Keywords
Head and neck - squamous cell - tobacco - young
Introduction
Head and neck cancer (HNC) is one of the most common cancers worldwide with annual
incidence more than 550,000 cases, of which around 300,000 deaths occur every year.[1] Head and neck squamous cell carcinoma (HNSCC) accounts about 90% of all HNC which
is the sixth leading cancer by incidence worldwide. HNSCC typically develops in sixth
to seven decades of life. However, some studies reveal that it has developed in younger
age group in different parts of world including India, China, USA, and Europe.[2]
[3]
[4]
[5]
[6] HNSCC incidence rate in patients below 40 years has reached 0.4%–3.6%.[7] The most common locations where HNSCC arises are the oral cavity, oropharynx, larynx,
and hypopharynx.[7]
[8] The main risk factors associated with HNSCC are environmental and lifestyle factors
such as chewing tobacco, alcohol consumption, and smoking. Recently, epidemiological
studies has emerged a strong association with human papillomavirus (HPV) in a subset
of HNSCC and in nonsmoking cases.[9]
[10] In north eastern parts of India in the states such as Assam, Meghalaya, Mizoram,
Tripura, Nagaland, and Manipur, the risk of HNSCC is further associated with the practice
of betel quid and areca nut chewing,[11] chewing of smokeless tobacco products,[12] and smoking of bidis and cigarettes.[13] However, there is an increase in the number of young HNSCC patients, without history
of any typical risk factors. Other risk factors associated with the prevalence of
HNSCC are poor dental hygiene, poor diet, immunosuppressant, submucous fibrosis, gastrointestinal
reflux, different inherited syndrome, and chronic iron deficiency anemia.[6]
[14]
[15]
[16]
[17]
[18]
Since remarkable differences exist in consumption of alcohol, tobacco, diet, literacy,
and social status in the north eastern region of India compared to other parts of
the country, we proposed to define in this article the environmental and lifestyle
risk factors, age group, tumor location, and literacy among the group of HNSCC patients
reported in hospital-based cancer registry at Dr. B Borooah Cancer Institute, Guwahati,
Assam, India, during January 2015–December 2015.
Methodology
The present study is a retrospective study conducted at Dr. B Borooah Cancer Institute,
Guwahati, on patients who were diagnosed with HNSCC during January 2015–December 2015.
A total of 362 patients ranging from age group 20–40 years who had histologically
confirmed cases of squamous cell carcinoma (SCC) of oral cavity, tonsil, oropharynx,
nasopharynx, hypopharynx, and larynx were included. Patients with imprecise and incomplete
information on clinical and histological data, previously treated cases, and SCC of
the other parts of the head and neck were excluded. The present study has been approved
by the institutional review board.
Data regarding tumor site, age, sex, education, habit of tobacco (smokeless and smoke)
consumption, and betel nut chewing habit were abstracted from hospital records and
analyzed using IBM SPSS version 19 (SPSS Inc., Chicago, IL, USA). The variables were
analyzed using Chi-square or Fisher’s exact test. P < 0.05 was considered as statistically significant.
Results
We reviewed the medical records of 362 HNSCC patients of whom 272 were males and 90
were females (the male to female ratio was 3:1). The mean and median ages were 38
and 39 (range: 20–40) years, respectively. The patients were divided into two groups,
below 39 years or younger (n = 184 patients) and 39 years above or older (n = 178 patients) based on median age. The mean and median ages in younger patients
were 34 and 35 years, and in older patients, they were 41 and 42 years. The male to
female ratio in younger and older groups were 2.2:1 and 4.4:1, respectively. The patients’
ages differ significantly with their sex [Table 1]. Among the patients in younger age group, 154 (83.7%) were tobacco chewers, 93 (50.5%)
were smoker, and 154 (83.7%) were betel nut chewer. However, in older age group, 149
(83.7%) were tobacco chewer, 100 (56.2%) were smoker, and 140 (78.7%) were betel nut
chewer. Patients’ chewing and smoking habit did not differ significantly with their
age.
Table 1
Characteristics of patients and patients' age
|
Patients' characteristics
|
Patients' age (years)
|
P
|
|
≥39
|
>39
|
|
|
Gender
|
|
|
|
|
Male
|
127 (69.0)
|
145 (81.5)
|
0.006
|
|
Female
|
57 (31.0)
|
33 (18.5)
|
|
|
Tobacco smokeless
|
|
|
|
|
Chewers
|
154 (83.7)
|
149 (83.7)
|
0.997
|
|
Nonchewers
|
30 (16.3)
|
29 (16.3)
|
|
|
Tobacco smoke
|
|
|
|
|
Smokers
|
93 (50.5)
|
100 (56.2)
|
0.283
|
|
Nonsmokers
|
91 (49.5)
|
78 (43.8)
|
|
|
Betel nut
|
|
|
|
|
Chewers
|
154 (87.7)
|
140 (78.7)
|
0.219
|
|
Nonchewers
|
30 (16.3)
|
38 (21.3)
|
|
The most prevalent site of HNSCC in younger patients was mouth (75/184 = 40.8%) while
in older patients, the most common site was hypopharynx (65/178 = 36.5%). The site
of HNSCC was significantly different with patients’ age (P = 0.012). In male, the highest frequencies were observed in two sites, mouth and
hypopharynx (85/272 = 31.3%) while in female, the highest cases were found in mouth
(40/90 = 44.4%). There was no significant difference between patients’ HNSCC site
and sex. Among tobacco chewers, the most common observable location of HNSCC was mouth
(122/303 = 40.3%) while among smokers, the most common location observed in hypopharynx
(80/193 = 41.5%). However, mouth was the most frequently observed site of HNSCC among
the patients who ever chewed betel nut (125/294 = 42.5%). The site of HNSCC was highly
associated with chewing and smoking habit (P < 0.05) [Table 2].
