Analytical Study of Etiopathological Factors Responsible for Oral Squamous Cell Cancer in Bihar Population.

BACKGROUND: Squamous cell carcinoma (SCC) of maxillofacial region is the most usual form of neoplasia causing malignancies in India and Asian continent. An increased prevalence of mortality rate by cancer of maxillofacial region was observed in various parts of the world.
OBJECTIVES: Our aim was to correlate age and gender with etiopathological factors contributing to oral squamous cell carcinoma (OSCC) in the urban population of Patna in 2 years.
MATERIALS AND METHODS: Data were extracted from hospital records. A total of 236 cases of histologically confirmed mild to advance stage of OSCC in either gender of 15-80 years of age range were evaluated.
RESULTS: Out of 236 histopathologically confirmed patients with OSCC, 172 were male and 64 were female. Insignificant difference was found in all age-groups and in all locations. Most common site was found to be buccal mucosa in both genders. Bony invasion was found to be least common. In our study, it was found that habits of chewing areca nuts, nicotine smoke addiction, consumption of alcohol, combination of chewing nuts and nicotine smoke addiction, and combination of alcohol and nicotine smoke addiction are significantly related to the development of OSCC. No significant association was found between histopathological conclusion and gender in all the four groups, and the prevalence was directly proportional to advancement of age.
CONCLUSION: We concluded that the OSCC do not have any significant relation with the age and gender. The habit of nicotine and areca nut chewing, nicotine smoke addiction, and combination of nicotine smoke addiction and alcohol and chewing nut and nicotine smoke addiction has significant relationship in the development of OSCC. Copyright:

INTRODUCTION

Neoplasia is the third cause of unnatural end of life in Indian population, after cardiovascular diseases and natural or human disasters. Cancer of maxillofacial region accounts for 40% of all malignancies. The ability to develop neoplasm is a characteristic of all cells that are capable of multiplication and growth. Cancer is an abnormal and unrestricted growth of body cells and is distinguished from other forms of illness.[1] In Indian population, the prevalence of oral and pharyngeal cancer is higher than that of other cancers. In most of the countries, mortality rate for oropharyngeal cancer is higher than that of all other cancers. Oropharyngeal cancer has severe functional and psychological consequences.[12]

Various types of primary and secondary malignancies occur in the oral cavity, including other types of epidermoid carcinoma, salivary gland carcinoma, and lymphoma, even if the most common cancer of maxillofacial region is squamous cell carcinoma (SCC).

Cancer of maxillofacial region affects males (M) more frequently than females (FM); in recent time, M:FM ratio is equal. Change in lifestyle and increased nicotine consumption are the basic reasons for increased number of cases in the young and the elderly FMs. In general, cancer affects middle-aged and older persons.[2]

Risk factors for cancer of maxillofacial region vary according to intraoral sites. For example, risk factors for cancer of labial region are different from intraoral sites. There are differences in the cancer of maxillofacial region; the prevalence rate varies by age, location, habit history, and epidemiological factors.[34567] Thus, descriptive data of cancer in maxillofacial region for each geographic area are important to understand the extent and severity of the problem.[8910]

Nicotine consumption habit is the most important cause of cancer, and itself accounts for highest rate of annual mortality. Betel quid chewing is the most common habit in India and Southeast Asia. Betel quid usually contains green leaf of vine of Piper betle, seed of areca palm or nut, slaked lime, and nicotine with added spices such as cardamom and cloves.

Development of oral malignancy has seen a major role of alcohol intake. It is seen that alcohol increases the microporosity of oral mucus membrane, acting synergistically with nicotine, it increases the risk of carcinogenesis. Mycotoxins, N‑nitroso compounds, urethane-like substitute, inorganic compounds such as arsenic, and others are the known carcinogens. The factors such as diet and nutrition, certain oral cavity washes, other environmental factors such as viral infection, fungal infection immunosuppression, occupational hazards, dental factors, syphilis, radiation, and eugenic factors are the well-known carcinogenic factors.

