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Interleukin-8 and laryngeal squamous cell carcinoma

Michele Grasso, Massimo Ralli, Griselda Agolli, Marco Fiore, Mauro Ceccanti, Paola Tirassa, Marco de Vicentiis, Antonio Greco


Laryngeal squamous cell carcinoma (LSCC) is the second most common neoplasm of the upper aerodigestive tract after cancer of the oral cavity. Over the past two decades, even though patients have benefited greatly from the latest advances in surgical techniques, chemotherapy and radiation therapy, the survival rate of LSCC has not improved significantly. It is reported that changes in the expression of cytokines and growth factors have implications in the malignant transformation of many cancers including head and neck squamous cell carcinoma and, more recently, LSCC. It has been hypothesized that some of these cytokines may be used as additional diagnostic markers in the sera of patients because of their excessive production by the tumor cells. This could be of great value since there are currently no reliable markers to predict either tumor development or relapse. Interleukin-8 (IL-8), a chemokine (C-X-C motif) ligand 8 (CXCL8), is now reported to play an important role in cancer invasion, angiogenesis and metastasis. Recent studies have shown an increased concentration of IL-8 in patients with LSCC and a positive association with lymph node metastasis and T classification. Interleukin-8 levels were not significantly associated with shorter overall survival and cancer progression-free survival. The investigation of the mechanisms of origin, invasion, and metastasis of the cancer is one of the emergent and most promising scientific fields in head and neck cancer, especially in LSCC. Biomarkers such as IL-8 could have a role as a screening test and as a support of the clinical decisions for appropriate therapy and postoperative care in individual patients.


interleukin-8, laryngeal squamous cell cancer, head and neck cancer, chemokines, cancer

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Obid R, Redlich M, Tomeh C. The treatment of laryngeal cancer. Oral Maxillofac Surg Clin North Am 2019; 31(1): 1-11. DOI:10.1016/j.coms.2018.09.001

Pries R, Wollenberg B. Cytokines in head and neck cancer. Cytokine Growth Factor Rev 2006; 17(3): 141-146. DOI:10.1016/j.cytogfr.2006.02.001

De Virgilio A, Ralli M, Longo L, Mancini P, Attanasio G, Atturo F, et al. Electrochemotherapy in head and neck cancer: A review of an emerging cancer treatment. Oncol Lett 2018; 16(3): 3415-3423. DOI:10.3892/ol.2018.9140

Marur S, Forastiere AA. Head and neck squamous cell carcinoma: Update on epidemiology, diagnosis, and treatment. Mayo Clin Proc 2016; 91(3): 386-396. DOI:10.1016/j.mayocp.2015.12.017

Steuer CE, El-Deiry M, Parks JR, Higgins KA, Saba NF. An update on larynx cancer. CA Cancer J Clin 2017; 67(1): 31-50. DOI:10.3322/caac.21386

Ciafre S, Carito V, Ferraguti G, Greco A, Chaldakov GN, Fiore M, et al. How alcohol drinking affects our genes: an epigenetic point of view. Biochem Cell Biol 2018. DOI:10.1139/bcb-2018-0248

Attilia F, Perciballi R, Rotondo C, Capriglione I, Iannuzzi S, Attilia ML, et al. Pharmacological treatment of alcohol use disorder. Scientific evidence. Riv Psichiatr. 2018; 53(3): 123-127. DOI:10.1708/2925.29414

Ceccanti M, Iannitelli A, Fiore M. Italian Guidelines for the treatment of alcohol dependence. Riv Psichiatr 2018; 53(3): 105-106. DOI:10.1708/2925.29410

Ceccanti M, Coriale G, Hamilton DA, Carito V, Coccurello R, Scalese B, et al. Virtual Morris task responses in individuals in an abstinence phase from alcohol. Can J Physiol Pharmacol. 2018; 96(2): 128-136. DOI:10.1139/ cjpp-2017-0013

Ferraguti G, Ciolli P, Carito V, Battagliese G, Mancinelli R, Ciafre S, et al. Ethylglucuronide in the urine as a marker of alcohol consumption during pregnancy: Comparison with four alcohol screening questionnaires. Toxicol Lett 2017; 275: 49-56. DOI:10.1016/j.toxlet.2017.04.016

