The high mortality and morbidity of head and neck cancer diagnosed at later stages highlights the need for early detection techniques and screening tools. We aim to determine whether oral swirls, a potential non-invasive screening tool for head and neck cancer, are able to predict the presence of oropharyngeal squamous cell carcinoma (SCC). Oral swirls are a simple, rapid and cost-effective method used to isolate salivary microRNAs from extracellular vesicles, which have previously been able to predict oral cavity squamous cell carcinoma with 87% sensitivity and 82% specificity. A multicentre study is underway within the Departments of Otorhinolaryngology, Head and Neck Surgery at Flinders Medical Centre in South Australia and Royal Melbourne Hospital in Victoria, as well as the Dental Oncology Unit of the Victorian Comprehensive Cancer Centre. Oral swirl samples are collected in the pre-treatment stage for known malignancies and in the clinic or pre-operative setting for normal controls. For this study, oral swirl samples have been collected from 113 participants across all sites, with 69 head and neck cancers including 30 oral cavity SCC, 24 oropharyngeal SCC and 8 unknown primary head and neck SCC. microRNA quantification will be performed with RT-qPCR using a multiplex primer pool of 7 microRNAs from a previously published protocol, with the addition of 4 key microRNAs identified in the literature as being dysregulated in oropharyngeal SCC. Differential microRNA expression between samples with known malignancy compared to controls will be used to build a predictive model to determine whether oropharyngeal SCC can be identified using an oral swirl test.