Assessment of C-Reactive Protein Level in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma Patient.

BACKGROUND: Potentially malignant disorders are highly prevalent in India. In this study, we assessed C-reactive protein (CRP) levels in patients with oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC).
METHODOLOGY: Sixty-four patients (OSMF and OSCC) were undertaken and were classified into 3 groups, OSMF patients (Group I, 34), OSCC (Group II, 30), and healthy controls (Group III, 26). Immunoturbidimetry method was used for the estimation of CRP levels.
RESULTS: Maximum cases in Group I was seen in the age group 40-60 years (males-10, females-3), Group II in the age group 40-60 years (males-11, females-5) and Group III (males-5, females-6). The mean CRP level in Group I was 6.12 ± 4.5 mg/l, in Group II was 28.4 ± 21.5 mg/l, and in Group III was 3.15 ± 2.19 mg/l. The difference was significant (P < 0.05).
CONCLUSION: Authors found that OSMF and oral cancer patients had increased CRP levels as compared to healthy subjects. Copyright:

INTRODUCTION

Potentially malignant disorders (PMDs) are highly prevalent in India. The high consumption of areca nut and tobacco among South Indians raises the alarm to control its use.[1] Nowadays, the cases of oral submucous fibrosis (OSMF) and oral cancer are increasing among females. Earlier, there had been a high prevalence of PMDs among males due to the rapid use of tobacco and their products. However, in the last few years, consumption among females has enhanced due to many reasons.[2]

OSMF leads to stiffness of mucosa and difficult mouth opening due to the formation of collagen bands in the buccal mucosa, labial mucosa, soft palate, etc. OSMF is associated with malignant transformation if timely intervention is not performed. Prompt identification and prevention of these PMDs may decrease the incidence and subsequently help in achieving better survival of patients who develop oral squamous cell carcinoma (OSCC).[3]

Oral cancer accounts significantly for head and neck region cancer. The incidence was found to be 300,000 universally. It is the foremost reason of deaths. It has <50% survival rate in 5 years. C-reactive protein (CRP), fibrinogen, and serum amyloid A protein are few examples of acute-phase proteins whose values alter in the presence of inflammation. CRP found to show an elevated level in malignancy is considered to be a prognostic factor.[4] Various inflammatory cytokines like interleukin (IL)-1 and IL-6 etc., encourage the production of CRP by hepatocytes. Tumor necrosis factor-α also contribute significantly. Studies have been done in the past showing alteration in CRP level in patients with PMDs.[5] Considering this, we attempted to assess CRP level in OSMF and OSCC patients.

METHODOLOGY

We recruited 64 cases of OSMF and OSCC disorders of both genders reported to the Department of Oral Medicine and Radiology. The diagnosis of PMDs and OSCC was made clinically as well as histopathologically. We included 26 healthy subjects as control. Ethical approval for the study was taken before starting it, followed by written consent in vernacular language from all subjects.

The demographic profile of all subjects was recorded in case history pro forma. Patients were divided into three groups. Group I comprised OSMF patients (34), group II had cases of OSCC (30), and Group III had healthy controls (26).

All patients underwent collection of 2-ml venous blood samples using the standard venipuncture technique. Serum from blood was separated with centrifugation technique. Immunoturbidimetry method was used for the estimation of CRP levels. Results of the study were entered in MS excel sheet for statistical inference using Statistical Package of Social Sciences (SPSS) version 21 (IBM, Armonk, NY, USA). Data were expressed as mean ± standard deviation, maximum and minimum values using Kruskal–Wallis test and analysis of variance. 0.05 value was set as significance.

RESULTS

Table 1 shows distribution of subjects in different groups.

Table 1

Distribution of subjects

Groups	Group I	Group II	Group III
Status	OSMF	OSCC	Control
n	34	30	26

OSMF: Oral submucous fibrosis, OSCC: Oral squamous cell carcinoma

Table 2 shows that maximum cases in Group I was seen in the age group 40–60 years (males-10, females-3), Group II in the age group 40–60 years (males-11, females-5), and Group III (males-5, females-6).

Table 2

Age-wise distribution

Age group (years)	Group I (34)		Group II (30)		Group III (26)
	Male	Female	Male	Female	Male	Female
20-40	7	8	6	4	5	5
40-60	10	3	11	5	5	6
>60	5	1	3	1	3	2
Total	22	12	20	10	13	13

Table 3 and Graph 1 shows that the mean CRP level in Group I was 6.12 ± 4.5 mg/l, in Group II was 28.4 ± 21.5 mg/l, and in Group III was 3.15 ± 2.19 mg/l. The difference was significant (P < 0.05).