Ceccanti M, Hamilton D, Coriale G, Carito V, Aloe L, Chaldakov G, et al. Spatial learning in men undergoing alcohol detoxification. Physiol Behav 2015; 149: 324-330. DOI:10.1016/j.physbeh.2015.06.034

Ferster APO, Schubart J, Kim Y, Goldenberg D. Association between laryngeal cancer and asbestos exposure: A systematic review. JAMA Otolaryngol Head Neck Surg 2017; 143(4): 409-416. DOI:10.1001/ jamaoto.2016.3421

Bychkov VA, Nikitina EG, Ibragimova MK, Kaigorodova EV, Choinzonov EL, Litviakov NV. Comprehensive meta-analytical summary on human papillomavirus association with head and neck cancer. Exp Oncol. 2016; 38(2): 68-72.

Syrjanen S, Rautava J, Syrjanen K. HPV in head and neck cancer - 30 years of history. Recent Results Cancer Res 2017; 206: 3-25. DOI:10.1007/978-3-319-43580-0_1

Shaikh MH, McMillan NA, Johnson NW. HPV-associated head and neck cancers in the Asia Pacific: A critical literature review and meta-analysis. Cancer Epidemiol. 2015; 39(6): 923-938. DOI:10.1016/j.canep.2015.09.013

Bologna-Molina RE, Castaneda-Castaneira RE, Molina- Frechero N, Perez-Rodriguez E. Human papilloma virus and its association with oral cancer. Rev Med Inst Mex Seguro Soc 2006; 44(2): 147-153.

Li X, Gao L, Li H, Gao J, Yang Y, Zhou F, et al. Human papillomavirus infection and laryngeal cancer risk: a systematic review and meta-analysis. J Infect Dis. 2013; 207(3): 479-488. DOI:10.1093/infdis/jis698

Tribius S, Wurdemann N, Laban S, Sharma SJ, Wagner S, Hoffmann TK, et al. Update on HPV-associated head and neck cancer-highlights of the 2018 ASCO Annual Meeting. HNO. 2018; 66(12): 888-895. DOI:10.1007/ s00106-018-0577-3

Wittekindt C, Wuerdemann N, Gattenlohner S, Brobeil A, Wierzbicka M, Wagner S, et al. The role of high-risk human papillomavirus infections in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 2017; 274(11): 3837-3842. DOI:10.1007/s00405-017-4718-1

Mallen-St Clair J, Alani M, Wang MB, Srivatsan ES. Human papillomavirus in oropharyngeal cancer: The changing face of a disease. Biochim Biophys Acta. 2016; 1866(2): 141-150. DOI:10.1016/j.bbcan.2016.07.005

Arndt O, Johannes A, Zeise K, Brock J. [High-risk HPV types in oral and laryngeal papilloma and leukoplakia]. Laryngorhinootologie. 1997; 76(3): 142-149. 10.1055/s- 2007-997403

de Vincentiis M, De Virgilio A, Bussu F, Gallus R, Gallo A, Bastanza G, et al. Oncologic results of the surgical salvage of recurrent laryngeal squamous cell carcinoma in a multicentric retrospective series: emerging role of supracricoid partial laryngectomy. Head Neck. 2015; 37(1): 84-91. DOI:10.1002/hed.23563

Bussu F, Paludetti G, Almadori G, De Virgilio A, Galli J, Micciche F, et al. Comparison of total laryngectomy with surgical (cricohyoidopexy) and nonsurgical organ-preservation modalities in advanced laryngeal squamous cell carcinomas: A multicenter retrospective analysis. Head Neck. 2013; 35(4): 554-561. DOI:10.1002/ hed.22994

De Virgilio A, Fusconi M, Gallo A, Greco A, Kim SH, Conte M, et al. The oncologic radicality of supracricoid partial laryngectomy with cricohyoidopexy in the treatment of advanced N0-N1 laryngeal squamous cell carcinoma. Laryngoscope 2012; 122(4): 826-833. DOI:10.1002/lary.23178

Patel KB, Nichols AC, Fung K, Yoo J, MacNeil SD. Treatment of early stage Supraglottic squamous cell carcinoma: meta-analysis comparing primary surgery versus primary radiotherapy. J Otolaryngol Head Neck Surg 2018; 47(1): 19. DOI:10.1186/s40463-018-0262-2

Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454(7203): 436-444. DOI:10.1038/nature07205

Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H, Gomez E, et al. Interleukins, from 1 to 37, and interferon-gamma: receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2011; 127(3): 701-721 e701-770. DOI:10.1016/j.jaci.2010.11.050

Wang F, Arun P, Friedman J, Chen Z, Van Waes C. Current and potential inflammation targeted therapies in head and neck cancer. Curr Opin Pharmacol. 2009; 9(4): 389-395. DOI:10.1016/j.coph.2009.06.005

Aloe L, Rocco ML, Balzamino BO, Micera A. Nerve growth factor: role in growth, differentiation and controlling cancer cell development. J Exp Clin Cancer Res 2016; 35(1): 116. DOI:10.1186/s13046-016-0395-y

Fiore M, Chaldakov GN, Aloe L. Nerve growth factor as a signaling molecule for nerve cells and also for the neuroendocrine-immune systems. Rev Neurosci 2009; 20(2): 133-145.

Aloe L, Manni L, Properzi F, De Santis S, Fiore M. Evidence that nerve growth factor promotes the recovery of peripheral neuropathy induced in mice by cisplatin: behavioral, structural and biochemical analysis. Auton Neurosci 2000; 86(1-2): 84-93. DOI:10.1016/S1566- 0702(00)00247-2

De Santis S, Pace A, Bove L, Cognetti F, Properzi F, Fiore M, et al. Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor. Clin Cancer Res. 2000; 6(1): 90-95.

Linkov F, Lisovich A, Yurkovetsky Z, Marrangoni A, Velikokhatnaya L, Nolen B, et al. Early detection of head and neck cancer: development of a novel screening tool using multiplexed immunobead-based biomarker profiling. Cancer Epidemiol Biomarkers Prev. 2007; 16(1): 102-107. DOI:10.1158/1055-9965.EPI-06-0602

Druzgal CH, Chen Z, Yeh NT, Thomas GR, Ondrey FG, Duffey DC, et al. A pilot study of longitudinal serum cytokine and angiogenesis factor levels as markers of therapeutic response and survival in patients with head and neck squamous cell carcinoma. Head Neck. 2005; 27(9): 771-784. DOI:10.1002/hed.20246

Mojtahedi Z, Khademi B, Yehya A, Talebi A, Fattahi MJ, Ghaderi A. Serum levels of interleukins 4 and 10 in head and neck squamous cell carcinoma. J Laryngol Otol 2012; 126(2): 175-179. DOI:10.1017/S0022215111002349

Hathaway B, Landsittel DP, Gooding W, Whiteside TL, Grandis JR, Siegfried JM, et al. Multiplexed analysis of serum cytokines as biomarkers in squamous cell carcinoma of the head and neck patients. Laryngoscope 2005; 115(3): 522-527. DOI:10.1097/01. mlg.0000157850.16649.b8

Topping KP, Fletcher LM, Agada FO, Alhamarneh O, Stafford ND, Greenman J. Head and neck tumour immunology: basic concepts and new clinical implications. J Laryngol Otol 2009; 123(1): 9-18. DOI:10.1017/ S0022215108003368

Hoffmann TK, Sonkoly E, Homey B, Scheckenbach K, Gwosdz C, Bas M, et al. Aberrant cytokine expression in serum of patients with adenoid cystic carcinoma and squamous cell carcinoma of the head and neck. Head Neck. 2007; 29(5): 472-478. DOI:10.1002/hed.20533

Riedel F, Zaiss I, Herzog D, Gotte K, Naim R, Hormann K. Serum levels of interleukin-6 in patients with primary head and neck squamous cell carcinoma. Anticancer Res. 2005; 25(4): 2761-2765.

