Abstract
Upper aerodigestive tract (UADT) malignancies account for significant proportion of all malignancies. The aim of the study is to know the demography and patterns of tobacco consumption and the proportion of non-tobacco consumers in patients with UADT carcinoma. Patient diagnosed with primary UADT carcinoma visiting outpatient department in a tertiary centre from February 2009 to May 2011 were included in the study. 150 patients were documented with UADT carcinoma and analysed. Among these 133 were males and 17 were female. 40% of them had smoking, 25% had smokeless tobacco, 13% had both smoking and smokeless tobacco and 22% hadn’t had any form of tobacco. Carcinoma larynx is the most common site and glottis is the commonest subsite. Most individuals who developed UADT carcinoma have used tobacco in some form. The high proportion of UADT carcinoma in non-tobacco consumer is alarming.
Keywords: UADT malignancy, Tobacco, Non-tobacco consumer, Glottis
Introduction
Upper aerodigestive tract (UADT) malignancies constitute approximately 4% of all malignancies [1]. In India UADT malignancy account for a significant proportion of all malignancies [2]. Tobacco usage remains the major causative factor for the development of UADT carcinoma [3, 4]. Different forms of tobacco are used in the form of raw tobacco, pan masala, gutkha, areca nut, betal nut and cigarettes [5, 6]. There is a paucity of information on carcinoma of UADT in patients who have never used tobacco products. Studies suggest that carcinoma of UADT in non tobacco users is rare and accounts for 3.4% of all carcinomas of UADT [7]. The data from our centre shows UADT carcinoma in non-tobacco consumers much more prevalent than described in literatures. Human Papilloma Virus (HPV) infection is the most important risk factor for developing UADT carcinoma in non-tobacco consumers. Since the smoking rate is declining, the incidence of HPV negative tobacco related oropharyngeal cancer has decreased; however, that of HPV-positive oropharyngeal cancer is increasing [8, 9]. Physical inactivity, diet and genetic factors may play a major role in UADT carcinoma in non-tobacco users [10–12].
The aim of the study is to know the demography and patterns of tobacco consumption and the proportion of non-tobacco consumers in patients with upper aerodigestive tract carcinoma. UADT carcinomas are analysed in terms of types of tobacco consumption i.e. smoking or smokeless tobacco, site of origin, grade of malignancy, frequency and abstinence from tobacco consumption.
Materials and Methods
The present study is carried out on patients visiting outpatient department of ENT in tertiary care hospital having UADT carcinoma during the period of February 2009 to May 2011. Details of pattern of tobacco consumption, proportion of non-tobacco consumers, duration of cessation or abstinence, site and grade of carcinoma were analysed. The ethical clearance from the institutional review board was been obtained for the study.
Study Design
Observational study.
Inclusion Criteria
Patients with carcinoma of UADT i.e. oral cavity, oropharynx, hypopharynx and larynx with a confirmed histopathology report were included in the study.
Statistical Analysis
Fisher’s exact test was used for the statistical analysis. p value less than 0.05 was taken as significant.
Results
This study was conducted over a period of 2 years and 3 months from February 2009 to May 2011 in 150 patients of carcinoma of upper aerodigestive tract presenting to ENT outpatient department of tertiary care hospital. Among these 150 patients, 133(88.6%) were males and 17(11.3%) were females.
In male population maximum patients 83.4% (111/133) consumed tobacco in some or the other form and 16.5% (22/133) did not consume tobacco in any form. In female population 64.8% (11/17) did not consume tobacco in any form while 35.2% (6/17) consumed tobacco (Table 1).
Table 1.
Distribution of patients with respect to gender and tobacco consumption
| Gender | Tobacco consumption | No tobacco consumption | Total | |||
|---|---|---|---|---|---|---|
| Only smoking (S) | Only smokeless tobacco (T) | S + T | Total | |||
| Male | 57 | 34 | 20 | 111 | 22 | 133 |
| Female | 2 | 4 | 0 | 6 | 11 | 17 |
| Total | 59 | 38 | 20 | 117 | 33 | 150 |
In this study we found that 40% (60/150) smoked cigarette, 25% (37/150) consumed smokeless tobacco and 13% (20/150) had both smoking and smokeless tobacco. 22% (33/150) patients did not consume tobacco in any form (Fig. 1).
