Head and neck cancers (HNCs) are the seventh most common cancer worldwide, accounting for 4–5% of all malignancies. Salivary metabolites, which serve as key metabolic intermediates and cell-signalling molecules, are emerging as potential diagnostic biomarkers for HNC. While current research has largely concentrated on these metabolites as biomarkers, a critical gap remains in understanding their fluctuations before and after treatment, as well as their involvement in oral side effects. Recent studies emphasise the role of the oral microbiome and its metabolic activity in cancer progression and treatment efficacy by bacterial metabolites and virulence factors. Oral bacteria, such as P. gingivalis and F. nucleatum, contribute to a pro-inflammatory environment that promotes tumour growth. Additionally, F. nucleatum enhances its virulence through flagellar assembly and iron transport mechanisms, facilitating tumour invasion and survival. Moreover, alterations in the oral microbiome can influence chemotherapy efficacy and toxicity through the microbiota–host irinotecan axis, highlighting the complex interplay between microbial communities and therapeutic outcomes. Salivary metabolite profiles are influenced by factors such as gender, methods, and patient habits like smoking—a major risk factor for HNC. Radiotherapy (RT), a key treatment for HNC, often causes side effects such as xerostomia, oral mucositis, and swallowing difficulties which impact survivors’ quality of life. Intensity-modulated radiotherapy (IMRT) aims to improve treatment outcomes and minimise side effects but can still lead to significant salivary gland dysfunction and associated complications. This review underscores the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes.

Introduction: This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and neck tumours treated with intensity-modulated-radiotherapy (IMRT). Methods: Saliva samples/clinical data were obtained from 40 head and neck cancer patients treated at Guy’s Hospital before -IMRT(T0) and after-IMRT (T1 = 6 m, T2 = 12 m) (ethics approval/consent). Salivary flow rate, total protein concentration, and secretion rate were determined from saliva samples and compared with pre-treatment values. OM was assessed, total/specific salivary proteins, including mucin 5B and 7, IgA, cystatin-S, albumin, and α-amylase, were quantified. Results: 95% patients experienced OM during IMRT, with 33 subjects reaching grade 2&3. At T1, there was a significant reduction in salivary flow rate, total protein secretion rate, α-amylase and cystatin-S compared to baseline. Remarkably IMRT did not significantly alter mucin 5B and 7, or the IgA secretion rate at any time point. At T1, all the analyzed proteins were associated with the OM outcomes. In addition, there was a significant inverse correlation between IgA concentration at T0 and the severity of OM during IMRT. Conclusion: This study revealed significant associations between several salivary proteins and OM in patients with head and neck cancer undergoing IMRT. Further longitudinal studies are needed to confirm these results. Clinical significance: The study contributes to the understanding of certain salivary proteins association with OM. This could be the first step towards identifying potential salivary markers that could offer perspectives for personalized medicine approaches to improve their quality of life (QoL). Research question: What is the association between salivary proteins and the occurrence and severity of OM in head and neck cancer patients? Aim: To assess the association between salivary protein composition with the clinical onset/severity of oral mucositis (OM) in head and neck cancer patients treated with intensity modulated radiotherapy. Null hypothesis: There is no association between salivary proteins and onset/severity of OM in HNC patients.

Objective: This study aimed to assess the salivary protein composition variations in head and neck cancer patients (HNC) undergoing Intensity-Modulated Radiotherapy (IMRT) and examined the correlation with the clinical onset/severity of oral mucositis (OM). Methods Saliva samples/clinical data were obtained from 40 HNC patients pre-IMRT(T0) and post-IMRT (T1=6m, T2=12m) treated at Guy’s Hospital (ethics approval/consent). Salivary flow rate (SFR), protein concentration (TPC) and secretion rate (TPSR) were determined from unstimulated, whole-mouth saliva samples and compared to pre-treatment levels. Clinical parameters/side effects such as OM was assessed, salivary proteins were quantified using BCA assay, SDS-PAGE/PAS-staining determined MUC5B and MUC7, ELISA assays: IgA, cystatin S and albumin; α-amylase activity by kinetic assays. Results 95 % patients experienced OM during IMRTwith 33 reaching grade 2&3. Furthermore, 6 months post-IMRT, a significant reduction, in SFR, TPSR, α-amylase and cystatin S compared with baseline. Remarkably IMRT did not significantly alter MUC5B/MUC7, and IgA secretion rates at any timepoint. Moreover, there were significant/negative correlations between IgA concentration at T0 with OM onset/severity during the cancer treatment, (p = 0.006). Conclusion This study reveals that IMRT prevents damage to salivary glands but does not prevent OM, suggesting that salivary mucins may not be involved in the onset /severity of OM.