Oral Rinse-Based Test Demonstrates Ability to Detect Recurrence of Head and Neck Cancer

Elizabeth J. Franzmann, MD, FACS

An oral rinse-based test designed to detect CD44 and total protein levels displayed potential utility in detecting head and neck cancer recurrence, according to a findings from an observational clinical study (NCT03148665) published in JAMA Otolaryngology – Head & Neck Surgery.¹

At a median follow-up of 36.7 months (IQR, 20.7-39.0), findings from Cox regression models that used CD44 or total protein level as a time-varying covariate showed that, among all enrolled patients (n = 172), a higher CD44 level had a statistically significantly association with a higher risk of disease recurrence (HR, 1.06; 95% CI, 1.00-1.12); total protein levels did not have a statistically significant association with disease recurrence. Additionally, data from a multivariate adjusted analysis demonstrated that both higher CD44 (HR, 1.13; 95% CI, 1.04-1.22) and total protein (HR, 3.51; 95% CI, 1.24-9.98) levels were associated with increased risk of disease recurrence.

“Our study suggests biomarker detection in saliva collected from an oral rinse after initial treatment offers potential to readily assess recurrence risk. Elevated levels of either of 2 biomarkers were associated with disease return,” Elizabeth J. Franzmann, MD, FACS, study coauthor, stated in a news release. Franzmann is director of head and neck research and a professor of otolaryngology at Sylvester Comprehensive Cancer Center and the University of Miami Miller School of Medicine in Florida.² “These patients suffer terribly,” she added. “The more we can minimize those effects by catching recurrence early, the better we can mitigate patient morbidity and mortality.”

The multicenter, nonrandomized study enrolled adult patients with treatment-naive oral and oropharyngeal squamous cell carcinoma. Eligible patients had no evidence of distant metastasis, T1-4N0-3M0 disease, and no prior history of treated upper aerodigestive tract cancer. They also planned to undergo therapy with curative intent, had an ECOG performance status of 3 or less, and had the ability to gargle and spit 5 cc of saline.¹

The objective of the study was to determine whether soluble CD44 and total protein, used in either a point-of-care test or as individual laboratory-based biomarkers, could monitor head and neck cancer recurrence. Patients provided a pretreatment salivary rinse sample, as well as additional samples at 3-, 6-, 12-, and 18-months following the completion of therapy. Patients were then followed for up to 3 years after the completion of therapy or disease recurrence, with additional follow-up taking place at 24-, 30-, and 36-month intervals.

At baseline, the mean patient age was 62.5 years (SD, 10.2). Most patients were male (70.9%), had never smoked (53.5%), formerly or currently drank alcohol (57.6%), were HPV positive (56.4%), and were White (85.5%).

Cancer sites consisted of the oropharynx (65.7%), oral cavity (29.7%), both oropharynx and oral cavity (0.6%), or the site was unknown (4.1%). Patients underwent surgery (52.3%), radiation therapy (43.6%), radiation and surgery (0.6%), and unknown treatments (3.5%) as their primary therapy. Overall clinical disease stages included stage I (16.3%), II (13.4%), III (14.0%), IVA (32.0%), and IVB (2.3%), or status was missing (22.1%).

Additional findings from the study demonstrated that patients with oral cavity cancer at baseline (n = 51) had a point-of-care test positivity rate of 92.2% compared with 77.3% among those with oropharyngeal cancer (n = 110). Among patients who underwent a baseline point-of-care test (n = 168), 33 patients had a negative test, 21.2% of whom experienced disease recurrence. Patients with a positive baseline test (n = 135) experienced disease recurrence at a rate of 21.5%.

“Our laboratory assays showed an association between biomarker levels and later recurrence,” Franzmann noted in the news release.² “Compared [with] patients with normal protein levels 3 months after treatment, patients with about twice as much total protein had an estimated 65% greater risk of recurrence.”

“It would be useful if we had a test that was inexpensive and could be performed and resulted while the patient was in the office. That’s the area we are focusing on,” she added in the news release.

References

1. Franzmann EJ, Qi Y, Peifer S, et al. Salivary CD44 and total protein levels to detect risk for oral and oropharyngeal cancer recurrence: a nonrandomized clinical trial. JAMA Otolaryngol Head Neck Surg. Published online August 15, 2024. doi:10.1001/jamaoto.2024.2490
2. Can a mouthwash-based test help predict head and neck cancer recurrence? News release. University of Miami Miller School of Medicine. August 15, 2024. Accessed September 4, 2024. https://www.eurekalert.org/news-releases/1054672