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ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 2  |  Page : 244-251
 

Squamous cell carcinoma of the oral cavity and oropharynx in patients aged 18–45 years: A case–control study to evaluate the risk factors with emphasis on stress, diet, oral hygiene, and family history


Department of Dental and Prosthetic Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Web Publication6-Jan-2017

Correspondence Address:
G C Chouksey
Department of Dental and Prosthetic Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.197725

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 » Abstract 

Background: Increasing incidence of squamous cell carcinoma (SCC) of the oral cavity and oropharynx is reported in young adults. However, there is a paucity regarding etiology and risk factors. Aim: To evaluate the exposure potential carcinogenic factors among a sample aged 45 years and younger, diagnosed with SCC of the oral cavity and oropharynx. Methodology: Eighty-five case samples aged 18–45 years, diagnosed with SCC of the oral cavity and oropharynx were compared with 85 controls who had never had cancer, matched for age and sex. This study was conducted by questionnaire-based interviews. Questionnaire contained items about exposure to the following risk factors: Caries prevalence, oral hygiene status, dental trauma, dental visit, stress, family history of cancer, environmental exposure to potential carcinogens, diet, body mass index (BMI), habits such as smoking, tobacco chewing, betel quid/pan, or supari. Statistical Analysis: Odds ratios (ORs) of oral and pharyngeal cancer and the corresponding 95% confidence intervals were estimated using multiple logistic regression models. P< 0.05 was considered statistically significant. Results: Elevated OR was seen in young adults who had poor oral hygiene, stress, dental trauma, low BMI, family history of cancer, exposure to environmental carcinogens, and habit of placement of quid for 11–20 years. Conclusions: An increased risk of oral and pharyngeal cancer was seen in cases who had poor oral hygiene, stress, dental trauma, low BMI, family history of cancer, exposure to environmental carcinogens, and habit of placement of quid.


Keywords: Caries prevalence, dental trauma, diet, family history, oral hygiene, squamous cell carcinoma, stress, young adult


How to cite this article:
Dholam K P, Chouksey G C. Squamous cell carcinoma of the oral cavity and oropharynx in patients aged 18–45 years: A case–control study to evaluate the risk factors with emphasis on stress, diet, oral hygiene, and family history. Indian J Cancer 2016;53:244-51

How to cite this URL:
Dholam K P, Chouksey G C. Squamous cell carcinoma of the oral cavity and oropharynx in patients aged 18–45 years: A case–control study to evaluate the risk factors with emphasis on stress, diet, oral hygiene, and family history. Indian J Cancer [serial online] 2016 [cited 2019 Dec 10];53:244-51. Available from: http://www.indianjcancer.com/text.asp?2016/53/2/244/197725



 » Introduction Top


Squamous cell carcinoma (SCC) in the oral cavity and oropharynx is uncommon before the age of 35 years.[1],[2] There is a paucity of information regarding its etiology, natural history, and optimal therapeutic management.[3] However, even when young patients have indulged in the risk factors of tobacco and alcohol, it is for considerably shorter periods compared with the older age group.[4]

It is essential to examine the potential risk factors such as environmental carcinogens, stress, previous viral infections, and familial episodes of cancer [2] and likely protective factors such as diet (consumption of fruits and vegetables) to provide a better insight to etiology of SCC.[5] Emerging evidence also shows role of human papillomavirus infection in some subsites.[6] Occupational exposures are a known risk factor for upper aerodigestive tract tumors.[7],[8],[9],[10],[11] Low socioeconomic status and a downward trajectory of social position over the life course are also confounding factors [5],[6] that increase the risk.[12],[13]

Aims

To evaluate the exposure potential carcinogenic factors among a sample aged 45 years and younger, diagnosed with SCC of the oral cavity and oropharynx.

Objectives

  • To assess caries prevalence and oral hygiene status in this group of patients
  • To find association of stress, environmental carcinogens, trauma, diet, family history, habits (duration and frequency), region of placement of quid, body mass index (BMI), and dental visits with occurrence of cancer
  • To find association of area where the tobacco quid was placed in the mouth with occurrence of cancer.



 » Methodology Top


Recruitment of cases and control

Patients aged between 18 and 45 years, newly diagnosed with SCC of oral cavity and oropharynx were included in the study. Subjects with cancers of the oral cavity (lip, buccal mucosa, lower alveolus, retromolar trigone, oral tongue, floor of mouth, upper alveolus, and hard palate) and oropharynx were observed. Patients with cancers of the salivary glands, nasopharynx, and hypopharynx were not included.

Control subjects were patients aged 18–45 years, with no history of trauma, precancerous lesions, cancerous lesions, or any other pathology in head and neck region. They were selected from the general population in the outpatient department. Controls were matched by age (±5 years) and sex with the study case subjects. Control to case ratio was 1:1.

