Cytokines in saliva increase in head and neck cancer patients after treatment

Abstract

Approximately one-third of advanced squamous cell carcinoma of the head and neck (HNSCC) recur within two years of treatment. Due to ease of collection, saliva is of interest to monitor changes that correlate with treatment. Previously this was a challenge due to xerostomia following conventional radiation. The emergence of gland-sparing radiation has made it possible to collect saliva post-treatment. Objective This study investigated changes in cytokines in saliva pre- to post-treatment to provide foundational knowledge for future studies exploring the use of saliva to monitor treatment response. Study Design Pre- and post-treatment saliva was evaluated for eight cytokines by multiplex assay and ELISA. Results In oropharyngeal HNSCC, secretion of EGF, GROα, IL-1α, IL-1β, IL-6, IL-8, TNFα, and VEGF increased significantly post-treatment. In additional patients, significant increases of GROα and IL-6 were validated but EGF showed no change. Conclusions The uniqueness of this study is the comparison of salivary cytokines from HNSCC patients pre- and post-treatment.

Salivary Cytokines in patients with Head and Neck Cancer (HNC) treated with Radiotherapy

“…Several studies reported increases in salivary IL-8, TNF-α, IL-1, IL-6 in HNC compared to controls but did not quantify changes post-treatment. A surprising finding observed by Russo et al (8) was the post-treatment increase in cytokines. The study quantified cytokines pre- and post-treatment.…”

“…Russo et al in 2016 (8) showed a post-treatment increase in multiple cytokines in stimulated whole saliva from patients with HNC. Eight cytokines — TNFα, EGF, GROα, IL-1α, IL-1β, IL-6, IL-8, and VEGF — were analyzed and quantified concurrently in a multiplex assay.…”

“…Cytokines have also been investigated in saliva as potential protein biomarkers of HNC (7)(5). In particular, various inflammatory and angiogenic cytokines have been proven to be increased in the saliva of tumor patients (8).…”

“…As the use of gland-sparing, intensity-modulated radiation therapy (IMRT) increases, Russo et al in 2016 (8) investigated a panel of cytokines in whole saliva from HNC patients, pre- and post-treatment. Even though most studies mention elevated concentrations of candidate tumor markers in saliva, this is not true for all of them, as reductions in peptide expression have also been reported (9).…”

Epigenetic stratification of head and neck cancer survivors reveals differences in lycopene levels, alcohol consumption, and methylation of immune regulatory genes

“…Survivors may also experience inflammatory issues, including lymphedema, ulceration of the mucosal membranes, and increased susceptibility to infection. Not only do HNC patients have higher cytokine levels than controls, but cytokine levels continue to remain high even after radiation and chemoradiation therapy [16][17][18]. Higher levels of interleukin 6 (IL-6) and C-reactive protein (CRP) have been associated with higher levels of fatigue after radiation [19].…”