Yang L, Huang Y, Zhou L, Dai Y, Hu G. High pretreatment neutrophil-to-lymphocyte ratio as a predictor of poor survival prognosis in head and neck squamous cell carcinoma: A systematic review and meta-analysis. Head Neck 2018. DOI:10.1002/hed.25583

Tham T, Bardash Y, Herman SW, Costantino PD. Neutrophil-to-lymphocyte ratio as a prognostic indicator in head and neck cancer: A systematic review and meta-analysis. Head Neck. 2018; 40(11): 2546-2557. DOI:10.1002/hed.25324

Takenaka Y, Oya R, Kitamiura T, Ashida N, Shimizu K, Takemura K, et al. Prognostic role of neutrophil-to-lymphocyte ratio in head and neck cancer: A meta-analysis. Head Neck 2018; 40(3): 647-655. DOI:10.1002/ hed.24986

Zhao QT, Yang Y, Xu S, Zhang XP, Wang HE, Zhang H, et al. Prognostic role of neutrophil to lymphocyte ratio in lung cancers: a meta-analysis including 7,054 patients. Onco Targets Ther 2015; 8: 2731-2738. DOI:10.2147/ OTT.S90875

Mascarella MA, Mannard E, Silva SD, Zeitouni A. Neutrophil-to-lymphocyte ratio in head and neck cancer prognosis: A systematic review and meta-analysis. Head Neck 2018; 40(5): 1091-1100. DOI:10.1002/hed.25075

Du J, Liu J, Zhang X, Chen X, Yu R, Gu D, et al. Pre-treatment neutrophil-to-lymphocyte ratio predicts survival in patients with laryngeal cancer. Oncol Lett 2018; 15(2): 1664-1672. DOI:10.3892/ol.2017.7501

Alfaro C, Sanmamed MF, Rodriguez-Ruiz ME, Teijeira A, Onate C, Gonzalez A, et al. Interleukin-8 in cancer pathogenesis, treatment and follow-up. Cancer Treat Rev. 2017; 60: 24-31. DOI:10.1016/j.ctrv.2017.08.004

Maccalli C, Parmiani G, Ferrone S. Immunomodulating and immunoresistance properties of cancer-initiating cells: Implications for the clinical success of immunotherapy. Immunol Invest. 2017; 46(3): 221-238. DOI:10.1080/08 820139.2017.1280051

Kotyza J. Interleukin-8 (CXCL8) in tumor associated non-vascular extracellular fluids: its diagnostic and prognostic values. A review. Int J Biol Markers 2012; 27(3): 169-178. DOI:10.5301/JBM.2012.9261

Zhu YM, Webster SJ, Flower D, Woll PJ. Interleukin-8/ CXCL8 is a growth factor for human lung cancer cells. Br J Cancer 2004; 91(11): 1970-1976. DOI:10.1038/ sj.bjc.6602227

Li A, Varney ML, Singh RK. Expression of interleukin 8 and its receptors in human colon carcinoma cells with different metastatic potentials. Clin Cancer Res 2001; 7(10): 3298-3304.

Atzpodien J, Kirchner H. Cancer, cytokines, and cytotoxic cells: interleukin-2 in the immunotherapy of human neoplasms. Klin Wochenschr 1990; 68(1): 1-11.

Hao W, Zhu Y, Zhou H. Prognostic value of interleukin-6 and interleukin-8 in laryngeal squamous cell cancer. Med Oncol. 2013; 30(1): 333. DOI:10.1007/s12032-012-0333-6

Wang Z, Gao ZM, Huang HB, Sun LS, Sun AQ, Li K. Association of IL-8 gene promoter-251 A/T and IL-18 gene promoter-137 G/C polymorphisms with head and neck cancer risk: a comprehensive meta-analysis. Cancer Manag Res. 2018; 10: 2589-2604. DOI:10.2147/CMAR. S165631

Guerra EN, Acevedo AC, Leite AF, Gozal D, Chardin H, De Luca Canto G. Diagnostic capability of salivary biomarkers in the assessment of head and neck cancer: A systematic review and meta-analysis. Oral Oncol 2015; 51(9): 805-818. DOI:10.1016/j.oraloncology.2015.06.010

Lee KD, Lee HS, Jeon CH. Body fluid biomarkers for early detection of head and neck squamous cell carcinomas. Anticancer Res 2011; 31(4): 1161-1167.

