Abstract

ObjectivesIonizing radiation increases the expression of a number of salivary proteins involved in immunoregulatory networks related to infection, injury, inflammation, and cancer. Our main objective was to analyze whether there are significant differences in salivary cytokines before and after radiotherapy and whether any of them are associated to better outcomes after radiotherapy serving as a potential predictive biomarker of response to the treatment.Materials and methodsWe analyzed a panel of eight salivary markers (IL-4, IL-6, IL-8, and IL-10; MCP-1; TNF-α; VEGF; and EGF) in a group of HNC patients (N = 30), before and after irradiation treatment pre- and post-RT. We also compared these results with a group of healthy controls (N = 37). In both groups, we used stimulated saliva and we performed immunoassays based on multi-analyte profiling technology (Luminex xMAP).ResultsIn our group of 30 HNC patients, 24 of them showed a good clinical response after radiotherapy treatment while 6 cases did not respond to radiotherapy. The data revealed a post-treatment increase in multiple cytokines in the stimulated saliva of HNC patients; the increases in IL-8 and MCP-1 were statistically significant (p ≤ 0.001 and p ≤ 0.0001, respectively). Analysis of receiver operating characteristic curves indicated the strong potential of IL-8 as a predictive biomarker of RT good outcomes (area under the curve = 0.84; p = 0.018).ConclusionsAfter analyzing the panel of salivary cytokines, IL-8 showed the best association to the response to radiotherapy; in this sense, low IL-8 levels in the saliva of HNC patients before receiving irradiation therapy are associated with positive RT outcomes.Clinical relevanceSalivary IL-8 expression in HNC patients undergoing RT may serve as a potential predictive biomarker of response to the treatment.

Highlights

  • Head and neck cancer (HNC) is a complex and heterogeneous pathology, encompassing a variety of tumors that originate from the pharynx, larynx, paranasal sinuses, nasal cavity, salivary glands, and oral cavity [1]

  • 60% of the patients were diagnosed at an advanced stage of disease (T3–T4), and 46.67% presented with neck metastasis

  • The development of oral mucositis after RT was observed in 90% of the cases; in particular, two patients developed mild mucositis, patients presented moderate mucositis, and severe mucositis was observed in patients

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Summary

Introduction

Head and neck cancer (HNC) is a complex and heterogeneous pathology, encompassing a variety of tumors that originate from the pharynx, larynx, paranasal sinuses, nasal cavity, salivary glands, and oral cavity [1]. It is the sixth most common neoplasia worldwide, with an incidence estimated at 650,000 cases and 330,000 deaths per year [2]. The majority of HNCs are epithelial tumors, of which 90% are squamous cell carcinomas (SCCs) with various degrees of differentiation [3]. The risk of developing this pathology increases with age, and the majority of cases occur in people aged 50 years or older [4]. A high-risk human papillomavirus infection, especially of type 16, has recently been implicated in malignant pathogenesis arising from the

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