Assessment of an Oral Rinse, Qualitative, Point-of-care Assay to Predict Head and Neck Squamous Cell Carcinoma (HNSCC)

Objectives: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cause of cancer mortality throughout the world affecting some 50,000 people in the US and 600,000 worldwide each year. The ability to detect the disease at an earlier stage could have significant impact on overall outcome. Previous studies have demonstrated that a combined salivary CD44, a tumor-initiating marker, and total protein (TP) assay was able to aid in the diagnosis of HNSCC. We sought to understand the performance of these biomarkers in a prospective case:control population using an easy to use qualitative, point-of-care device which evaluates the presence of pre-validated thresholds for CD44 and total protein in an oral rinse solution.
Methods: Saline oral rinse specimens (~5ml) from 134 patients (38 HNSCC cases; 96 controls) were obtained from biorepositories. Samples were thawed, gently swirled and the point of care device submerged for 20 minutes. Two independent operators reported results using a graphic visualization tool as a guide. A test was considered positive if a CD44 band was observed or TP levels were >/= 2 or 3 (scale 0-7). A weighted kappa was used to assess agreement between operators along with sensitivity, specificity and the NPV.
Results: The mean age of HNSCC (cases) was 60 years, 60% male, 97% white and 74% smokers vs. (controls): 43 years, 28% male, 96% white and 0% smokers. Agreement between operators with a weighted kappa was 75% (95% CI: 65.91% - 83.34%) for CD44 and 72% (95% CI: 65.03%-79.79%) for TP, McNemar's p-value 0.97 and 0.91, respectively. The sensitivity ranged from 70-84% with a specificity of 30-50%, and was dependent upon an operator selected TP value of 2 vs. 3 as a positive test result. Using a disease prevalence of 9.27%, the NPV was >90%.
Conclusions: An easy to administer point-of-care device reliably identifies elevated levels of either CD44 or TP in oral salivary rinses. A patient with a negative test result, in conjunction with clinical judgement, has a lower likelihood of oral / oropharyngeal cancer while a positive test result would warrant further discrimination including repeating the assay or using a more quantitative assessment of the individual biomarkers.