|Year : 2016 | Volume
| Issue : 4 | Page : 538-541
Squamous cell carcinoma of the upper aerodigestive tract in exclusive smokers, chewers, and those with no habits
S Nair1, S Datta2, S Thiagarajan3, S Chakrabarti1, D Nair1, P Chaturvedi1
1 Department of Head and Neck Surgery, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Head and Neck Surgery, Narayana Hrudayalaya, Kolkata, West Bengal, India
3 Department of Head and Neck Surgery, Malabar Cancer Centre, Thalassery, Kerala, India
|Date of Web Publication||21-Apr-2017|
Department of Head and Neck Surgery, Malabar Cancer Centre, Thalassery, Kerala
Source of Support: None, Conflict of Interest: None
BACKGROUND: Tobacco consumption is the major risk factor for developing head and neck squamous cell cancer (SCC). The site of development of HNSCC may depend on the way the tobacco is consumed. While laryngeal cancers are more common among smokers, oral cancers are more common among tobacco chewers. Since the use of smokeless tobacco is increasing, it is important to know whether this difference is restricted only to site wise distribution or it has other clinical and pathological implications. PATIENTS AND METHODS: We analyzed a prospectively collected dataset of HNSCC patients other than nasopharyngeal cancers attending our outpatient department at a single unit of the head and neck services at Tata Memorial Hospital, Mumbai, India, between January 2010 and September 2011. There were 747 eligible patients and were divided into three groups: Those with chewing as the only habit (chewers), those with smoking as the only habit (smokers), and those with no habits. Patients with regular use of alcohol were excluded from the study. The clinical and pathological parameters were analyzed. RESULTS: Of the 747 patients, the tobacco chewers formed 69.3% followed by smokers (19.5%) and patients with no habits (11.1%). Majority of smokers were men (98%). Site distribution revealed patients with chewing as the only habit had oral cancers (most commonly gingivobuccal complex cancers) as the most common site and those with smoking as the only habit had larynx as the most common site. In patients with no habits, oral tongue was found to be the most common site. No statistically significant pathological differences were observed in between these groups in patients who underwent surgery (n = 366) at the initial modality of treatment. CONCLUSIONS: There is a direct relationship between the form of tobacco use and site of appearance of HNSCC. However, there are no differences in clinical or pathological parameters between HNSCC caused by tobacco chewing or tobacco smoking.
Keywords: Ghutka, masheri, panmasala, smokeless tobacco
|How to cite this article:|
Nair S, Datta S, Thiagarajan S, Chakrabarti S, Nair D, Chaturvedi P. Squamous cell carcinoma of the upper aerodigestive tract in exclusive smokers, chewers, and those with no habits. Indian J Cancer 2016;53:538-41
|How to cite this URL:|
Nair S, Datta S, Thiagarajan S, Chakrabarti S, Nair D, Chaturvedi P. Squamous cell carcinoma of the upper aerodigestive tract in exclusive smokers, chewers, and those with no habits. Indian J Cancer [serial online] 2016 [cited 2019 Aug 21];53:538-41. Available from: http://www.indianjcancer.com/text.asp?2016/53/4/538/204759
| » Introduction|| |
Head and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy in the world, with about 600,000 new cases diagnosed annually. Though there are many risk factors associated its development, tobacco usage as smoking or chewing in various forms remains the major causative factor. Reports by several health authorities, including the US general surgeon, suggests an increase in the use of smokeless tobacco causing additional risk of developing oral cancers. An accurate estimation of risk, however, is not possible due to the lack of large epidemiological studies. A recent case–control study in the United States, suggests a statistically significant association between the use of smokeless tobacco and risk of HNSCC in never smokers.
Compared to the rest of the world, the incidence of HNSCC is far more common in India and accounts for up to 30% of the country's cancer burden. Similarly, the site wise distribution of HNSCC is also quite different from the rest of the world. Laryngeal cancers are more common in the Western world whereas oral cancers are more common in India. These differences between India and Western world may be due to the difference in tobacco consumption pattern in these populations. Contrary to the United States, where 20.6% of the adults are smokers and <5% of men and women use smokeless tobacco, in India, 21% of adults use only smokeless tobacco, 9% are exclusive smokers, and 5% use both forms of tobacco.
