Salivary Cytokines in Patients with Head and Neck Cancer (HNC) Treated with Radiotherapy

Overview

Journal J Clin Exp Dent

Specialty Dentistry

Date 2019 Nov 9

PMID 31700580

Citations 5

Authors

Sara Principe

Valentina Dikova

Jose Bagan

Affiliations

Soon will be listed here.

Abstract

Background: Head and Neck cancer (HNC) is the sixth most common cancer in the world. The 5-year survival rate depends on early diagnosis and appropriate therapy. Typically, late diagnosis requires not only surgical intervention, but also radiotherapy treatment combined or not with chemotherapy. Ionizing radiation is known to increase the expression of a number of cytokines involved in inflammation, wound healing and toxicity areas. Salivary cytokines have promising features to be used as biomarkers for disease screening and outcome prediction in this malignancy. The aim of this article is to analyze the role of salivary inflammatory response elements in HNC patients treated with radiotherapy, their modulation and association with the treatment outcome.

Material And Methods: A bibliographical search was performed on Pubmed, Cochrane and Embase using the following keywords: cytokines, saliva, head and neck cancer, radiotherapy. The cut-off point for the research were scientific papers published over the last 10 years. After a two-step selection process, 15 articles were identified and subjected to review.

Results: Radiotherapy treatment was shown to influence a number of salivary cytokines. A trend towards a growth of IL-1β, IL-6, IL-8, MCP-1, and TNF-α levels was observed and it correlated with the irradiation dose.

Conclusions: The analysis of salivary cytokines could be a useful biomarker for predicting radiotherapy outcome in HNC. However, large-scale investigations are required to validate the use of these cytokines in predicting and diagnosing HNC, as well as evaluating the response to the treatment. Cytokines, saliva, head and neck cancer, radiotherapy.

Citing Articles

Effect of Dendrobium Officinale on Radioactive Oral Mucositis of Nasopharyngeal Carcinoma and Changes of Oral Microecology.

Yang J, Liu Y, Yao H, Sun M, Tong Y, Ma G Integr Cancer Ther. 2025; 24():15347354251313524.

PMID: 39811879 PMC: 11733883. DOI: 10.1177/15347354251313524.

Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort Study.

Brandt E, Keskin M, Raisanen I, Tervahartiala T, Makitie A, Harmankaya I Biomedicines. 2024; 12(1).

PMID: 38275388 PMC: 10813307. DOI: 10.3390/biomedicines12010027.

Mitogen-activated protein kinase-activated protein kinase-2 (MK2) and its role in cell survival, inflammatory signaling, and migration in promoting cancer.

Morgan D, Berggren K, Spiess C, Smith H, Tejwani A, Weir S Mol Carcinog. 2021; 61(2):173-199.

PMID: 34559922 PMC: 8799529. DOI: 10.1002/mc.23348.

Salivary IL-8 as a putative predictive biomarker of radiotherapy response in head and neck cancer patients.

Principe S, Zapater-Latorre E, Arribas L, Garcia-Miragall E, Bagan J Clin Oral Investig. 2021; 26(1):437-448.

PMID: 34251535 PMC: 8791883. DOI: 10.1007/s00784-021-04017-0.

Chemokine-Cytokine Networks in the Head and Neck Tumor Microenvironment.

Nisar S, Yousuf P, Masoodi T, Wani N, Hashem S, Singh M Int J Mol Sci. 2021; 22(9).

PMID: 33925575 PMC: 8123862. DOI: 10.3390/ijms22094584.

References

Epstein J, Gorsky M, Guglietta A, Le N, Sonis S . The correlation between epidermal growth factor levels in saliva and the severity of oral mucositis during oropharyngeal radiation therapy. Cancer. 2001; 89(11):2258-65. DOI: 10.1002/1097-0142(20001201)89:11<2258::aid-cncr14>3.0.co;2-z. View

Guerra E, Rego D, Elias S, Coletta R, Mezzomo L, Gozal D . Diagnostic accuracy of serum biomarkers for head and neck cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2016; 101:93-118. DOI: 10.1016/j.critrevonc.2016.03.002. View

Sahibzada H, Khurshid Z, Khan R, Naseem M, Siddique K, Mali M . Salivary IL-8, IL-6 and TNF-α as Potential Diagnostic Biomarkers for Oral Cancer. Diagnostics (Basel). 2017; 7(2). PMC: 5489941. DOI: 10.3390/diagnostics7020021. View