Table 2
Characteristics of patients and tumor site
|
Patients' characteristics
|
Tumor site
|
P
|
|
Lip
|
Tongue
|
Mouth
|
Tonsil
|
Oropharynx
|
Nasopharynx
|
Hypopharynx
|
Larynx
|
|
|
Age (years)
|
|
|
|
|
|
|
|
|
|
|
≤39
|
3 (1.6)
|
27 (14.7)
|
75 (40.8)
|
13 (7.1)
|
9 (4.9)
|
13 (7.1)
|
36 (19.6)
|
8(4.3)
|
0.012
|
|
>39
|
2 (1.1)
|
27 (15.2)
|
50 (28.1)
|
10 (5.6)
|
8 (4.5)
|
5 (2.8)
|
65 (36.5)
|
11 (6.2)
|
|
|
Gender
|
|
|
|
|
|
|
|
|
|
|
Male
|
5 (1.8)
|
37 (13.6)
|
85 (31.3)
|
18 (6.6)
|
12 (4.4)
|
14 (5.1)
|
85 (31.3)
|
16 (5.9)
|
0.102
|
|
Female
|
0
|
17 (18.9)
|
40 (44.4)
|
5 (5.6)
|
5 (5.6)
|
4 (4.4)
|
16 (17.8)
|
3 (3.3)
|
|
|
Tobacco smokeless
|
|
|
|
|
|
|
|
|
|
|
Chewers
|
5 (1.7)
|
43 (14.2)
|
122 (40.3)
|
18 (5.9)
|
15 (5.0)
|
14 (4.6)
|
71 (23.4)
|
15 (5.0)
|
<0.05
|
|
Nonchewers
|
0
|
11 (18.6)
|
3 (5.1)
|
5 (8.4)
|
2 (3.4)
|
4 (6.8)
|
30 (50.8)
|
4 (6.8)
|
|
|
Tobacco smoke
|
|
|
|
|
|
|
|
|
|
|
Smokers
|
1 (0.5)
|
24 (12.4)
|
51 (26.4)
|
10 (5.2)
|
12 (6.2)
|
14 (7.3)
|
80 (41.5)
|
1 (0.5)
|
<0.05
|
|
Nonsmokers
|
4 (2.4)
|
30 (17.8)
|
74 (43.8)
|
13 (7.7)
|
5 (3.0)
|
4 (2.4)
|
21 (12.4)
|
18 (10.7)
|
|
|
Betel nut
|
|
|
|
|
|
|
|
|
|
|
Chewers
|
5 (1.7)
|
54 (18.4)
|
125 (42.5)
|
20 (6.8)
|
11 (3.7)
|
7 (2.4)
|
56 (19.4)
|
16 (5.4)
|
<0.05
|
|
Nonchewers
|
0
|
0
|
0
|
3 (4.4)
|
6 (8.8)
|
11 (16.2)
|
45 (66.2)
|
3 (4.4)
|
|
Next, we investigated the relation between chewing and smoking habit and education
status of the patients. We observed that out of 303 tobacco chewers, 198 (65.3%) were
illiterate. Further, 181 (61.6%) patients were illiterate among betel nut chewers.
Education status was statistically significant with chewing habit (P < 0.05). Moreover, 131 (67.9%) patients were identified as illiterate smokers. Smoking
habit did not differ significantly with education status [Table 3]
Table 3
Characteristics of patients and patients' education status
|
Patients' characteristics
|
Education status
|
P
|
|
Literate
|
Illiterate
|
|
|
Tobacco smokeless
|
|
|
|
|
Chewers
|
105 (34.7)
|
198 (65.3)
|
0.001
|
|
Nonchewers
|
8(13.6)
|
51 (86.4)
|
|
|
Tobacco smoke
|
|
|
|
|
Smokers
|
62 (32.1)
|
131 (67.9)
|
0.690
|
|
Nonsmokers
|
51 (30.2)
|
118 (69.8)
|
|
|
Betel nut
|
|
|
|
|
Chewers
|
113 (38.4)
|
181 (61.6)
|
<0.05
|
|
Nonchewers
|
0
|
68 (100)
|
|
Further, we have performed univariate analysis between education (odds ratio [OR]
3.381, 95% confidence interval [CI] 1.547–7.389, P = 0.002) and habit of tobacco consumption. The risk of developing HNSCC was statistically
higher among illiterate tobacco chewers which was about three times more than nonchewers.