Though the carcinogenic pathways of smokeless and smoking form of tobacco are more or less similar, smoking is associated with cancer of almost all subsites of the head and neck region whereas smokeless tobacco use is usually associated with cancer of the oral cavity. Since the use of smokeless tobacco is increasing globally, it is important to know whether this difference is only restricted to site wise distribution or it also plays a role in other clinical and pathological parameters.
| » Patients and Methods|| |
We analyzed a prospectively collected dataset of patients attending our outpatient department at a single unit of the head and neck services at Tata Memorial Hospital, Mumbai, India, between January 2010 and September 2011. Patients with biopsy proven SCC of the upper aerodigestive tract (UADT) with habits of either smoking or chewing (smokeless tobacco) alone or none were included in the study. Patients with non-UADT tumors, nasopharyngeal carcinoma, histology other than SCC, and those with daily use of alcohol were excluded from the study. Out of the total 1070 patients recorded in the database, 747 patients were found eligible. They were divided into three groups: Those with chewing as the only habit (chewers), those with smoking as the only habit (smokers) and those with no habits (no habits) [Table 1]. We analyzed the site wise incidence of HNSCC among smokers, chewers, and patients with no tobacco habits. Since a large number of patients had oral cancer, a separate analysis was done for the two most commonly affected subsites of the oral cavity, i.e., buccal mucosa-gingivobuccal sulcus (BM-GBS) and tongue.
The histopathological reports were collected and analyzed for those patients who underwent surgery as the initial modality of treatment (n = 366) at Tata Memorial Hospital (TMH).
The aim of this analysis was to find out whether there were differences of various histopathological parameters such as pathological tumor type, grade, presence of lymphovascular emboli (lymphovascular invasion [LVI]), perineural invasion (PNI), extracapsular spread (ECS) of nodal metastasis, margin status, bone or cartilage erosion, soft tissue and skin infiltration, and the clinical T and N stage among these three separate group of patients, i.e., smokers, chewers, and those with no habits. Statistical analysis was done using SPSS 19.0 (IBM, Armonk, NY, USA). Chi-square test was performed to look for statistical association between various factors, and a P ≤ 0.05 was considered to be statistically significant.
| » Results|| |
Out of the 747 patients included in the study, 586 (78%) were men and 161 (22%) were women, aged between 17 and 78 years (mean: 49 years, median: 47 years). Most of the chewers (age ≤47 = 269 [52.7%] age >47 = 249 [47.3%]) and those with no habits (age ≤47 = 45 [55.3%] age >47 = 38 [44.7%]) were almost equally distributed on either side of the median age, majority of smokers were older than 47 years (age ≤47 = 45 [31.3%] age >47 = 101 [68.9%]). However, these associations had no statistical significance. Majority of the patients (518, 69.3%) were chewers alone (mean duration of chewing: 19 years) and they used tobacco in different forms (tobacco with lime [n = 356, 47.6%], masheri [n = 49, 6.5%], ghutka [n = 50, 6.7%], panmasala [n = 28, 3.9%], and betel leaves/nuts [n = 30, 4%]). Some of the patients used tobacco in more than one form (n = 234, 31.3%). There was no information regarding the type of tobacco used in 29 (10.2%) patients. One hundred and forty-six (19.5%) patients were smokers alone (mean duration of smoking: 26 years) and 83 (11.1%) had no habits. No further information regarding the smoking habits could be gathered from the available information in the database. While overwhelming majority of tobacco smokers were men (n = 143, 98%) with only 2% (n = 3) as women, the chewers had more equitable gender distribution (men n = 388 [74.9%] and women n = 130 [25.1%]). There was no significant gender difference noted among patients with no habits (male = 45, 55.3%; female = 38, 44.7%). Most of the patients with habits did not consume alcohol (teetotalers = 690, 92.3%) whereas 57 (7.6%) of them occasionally (social) consumed alcohol.
