INHBA–S100A16 dysregulation enables a noninvasive molecular stratification platform for rapid detection of oral squamous cell carcinoma - results from a large diagnostic case-control study

Sep 22, 2026

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Early diagnosis of oral squamous cell carcinoma (OSCC) is critical, yet most oral potentially malignant disorders (OPMDs) are benign, leading patients to undergo unnecessary invasive scalpel biopsies that cause diagnostic delays and harm. A rapid non-invasive molecular diagnostic tool could improve early detection and reduce procedures. This study assessed whether a validated microbiopsy-based multigene assay (qMIDSV2) can be adapted into a rapid brush biopsy test (qMIDSV3) for accurate OSCC detection.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Background

Epidemiology and burden of oral cancer

OPMDs and malignant transformation risk

Methods

Study design and participants

Brush biopsy and qPCR gene panel

Malignancy index algorithm

Results

Diagnostic performance metrics

False-positive and false-negative behavior

Conclusions

Clinical utility for rapid triage and surveillance

Teh etal. Biomarker Research (2026) 14:76 Biomarker Research [https://doi.org/10.1186/s40364-026-00963-7](https://doi.org/10.1186/s40364-026-00963-7) RESEARCH Open Access INHBA–S100A16 dysregulation enables a noninvasive molecular stratification platform for rapid detection of oral squamous cell carcinoma: results from a large diagnostic case-control study Muy-Teck Teh1*, Ranjitkumar Patil2, Satyajit Ashok Tekade3, Deepika Mishra4, Akhilanand Chaurasia2 and Ahmad Waseem1 Abstract Background Early diagnosis of oral squamous cell carcinoma (OSCC) is critical, yet most oral potentially malignant disorders (OPMDs) are benign, and patients frequently undergo unnecessary invasive scalpel biopsies, creating diagnostic delays and patient harm. A rapid, non-invasive molecular diagnostic tool could improve early detection and reduce unnecessary procedures. This study aims to determine whether a previously validated microbiopsy-based multigene assay (qMIDSV2) could be adapted into a rapid, non-invasive brush biopsy test (qMIDSV3) for accurate OSCC detection. A prespecified hypothesis was that qMIDSV3 could distinguish OSCC from low-risk OPMD and contralateral normal mucosa with high diagnostic sensitivity. Methods This prospective diagnostic case-control study validated a multigene mRNA test (qMIDSV3) for OSCC detection using 1090 oral brush biopsies from 545 patients. Each patient provided paired brush biopsies from oral lesion and contralateral non-lesion mucosa, including OSCC (n = 443), oral leukoplakia (OL; n = 63), and oral lichen planus (OLP; n = 39) . qPCR quantified mRNA levels of four genes (INHBA, S100A16, YAP1, POLR2A) from each brush biopsy, and an algorithm generated a malignancy index for cancer risk stratification. Results qMIDSV3 distinguished OSCC from OL and OLP with AUC 0 . 975, sensitivity 95 . 7%, specificity 95 . 1%, and overall accuracy 95 . 5% . False-positive and false-negative rates were 4 . 9% and 4 . 3%, demonstrating high specificity for detecting malignant cells rather than premalignant or inflammatory lesions. Conclusions Our findings highlight the clinical utility of qMIDSV3 as a rapid case-finding or triage test, potentially sparing over 90% of low-risk OPMD patients from unnecessary invasive tissue biopsies while accurately identifying OSCC cases. Non-invasive brush biopsy allows safe, repeatable sampling for long-term surveillance with minimal *Correspondence: Muy-Teck Teh[m.t.teh@qmul.ac.uk](m.t.teh@qmul.ac.uk) Full list of author information is available at the end of the article © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/.)[.](http://creativecommons.org/licenses/by/4.0/.) Teh et al. Biomarker Research (2026) 14:76 Page 2 of 13 patient harm and enhancing early oral cancer detection. By reducing unnecessary scalpel biopsies and specialty referrals, qMIDSV3 provides a molecularly guided and rapid triage pathway. Keywords qMIDS, INHBA, S100A16, YAP1, POLR2A, Oral cancer, Head and neck cancer, Early oral cancer biomarkers, Squamous cell carcinoma, mRNA, Brush biopsy, RT-qPCR, Non-invasive, Oral cancer screening, Early

FAQs

Why is early diagnosis of OSCC challenging with current approaches?

Most oral potentially malignant disorders are benign, so patients often undergo unnecessary invasive scalpel biopsies. This creates diagnostic delays and patient harm.

What is qMIDSV3 and how was it tested in this study?

qMIDSV3 is a rapid non-invasive brush biopsy multigene mRNA test using qPCR for four genes (INHBA, S100A16, YAP1, POLR2A) and an algorithm to generate a malignancy index. The prospective case-control study used 1090 oral brush biopsies from 545 patients.

How well did qMIDSV3 distinguish OSCC from low-risk OPMD and normal mucosa?

qMIDSV3 distinguished OSCC from oral leukoplakia and oral lichen planus with AUC 0.975, sensitivity 95.7%, specificity 95.1%, and overall accuracy 95.5%. The false-positive and false-negative rates were 4.9% and 4.3%.

Sep 22, 2026

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