Genetic Alterations in HPV-associated Oropharyngeal Squamous Cell Carcinoma of Patients with Treatment Failure

Introduction:

An increasing number of oropharyngeal squamous cell carcinoma (OPSCC) is associated with human papillomavirus (HPV). Despite different biological and clinical features HPV+ and HPV- OPSCC are treated equally. Due to improved survival rates compared to patients with HPV- OPSCC, de-escalating treatment strategies are discussed for patients with HPV+ OPSCC. However, a subgroup of patients with HPV+ OPSCC might not benefit from de-escalated treatment due to an increased risk of treatment failure. Therefore, we aimed to identify genetic alterations as potential biomarkers associated with a risk of treatment failure.

Methods:

Primary tumor tissue of 12 patients with HPV+ OPSCC and severe course (SC) and best-matching pairs with a favorable course (FC) of disease was analyzed by targeted next generation sequencing and a SNP array for genetic and chromosomal aberrations.

Results:

No significant differences were observed between SC and FC patients on a chromosomal level. However, on the selected gene panel SC patients had more mutations than FC patients. Especially, STK11, HRAS, PIK3R1 and TP63 were strikingly more frequently altered in SC patients than in FC patients. Additionally, the combination of mutations and chromosomal aberrations on chromosomes 16 and 19 might influence outcome.

Conclusion:

Compared to SC patients FC patients had a higher number of genetic mutations in the genes studied. Our research shows that genetic markers could be used to identify patients at risk for treatment failure.

Publication History

Publication Date:
23 April 2019 (online)