Simple Oral Rinse May Detect Head and Neck Ca Early

LOS ANGELES—A simple oral rinse could detect head and neck squamous cell carcinoma (HNSCC) by showing elevations in CD44, a protein that is a potential biomarker for HNSCC, and also CD44 hypermethylation, investigators reported at the 2007 American Association for Cancer Research annual meeting (abstract 3506).

"Our study has shown that an oral rinse test that is simple enough to be administered at any community health center is likely to detect cancer nearly 90% of the time," said Elizabeth Franzmann, MD, assistant professor of otolaryngology, University of Miami Sylvester Comprehensive Cancer Center, Miami.

While CD44 exists on the surface of cells in healthy tissue, the protein is elevated at least sevenfold in head and neck cancer. The oral rinse flushes out CD44 by washing over the cellular membranes of interest in the throat and mouth, she explained.

At a press conference, Dr. Franzmann noted that the primary risk factors for head and neck cancer are tobacco and alcohol use. "Over 50 million people fall into this group, but we are not screening for this," she said. The "swish and gargle" test is even simpler than screening for prostate cancer with PSA and cervical cancer with Pap smears, she said, and has a comparable sensitivity and specificity.

"We are developing a simple, noninvasive, inexpensive test that reliably detects head and neck cancer before clinically evident disease presents itself. Modifications involving additional markers are in progress and will likely lead to even more accurate testing that can be done in the outpatient setting," she said. Outpatient testing would eliminate lack-of-access issues that are frequent barriers to screening programs. This would be especially valuable for minorities, who are disproportionately affected with head and neck cancer, she noted.

The study attempted to determine if soluble CD44 alone was sufficient to differentiate HNSCC from benign diseases. Oral rinses were collected from 102 head and neck cancer patients and 69 control subjects with benign diseases of the upper aerodigestive tract (UADT) and a history of tobacco or alcohol use, Dr. Franzmann said. The test was also performed on six patients with various grades of UADT squamous cell dysplasia.

The investigators further evaluated CD44 promoter hypermethylation using methylation-specific PCR on oral rinses from 11 HNSCC subjects with false-negative CD44 tests (low soluble CD44 levels) and 11 control patients matched for risk factor behavior, demographics, and soluble CD44 level.

Mean salivary soluble CD44 levels were 24.4 ng/mL for HNSCC patients, compared with 9.9 ng/mL for control subjects with benign disease (P < .0001). "After controlling for potential confounders, we found that soluble CD44 levels were elevated in head and neck cancer patients regardless of risk behavior or demographic factors," Dr. Franzmann reported.

Depending on the cut-points and HNSCC site, sensitivity ranged from 62% to 70%, and specificity from 75% to 88%. Fifty percent of patients without invasive disease had elevated soluble CD44 levels that were associated with either the presence of dysplasia or imminent malignant progression.

In the hypermethylation pilot study, 9 of 11 HNSCC patients with low soluble CD44 levels vs none of 11 control subjects demonstrated CD44 promoter hypermethylation. This suggests that in HNSCC patients, when soluble CD44 levels are low, CD44 hypermethylation is usually present. Since controls did not show CD44 hypermethylation, this marker in combination with the soluble CD44 test may significantly increase sensitivity without adversely affecting specificity, Dr. Franzmann suggested.