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.