Diet and nutrition has shown association with cancer of maxillofacial region in several studies. Certain foods, namely different modified meat, cakes and sweets, butter, eggs, soups, red meat, yogurt, cheese, pulses, rice, millet, and bread, are few of the food groups, which are reported to have higher risk of cancer of maxillofacial region. This relationship between diet and nutrition to the peril of differentiation of normal tissue to cancer has been recognized by several epidemiological and laboratory surveys.[11]

Environmental factors have long been interdependent with cancer development. Viral infections have been strongly interdependent with the malignant tumors of the squamous epithelium, including the oral squamous epithelium. Herpes simplex virus (HSV), Epstein–Barr virus (EBV), human papilloma virus (HPV), and many more are some common viruses interdependent with the development of cancer of maxillofacial region. Along with viral infections, fungal infections also play a role in the cancer of maxillofacial regions, specially the fungal infections such as by Candida species; Candida albicans has a proven role in the differentiation of normal tissue to oral premalignant lesions and conditions.

It is a well-established fact that immunologically suppressed individuals are commonly prone to the development of cancer of maxillofacial regions. Human immunodeficiency virus (HIV)‑infected patients are prone to progressing Kaposi’s sarcoma and lymphomas. Organ transplantation and grafting on immunosuppression have shown to develop cancer of labial region to which the factors that increase the risk are increased predisposition to sunbeam exposure and other risk factors such as nicotine smoke addiction.

Certain occupations are also known to be interdependent with cancer, especially the occupations involving the predisposition to disproportionate sunbeam exposure/ultraviolet (ultraviolet radiation) light are known to cause lip cancers. Ultraviolet radiation or rays also causes actinic cheilitis, which may transform to oral squamous cell carcinomas (OSCCs). Cancers of posterior mouth, pharynx, and upper respiratory tract can be caused by strong acids such as sulfur dioxide, insecticide exposures, and mists from strong inorganic acids and petroleum or fossil fuels.[12]

Inconsistent oral hygiene, incorrect dental status (sharp or broken teeth due to dental decay or trauma), and chronic ulceration from an inappropriate denture are known to be interdependent with cancer of maxillofacial regions, more so the use of mouthwash has also been associated to cause cancer of maxillofacial region as they usually contains ethanol as a solvent for other ingredients or as a preservative agent.

Tertiary syphilis along with other risk factors such as nicotine and alcohol consumption is also known to influence the development of cancer of maxillofacial region. However, nowadays, it is rare entity, as the infection is evaluated and treated before the commencement of advanced stage.[13]

Development of salivary gland tumors shows substantial evidence for the relationship between its development and predisposition to ionizing radiation. The risk for the development of salivary gland tumor due to ionizing radiations shows an increase in rate by 6.4‑fold.[14]

It is observed that few individuals are eugenically prone to the development of cancers, though the eugenic or familial disposition to cancer of maxillofacial regions is restricted by the coexisting risk factors such as nicotine smoke addiction and alcohol consumptions. It is also believed that these subjects are unable to metabolize carcinogens or procarcinogens. The ability to repair the DNA damage may be impaired in these individuals.

We conducted this study to ascertain the role of gender, age along with the known carcinogenic habits, and substance abuse in the development of OSCC in the population of Patna. Our study analyzed histopathological and etiological factors responsible for OSCC and also emphasized on the risk factors and outcome in Patna population.

MATERIALS AND METHODS

A total of 1200 cases of oral mucosal lesions were evaluated from hospital data record files. Only 236 patients, a histopathological conclusion of primary malignant neoplasm of oral cavity, were selected for the study.

Data collected from patient records included general information regarding gender, occupation, economic status, and personal and habit history. General, intraoral, and extraoral examination were evaluated. Anatomic location (International Classification of Disease for Oncology), Tumor size, Nodes involvement, Metastasis (TNM) staging, carcinogenesis evidence, nicotine and alcoholic habits, association with other tumors of the upper respiratory and digestive tract, and systemic disorders were also evaluated.

