Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical Oral Investigations
Published in: Clinical Oral Investigations 4/2016

01-05-2016 | Original Article

Salivary and serum interleukin-6 levels in proliferative verrucous leukoplakia

Authors: Leticia Bagan, Guillermo T. Sáez, M. Carmen Tormos, Carlos Labaig-Rueda, Judith Murillo-Cortes, Jose V. Bagan

Published in: Clinical Oral Investigations | Issue 4/2016

Login to get access

Abstract

Background

Cytokines and chemokines have been analysed in patients with oral squamous cell carcinoma and potentially malignant disorders. We selected interleukin-6 (IL-6) because it is a multifunctional interleukin reported to be altered in potentially malignant oral disorders and in malignant lesions. To date, this has not been evaluated or tested in proliferative verrucous leukoplakia (PVL), however.

Objectives

This study aimed to analyse the differences in serum and saliva IL-6 levels among patients with PVL, oral squamous cell carcinoma (OSCC) and healthy controls and to examine the relationship between salivary IL-6 levels and the extent of the verrucous area.

Methods

Using an enzyme-linked immunosorbent assay, we determined the serum and saliva IL-6 levels in three groups: 20 patients with PVL, 20 with OSCC and 20 healthy controls.

Results

There were significant (p < 0.01) differences in the serum and saliva IL-6 levels among the three groups and among the three grades of extent of the verrucous areas (p = 0.01). In the OSCC group, there was a significant difference in the saliva IL-6 levels between patients with and without lymph node metastasis at diagnosis (p = 0.02).

Conclusions

We found that patients with OSCC had the highest salivary and serum IL-6 levels, while PVL had lower values than OSCC, but higher than the controls, and these altered levels were associated with the extent of the verrucous areas.