Guerra E, Acevedo A, Ferreira Leite A, 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):805-18. DOI: 10.1016/j.oraloncology.2015.06.010. View

Bossi P, Bergamini C, Miceli R, Cova A, Orlandi E, Resteghini C . Salivary Cytokine Levels and Oral Mucositis in Head and Neck Cancer Patients Treated With Chemotherapy and Radiation Therapy. Int J Radiat Oncol Biol Phys. 2016; 96(5):959-966. DOI: 10.1016/j.ijrobp.2016.08.047. View

Elrefaey S, Massaro M, Chiocca S, Chiesa F, Ansarin M . HPV in oropharyngeal cancer: the basics to know in clinical practice. Acta Otorhinolaryngol Ital. 2015; 34(5):299-309. PMC: 4299160. View

Huang S, OSullivan B . Oral cancer: Current role of radiotherapy and chemotherapy. Med Oral Patol Oral Cir Bucal. 2013; 18(2):e233-40. PMC: 3613874. DOI: 10.4317/medoral.18772. View

Schapher M, Wendler O, Groschl M . Salivary cytokines in cell proliferation and cancer. Clin Chim Acta. 2011; 412(19-20):1740-8. DOI: 10.1016/j.cca.2011.06.026. View

Epstein J, Emerton S, Guglietta A, Le N . Assessment of epidermal growth factor in oral secretions of patients receiving radiation therapy for cancer. Oral Oncol. 1998; 33(5):359-63. DOI: 10.1016/s1368-8375(97)00009-2. View

10.

Osman T, Costea D, Johannessen A . The use of salivary cytokines as a screening tool for oral squamous cell carcinoma : A review of the literature. J Oral Maxillofac Pathol. 2012; 16(2):256-61. PMC: 3424944. DOI: 10.4103/0973-029X.99083. View

11.

St John M, Li Y, Zhou X, Denny P, Ho C, Montemagno C . Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2004; 130(8):929-35. DOI: 10.1001/archotol.130.8.929. View

12.

Citrin D, Hitchcock Y, Chung E, Frandsen J, Urick M, Shield W . Determination of cytokine protein levels in oral secretions in patients undergoing radiotherapy for head and neck malignancies. Radiat Oncol. 2012; 7:64. PMC: 3439271. DOI: 10.1186/1748-717X-7-64. View

13.

Sahebjamee M, Eslami M, AtarbashiMoghadam F, Sarafnejad A . Salivary concentration of TNFalpha, IL1 alpha, IL6, and IL8 in oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal. 2008; 13(5):E292-5. View

14.

Eisbruch A, Marsh L, Martel M, Ship J, Haken R, Pu A . Comprehensive irradiation of head and neck cancer using conformal multisegmental fields: assessment of target coverage and noninvolved tissue sparing. Int J Radiat Oncol Biol Phys. 1998; 41(3):559-68. DOI: 10.1016/s0360-3016(98)00082-0. View

15.

Lo Nigro C, Denaro N, Merlotti A, Merlano M . Head and neck cancer: improving outcomes with a multidisciplinary approach. Cancer Manag Res. 2017; 9:363-371. PMC: 5571817. DOI: 10.2147/CMAR.S115761. View

16.

Juretic M, Cerovic R, Belusic-Gobic M, Brekalo Prso I, Kqiku L, Spalj S . Salivary levels of TNF-α and IL-6 in patients with oral premalignant and malignant lesions. Folia Biol (Praha). 2013; 59(2):99-102. View

17.

Rathnayake N, Akerman S, Klinge B, Lundegren N, Jansson H, Tryselius Y . Salivary biomarkers for detection of systemic diseases. PLoS One. 2013; 8(4):e61356. PMC: 3634781. DOI: 10.1371/journal.pone.0061356. View

18.

Russo N, Bellile E, Murdoch-Kinch C, Liu M, Eisbruch A, Wolf G . Cytokines in saliva increase in head and neck cancer patients after treatment. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016; 122(4):483-490.e1. PMC: 5031552. DOI: 10.1016/j.oooo.2016.05.020. View

19.

Rhodus N, Ho V, Miller C, Myers S, Ondrey F . NF-kappaB dependent cytokine levels in saliva of patients with oral preneoplastic lesions and oral squamous cell carcinoma. Cancer Detect Prev. 2005; 29(1):42-5. DOI: 10.1016/j.cdp.2004.10.003. View