A noninvasive oral brush biopsy test adapted from a molecular assay was able to quickly distinguish oral squamous cell carcinoma from other oral disorders with high accuracy, according to results from a large diagnostic case-control study published in Biomarker Research.
“Oral cancer survival is directly linked to how early it is found, yet our current diagnostic pathway is blunt—most patients with a suspicious lesion end up having an invasive biopsy even when the overwhelming likelihood is that it is benign. This test changes that. It gives clinicians a rapid, accurate, and noninvasive way to triage patients, and crucially, it can be repeated. That means we can now monitor patients with persistent premalignant lesions regularly and systematically—and pick up cancers much earlier than we would have been able to before,” said lead researcher Muy-Teck Teh, BSc (Hons), PhD, FHEA, Professor of Molecular Oral Oncology at Queen Mary University of London.
Background and Study Methods
Researchers sought to determine if a previously validated microbiopsy-based multigene assay could be adapted and used as a rapid, noninvasive brush biopsy test for the detection of oral squamous cell carcinoma (qMIDSV3). They believed that the adapted test could differentiate oral squamous cell carcinoma from low-risk oral potentially malignant disorders and contralateral normal mucosa.
They conducted a prospective diagnostic case-control study to validate the multigene mRNA test for detecting oral squamous cell carcinoma. They used 1,090 oral brush biopsies paired with contralateral nonlesion mucosa from 545 patients.
Quantitative polymerase chain reaction testing quantified mRNA levels of INHBA, S100A16, YAP1, and POLR2A genes from each brush biopsy. The researchers created a qMIDS algorithm to compute a malignancy index to stratify cancer risk for each patient.
Key Findings
The adapted qMIDSV3 brush biopsy test differentiated oral squamous cell carcinoma from oral leukoplakia and oral lichen planus with an area under the curve of 0.975, a sensitivity of 95.7%, a specificity of 95.1%, and an overall accuracy of 95.5%. The false-positive rate was 4.9% and the false-negative rate was 4.3%.
“We were genuinely astonished by the fact that the brush swab test performance is comparable to a microbiopsy,” Dr. Teh said. “It suggests that the biological signal captured by these four genes is sufficiently strong and consistent that it can be detected even from the superficial exfoliated cells collected by a brush biopsy. The clinical implications are significant: patients no longer need even a minimally invasive procedure to benefit from molecularly guided triage.”
INHBA and S100A16 were also identified as key biomarkers for oral squamous cell carcinoma in brush biopsies.
The study authors determined that the qMIDSV3 test could be used as a rapid case-finding or triage test, which could possibly spare most patients with low-risk oral potentially malignant disorders from invasive tissue biopsies that may be unnecessary. The brush biopsy test enabled safe, repeatable sampling for long-term surveillance for potential oral squamous cell carcinoma.
DISCLOSURES: Dr. Teh declared that patents have been filed by QM Innovation Ltd for the qMIDS technology covering its methodology and clinical applications. No disclosures were reported by the other authors.
