Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Is high-risk cutaneous squamous cell carcinoma of the head and neck a suitable candidate for current targeted therapies?

Author information

Affiliations

  • 1. Medicine, Gosford Hospital, Gosford, New South Wales, Australia
      Authors
    • Zilberg C 1, 2
    (1 author)
  • 2. Medicine, The University of Sydney, Sydney, New South Wales, Australia.
      Authors
    • Zilberg C 1, 2
    • Lee MW 2
    (2 authors)
  • 3. Medical Genomics, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
      Authors
    • Kraitsek S 3
    (1 author)
  • 4. Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
      Authors
    • Ashford B 4
    • Ranson M 4
    (2 authors)
  • 5. The Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.
      Authors
    • Shannon K 5
    • Ch'ng S 5
    • Low TH 5
    • Palme C 5
    • Clark J 5
    (5 authors)
    • Show all (8)

ORCIDs linked to this article

Show all (7)

Journal of Clinical Pathology, 12 Jul 2019, 73(1):17-22
https://doi.org/10.1136/jclinpath-2019-206038 PMID: 31300530 

Abstract 

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.

Full text links 

Read article at publisher's site: https://doi.org/10.1136/jclinpath-2019-206038

Citations & impact 

Impact metrics

5
Citations
Jump to Citations

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/63852929
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/63852929

Smart citations by scite.ai
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
Explore citation contexts and check if this article has been supported or disputed.
https://scite.ai/reports/10.1136/jclinpath-2019-206038

Supporting
Mentioning
Contrasting
0
2
0

Article citations

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.