Fig. 1.
Pattern of tobacco consumption
We observed that patients had UADT carcinoma even after cessation of tobacco consumption (Table 2).
Table 2.
Distribution of patients with respect to duration of cessation (in years) of tobacco consumption
| Duration of cessation of tobacco consumption (in years) | Number of patients | Percentage |
|---|---|---|
| < 1 | 9 | 7.7 |
| 1–5 | 72 | 61.5 |
| 6–10 | 28 | 24 |
| 11–15 | 5 | 4.27 |
| 16–20 | 1 | 0.85 |
| 21–25 | 2 | 1.7 |
| Total | 117 | 100 |
We had maximum cases of carcinoma larynx (105/150), glottis was the most common subsite affected, followed by hypopharynx (26/150), oral cavity (17/150) and oropharynx (2/150).
Among carcinoma of larynx patients, 73.34% (77/105) patients consumed tobacco and 26.66% (28/105) patients did not consume tobacco in any form. In hypopharynx carcinoma, 84.62% (22/26) consumed tobacco and 15.38% didn’t consume tobacco in any form. Carcinoma oral cavity had 94.12% (16/17) tobacco users and 5.8% (1/17) non tobacco users. One patient with carcinoma oropharynx consumed tobacco while one didn’t have any history of tobacco consumption (Table 3).
Table 3.
Distribution of patients with respect to site of carcinoma and tobacco consumption
| Site of tumour | Tobacco consumption | No tobacco consumption | Total | p value | |||
|---|---|---|---|---|---|---|---|
| Only smoking (S) | Only smokeless tobacco (T) | S + T | Total | ||||
| Oral cavity | 1 | 13 | 2 | 16 | 1 | 17 | < 0.001 |
| Oropharynx | 1 | 1 | 0 | 2 | 0 | 2 | |
| Hypopharynx | 7 | 9 | 6 | 22 | 4 | 26 | |
| Larynx | 50 | 15 | 12 | 77 | 28 | 105 | |
| Total | 59 | 38 | 20 | 117 | 33 | 150 | |
Among tobacco users, further it was divided between smoking and smokeless for each site. Smoking is common among laryngeal carcinoma whereas smokeless common in oral cavity. Using Fisher exact test p value is < 0.001 showing association between site of tumour and type of tobacco consumption statistically significant (Table 3).
We found that 80/150 patients (53.33%) had moderately differentiated carcinoma in both tobacco consuming and non-tobacco consuming patients.
Out of 33 non-tobacco consuming patients, 22/33 patients (66.66%) developed moderately differentiated carcinoma.
Thus in both tobacco consuming and non tobacco consuming patients, most common grade was moderately differentiated carcinoma (Table 4).
Table 4.
Distribution of patients with respect to grade of carcinoma and tobacco consumption
| Grade of carcinoma | Tobacco consumption | No tobacco consumption | Total | |||
|---|---|---|---|---|---|---|
| Only smoking (S) | Only smokeless tobacco(T) | S + T | Total | |||
| Well differentiated | 24 | 19 | 4 | 47 | 9 | 56 |
| Moderately differentiated | 28 | 17 | 13 | 58 | 22 | 80 |
| Poorly differentiated | 7 | 2 | 3 | 12 | 2 | 14 |
| Total | 59 | 38 | 20 | 117 | 33 | 150 |
Discussion
This study as carried out on 150 patients of upper aerodigestive tract carcinoma to study the patterns of tobacco consumption and proportion of non tobacco consumers among them.
According to literature most individuals who develop UADT carcinoma use tobacco products extensively. An estimated 90% of these carcinomas have been attributed to this risk factor of tobacco consumption [13]. In our study, we found that 78% (117/150) patients consumed tobacco in some or other form. Hodge et al. [7] found that carcinoma of UADT in non tobacco consumers is rare accounting only 3.4% of all UADT carcinomas. Wiseman et al., reported that non-tobacco consuming patients represent 2.4% of the all treated for head and neck cancer at their institute. Another multicentre North American epidemiological study examining a cohort of 1114 oral and pharyngeal cancer patients, 3.9% non- tobacco consuming patients were reported [14]. In our study, the non tobacco consumer group constituted about 22% (33/150) of total patients. In female population, the figure of carcinoma in non-tobacco consumer was even higher (64.8%). This percentage is significantly higher and alarming as compared to the findings mentioned in literature.
