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Updated: Jan 22, 2026
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Is high-risk cutaneous squamous cell carcinoma of the head and neck a suitable candidate for current targeted
Catherine Zilberg1,2, Matthew Weicai Lee2, Spiridoula Kraitsek3
1Medicine, Gosford Hospital, Gosford, New South Wales, Australia catezilberg@gmail.com.
Objective:
Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy, most frequently affecting the head and neck. Treatment often requires surgery and can have significant functional morbidity. Research into disease pathogenesis and second line medical management of cSCC is limited. We assess genetic mutations in high-risk, primary head and neck cutaneous squamous cell carcinomas (HNcSCC) that may hinder or be beneficial for use of targeted therapy in disease management.
Methods:
Genetic alterations and variant allele frequencies (VAFs) were analysed using a clinically relevant 48 gene panel in 10 primary high-risk non-metastatic treatment-naïve HNcSCC to evaluate applicability of targeted therapeutics. Variants present at all VAFs were evaluated for pathogenicity. Somatic mutation patterns of individual tumours were analysed.
Results:
High-risk HNcSCC showed a high proportion (82%) of C to T transitions in keeping with ultraviolet-mediated damage. There was significant intratumour genetic heterogeneity in this cohort (MATH scores 20-89) with the two patients <45 years of age showing highest intratumour heterogeneity. TP53 was altered at VAF >22% in all cases, and mutations with highest VAF were observed in tumour suppressor genes in 80%. 70% of cases demonstrated at least one mutation associated with treatment resistance (KIT S821F, KIT T670I, RAS mutations at codons 12 and 13).
Conclusion:
We demonstrate high proportion tumour suppressor loss of function mutations, high intratumour genetic heterogeneity, and presence of well recognised resistance mutations in treatment naïve primary HNcSCC. These factors pose challenges for successful utilisation of targeted therapies.
Insights
Genetic mutations in head and neck cutaneous squamous cell carcinoma (HNcSCC) present challenges for targeted therapy. High tumor heterogeneity and resistance mutations were found in treatment-naïve patients.
Area of Science:
- Oncology
- Genetics
- Dermatology
Background:
- Cutaneous squamous cell carcinoma (cSCC) is a prevalent malignancy, often affecting the head and neck.
- Treatment for cSCC frequently involves surgery, potentially leading to significant functional impairment.
- Limited research exists on the pathogenesis and medical management of advanced cSCC.
Purpose of the Study:
- To investigate genetic mutations in high-risk, primary head and neck cutaneous squamous cell carcinomas (HNcSCC).
- To assess how these mutations may impact the effectiveness of targeted therapies.
- To evaluate the applicability of targeted therapeutics in managing HNcSCC.
Main Methods:
- Analysis of genetic alterations and variant allele frequencies (VAFs) using a 48-gene panel.
- Evaluation of 10 primary, high-risk, non-metastatic, treatment-naïve HNcSCC cases.
- Assessment of variant pathogenicity and somatic mutation patterns.
Main Results:
- 82% of HNcSCC cases exhibited C to T transitions, indicative of UV damage.
- Significant intratumour genetic heterogeneity was observed (MATH scores 20-89).
- TP53 alterations were present in all cases (VAF >22%), and 70% had mutations linked to treatment resistance (e.g., KIT, RAS).
Conclusions:
- Primary HNcSCC exhibits substantial tumour suppressor loss-of-function mutations and high intratumour genetic heterogeneity.
- The presence of known resistance mutations poses challenges for targeted therapy efficacy.
- Further research is needed to overcome these genetic hurdles in HNcSCC treatment.
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