Nonhealing ulcer with or without induration/nonhealing socket

White patch with firm consistency

Red lesion or lesion with erythematous appearance

Abnormal lump in the oral cavity with increase in size

Exophytic/ulceroproliferative growth

Mass or lump in the maxillofacial and neighboring regions such as lymph node enlargement

Tooth pain and referral pain

Bleeding from the oral cavity

All the data were collected and transferred to Microsoft Excel. Both descriptive and analytical statistics were used for the calculation of the data. Percentage and proportions were calculated. Continuous data were calculated and tabulated as mean and standard deviation (SD). Groups were compared by Student’s t test and chi-square test (χ2). A two-tailed P < 0.05 was considered statistically significant. The statistical software used for analyzing data was Statistical Package for the Social Science (SPSS), version 20.0. The results were considered significant at a two-tailed level of 0.05.

RESULTS

A total of 236 patients histopathologically confirmed with OSCC were added to this observational study.

The tabulated data [Table 1] show distribution of M and FM according to age and location. Nonparametric χ2 test has been used to test the significance of difference observed in the distribution of M and FM. On applying the test, insignificant difference (P > 0.05) was found in all age-groups and in all locations. Most common site was found to be buccal mucosa in both genders. Bony invasion was found to be the least common.

Table 1

Demographic variables

Variables	Groups	M (n = 172)	FM (n = 64)	Total	P value
Age-group	A-15–30	28	10	38	0.83 NS
	B-30–45	46	18	64	0.93 NS
	C-46–60	54	24	88	0.46 NS
	D-60<	39	17	56	0.61 NS
Location	Lips	30	9	39	0.48 NS
	Alveolus	28	14	42	0.37 NS
	Buccal mucosa	60	19	79	0.37 NS
	Floor of oral cavity	14	8	22	0.34 NS
	Lingulae	18	7	25	0.97 NS
	Retromolar area	12	5	17	0.87 NS
	Hard palate	4	0	4	0.21 NS
	Intra-bony (mandibular)	6	2	8	0.86 NS

> 0.1 = NS-non significant

Table 2 shows the distribution of M and FM according to habits. Nonparametric χ2 test has been used to test the significance of difference observed in the distribution of M and FM in habits. On applying the test, significant difference (P < 0.05) was found in chewing areca nuts (P = 0.007), nicotine smoke addiction (P = 0.0036), consumption of alcohol (P < 0.0001), combination of chewing nuts and nicotine smoke addiction (P < 0.0001), and in combination of alcohol and nicotine smoke addiction (P < 0.0001).

Table 2

Habits with frequency and duration

Habits	Type	M (%)	FM (%)	Total	P value
Chewing	Tobacco	66	27	93	0.71 NS
	Areca nut	30	22	52	0.007 HS
	Betel quid	24	11	35	0.36 NS
Nicotine smoke addiction	Bidi	38	4	42	0.0036 HS
	Cigarette	14	0	14	0.017 S
Alcohol		106	12	118	<0.0001 HS
Frequency (per day)	1–5	102	38	140	0.81 NS
	6–10	54	24	78	0.46 NS
	10<	16	5	21	0.67 NS
Combination	Chewing + nicotine smoke addiction	52	4	56	<0.0001 HS
	Alcohol + chewing	34	12	46	0.78
	Alcohol + nicotine smoke addiction	60	4	64	<0.0001 HS
Duration (years)	1–10	72	28	100	0.93 NS
	11–20	41	22	63	0.13 NS
	20<	12	4	16	0.80 NS

>0.05 = NS- non- significant, <0.05 = S- significant, <0.01 = HS-highly significant

Table 3 shows distribution of M and FM according to clinical findings. After applying nonparametric χ2 test, significant difference (P < 0.05) was found only in neck lump (P = 0.004). All other clinical findings were found to be statistically nonsignificant.

Table 3

Clinical findings

Clinical findings	M (%)	FM (%)	P value
Oral ulceration	122	41	0.18 NS
Difficulty in swallowing	62	21	0.54 NS
Difficulty in oral cavity opening	105	32	0.07 NS
Neck lump	58	10	0.004 HS
Pain	68	23	0.50 NS
Change in voice	24	9	0.95 NS

>0.05 = NS- non- significant, <0.05 = S- significant, <0.01 = HS-highly significant

No significant association was found between histopathological conclusion and gender in all the four groups [Table 4]. Histopathologically confirmed OSCC was found to be in very few patients, prevalence was directly proportional to the advancement of age.