The questionnaire

This study was conducted by questionnaire-based interviews which were conducted by a single investigator for the study subjects and the controls. The questionnaire contained questions pertaining to demographic details such as age, gender, education, occupation, and BMI. Information related to age at diagnosis of tumor, tumor site, tumor stage, and treatment details was obtained. Details of consumption of the amount of fresh fruits and vegetables consumed regularly, stress, dental trauma, environmental exposure to potential carcinogens, dental/oral health, and general health questions were noted. Familial episodes of cancer were also recorded. Caries prevalence and oral hygiene were assessed with decayed, missing, filled teeth (DMFT) index and oral hygiene index simplified (OHIS), respectively. Age at the initiation of tobacco habits and alcohol use before cancer diagnosis was recorded. Details of smoking and tobacco chewing included type, number per day, and duration of the habit. To account for the social habits among Asian ethnic minorities, additional questions on consumption of betel quid/pan or supari were included. This study was approved by the Institutional Review Board and was registered with the Clinical Trials Registry-India (CTRI/2014/07/004762).

Statistical analysis

Demographic variables were presented as mean (standard deviation), median, or frequencies (percentages). Categorical variables were analyzed using Chi-square test or Fisher's exact test (for binary data). Odds ratios (ORs) of oral and pharyngeal cancer and the corresponding 95% confidence intervals (CI) were estimated using multiple logistic regression models. P < 0.05 was considered statistically significant. Analysis was conducted using IBM SPSS version 20.


 » Results Top


Association of caries prevalence, oral hygiene, stress, environmental carcinogens, trauma, diet, family history, habits (duration and frequency), region of placement of quid, BMI, and dental visits with occurrence of cancer in this case and control study was as follows.

Demographic characteristics

Eighty-nine percent of the sample was male with more than 60% of case and control samples in the age group of 31–40 years. Only 18% of the case and 31% of the control sample belonged to high educational qualification. Approximately 50% of the population was in the laborer group and <12% of the subjects were unemployed.

Mixed diet was prevalent in more than 70% of patients and 90% used right hand to eat the food.

Sixty-five percent of the patients had histologically proven moderately differentiated SCC. Thirty-nine percent of the patients had Stage IV cancer at the time of diagnosis. Sixty percent of the patients were in the age group of 31–40 years. Most common cancer seen was involving buccal mucosa (39%) followed by the tongue (31%). Cancer involving tonsil/oropharynx was seen in 6% of the case subjects. Fifteen percent of the patients were treated by surgery alone while 78% received radiation therapy along with surgery.

DMFT score between 1 and 10 was seen in more than 80% of cases and controls, but the result was not statistically significant [Table 1].
Table 1: Caries prevalence, oral hygiene status, dental trauma, dental visit

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Moderate and poor oral hygiene was seen in 45% and 34% of the case samples, respectively. On the contrary, 64% of the control samples had good oral hygiene. Hence, an increased risk is seen in samples who have OHIS scoring 3–4 (OR: 4.385, 95% CI: 2.112–9.101) and 5–6 (OR: 17.4000, 95% CI: 5.858–51.686) [Table 1].

Dental trauma was seen in 33% of case samples as compared with 4% of control samples (P = 0.000); hence, an increased risk of oral cancer was seen in samples who have dental trauma (OR: 13.427, 95% CI: 3.894–46.292) [Table 1].

No significant difference was seen in dental visit among the cases and control samples as majority visited less than once a year [Table 1].

Forty-eight (48%) percent of the case samples felt that stress was associated with their current health problem (P = 0.000), with an increased risk seen in samples who have stress associated with their current health problem (OR: 5.669, 95% CI: 2.693–11.930) [Table 2].
Table 2: Stress

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Twenty-six percent of case samples had family history of cancer compared with 48% of control subjects (P = 0.003). In subjects with a positive family history, association with cancer was statistically significant (OR: 0.375, 95% CI: 0.197–0.715) [Table 3].
Table 3: Environmental carcinogens, family history of cancer

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Eighty-eight percent of case samples and 45% of control subjects had lifestyle that increased the risk of cancer (P = 0.000, OR: 9.276, 95% CI: 4.226–20.363). The findings with other causes namely naturally occurring exposures, medical treatments, workplace, household exposure, and pollution were not statistically significant [Table 3].