Clinical relevance

Salivary and plasma IL-6 are altered in patients with PVL, with more extensive verrucous areas being associated to the highest IL-6 levels. This could be a significant tool for monitoring patients with PVL, their progression to more advances stages and their recurrences.
Literature
1.
Hansen LS, Olson JA, Silverman S Jr (1985) Proliferative verrucous leukoplakia. A long-term study of thirty patients. Oral Surg Oral Med Oral Pathol 60:285–298CrossRefPubMed
2.
Silverman S Jr, Gorsky M (1997) Proliferative verrucous leukoplakia: a follow-up study of 54 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84(2):154–157CrossRefPubMed
3.
Gandolfo S, Castellani R, Pentenero M (2009) Proliferative verrucous leukoplakia: a potentially malignant disorder involving periodontal sites. J Periodontol 80:274–281CrossRefPubMed
4.
Bagán JV, Murillo J, Poveda R, Gavaldá C, Jiménez Y, Scully C (2004) Proliferative verrucous leukoplakia: unusual locations of oral squamous cell carcinomas, and field cancerization as shown by the appearance of multiple OSCCs. Oral Oncol 40:440–443CrossRefPubMed
5.
Bagan JV, Jimenez Y, Sanchis JM, Poveda R, Milian MA, Murillo J, Scully C (2003) Proliferative verrucous leukoplakia: high incidence of gingival squamous cell carcinoma. J Oral Pathol Med 32:379–382CrossRefPubMed
6.
Pentenero M, Meleti M, Vescovi P, Gandolfo S (2014) Oral proliferative verrucous leukoplakia: are there particular features for such an ambiguous entity? A systematic review. Br J Dermatol 170:1039–47CrossRefPubMed
7.
Zakrzewska JM, Lopes V, Speight P, Hopper C (1996) Proliferative verrucous leukoplakia: a report of ten cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 82:396–401CrossRefPubMed
8.
Eversole LR (2000) Papillary lesions of the oral cavity: relationship to human papillomaviruses. J Calif Dent Assoc 28:922–927PubMed
9.
Palefsky JM, Silverman S Jr, Abdel-Salaam M, Daniels TE, Greenspan JS (1995) Association between proliferative verrucous leukoplakia and infection with human papillomavirus type 16. J Oral Pathol Med 24:193–197CrossRefPubMed
10.
Gopalakrishnan R, Weghorst CM, Lehman TA, Calvert RJ, Bijur G, Sabourin CL, Mallery SR, Schuller DE, Stoner GD (1997) Mutated and wild-type p53 expression and HPV integration in proliferative verrucous leukoplakia and oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 83:471–477CrossRefPubMed
11.
Campisi G, Giovannelli L, Ammatuna P, Capra G, Colella G, Di Liberto C, Gandolfo S, Pentenero M, Carrozzo M, Serpico R, D’Angelo M (2004) Proliferative verrucous vs conventional leukoplakia: no significantly increased risk of HPV infection. Oral Oncol 40:835–840CrossRefPubMed
12.
Fettig A, Pogrel MA, Silverman S Jr, Bramanti TE, Da Costa M, Regezi JA (2000) Proliferative verrucous leukoplakia of the gingiva. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90:723–730CrossRefPubMed
13.
Kresty LA, Mallery SR, Knobloch TJ, Li J, Lloyd M, Casto BC, Weghorst CM (2008) Frequent alterations of p16INK4a and p14ARF in oral proliferative verrucous leukoplakia. Cancer Epidemiol Biomarkers Prev 17:3179–3187CrossRefPubMed
14.
Klanrit P, Sperandio M, Brown AL, Shirlaw PJ, Challacombe SJ, Morgan PR, Odell EW (2007) DNA ploidy in proliferative verrucous leukoplakia. Oral Oncol 43:310–316CrossRefPubMed
15.
Cabay RJ, Morton TH Jr, Epstein JB (2007) Proliferative verrucous leukoplakia and its progression to oral carcinoma: a review of the literature. J Oral Pathol Med 36:255–261CrossRefPubMed
16.
Bagan J, Scully C, Jimenez Y, Martorell M (2010) Proliferative verrucous leukoplakia: a concise update. Oral Dis 16:328–332CrossRefPubMed
17.
Bagan JV, Jiménez-Soriano Y, Diaz-Fernandez JM, Murillo-Cortés J, Sanchis-Bielsa JM, Poveda-Roda R, Bagan L (2011) Malignant transformation of proliferative verrucous leukoplakia to oral squamous cell carcinoma: a series of 55 cases. Oral Oncol 47:732–735CrossRefPubMed
18.
Carrard VC, Brouns ER, van der Waal I (2013) Proliferative verrucous leukoplakia; a critical appraisal of the diagnostic criteria. Med Oral Patol Oral Cir Bucal 18:e411–e413CrossRefPubMedPubMedCentral
19.
Jureti M, Cerovi R, Belui-Gobi M, Brekalo Pro I, Kqiku L, Palj S, Pezelj-Ribari S (2013) Salivary levels of TNF- and IL-6 in patients with oral premalignant and malignant lesions. Folia Biol 59:99–102
20.
