Related Experiment Video
Updated: Oct 5, 2026
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Diversity within: a systematic review of intratumor heterogeneity in head and neck squamous cell carcinoma
Vivek Nayyar1, Beryl Rachel J1, Sachendra Kumar2
1Department of Oral Pathology and Microbiology, All India Institute of Medical Sciences, New Delhi, India.
Objective:
Head and neck squamous cell carcinoma (HNSCC), is a common, morbid, and frequently lethal malignancy with complex molecular landscapes that influence treatment outcomes and resistance. This systematic review aimed to evaluate the frequency and nature of intratumor heterogeneity (ITH) across multiple tumor regions.
Design:
We systematically reviewed and screened studies on HNSCC intratumor heterogeneity. Mutation and heterogeneity rates were extracted, quality-assessed, and analyzed to classify genes by heterogeneity levels.
Results:
We identified five eligible studies, analyzing 59 reported cases; after correcting for a partially overlapping patient cohort shared between 2 of the included studies, 57 unique cases were analyzed. Among them, 51 cases (89.5%) exhibited significant spatial heterogeneity, while only 6 cases (10.5%) showed mutational homogeneity. The most frequently mutated gene was TP53 (85.96%), which also showed the lowest ITH (34.69%), suggesting clonal origin. Other commonly mutated genes included TGFBR2, NOTCH1, CDKN2A, and EGFR. Notably, KRAS, NRAS, and BRAF genes associated with the MAPK and PI3K pathways exhibited 100% heterogeneity, implying subclonal and late-arising mutations. EGFR mutations, which are commonly targeted in several other malignancies, were observed in 30.43% of cases, with a heterogeneity rate of 64.29%.
Conclusion:
Understanding ITH is key to precision oncology, improving personalized treatment and outcomes in HNSCC, though larger studies are needed to confirm its prognostic and therapeutic relevance.