Surprisingly, more than 94% of the samples (cases and controls) had zero serving of fresh fruits in a day. Green leafy vegetables were mostly consumed once or twice a week by both case and control samples. More than 60% of the subjects consumed one serving per day of other vegetables including roots and tubers. All results were not statistically significant [Table 4].
Table 4: Diet and body mass index

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Eighty-six percent of case and 65% of control samples had BMI <25. Among control subjects, overweight and obese category was seen in 29% and 6%, respectively. An increase in risk of oral and pharyngeal cancer was associated with underweight as compared to overweight (P = 0.012, OR: 0.244, 95% CI: 0.066–0.034) [Table 4].

Habit of chewing tobacco was seen in 74% of case samples and 31% of control samples. Smoking was noted in 31% and 18% of case and control samples, respectively. Twenty percent and 6% of case and control samples consumed alcohol. Betel nut/pan/supari chewing was seen in 35% of case and 22% of control samples. Indulgence in habits was seen after attaining 16 years of age [Table 5].
Table 5: Habits (duration and frequency)

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The habit of placing quid in the mouth was seen in 61 (72%) case subjects and 26 (31%) control subjects. Fifty-nine percent (36/61) of the case samples placed the quid in the mouth for almost 11–20 years (P = 0.006). An increase in risk of oral and pharyngeal cancer was associated with placement of quid in mouth for 11–20 years (OR: 5.368, 95% CI: 1.816–15.872) [Table 6].
Table 6: Region of quid placement

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More than 57% (35/61) of the case subjects and 38% (10/26) of the control samples had the habit of placing quid in the left buccal fold. Lesion was noticed in the same area where the tobacco quid was placed in the mouth in 59% (36/61) of the case subjects [Table 6].


 » Discussion Top


The primary aim of this case–control study was to evaluate the major risk factors for SCC of the oral cavity and oropharynx in patients aged 18–45 years with emphasis on stress, diet, oral hygiene, and family history. In total, 85 cases and 85 controls were recruited for the study. This is the one of the largest case–control study so far to be undertaken on young subjects diagnosed with cancer of oral cavity and oropharynx in India.

Oral SCC is more common in men than in women;[14],[15],[16],[17] however, there have been conflicting reports. In the present study, 76 (89%) of the cases were found to be men and only 9 (11%) women, a ratio of 8.4:1. These findings are in accordance to the studies of Llewellyn et al.,[18] Iamaroon et al.,[19] and Ribeiro et al.[20] that reported higher incidences in men under 45 years old. However, Kuriakose et al.[21] reported that cancer prevailed more in women in a proportion of 1.2:1 in a group of patients less than 35 years old.

Guha et al.[22] stated that poor general oral condition was associated with an increased risk of oral cavity and oropharyngeal cancers. It has been previously observed that periodontitis is associated with increased risk of head and neck SCC (HNSCC).[23],[24] In the present study, analysis of oral hygiene by OHIS showed that more case subjects had moderate and poor oral hygiene, i.e. 45% and 34%, respectively. On the contrary, 64% of the controls samples had good oral hygiene. Hence, an increased risk was seen in samples who have OHIS scoring 3–4 and 5–6 [Table 1].

The results of this study showed that more than 80% of cases and controls had 1–10 teeth affected by caries, but the result was not statistically significant [Table 1]. Tezal et al. found that dental caries was associated with HNSCC.[25] The DMFT index is an indicator of the overall dental status in the oral cavity, but the decayed tooth or a badly filled tooth can cause chronic trauma and infection, leading to oral cancer.

Dental factors namely trauma due to sharp teeth, less than ideal fillings, badly fitting dentures or unsuitable denture-bearing tissue, and loose anchoring attachments contribute to the etiology of oral SCC.[26],[27],[28] Dental trauma as a risk factor was statistically significant (P = 0.000) with an increased risk seen in samples who have dental trauma [Table 1]. A review relating cancer to trauma by Monkman et al. found no evidence to suggest that single uncomplicated trauma can cause cancer. However, they concluded that trauma in combination with other factors may act as a co-carcinogen. There was adequate evidence suggesting that metastatic spread of malignant tumors can be affected by trauma.[29] Early recognition of the lesions in oral soft tissues caused due to dental irritation as well as multidisciplinary management may help in the prognosis of these cases.[26]

Early detection of precancerous lesion was absent in all the study patients due to lack of timely oral screening.[2] No significant difference was seen in dental visit among both the groups [Table 1].

An increased risk of oral and pharyngeal cancer was seen in samples who have stress associated with their current health problem [Table 2]. In a study by Llewellyn et al.,[30] it was found that the risk of delay in presentation among younger patients with oral cancer was also 7-fold higher for patients reporting stress in the period prior to diagnosis. This may be because of other commitments at work or home preventing the patient from attending to symptoms more carefully or indeed making the time to visit a health care professional. Stress is unfortunately a symptom of modern life but may be responsible for longer delays in diagnosis.