Most of these patients presented with nonhealing long standing painful ulcers (n = 341, 45.6%) and growth/swelling (n = 164, 21.9%) with a median duration of 4.5 months. Most commonly affected sites were oral cavity, oropharynx, hypopharynx, and larynx in diminishing order [Table 1]. Forty-two patients had associated premalignant lesion with their malignancy (oral submucosal fibrosis - 27 [8.2%], leukoplakia - 14 [4.2%] and 1 [0.3%] had both). All the patients were staged using the American Joint Committee on Cancer staging system. Clinically, for nine (2.5%) patients, the primary disease could not be estimated (Tx) as they were operated outside and came to our institution for adjuvant treatment. As mentioned previously, 366 patients were eligible for clinicopathological analysis, as in all those cases surgery and subsequent histopathology were performed at our institution. Clinically, 22 (6%) patients had stage I disease, 77 (22%) had stage II, 63 (18%) had stage III, and 210 (54%) had stage IV disease [Table 2]. All patients had surgery as the first line of management. Taking a cuff of 0.5 cm of normal tissue around the surgical specimen as a tumor-free margin, the margins were free in 327 patients (89.3%) and close/positive (<0.5 cm) in 27 (7.6%). Eighty-one cases (22.1%) had perineural invasion, and 6 (1.6%) had lymphovascular lesion embolization. Finally, based on pathological data, these patients were grouped as stage I (n = 50, 14%), stage II (n = 56, 16%), stage III (n = 44, 13%), and stage IV (n = 201, 57%).
Statistical significance was looked for association between habits and various sites in the UADT [Table 3] as well as for any significance between the type of habits and various variables such as age, sex, clinical and pathological T stage and N stage, histopathological features such as ECS in node positive neck. There was a strong statistical association between the habits and the most common UADT site associated with malignancy [Table 3]. Patients with chewing as the only habit had gingivobuccal complex (GBC) as the most common site of malignancy and those with only smoking as habit had larynx as the most common site. Interestingly, in patients with no habits, oral tongue was found to be the most common site. All were found to be statistically significant.
Though no statistical significance observed between age and the habits, exclusive smokers were predominantly older than 47 years (age ≤47 years, n = 14 [31%]; age >47 years, n = 31 [69%]). While smokers were mostly men, a significant percent of women chewed tobacco (chewers: Men 75%, women 25%) indicating the local cultural influences of the society in developing habits. Among patients with no habits, the percentage of men and women were nearly the same (55–45%). While smokers (79%) typically presented late with locally advanced disease (pathological T stage, P< 0.001), no such association was noticed among other groups. Smokers with metastatic neck nodes had higher incidence of ECS. Patients with no habits were predominantly node negative (N0, P< 0.01). Religion and level of education did not have any influence on the status of habits.
| » Discussion|| |
Tobacco, alcohol, areca nut, and human papillomavirus are the common etiologic factors for HNSCC. Their carcinogenic mechanisms are unique and have a distinct presentation and behavior. Based on studies conducted world over, tobacco use in various forms (smoking and tobacco chewing) constitutes the most important risk factor for the development of HNSCC. While tobacco is used in various forms in different parts of the word, the use of chewable form is gradually increasing. This increasing trend of using smokeless tobacco could be due to their availability as branded products, convenience of use, perceived safety, lower price when compared to cigarettes and lack of regulations. Various forms such as dipping tobacco (moist snuff) are being branded and shipped as premium products. The aim of our study was to understand the influence of both forms of tobacco products (smoking versus smokeless) in the development and progress of head and neck SCC (HNSCC). We, therefore, studied patients with a single habit of either smoking or chewing or those who did not have any of these habits. Most of the patients in our study were teetotalers (327, 90%), but there were 29 patients (10%) who occasionally used alcohol. As described in an earlier study, the synergistic influence of occasional alcohol drinking on tobacco-related habits is minimal; hence, the patients with occasional alcohol use were not excluded in the analysis. It was considered that these small levels of alcohol consumption would not have a confounding effect on the results. We grouped all eligible patients (n = 747) into three consisting of those who were exclusive chewers, exclusive smokers, or those with no habits at all.
