Treatment-related changes in salivary CD44 and total protein in patients with oral and oropharyngeal cancer.

Abstract

e18061 Background: Prior smaller-scale studies have demonstrated elevated salivary CD44 and total protein (TP) in patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC), highlighting biomarker potential as an early detection tool. However, the effects of treatment remain poorly understood. This post-hoc analysis of a multi-institutional study aims to characterize the effects of primary surgery versus radiotherapy on these biomarkers. Methods: Oral rinses were collected from biopsy-proven, newly diagnosed OOPSCC patients at five institutions (UCSD, San Diego VA, Johns Hopkins, Greater Baltimore Medical Center, and NYU) from 2017-2019. Rinses were collected at enrollment and 3-, 6-, 12-, and 18-months post-treatment. CD44 ELISA assays and modified Lowry protein were performed to calculate biomarker levels. Patients were followed for 3 years, and we excluded those with recurrent or persistent disease. Paired samples T-tests were used to assess biomarker changes over time within groups, while independent samples T-tests compared levels and changes between treatment groups. Due to the non-normality of biomarker data, LN-transformed values were used for analysis. Results: In total,135 OOPSCC patients were analyzed. Our cohort had a mean age of 62.3 years (SD=10.82) and had 93 (68.9%) male participants. 38 (28.1%) of patients had oral cavity cancer, 94 (69.6%) had oropharyngeal cancer, and 3 (2.2%) had oral cavity and oropharyngeal involvement. At 3 months post-treatment, CD44(log) levels were significantly lower in the primary surgery group (mean = 1.361, SD = 0.691) compared to the radiation group (mean=1.688, SD=0.833, p = 0.032). Comparatively, CD44(log) increased in the radiation group (enrollment mean=1.520, SD=0.595) and decreased in the surgery group (enrollment mean=1.586, SD=0.654) from enrollment to 3 months post-treatment (p=0.035). Intragroup analysis of the radiation group showed decreased CD44 (log) levels at 12 months (mean=1.579, SD=0.644) vs the elevated 3-month values (mean=1.688, SD=0.833, p=0.048). TP levels in the radiation group decreased from enrollment (mean=0.386, SD=0.168) to 18 months (mean=0.324, SD=0.136; p=0.045). Intragroup analysis for surgical treatment revealed an initial decrease in TP levels from enrollment (mean=0.388, SD=0.168) to 3 months (0.318, SD=0.165; p=0.021). Conclusions: Our study demonstrates differing effects of primary surgery vs radiotherapy on salivary CD44 and TP in OOPSCC patients. CD44(log) levels were lower among patients receiving primary surgery at 3 months post-treatment, while radiated patients saw elevated levels. TP followed a similar short-term decrease in primary surgery patients but did not change among radiation patients. Although radiation patients had a sustained decrease in TP at 18-months vs. enrollment values, neither TP nor CD44 differed between radiation and surgery at 18 months.