An inexpensive oral rinse test has been shown to distinguish head and neck cancer patients from people who are at high risk for the disease, and offers hope that the diagnosis of oral cancer could be made at a much earlier stage than it is currently.
The test, OraMark (from Vigilant Biosciences), measures levels of a specific biomarker and total protein in a sample of saliva and has just become commercially available. The official launch coincided with the opening of American Society of Clinical Oncology 2016 Annual Meeting in Chicago.
“The reason head and neck cancer usually gets diagnosed late is because it can masquerade as a more benign condition, like a sore throat, so patients won’t realize it’s serious or they’ll go to the doctor and be told it’s a throat infection and maybe they’ll get antibiotics,” said Elizabeth Franzmann, MD, associate professor of otolaryngology at the University of Miami Leonard Miller School of Medicine, and chief scientific officer and scientific cofounder of Vigilant Biosciences, the company that makes the oral rinse test.
“Patients might feel a bit better with antibiotics but symptoms never go away completely, so they’ll go back a few months later, and finally someone might send them on to have a biopsy done. That’s where the delay comes in,” she told Medscape Medical News.
“This test is the first quantitative oral rinse test that accurately measures a tumor-initiating and stem-cell-associated biomarker for oral cancer detection at its earliest stages and picks up head and neck cancer regardless of its etiology,” she explained.
Published Results Encouraging
The test measured levels of a salivary marker, CD44, that is involved in cell proliferation, cell migration, and tumor initiation, and is overexpressed in premalignant lesions. It also measures total protein, which is known to be a good marker of oral cancer. Both are overexpressed in oral cavity and oropharyngeal cancers.
A validation study using a research version of the test was published online March 28 in Cancer Research Prevention.
The study was a case–control, hospital-based evaluation of salivary markers in patients with oral cancer and control subjects.
The control subjects in the hospital-based portion of the study were matched for known oral cancer risk factors, as well as for age, sex, and race. There were no significant differences between case and control subjects with respect to the overall risk-factor burden for oral cancer. (In fact, 10% of control subjects had a history of some form of cancer, so they were at even greater risk for oral cancer than “normal” control subjects).
“We wanted to see if our test could distinguish between patients with oral cancer and those at high risk for oral cancer,” Dr Franzmann noted. And “it did.”
Indeed, a CD44 count of at least 5.33 ng/mL was “highly” associated with oral cancer (adjusted odds ratio, 14.489; P < .0001), compared with a reference group with a CD44 count below 2.22 ng/mL and a total protein count below 1.23 mg/mL.
“This provides strong evidence that CD44 and total protein levels are associated with oral cancer, independent of risk factors,” Dr Franzmann suggested.
In fact, on multivariate analysis adjusted for all confounding factors, researchers found that both progression-free survival and overall survival were reduced by more than threefold in patients with high CD44 levels, compared with cancer patients with lower CD44 levels.
These findings suggest that the quantitative oral test has the potential to identify more aggressive forms of oral cancer, the researchers point out.
The team then assessed whether the specificity of the test would be higher when used in the community, outside of a hospital-based setting. The community they chose to test was impoverished, and many residents smoked and drank more than those with oral cancer, and they usually had poor oral health — another risk factor for oral cancer.
The 150 community participants were assessed with the oral rinse test at baseline and at 1-year follow-up. During that year, they were invited to partake in a cancer-prevention program. “We taught them about nutrition and we gave them access to smoking-cessation programs and low-cost dental care,” Dr Franzmann explained.
At baseline, the specificity of the oral rinse test was 74% in the community-based group, but at follow-up, the specificity reached 95% when both baseline and 1 year tests were positive.
The researchers also studied oral rinse tests from 21 healthy volunteers. In this group, the specificity of the test was over 95%.
Intriguingly, during the year-long study period, when the community group received cancer-prevention interventions, CD44 levels dropped by a significant 24% from baseline (P < .0001). There was also a significant drop in mean total protein levels (P = .036).
“This is one of the beauties of the test,” Dr Franzmann said.
“We know that if you catch oral cancer in its earliest stage, before it has invaded the basement membrane and becomes a real cancer, you can reverse the process with behavioral modification, like stopping smoking, so we may be able to reverse the process before it becomes a real problem in patients at risk for oral cancer,” she said.
Setting of Recurrence
A test that could pick up head and neck cancer at an early stage would be particularly useful in patients at risk for recurrent disease, said David Sidransky, MD, from Johns Hopkins University in Baltimore.
“If somebody has had a cancer and you are worried about it coming back, that would be the easiest circumstance in which to use such a test, to really monitor a patient, to make sure that if the tumor comes back, you find it early,” he told Medscape Medical News. Then patients get less surgery, less radiation, less chemotherapy; they simply have to endure less for us to be able to take care of it.”
“That’s one good situation for the use of a test for oral cancer,” he pointed out.
The screening situation is somewhat less clear, as head and neck cancer, although not uncommon in patients who smoke and drink, is not that common in people who are not smokers or heavy drinkers.
“You would really want to enrich your screening population and target those who smoke the most or who smoke and drink,” Dr Sidransky explained.
Head and neck cancer is often asymptomatic, he said. Unless patients are seeing their physician or their dentist, tumors are easily missed until they are more advanced.
“When tumors are advanced, treatments are much more advanced, too,” he noted.
The OraMark test will be available to clinicians in the United States as a laboratory-developed test in second half of 2016 through OncAlert Labs, LLC, a CLIA-certified laboratory and a Vigilant Biosciences–affiliated company. Drs Franzmann and one of her coauthors hold intellectual property used in the study, and could benefit from its commercialization. Dr Sidransky has disclosed no relevant financial relationships.