Human Papilloma Virus has been linked to development of head and neck carcinoma as a causative agent in non-tobacco user. HPV was detected in 25% of patients in a prospective study involving 253 newly diagnosed or recurrent head and neck squamous cell carcinoma [15]. In a study by Junor and associates involving patients at the Edinburgh Cancer Center, 41% of head and neck cancers were HPV-positive between 1999 and 2001 and 63% were HPV-positive between 2003 and 2005 [16].
In a study by Platek et al. [10] in 2017 found significant association between physical inactivity and head and neck cancer (HNC). These data support the evidence of physical inactivity as an independent risk factor for head and neck cancer.
The diet plays an important role in the pathogenesis of HNC. Shu-Chun et al., studied the diet and risk of HNC. They found that intake of red meat and processed meat were positively associated with head and neck cancer. They also found the inverse association between higher frequency of fruits intake and vegetables and HNC [11]. Pesticides exposure was related to the development of HNC [17].
Different genes are studied for its association with HNC. Among these, a statistically significant association was reported for glutathione S-transferases (GSTM1), glutathione S-transferases (GSTT1) and human microsomal epoxide hydrolase (EPHX1) genes. An increased risk for HNC was also associated reported for P53 codon 72 Pro/Pro, ALDH2 and three variants of the ADH gene: ADH1B (rs1229984), ADH7 (rs1573496) and ADH1C (rs698) [12].
In our study, there was a male predominance. Amongst the tobacco consuming group, 94.8% (111/117) were males and 5.1% (6/117) were females. In non-tobacco consuming group, 66.66% (22/33) patients were males and 33.33% (11/33) were females. Thus we observe that both tobacco consuming and non tobacco consuming group, maximum patients were males. According to the study by Hodge et al. [7] in non tobacco consumers, upper aerodigestive tract carcinoma mostly occurred in women whereas study by Koch et al. [18] showed a male predominance in their study on non-tobacco consumers.
In the study conducted by Hodge et al. [7] on Upper aerodigestive tract carcinoma in non tobacco consumers, there were 60% well differentiated and 34% moderately differentiated carcinoma and 6% poorly differentiated. In our study, there were 66.66% moderately differentiate, 27.2% well differentiated and 6.06% poorly differentiated carcinoma. Among the tobacco consuming group, there was a similar finding. In our study, we found that the distribution of grade of carcinoma was almost similar in both tobacco consuming and non tobacco consuming groups.
In a study by Spitz et al. [19] the most common site involved amongst both males and females was larynx and glottis was the most common subsite in larynx. Agudelo et al., reported that amongst the patients with carcinoma of larynx, 3.3% of patients were non tobacco consuming [14]. However, in our study, this percentage of non-tobacco consuming patients with carcinoma larynx was higher 26.6% (28/105).
Wynder and Stellmsn contended that 10–15 years of smoking abstinence were required in long term men and women smokers before their risks for laryngeal cancer approximated that of non-smokers [18, 20]. Burch et al. [21] reported that risk for laryngeal cancer decreased only after 30 years of abstinence. In our study, it was found that 7% (8/117) patients had carcinoma even after cessation of tobacco consumption for more than 10 years.
Conclusion
Most individuals who developed upper aerodigestive tract carcinoma (UADT) have used tobacco in some form. The high proportion of UADT carcinoma in non-tobacco consumer is alarming and cannot be ignored. Risk factors like HPV, physical inactivity, diet and genetic factors have been hypothesized to play a role in head and neck cancer development in non tobacco consuming patients. More study is required to identify the pathogenesis of UADT carcinoma in non-tobacco consuming group of patients.
Key Message
The proportion of UADT in non-tobacco user is rising. Risk factors like HPV, physical inactivity, diet and genetic factors have to be considered in these patients.
Footnotes
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