Current evidence suggests that damage to genetic blueprint of cells (DNA) can cause cancer.[31] Some of these changes may be inherited from our parents while others may be caused by environmental factors.

Onset of cancer at an early age is thought to be an indicator of hereditary cancer.[32] Studies have shown higher familial risks in first-degree relatives where the cancer was diagnosed at a young age.[33],[34] Increased risk more than 2-fold in siblings is seen if the onset occurred before age 50.[35] However, in this study, we found that more control samples (48%) had family history of cancer than case samples (26%) [Table 3]. A possible reason to explain this is that control subjects were mostly people who accompanied cases and were their relatives.

Environmental factors can include a wide range of exposures, such as lifestyle factors (nutrition, tobacco use, physical activity, etc.), naturally occurring exposures (ultraviolet light, radon gas, infectious agents, etc.), medical treatments (radiation and medicines including chemotherapy, hormone drugs, drugs that suppress the immune system, etc.), workplace exposures, household exposures, and pollution. In this study, risk of lifestyle factors was found to be statistically significant. However, only 40% of both case and control samples were exposed to naturally occurring environmental carcinogens and workplace exposures. Fifty-eight percent of both the groups were exposed to pollution [Table 3]. None of them had any previous medical treatments that could be termed under environmental carcinogens. Household exposures were seen in 27% and 32% of the case and control samples, respectively. However, all the other factors (naturally occurring exposures, medical treatments, workplace, household exposure, and pollution) were not found to be significant.

The protective role of vegetables and fruits on oral cavity and pharyngeal (OCP) cancer has been attributed to several micronutrients, including carotenoids and Vitamins C and E, found to be inversely related to OCP cancer.[36],[37],[38],[39],[40] These components display both complementary and overlapping mechanisms of action, including antioxidant effects and binding and dilution of carcinogens in the digestive tract.[41],[42] In this study, diet as a risk factor for OCP cancer was not statistically significant [Table 4]. The results are similar to another study on young adults where no significant difference was seen between males and females in the amount of fresh fruits and vegetables consumed in childhood and the 10 years before diagnosis.[2] However, case–control studies have consistently shown that oral cancer patients of all ages tend to have histories of diets low in fruit and vegetables.[43],[44],[45],[46],[47],[48],[49] Not many studies have quantified diet as a risk factor in young cancer cases.

Eighty-six percent of case and 65% of control samples had BMI <25 [Table 4]. In the overweight and obese category, more number of control subjects here as compared to case subjects. The findings of this study confirm that patients with cancers of the oral cavity and oropharynx tend to have a lower BMI, although this could be partly a consequence of the habits and the disease leading to poor nutritional status, rather than a cause, of the oral lesions. This is in accordance to the study by Rodriguez et al.[50] and Franceschi [51] and Radoï et al.[52]

Among the various habits [Table 5] namely chewing tobacco, smoking, alcohol consumption, betel nut/pan/supari chewing, and placement of quid in the mouth, significant risk was seen in patients who had the habit of placing quid in the mouth for 11–20 years (P = 0.006). This finding is not consistent with previous studies of young patients, whereby none of the usual risk factors of smoking, chewing tobacco, and excessive drinking contributed to the disease.[2],[53],[54],[55]

There is a strong correlation between hand used to eat the food, area where the tobacco quid was placed in the mouth, and where the lesion was first noticed in the mouth [Table 6].

This is not a retrospective study; hence, there was no recall bias. The subjects did not have problems understanding the questions as the interview was conducted by a single clinician. Cases who were diagnosed and were undergoing cancer treatment at the institution were enrolled. The limitation of this study is that control samples were selected from general population at the outpatient department who were mostly relatives of the patient. A more detailed screening with respect to nutrition and viral infections with emphasis on would give us further insight into the assessment of additional factors contributing to oral cancers.


 » Conclusion Top


Poor oral hygiene, chronic dental trauma and infection associated with carious and periodontally affected teeth, increases the risk of oral and pharyngeal carcinoma. Stress of commitment from work or family results in negligence and delays the patient from attending the ongoing symptoms. Among the environmental factors, lifestyle factors mainly nutrition, tobacco use, and physical activity too increase the risk of oral cancer. Role of genetic and hereditary factors too was found to play a role in the occurrence of SCC of oral cavity and oropharynx. Among the various habits, placement of quid in mouth contributed to occurrence of oral cancer. A strong correlation was seen among patients who used right hand to eat the food with occurrence of lesion on the left side of oral cavity. The presence of habits affects physical health and causes low BMI in cancer patients. Dietary factors with particular emphasis on fruits and vegetables and frequency of dental visit were not found to be significant.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]

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