Lisa Cheng YS, Jordan L, Gorugantula LM, Schneiderman E, Chen HS, Rees T (2014) Salivary interleukins 6 and 8 in oral cancer patients and in patients with chronic oral inflammatory diseases. J Periodontol 85:956–65CrossRefPubMed
21.
Brailo V, Vucicevic-Boras V, Lukac J, Biocina-Lukenda D, Zilic-Alajbeg I, Milenovic A, Balija M (2012) Salivary and serum interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha in patients with leukoplakia and oral cancer. Med Oral Patol Oral Cir Bucal 17:e10–e15CrossRefPubMedPubMedCentral
22.
Chang KP, Kao HK, Wu CC, Fang KH, Chang YL, Huang YC, Liu SC, Cheng MH (2013) Pretreatment interleukin-6 serum levels are associated with patient survival for oral cavity squamous cell carcinoma. Otolaryngol Head Neck Surg 148:786–791CrossRefPubMed
23.
Sato J, Goto J, Murata T, Kitamori S, Yamazaki Y, Satoh A, Kitagawa Y (2010) Changes in saliva interleukin-6 levels in patients with oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110:330–336CrossRefPubMed
24.
Korostoff A, Reder L, Masood R, Sinha UK (2011) The role of salivary cytokine biomarkers in tongue cancer invasion and mortality. Oral Oncol 47:282–287CrossRefPubMed
25.
Vairaktaris E, Yapijakis C, Serefoglou Z, Avgoustidis D, Critselis E, Spyridonidou S, Vylliotis A, Derka S, Vassiliou S, Nkenke E, Patsouris E (2008) Gene expression polymorphisms of interleukins-1 beta, -4, -6, -8, -10, and tumor necrosis factors-alpha, -beta: regression analysis of their effect upon oral squamous cell carcinoma. J Cancer Res Clin Oncol 134:821–832CrossRefPubMed
26.
St John MA, Li Y, Zhou X, Denny P, Ho CM, Montemagno C, Shi W, Qi F, Wu B, Sinha U, Jordan R, Wolinsky L, Park NH, Liu H, Abemayor E, Wong DT (2004) Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 130:929–935CrossRefPubMed
27.
Chang KP, Chang YT, Liao CT, Yen TC, Chen IH, Chang YL, Liu YL, Chang YS, Yu JS, Wu CC (2011) Prognostic cytokine markers in peripheral blood for oral cavity squamous cell carcinoma identified by multiplexed immunobead-based profiling. Clin Chim Acta 412:-12
28.
Punyani SR, Sathawane RS (2013) Salivary level of interleukin-8 in oral precancer and oral squamous cell carcinoma. Clin Oral Investig 17:517–524CrossRefPubMed
29.
Katakura A, Kamiyama I, Takano N, Shibahara T, Muramatsu T, Ishihara K, Takagi R, Shouno T (2007) Comparison of salivary cytokine levels in oral cancer patients and healthy subjects. Bull Tokyo Dent Coll 48:199–203CrossRefPubMed
30.
Rhodus NL, Cheng B, Myers S, Miller L, Ho V, Ondrey F (2005) The feasibility of monitoring NF-kappaB associated cytokines: TNF-alpha, IL-1alpha, IL-6, and IL-8 in whole saliva for the malignant transformation of oral lichen planus. Mol Carcinog 44:77–82CrossRefPubMed
31.
Sun A, Wang JT, Chia JS, Chiang CP (2005) Serum interleukin-8 level is a more sensitive marker than serum interleukin-6 level in monitoring the disease activity of oral lichen planus. Br J Dermatol 152:1187–1192CrossRefPubMed
32.
Gu GM, Martin MD, Darveau RP, Truelove E, Epstein J (2004) Oral and serum IL-6 levels in oral lichen planus patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 98:673–678CrossRefPubMed
33.
Brailo V, Vucievi-Boras V, Ceki-Arambasin A, Alajbeg IZ, Milenovi A, Lukac J (2006) The significance of salivary interleukin 6 and tumor necrosis factor alpha in patients with oral leukoplakia. Oral Oncol 42:370–373CrossRefPubMed
34.
Matsuki Y, Yamamoto T, Hara K (1992) Detection of inflammatory cytokine messenger RNA (mRNA)-expressing cells in human inflamed gingiva by combined in situ hybridization and immunohistochemistry. Immunology 76:42–47PubMedPubMedCentral
35.
Jones KG, Brull DJ, Brown LC, Sian M, Greenhalgh RM, Humphries SE, Powell JT (2001) Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms. Circulation 103:2260–2265CrossRefPubMed
36.
Nishimoto N (2010) Interleukin-6 as a therapeutic target in candidate inflammatory diseases. Clin Pharmacol Ther 87:483–487CrossRefPubMed
37.
Nibali L, Fedele S, D’Aiuto F, Donos N (2012) Interleukin-6 in oral diseases: a review. Oral Dis 18:236–243CrossRefPubMed
38.
Prasad G, McCullough M (2013) Chemokines and cytokines as salivary biomarkers for the early diagnosis of oral cancer. Int J Dent. 2013: Article 813756, 7 pages
39.
40.
Sharma M, Bairy I, Pai K, Satyamoorthy K, Prasad S, Berkovitz B, Radhakrishnan R (2011) Salivary IL-6 levels in oral leukoplakia with dysplasia and its clinical relevance to tobacco habits and periodontitis. Clin Oral Investig 15:705–714CrossRefPubMed