We found that chewing was the predominant habit among patients with cancer of the oral cavity (81.6%), paranasal sinus (PNS) (66.7%), and hypopharynx (46.1%). On the other hand, smoking was the predominant habit among the cancer of the larynx (62.1%) and oropharynx (55.4%). While a large number of oral cancer patients were chewers and laryngeal cancer patients were smokers, this trend was not noticed for oropharynx and hypopharynx, where exclusive chewers and smokers were equally affected. Since majority of patients were having oral cancers, we further analyzed the influence of habits on two main subsites of the oral cavity, i.e., GBC and tongue. While tobacco chewers had higher incidence of GBC cancers compared to tongue, tongue cancers were more common among patients with no tobacco habits.
According to the International Agency for Research on Cancer (IARC) monographs, chewing of tobacco are only associated with cancer of the oral cavity whereas smoking is associated with cancer of all subsites of the head and neck region. However, several case–control studies contradicts with this finding of the IARC monograph. A multi-centric case–control study from India found that even though bidi smoking was the strongest risk factor for hypopharyngeal cancer, there was a significant association between tobacco chewing and cancer of the hypopharynx. The association was even stronger among the tobacco chewers who did not have the habit of smoking. In our study, both chewing and smoking were the significant contributors of the cancer of the hypopharynx (46% and 36%). The marginally higher percentage of chewer may be due to the fact that chewing is far more common form of tobacco addiction compared to smoking in Indian population. For the cancer of the oropharynx also, studies show a marginally increased risk associated with chewing of tobacco (odds ratio [OR], 1.2-2.4) whereas the risk was much higher for smoking (OR 5.5–7.2)., In the present study, smoking was the predominant habit among the cancer of the oropharynx compared to chewing (55% vs. 35%) despite predominant chewers in the study population. For the cancer of the larynx, all the studies found strong association with smoking and not with chewing., Our findings are also not significantly different. Sixty-two percent of laryngeal cancer patients in our study were smokers as compared to 21% chewers and another 17% with no tobacco habits.
Majority of our patients were oral cancer patients. In our study, 82% of them were chewers whereas only 9% of them were smokers. A number of studies have already established that for oral cancer, relative risk associated with tobacco chewing is much higher than relative risk associated with smoking. When we separately analyzed the two most common subsites of the oral cavity, i.e., BM-GBS complex and tongue, we found there were 87% of chewers among the BM-GBS complex cancer patients whereas the percentage was little lower among the patients with tongue cancer (72%). The higher number of BM-GBS complex cases compared to tongue cancer cases (346 vs. 167) and higher percentage of chewers in the BM-GBS complex group compared to tongue cancer group probably reflects the stronger association of BM-GBS complex cancer with chewing habit compared to tongue cancer which has already been established by previous studies., Another interesting finding of our study was a significant number (20%) of tongue cancer cases had no habit. We believe this may be due to the fact that sharp tooth plays a significant role in causation of the cancer of the tongue. Another finding of our study was most patients with PNS cancer had history of chewing habit. According to the IARC monographs, there is an association between cancer of the PNS and smoking, whereas there is no association with chewing. Our finding contradicts with this finding. However, considering the very small number of PNS cancer cases in our study, we believe it wound not be justified to make any conclusion from our finding.
