Detection of Tumor-Specific Genetic Aberrations in Liquid Biopsies of Patients with HPV-associated Oropharyngeal Squamous Cell Carcinoma

Introduction:

In addition to tobacco and alcohol, infection with HPV is recognized as major risk factor for the development of oropharyngeal squamous cell carcinoma (OPSCC). Although HPV-associated OPSCC have a more favorable prognosis and differ in their clinical and biological characteristics from HPV-negative OPSCC, both entities are treated equally. The aim of the project is the identification and detection of genetic aberrations associated with an unfavorable course of disease in HPV-positive OPSCC.

Methods:

An HPV-specific panel for targeted next generation sequencing (tNGS) was designed (covering regions of 24 genes). DNA from HPV-associated primary tumors (n = 26) and sequential plasma samples was sequenced. HPV-DNA in cell-free DNA (cfDNA) was analyzed by qPCR. Chromosomal aberrations were determined with a SNP-array.

Results:

Tumor-specific mutations and HPV-DNA can be detected pre-therapeutically in cfDNA; posttherapeutically, its amount decreases correlating to treatment strategies. With our limited tNGS HPV panel, patients with an unfavorable course of disease accumulate around 2.4-times more mutations compared to patients with a favorable course. So far, chromosomal aberrations have been analyzed in patients with a severe course of disease. Some regions (e.g. loss of CYLD on chromosome 16q12) are altered in several samples.

Conclusions:

Patients with HPV-associated OPSCC and an unfavorable course of disease have more genetic aberrations than those with a favorable course. The impact of these mutations and aberrations will be further analyzed bioinformatically. HPV-DNA and tumor-specific mutations could be detected in cfDNA pre-, but not post-therapeutically.

Publication History

Publication Date:
18 April 2018 (online)