41.
Shkeir O, Athanassiou-Papaefthymiou M, Lapadatescu M, Papagerakis P, Czerwinski MJ, Bradford CR, Carey TE, Prince ME, Wolf GT, Papagerakis S (2013) In vitro cytokine release profile: predictive value for metastatic potential in head and neck squamous cell carcinomas. Head Neck 35(11):1542–1550CrossRefPubMedPubMedCentral
42.
Hwang YS, Lee SK, Park KK, Chung WY (2012) Secretion of IL-6 and IL-8 from lysophosphatidic acid-stimulated oral squamous cell carcinoma promotes osteoclastogenesis and bone resorption. Oral Oncol 48:40–48CrossRefPubMed
43.
Nibali D’AF, Donos N, Griffiths GS, Parkar M, Tonetti MS, HumphriesSE BPM (2009) Association between periodontitis and common variants in the promoter of the interleukin-6 gene. Cytokine 45:50–54CrossRefPubMed
44.
Prso IB, Kocjan W, Simi H, Brumini G, Pezelj-Ribari S, Borci J, Ferreri S, Karlovi IM (2007) Tumor necrosis factor-alpha and interleukin 6 in human periapical lesions. Mediators Inflamm. 2007:38210
45.
Zhang Y, Lin M, Zhang S, Wang Z, Jiang L, Shen J, Bai J, Gao F, Zhou M, Chen Q (2008) NF-kappaB-dependent cytokines in saliva and serum from patients with oral lichen planus: a study in an ethnic Chinese population. Cytokine 41:144–149CrossRefPubMed
46.
Guimarães AL, Correia-Silva Jde F, Sá AR, Victória JM, Diniz MG, Costa Fde O, Gomez RS (2007) Investigation of functional gene polymorphisms IL-1beta, IL-6, IL-10 and TNF-alpha in individuals with recurrent aphthous stomatitis. Arch Oral Biol 52:268–272CrossRefPubMed
47.
48.
Sato J, Ohuchi M, Abe K, Satoh T, Abe T, Yamazaki Y, Satoh A, Notani K, Kitagawa Y (2013) Correlation between salivary interleukin-6 levels and early locoregional recurrence in patients with oral squamous cell carcinoma: preliminary study. Head Neck 35:889–894CrossRefPubMed
49.
Sundelin K, Roberg K, Grénman R, Håkansson L (2005) Effects of cytokines on matrix metalloproteinase expression in oral squamous cell carcinoma in vitro. Acta Otolaryngol 125(7):765–773CrossRefPubMed
50.
Hodge DR, Peng B, Cherry JC, Hurt EM, Fox SD, Kelley JA, Munroe DJ, Farrar WL (2005) Interleukin 6 supports the maintenance of p53 tumor suppressor gene promoter methylation. Cancer Res 65(11):4673–4682CrossRefPubMed
51.
Tamura S, Ouchi KF, Mori K, Endo M, Matsumoto T, Eda H, Tanaka Y, Ishitsuka H, Tokita H, Yamaguchi K (1995) Involvement of human interleukin 6 in experimental cachexia induced by a human uterine cervical carcinoma xenograft. Clin Cancer Res 1(11):1353–1358PubMed
52.
Hu S, Arellano M, Boontheung P, Wang J, Zhou H, Jiang J, Elashoff D, Wei R, Loo JA, Wong DT (2008) Salivary proteomics for oral cancer biomarker discovery. Clin Cancer Res 14:6246–6252CrossRefPubMedPubMedCentral
53.
Duffy SA, Taylor JM, Terrell JE, Islam M, Li Y, Fowler KE, Wolf GT, Teknos TN (2008) Interleukin-6 predicts recurrence and survival among head and neck cancer patients. Cancer 113(4):750–757CrossRefPubMed
Metadata
Title
Salivary and serum interleukin-6 levels in proliferative verrucous leukoplakia
Authors
Leticia Bagan
Guillermo T. Sáez
M. Carmen Tormos
Carlos Labaig-Rueda
Judith Murillo-Cortes
Jose V. Bagan
Publication date
01-05-2016
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 4/2016
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-015-1551-z

Other articles of this Issue 4/2016

Clinical Oral Investigations 4/2016 Go to the issue

Letter to the Editor

Reply to the Letter to the Editor regarding “Did we learn something new on pemphigoid autoimmune blistering diseases?” by Nili Tickotsky, CLOI-D-15-00596

Original Article

Relationship between periodontal parameters and plasma cytokine profiles in pregnant woman with preterm birth or low birth weight

Original Article

Short-term effects of systematic premolar extraction on lip profile, vertical dimension and cephalometric parameters in borderline patients for extraction therapy—a retrospective cohort study

Original Article

Implant treatment in periodontally compromised subjects—quality of life and patient satisfaction

Letter to the Editor

Did we learn something new on pemphigoid autoimmune blistering diseases?

Review

Does periodontal treatment have an effect on clinical and immunological parameters of periodontal disease in obese subjects? A systematic review and meta-analysis