Table 3

Assessment of C-reactive protein in all groups

Groups	Mean	SD	Maximum	Minimum	P
Group I	6.12	4.5	1.5	8.4	0.01
Group II	28.4	21.5	11.3	37.2
Group III	3.15	2.19	0.8	6.3

SD: Standard deviation

Graph 1

Assessment of C-reactive protein in all groups

DISCUSSION

Tobacco is the leading cause of PMDs and OSCC. Tobacco is consumed as smoking form and smokeless form.[6] Various forms of smoking tobacco is cigarette, bidi, hookah, hookli, etc. Smokeless form of tobacco comprised of chaini khaini, zarda, pan masala, mawa, mishri, etc. Tobacco contains carcinogen products polycyclic hydrocarbon, nitrosamine, etc.[7]

The onset of OSMF is sudden. Patients experience multiple symptoms for which they report to the dental surgeon. The foremost complaint of the patients is the burning sensation on eating spicy and hot beverages. With the passage of time, multiple blisters and ulceration start appearing on the palate. Recurrent stomatitis and excessive salivation occur within few days, and ultimately xerostomia occurs.[8] The composition of areca nut is arecoline, arecadine, guvacoline, guvacine, and isoguvacine. Research reveals that there is nitrosation of arecoline with use resulting in the formation of arecanut specific nitrasamine.[9] These compounds are potential carcinogens and cause alkylation of. In this study, we assessed CRP level in OSMF and OSCC patients.

We found that there were 34 cases of OSMF, 30 cases of OSCC, and 26 controls. Age group 20–40 years had 7 males and 8 females in Group I, 6 males and 4 females in Group II, and 5 males and 5 females in Group III, Age group 40–60 years had 10 males and 3 females, Group II had 11 males and 5 females in Group II, and 5 males and 6 females in Group III. Age >60 comprised of 5 males and 1 female in Group I, 3 males and 1 female in Group II and 3 males and 2 females. Vankadara et al.[10] recruited 30 healthy controls (Group I), while Group II had 30 patients of leukoplakia, OSMF and OLP and Group III had 30 cases of squamous cell carcinoma. The result showed that mean CRP levels in Group I was 3.88 ± 4.50 mg/l with range from 0.1 to 18.3 mg/l. In Group II, mean CRP level was 5.59 ± 9.86 mg/l with rang from 0.8 to 53.9 mg/l. In Group III, mean CRP level was 31.72 ± 31.01 mg/l, which rang from 3.3 to 96 mg/l.

We found that mean CRP level in Group I was 6.12 ± 4.5 mg/l, in Group II was 28.4 ± 21.5 mg/l and in Group III was 3.15 ± 2.19 mg/l. Gosavi and Torkadi[11] conducted a study with 50 healthy, 50 OSMF and 50 OSCC individuals who were divided into Group I, Group II and Group III, respectively. The mean value of serum CRP in Group I was 2.20 ± 1.74 mg/L; in Group II, it was 5.40 ± 4.79 mg/L and in Group III, it was 12.17 ± 11.38 mg/L.

Kaja et al.[12] consisted of 20 cases of oral PMDs (Leukoplakia-10, Oral Sub mucous fibrosis-10). Mean CRP levels in leukoplakia was 0.33 ± 0.17, in OSMF was 0.58 ± 0.83 where as in controls it was 0.26 ± 0.05. In PMDs, CRP was slightly elevated when compared with the controls.

It is mentioned in the literature that CRP level increases significantly in tissue in active phase of disease and in cancer patients. It is a receptive marker of inflammation. It is evident stimulation by IL-6 significantly CRP levels in the liver and additional organs. CRP can be increased by both acute and chronic stimulation.[13] It is a defensive mechanism against viral and bacterial infections. Elevation of CRP has also been seen in connective tissue diseases, cardiovascular diseases, infections, inflammatory conditions, tuberculosis, rheumatoid arthritis, and women using oral contraceptives.[14] Anand Kumar and Bhateja[15] also observed that the level of serum CRP level was significantly higher in OSMF cases in comparison to the control group.

The shortcoming of the study is the small sample size.

CONCLUSION

The authors found that OSMF and oral cancer patients had increased CRP level as compared to healthy subjects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.