Furthermore, multivariate analysis showed significant effect of education (OR 3.618,
95% CI 1.643–7.970, P = 0.001) and gender (OR 1.916, 95% CI 1.032–3.554, P = 0.039) on tobacco-chewing habit. The risk of prevalence HNSCC among males was about
two times higher in tobacco chewers than nonchewers. Among the illiterate tobacco
chewers, there is four times higher risk of prevalence HNSCC than nonchewers [Table 1]
[2]
[3].
Discussion
HNSCC is the most commonly diagnosed cancer worldwide. Over 200,000 cases of HNC occur
each year in India. Nearly 80,000 oral cancers are diagnosed every year in our country.[19] The true global incidence of HNSCC in young patients is unclear because most epidemiological
studies do not report its incidence by age stratification. In India, HNC accounts
for 30% of all cancers.[19] The population of north east India is associated with distinct demographic profile,
lifestyle, food habits, and customary practices, which implicts toward higher susceptibility
to develop HNSCC. HNSCC usually occurs in the sixth to seventh decades of life, but
Llewellyn et al. have shown increased incidence of HNSCC among young.[3] Various epidemiological studies had reported a strong association with HPV in a
subset of young HNSCC and nonchewers and smokers.[9] The percentage of HNSCC in younger individuals varies depending on the cutoff age
chosen. In our study, we have taken the cutoff age as 39 years. According to Llewellyn
et al., the incidence of HNSCC in younger individuals ranges from 0.4% to 3.6%[3] when the cutoff age was taken as <40 years. However, our study showed 50.8% cases
in younger age group when young were defined 39 years or below. The mean age was 41
years in older age group. This significant bias may be due to habit of consuming tobacco
(smokeless and smoke) and chewing betel nut at early ages in the region of north east
India. This is observed in our study as well. Considering the gender in the present
study, males were more commonly affected than females which implicate the increased
use of tobacco and betel nuts in males. This finding was similar to the study conducted
by Toner and O’Regan.[6] Smoking, tobacco, and alcohol consumption are main risk factors for HNC.[20]
The most common site of cancer in the present study population was oral cavity. This
finding is different from the previous other studies by Gawecki et al.[21] SCC of larynx and hypopharynx in young patients are rare and account for approximately
10% and 1% of all HNSCCs in patients aged <40 years.[22] In patients younger than 39 years, oral cavity was the most common site; however,
hypopharynx was more common in patients older than 39 years and equal to 40 years
which was different from the other studies.[23] On contrary to the findings in other studies, oral cavity and hypopharynx were the
two most commonly affected sites in males, whereas in females, it was the oral cavity
which was found to be more frequent in our study.[24]
Tobacco both in smokeless and smoked form is known as one of the major risk factors
for HNSCC. Various Indian studies had shown that tobacco smoking in the form of cigarettes,
bidis, cigar/chutta/cheroot, dhunti (Goa), the water pipes/hookah (north India), reverse
chutta smoking (in coastal Andhra Pradesh and Orissa), Hookli (Gujarat), and chillum
(Northeast part of India) has attributed to the development of HNSCC. In India, around
57% of all men and 11% of women between 15 and 49 years of age use some form of tobacco.
Uses of smokeless tobacco as well as betel quid (pan) with lime and zarda are widespread
in many parts of India.[25] Tobacco consumption in India is growing at a rate of 2%–3% per annum.[26] A high incidence of smoking was reported among youth from Bangladesh, India, and
Indonesia.[27] The high prevalence of tobacco usage has led to increase in disease burden and high
health-care costs in developing countries. In our study, 40.3% of the tobacco chewers
had oral cancers which is similar to that observed by O’Regan et al.[28] Mafi et al. has found 81.7% of SCC in larynx with the habit of smoking; however, in our study,
it was observed that 41.5% of patients had SCC of hypopharynx.[23] Among the betel nut chewers, oral cavity was the most common affected site in our
study group. This finding is similar to the other studies.[29]
Illiteracy was significantly associated with tobacco use in our study. This is consistent
with many other studies.[30] Illiteracy and lack of awareness among the general population about the side effects
of tobacco have emerged as major public health problem in north east India.
The limitations of our study include that the study was a retrospective one resulting
in missing of data and small number of patients. Hence, further prospective studies
will be of greater value in this respect. However, the strength of our study is that
this is the first study from north east India on young HNC patients.
Conclusion
Tobacco and betel nut consumption are the major risk factors for HNSCC. There was
a positive association between tobacco use, male gender, and low education levels,
and incidence of HNSCC in north eastern states is higher than the other states. Since
HNSCC cancers are highly preventable cancers, we should inform the general public,
especially the younger illiterate population about the adverse health consequences
of tobacco and betel nut use.