From our study, we could find a specific pattern of association of cancer of the different subsites of the head and neck region with different tobacco consumption habit like oral cancer is almost exclusively associated with tobacco chewing and laryngeal cancer with smoking. Hypopharyngeal and oropharyngeal cancers are associated with both smoking and chewing; however, the association is stronger with smoking for oropharyngeal cancer and with chewing for hypopharyngeal cancer. We believe this pattern of association can be due to the differences in exposure to tobacco between smoking and chewing. Chewers keep the tobacco mainly in the oral cavity, so there is a very strong association of tobacco chewing with oral cancer. A significant amount of this tobacco is swallowed. During swallow, tobacco passes through the oropharynx and hypopharynx. However, in oropharynx, it remains for short duration whereas a significant portion of tobacco can accumulate in the pyriform sinus and remains there for longer time. In case of smoking, though the smoke passes through the oral cavity, the contact time is small. The small association of oral cancer with smoking, which was previously stated by the IARC monograph and several Indian studies , was not apparent in our study. The reason may be the weak association of smoking had been masked by very strong association of chewing. During its passage to the lung, the tobacco smoke comes in contact to the oropharynx and thereafter changes its direction. The contact time becomes larger in the oropharynx as during this change of direction, there is turbulence of tobacco smoke in the oropharynx. This might be responsible for the strong association of smoking with oropharyngeal cancer noticed in our study. In its way to the larynx, tobacco smoke comes in contact with the hypopharynx, which is responsible for the small association of hypopharyngeal cancer with smoking noticed in our study. Finally, tobacco smoke enters into the larynx. As chewable form of tobacco does not come in contact with larynx except a small part of the supraglottic region, larynx becomes exclusively exposed to tobacco smoke. This is responsible for the strong association of laryngeal cancer with smoking. Analysis of the patients treated surgically did not reveal any significant differences in histopathological features for tumors developed either in patients who were smokers or chewers.
| » Conclusions|| |
From our study, we found that there is a direct relationship between site wise distribution of SCC of the head and neck region and pattern of tobacco exposure. Oral cancer is the most common cancer among the chewers whereas laryngeal cancer is more common among the smokers. Oropharyngeal and hypopharyngeal cancers are associated with both smoking and chewing of tobacco, but for hypopharynx association is stronger with chewing whereas for oropharynx association is stronger with smoking. Tobacco-related HNSCC have higher chances of nodal metastasis when compared to nontobacco-related HNSCC. However, there are no differences in clinical or pathological parameters between HNSCC caused by tobacco chewing or tobacco smoking.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Parkin DM, International Agency for Research on Cancer, editors. Cancer Incidence in Five Continents. Vol. 8. Lyon: IARC Press; 2002. p. 781.
Zhou J, Michaud DS, Langevin SM, McClean MD, Eliot M, Kelsey KT. Smokeless tobacco and risk of head and neck cancer: Evidence from a case-control study in New England. Int J Cancer 2013;132:1911-7.
Kulkarni MR. Head and neck cancer burden in India. Int J Head Neck Surg 2013;4:29-35.
Sankaranarayanan R. Oral cancer in India: An epidemiologic and clinical review. Oral Surg Oral Med Oral Pathol 1990;69:325-30.
IARC. Monogr Eval Carcinog Risks Hum 2007;89:1-592.
Balaram P, Sridhar H, Rajkumar T, Vaccarella S, Herrero R, Nandakumar A, et al.
Oral cancer in Southern India: The influence of smoking, drinking, paan-chewing and oral hygiene. Int J Cancer 2002;98:440-5.
9. Sapkota A, Gajalakshmi V, Jetly DH, Roychowdhury S, Dikshit RP, Brennan P, et al.
Smokeless tobacco and increased risk of hypopharyngeal and laryngeal cancers: A multicentric case-control study from India. Int J Cancer 2007;121:1793-8.
Winn DM. Smokeless tobacco and cancer: The epidemiologic evidence. CA Cancer J Clin 1988;38:236-43.
Znaor A, Brennan P, Gajalakshmi V, Mathew A, Shanta V, Varghese C, et al.
Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men. Int J Cancer 2003;105:681-6.
Jayalekshmi PA, Gangadharan P, Akiba S, Koriyama C, Nair RR. Oral cavity cancer risk in relation to tobacco chewing and bidi smoking among men in Karunagappally, Kerala, India: Karunagappally cohort study. Cancer Sci 2011;102:460-7.
Sankaranarayanan R, Duffy SW, Day NE, Nair MK, Padmakumary G. A case-control investigation of cancer of the oral tongue and the floor of the mouth in Southern India. Int J Cancer 1989;44:617-21.
[Table 1], [Table 2], [Table 3]