Salivary markers and risk factor data: A multivariate modeling approach for head and neck squamous cell carcinoma detection

Abstract

Abstract.Background: Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease largely due to late stage diagnosis. Prior work indicates that soluble CD44 (solCD44) and total protein may be useful diagnostic markers for HNSCC. In this study we combine the markers solCD44, IL-8, HA, and total protein with demographic and risk factor data to derive a multivariate logistic model that improves HNSCC detection as compared to our previous data using biomarkers alone. Methods: We performed the solCD44, IL-8, HA, and total protein assays on oral rinses from 40 HNSCC patients and 39 controls using ELISA assays. Controls had benign diseases of the upper aerodigestive tract and a history of tobacco or alcohol use. All subjects completed a questionnaire including demographic and risk factor data. Results: Depending on cancer subsite, differences between cases and controls were found for all markers. A multivariate logistic model including solCD44, total protein and variables related to smoking, oral health and education offered a significant improvement over the univariate models with an AUC of 0.853. Sensitivity ranged from 75-82.5% and specificity from 69.2-82.1% depending on predictive probability cut points. Conclusion: A multivariate model, including simple and inexpensive molecular tests in combination with risk factors, results in a promising tool for distinguishing HNSCC patients from controls. Impact: In this case-control study, the resulting observations led to an unprecedented multivariate model that distinguished HNSCC cases from controls with better accuracy than the current gold standard which includes oral examination followed by tissue biopsy. Since the components are simple, noninvasive, and inexpensive to obtain, this model combining biomarkers, risk factor and demographic data serves as a promising prototype for future cancer detection tests.

CD44 interacts with EGFR and promotes head and neck squamous cell carcinoma initiation and progression

“…Our prior work shows that breakdown products of CD44 are overexpressed in oral rinses from HNSCC patients compared to controls (8–10, 22). CD44 overexpression in HNSCC tissue is also associated with a worse prognosis (23–25).…”

Risk Stratification System for Oral Cancer Screening

“…Exclusion decisions were blinded to marker level results. The resulting marker panel was validated using 27 oral cavity and oropharyngeal cases and 39 high-risk controls enrolled between 2004 and 2006 in a previous case-control study (31). …”

“…Soluble CD44 (solCD44), released by proteinases, is detectable in body fluids (28,29). Prior work suggests that total protein is also an effective oral cancer marker (30,31). Both can be measured with simple, inexpensive assays and are overexpressed in oral cavity and oropharyngeal cancers suggesting usefulness in both HPV positive and negative disease (29–32).…”

Chemokines and Cytokines as Salivary Biomarkers for the Early Diagnosis of Oral Cancer

“…Using an array of biomarkers from oral rinses from 40 HNSCC patients and 39 controls assessed by ELISA assays, it has been shown that it is possible to distinguish HNSCC cases from controls, particularly when the patients demographics were also considered [12]. Further, extensive analyses of the plasma levels of 48 proteins (26 cytokines, 10 chemokines, and 12 growth factors) in 111 untreated OSCC patients, 112 healthy individuals, and 107 individuals with potentially malignant oral mucosal lesions showed that the levels of 12 proteins were significantly dysregulated in OSCC patients serum [13].…”