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J Bagh College Dentistry Vol. 21(1), 2009 Serum and salivary levels… in the diagnosis of OSCC. Moreover, significant increase in the concentrations of serum and salivary IL-6 and IL-8 among OSCC patients when compared with that of control group may also help in the same aspect. Elevated serum IL-6 level in OSCC patients was in accordance with other studies [4,9-12] . This finding is also in agreement with the finding of other investigators, who reported significant increase in the level of serum IL-6 in patients with other forms of cancers like ovarian cancer, renal cell carcinoma, colorectal cancer, esophageal squamous cell carcinoma, and cervical cancer [ 2,6,14,19] . In this study, the area under ROC curve for serum IL-6 (0.8) of patients with OSCC was higher than the determined of an equivocal test of 0.5 with optimum cut-off value that can be used for diagnosis purpose of highest accuracy (positive test ≥ 7.5pg/ml) yields a specificity of 90% and a sensitivity of 63.3%, indicated that serum IL-6 serve as useful biomarker in the diagnosis of OSCC than salivary IL-6 since the area under ROC for salivary IL-6 (0.73) was higher than the determined of an equivocal test of 0.5 with optimum cut-off value of highest accuracy (positive test ≥ 26.3 pg/ml) yields a specificity of 100% and a sensitivity of 60%. Elevated serum IL-8 in OSCC patients was in accordance with the results of Chen and coworkers 1999 [4] , who demonstrated a significant increase of IL-8 level in serum of patients with OSCC. This finding is in agreement with finding of other investigators, who demonstrated a significant increase in serum IL-8 in patients with colorectal cancer [14] , hepatocellular carcinoma [15] , metastatic melanoma [16] , cervical cancer [6] and endometrial cancer [5] . IL-8 was also detected in tumor specimens and primary cell cultures from patients with HNSCC [3,7,8 20,22] . IL-8 level was detected at higher concentrations in saliva of patients with OSCC than control group. This finding supported the findings reported by John, et al., 2004 [12] . In this study, detection of IL-8 in saliva and serum holds great potential for OSCC diagnosis as the area under ROC curve for both serum and salivary IL-8 was (0.9) which is higher than the determined of an equivocal test of 0.5 with optimum cut-off value of highest accuracy(≥ 45 pg/ml) yields a specificity of 100% and a sensitivity of 66.7% for serum IL-8 and optimum cut-off value of highest accuracy (≥867.5pg/ml) yields a specificity of 100% and a sensitivity of 70% for salivary IL-8. These findings were in agreement with previous studies [4,12] . These variations in serum cytokine concentrations observed among individual patients with OSCC, indicates that serum levels of cytokines may also depend in part upon individual host inflammatory responses within the tumor, and biologically active cytokines contribute to altered immune status in OSCC patients [21] . Salivary cytokines concentration increase in patients with OSCC because these cytokines play a role in the initiation of local inflammation and activation of lymphocyte responses ; therefore it can not be considered as specific markers since the oral cavity may be a site for several inflammatory conditions such as periodentitis particularly in elderly. The use of the fluid phase of saliva for detection of tumor markers has unique advantages over the use of exfoliated cells. Depending on the location of the tumor, one may not be able to easily access and swab the tumor bed. Although salivary biomarkers could not identify the site from which the tumor originated, they could at least identify patients at risk. The ability to analyze saliva would therefore be beneficial in the diagnosis of OSCC although the use of saliva has been criticized as a diagnostic medium since informative analyses are generally present in lower amounts than in serum [12,21] . However, saliva based test could be a cost-effective adjunctive tool in the diagnosis of patients with OSCC may have contribution in early diagnosis and management. REFERENCES 1- Bhatti N, Downer MC, Bulman JS. Public Knowledge and attitudes on oral cancer: a pilot investigation. J Inst Health Educ 1995; 32:112-7. 