Abstract Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease that is cured only 50% of the time. If diagnosed early, survival rates could reach 80%. CD44 comprises a family of isoforms that, in certain tumors, are alternatively spliced and overexpressed in tissues and in circulation as soluble CD44 (solCD44). Our previous pilot data in 26 HNSCC patients and 10 normal controls showed mean salivary solCD44 levels were 7 times higher in HNSCC patients (p<0.001). Here we combine our previous experience with additional patients to examine the salivary solCD44 test as a screening tool for HNSCC. We performed a solCD44 ELISA (Bender MedSystems) on saliva from 55 HNSCC patients and 22 normal volunteers. To correct for patients’ varying hydration status, we normalized the solCD44 levels to protein (Bio-Rad Laboratories). All samples were performed in triplicate. A test was considered positive if either the solCD44 or the normalized solCD44 test was positive using preliminary cut-off points. To test if the matrix (saliva) affects results, we measured solCD44 levels in serial dilutions of two saliva samples. Salivary solCD44 levels were significantly elevated in saliva from HNSCC patients (mean=9.198) compared to normals (mean=3.523, p<0.005). Using preliminary cut-off points, the test detected HNSCC with 60% sensitivity and 91% specificity. Salivary solCD44 levels were more elevated in patients with oral cavity/ oropharyngeal cancers (mean=11.48, n=29) than patients with larynx/ hypopharynx cancers (mean=5.638, n=22, p<0.05). The test detected 66% of oral cavity / oropharyngeal tumors. The test detected 100% of patients with cervical metastases of unknown primary site (n=3). Levels did not vary significantly with stage. Matrix effects were noted in one of the two samples studied. In this preliminary analysis, the salivary solCD44 ELISA appears to effectively detect HNSCC. The test is most effective in detecting oral cavity/ oropharyngeal tumors, the most common sites for HNSCC. Since early detection of HNSCC results in significantly improved survival, the salivary solCD44 test may be an effective HNSCC screening tool alone or in combination with other markers. Further study on more patients is warranted. Assays should be optimized to minimize matrix effects.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]