Kilic I, Guldiken S, Sipahi T, Palabiyik O, Akker M, Celik O, et al. Investigation of VEGF and IL-8 gene polymorphisms in patients with differentiated thyroid cancer. Clin Lab 2016; 62(12): 2319-2325. DOI:10.7754/ Clin.Lab.2016.160403

Gokhale AS, Haddad RI, Cavacini LA, Wirth L, Weeks L, Hallar M, et al. Serum concentrations of interleukin-8, vascular endothelial growth factor, and epidermal growth factor receptor in patients with squamous cell cancer of the head and neck. Oral Oncol. 2005; 41(1): 70-76. DOI:10.1016/j.oraloncology.2004.06.005

Bleotu C, Chifiriuc MC, Grigore R, Grancea C, Popescu CR, Anton G, et al. Investigation of Th1/Th2 cytokine profiles in patients with laryngo-pharyngeal, HPV-positive cancers. Eur Arch Otorhinolaryngol 2013; 270(2): 711- 718. DOI:10.1007/s00405-012-2067-7

Li KC, Huang YH, Ho CY, Chu CY, Cha ST, Tsai HH, et al. The role of IL-8 in the SDF-1alpha/CXCR4-induced angiogenesis of laryngeal and hypopharyngeal squamous cell carcinoma. Oral Oncol 2012; 48(6): 507-515. DOI:10.1016/j.oraloncology.2012.01.006

Swenson WG, Wuertz BR, Ondrey FG. Tobacco carcinogen mediated up-regulation of AP-1 dependent pro-angiogenic cytokines in head and neck carcinogenesis. Mol Carcinog 2011; 50(9): 668-679. DOI:10.1002/ mc.20775

Melinceanu L, Sarafoleanu C, Lerescu L, Tucureanu C, Caras I, Salageanu A. Impact of smoking on the immunological profile of patients with laryngeal carcinoma. J Med Life 2009; 2(2): 211-218.

Eyigor M, Eyigor H, Osma U, Yilmaz MD, Erin N, Selcuk OT, et al. Analysis of serum cytokine levels in larynx squamous cell carcinoma and dysplasia patients. Iran J Immunol 2014; 11(4): 259-268. DOI:IJIv11i4A4

Starska K, Forma E, Brys M, Glowacka E, Lewy-Trenda I, Lukomski M, et al. The expression of TLR pathway molecules in peripheral blood mononuclear cells and their relationship with tumor invasion and cytokine secretion in laryngeal carcinoma. Adv Med Sci 2012; 57(1): 124-135. DOI:10.2478/v10039-011-0058-3

Szczepanski M, Stelmachowska M, Stryczynski L, Golusinski W, Samara H, Mozer-Lisewska I, et al. Assessment of expression of toll-like receptors 2, 3 and 4 in laryngeal carcinoma. Eur Arch Otorhinolaryngol 2007; 264(5): 525-530. DOI:10.1007/s00405-006-0215-7

Ralli M, de Vincentiis M, Greco A. Large parapharyngeal mass: a challenging differential diagnosis. Lancet Oncol 2018 Mar;19(3):e181. DOI:10.1016/S1470- 2045(17)30579-X.

Altissimi G, Ralli M, Sementilli G, Fiorentino F, et al. Adult-Type Rhabdomyoma of the Larynx: Clinicopathologic Study of an Uncommon Tumor in a Rare Location. Case Rep Otolaryngol 2017;2017:7186768. DOI:10.1155/2017/7186768

Ralli M, de Vincentiis M, Greco A. First, Rule Out Cancer: Giant Lipoma. Am J Med 2018 Feb;131(2):146-147. DOI:10.1016/j.amjmed.2017.09.013.

Ralli M, Altissimi G, Turchetta R, Rigante M. Metastatic Renal Cell Carcinoma Presenting as a Paranasal Sinus Mass: The Importance of Differential Diagnosis. Case Rep Otolaryngol 2017;2017:9242374. DOI:10.1155/2017/9242374.



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About The Authors

Michele Grasso
Sapienza University of Rome, Italy

Department of Sense Organs

Massimo Ralli
Sapienza University of Rome, Italy

Department of Sense Organs

Griselda Agolli
Sapienza University of Rome, Italy

Department of Sense Organs

Marco Fiore
Institute of Cell Biology and Neurobiology, IBCN-CNR, Rome, Italy

Mauro Ceccanti
Centro Alcologico Regione Lazio, Rome, Italy

Paola Tirassa
Institute of Cell Biology and Neurobiology, IBCN-CNR, Rome, Italy

Marco de Vicentiis
Sapienza University of Rome, Italy

Department of Oral and Maxillofacial Sciences

Antonio Greco
Sapienza University of Rome, Italy

Department of Sense Organs

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