2-Blay JY, Rossi JF, Wijdenes J,et al. Role of interleukin- 6 in the paraneoplastic inflammatory syndrome associated with renal cell carcinoma. Int J Cancer 1997; 72: 424-30. 3-Chen Z, Colon I, Ortiz N, et al. Effects of interleukin-1 alpha, interleukin-1 receptor antagonist, and neutralizing antibody on proinflammatory cytokine expression by human squamous cell carcinoma lines. Cancer Res 1998; 58: 3668-76. 4-Chen Z, Malhotra PS, Thomas GR, et al. Expression of Proinflammatory and Proangiogenic Cytokines in Patients with Head and Neck Cancer. Clinical Cancer Research 1999; 5: 1369-79. 5-Chopra V, Dinh TV, Hannigan EV. Serum levels of interleukins, growth factors and angiogenin in patients with endometrial cancer. J Cancer Res Clin Oncol. 1997; 123: 167-72. 6-Chopra V, Dinh TV, Hannigan E.V. Circulating serum levels of cytokines and angiogenic factors in patients with cervical cancer. Cancer Invest 1998; 16: 152-9. 7-Cohen RF, Contrino J, Spiro JD, et al. Interleukin-8 exoression by head and neck squamous cell carcinoma. Arch Otolarygol Head Neck Surg 1995; 121: 202-9. 8-Eisma RJ, Spiro JD, Kreutzer DL. Role of angiogenic factors: Coexpression of interleukin-8 and vascular Oral Diagnosis 63
J Bagh College Dentistry Vol. 21(1), 2009 Serum and salivary levels… endothelial growth factor in patients with head and neck squamous carcinoma. Laryngoscope 1999; 109: 687-93. 9-Gallo O, Gori AM, Attanasio M,et al. Interleukin-6 and acute phase proteins in head and neck cancer. Eur Arch Otorhinolaryngol 1995; 252: 159-62. 10-Gleich LL, Biddinger PW, Duperier FD, Gluckman JL. Tumor angiogenesis as a prognostic indicator in T2-T4 oral cavity squamous cell carcinoma: a clinicalpathological correlation. Head Neck 1997; 19: 276-80. 11-Jablonska E, Piotrowski L, Grabowska Z. Serum Levels of IL-IB, IL-6, TNF-a, STNF-RI and CRP in patients with oral cavity cancer. Patho and Onco Res 1997; 3: 126-9. 12-John MAR, Yang L, Zhou X, Denny P, Ho CM. Interleukin 6 and Interleukin 8 as potential biomakers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2004; 130: 929-35. 13-Mann EA, Spiro JD, Chen LL, Kreutzer DL. Cytokine expression by head and neck squamous cell carcinoma. Am J Surg 1992; 164: 567-73. 14-Oka M, Yamamoto K, Takahashi M, et al. Relationship between serum levels of interleukin 6, various disease parameters, and malnutrition in patients with esophageal squamous cell carcinoma. Cancer Res 1996; 56: 2776-80. 15-Sakamoto K, Masuda T, Mita S, et al. Interleukin-8 is constitutively and commonly produced by various human carcinoma cell lines. Int J Clin Lab Res 1992; 22: 216-9. 16-Scheibenbogen C, Mohler T, Haefele J, et al. Serum interleukin-8 (IL-8) is elevated in patients with metastatic melanoma and correlates with tumor load. Melanoma Res 1995; 5: 179-81. 17-Silverman S Jr. Demographics and occurrence of oral and pharyngeal cancers. The outcomes, the trends, the challenge. J Am Dent Ass 2001; 132: 75-115. 18-Swango PA. Cancer of the Oral Cavity and Pharynx in the United States: An epidemiologic overview. J Public Health Dent 1996; 56: 309-18. 19-Ueda T, Shimada E, Urakawa T. serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis. J Gastroenterol 1994; 29: 423-9. 20-Watanabe H, Iwase M, Ohashi M, Nagumo M. Role of interleukin-8 secreted from human oral squamous cell carcinoma cell lines. Oral Oncol 2002; 38: 670-9. 21-Woods KV, Naggar AEI, Clayman GL, Grimm EA. Variable expression of cytokines in human head and neck squamous cell carcinoma cell lines and consistent expression on surgical specimens. Cancer Res 1998; 58: 3132-41. 22-Yamamura M, Modlin R, Ohmen J, Moy R. Local expression of anti-inflammatory cytokines in cancer. J Clin Investig 1993; 91: 1005-10. Table 1: Level of interleukins ( in pg/ml) in serum among OSCC patients and control group. Interleukins (Oral Controls Cancer) (n=20) (n=30) P Serum IL-1α [NS] concentration Range (0 - 5) (0 - 137.5) Median 1.3 3.8 Interquartile range (0 - 5) (0 - 12.5) Serum IL- 6 concentration
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Scientific Journal Published by the
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Contents i ii vi Editor and Editori
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Instruction for the Authors The Jou
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