Table 4

Age-group and gender sensitive histopathological conclusion

Type	Group A		Group B		Group C		Group D		Total	P value
	M	FM	M	FM	M	FM	M	FM
Poorly differentiated	18	7	20	11	30	14	20	8	128	0.92
Moderately differentiated	6	2	13	3	16	5	8	5	58	0.67
Well differentiated	3	1	9	2	5	3	6	2	31	0.82
OSCC	1	0	4	2	3	2	5	2	19	0.88
Total	28	10	46	18	54	24	39	17	236

DISCUSSION

Of the malignant oral lesions, it is found that OSCC is the most common, accounting to 90% of all cancer of maxillofacial regions. It is also evident that OSCC has a very high rate of mortality with 5-year survival rate of only 50%.[15]

Global highest number of cancer of maxillofacial regions is reported in India, that is, approximately 20%, and approximately 1% is reported to have a premalignant condition.[16]

In this study, approximately 16% of the OSCC are from the age-group of 15–30 years, which is the youngest age-group of this study. Of which, the number of Ms affected are more as compared to FMs, but the difference is statistically nonsignificant, which can be interpreted as the percentage of FMs affected with OSCCC in early age is equal to the percentage of Ms affected in the same age. Hence, it can be concluded that both the genders are equally susceptible to OSCC in this age-group. It is evident that the number of Ms is more as compared to FMs, which does not correlate with the gender but with the habit. It was found that the more Ms have habits related to the OSCC as compared to FMs, hence gender has nothing to do with the prevalence of disease but it is the habit, which is more important. Our results were found to be consistent with the previous study conducted by Singh et al.,[16] Boyle and Ferlay,[2] Farley et al.,[3] and Gillison et al.[4] The most common age-group susceptible for OSCC was found to be 46–60 years. Our results are similar to that of Singh et al.,[16] but it is observed that the number of patients younger than this age-group is increasing as evident in the study conducted by Tandon et al.,[17] which can be attributed to the fact that the substance abuse is increasing in this age-group.

We found that the most common site for OSCC is mucosa of buccal region, affecting 33.47% of the cases, followed by alveolus, lips, lingulae, and floor of oral cavity, which is in unison with Tandon et al.;[17] however, in a study conducted by Dias and Almeida,[18] they found lingulae to be the most common site in Portuguese population. Also in the studies conducted in Europe and other developed countries, similar findings were observed, this may be because of the difference in population and their habits, as in India, the most common site for keeping the nicotine is buccal mucosa for prolonged time.

In this study, a strong association is seen with the areca nut chewing. It is well-established fact that nicotine- and areca-chewing habits have significantly higher association with the OSCC, which is also evident in this study, as these are the most common substance abuse observed in current population, and this is consistent with the study conducted by Krishna et al.[19]

It is also observed that chewing and nicotine smoke addiction together significantly increases the risk of OSCC, also alcohol along with nicotine smoke addiction has a synergistic effect in progressing OSCC, although along with nicotine chewing, it does not show any significant rise in the prevalence of SCC.

The most common clinical finding in the patients of OSCC was oral ulceration followed by difficulty in swallowing and moth opening, although only lump in neck came out to be significantly important in statistical analysis.

More number of poorly differentiated OSCC were observed in this study though the numbers could not reach the statistically significant level, whereas in the study conducted by Tandon et al.,[17] more commonly well-differentiated OSCC was observed. In other studies, moderately differentiated OSCC was more commonly reported, this may be because of different prevalent habits in those regions.[181920]

CONCLUSION

OSCC is long known to be interdependent with the tobacco. It is known to manifest usually in the middle-aged group but its number is increasing in younger age-group. This study confirms the previously established fact that nicotine is contributory to the OSCC. It is concluded that the middle-aged group is commonly prone to the disease with increasing number of younger ones, this could be due to increasing number of substance abuse seen in younger population these days. Gender does not play a significant role in OSCC, but it is the habit that contributes to its numbers. Chewing along with nicotine smoke addiction and alcohol along with nicotine smoke addiction have a synergistic effect in progressing OSCC. Also the differentiation of OSCC depends somewhat on the type of habit; further long-term studies are needed to establish this fact.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.