AUTHOR=Yu Haiyang , Yu Wang , Enwu Yuan , Ma Jun , Zhao Xin , Zhang Linlin , Yang Fang TITLE=Enhancing head and neck cancer detection accuracy in digitized whole-slide histology with the HNSC-classifier: a deep learning approach JOURNAL=Frontiers in Molecular Biosciences VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1652144 DOI=10.3389/fmolb.2025.1652144 ISSN=2296-889X ABSTRACT=Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common cancer worldwide, with pathologists routinely analyzing histological slides to diagnose cancer by evaluating cellular heterogeneity, a process that remains time-consuming and labor-intensive. Although no previous studies have systematically applied deep learning techniques to automate HNSCC TNM staging and overall stage prediction from digital histopathology slides, we developed an inception-ResNet34 convolutional neural network model (HNSC-Classifier) trained on 791 whole slide images (WSIs) from 500 HNSCC patients sourced from The Cancer Genome Atlas (TCGA) Head and Neck Squamous Cell dataset. Our pipeline was designed to distinguish cancerous from normal tissue and to predict both tumor stage and TNM classification from histological images, with the dataset split at the patient level to ensure independence between training and testing sets and performance evaluated using comprehensive metrics including receiver operating characteristic (ROC) analysis, precision, recall, F1-score, and confusion matrices. The HNSC-Classifier demonstrated exceptional performance with areas under the ROC curves (AUCs) of 0.998 for both cancer/normal classification and TNM system stage prediction at the tile level, while cross-validation showed high precision, recall, and F1 scores (>0.99) across all classification tasks. Patient-level classification achieved AUCs of 0.998 for tumor/normal discrimination and 0.992 for stage prediction, significantly outperforming existing approaches for cancer stage detection. Our deep learning approach provides pathologists with a powerful computational tool that can enhance diagnostic efficiency and accuracy in HNSCC detection and staging, with the HNSC-Classifier having potential to improve clinical workflow and patient outcomes through more timely and precise diagnoses, serving as an automated decision support system for histopathological analysis of HNSCC.