade I (WD) tumors were the most common (67
cases, 62.04%) followed by Grade II (MD) tumors (38 cases, 35.19%). Most studies report
HNC to be histologically WD or MD tumors.[8] However, Effiom et al. in their study reported PD tumors to be the most common.[18] Pires et al. found a relationship between the grade of tumor and gender of the patients. Males
were mostly diagnosed with MD and PD tumors while females with WD and MD tumors. They
also suggested an association of grade of tumor with site. According to their observations,
WD tumors are more common in buccal mucosa, buccal sulcus, and lower lip, whereas
borders of tongue, ventral tongue, floor of mouth, and gingiva are the common sites
for MD tumors.[8] In the present study, Grade I SCC was most common in both buccal mucosa and tongue
(72.22% and 65.38%, respectively).
The correlation between microscopic grade and anatomic site of the tumor was found
to be statistically significant in the present study. An attempt was made by Shenoi
et al. to correlate sets of two variables, i.e., site and habits, staging and anatomic site,
stage and duration of illness, stage and habits, and stage and age of patient. However,
none of these correlations was reported to be statistically significant by them.[17]
Conclusion
The present study has revealed that males having an age range of 40–59 years were
the most common population affected by HNSCC. Such tumors are strongly associated
with addiction and only 19.44% cases were not addicted to any substances. Buccal mucosa
is the most common anatomic location of HNSCC in the present study followed by dorsal
surface of tongue. Ulceroproliferative and exophytic lesions were the most common
macroscopic appearances while Grade I (WD) SCC was the predominant microscopic pattern
in most sites. The histologic grading was statistically significant when correlated
with anatomic site. Although these features have similarities with other studies conducted
in India and abroad, some distinctive observations noted in this study were the macroscopic
appearance and microscopic grade.
