Abstract 897P
Background
Among genetic changes identified by targeted next generation sequencing (NGS), PI3K pathway alterations constitute the most common molecular events in HPV positive (HPV+) OSCC in non-smokers. However, few studies have reported genomic alterations in HPV + smokers.
Methods
Our aim is to evaluate genomic alterations in smokers with OSCC. DNA samples are obtained from tumor tissues and blood-paired samples at baseline and analyzed using OncoDNA sequencing panel to detect sequence and copy number variations in 313 cancer-associated genes. Genes are assigned to 6 major pathways. HPV DNA status is determined by p16 immunohistochemical staining and PCR. Statististical analysis was performed using SPSS 25. Categorical data were compared using Fisher's exact test and correlations were examined using non-parametric tests.
Results
The sample collection is ongoing. Data from the first 56 patients are presented here. As expected, p16+ patients have higher HPV positivity rate (100% vs. 41.7% in p16- patients, p<0.001). PI3K pathway alterations are more frequent in HPV+ OSCC [50% vs. 0% in p16- patients, p=0.019]. Patients with higher TNM stage showed increase in alterations in TP53/Cell cycle/DNA repair pathways (p=0.049). Interestingly, the presence of detectable genomic alterations of TP53/Cell cycle/DNA repair pathways in peripheral blood and HPV/p16 negative tumor status were associated with higher risk for death [60% vs, 18.8%, p=0.008, 87.5% vs. 20.5%, p=0.001, respectively]. This was also confirmed for overall survival. Detection of any mutation and the presence of TP53 mutation in peripheral blood were correlated with worse OS (17.4 vs. 32.5 months, p=0.006 and.15.6 vs. 30.2 months, p=0.006), respectively and were independent prognostic markers for OS [Cox HR 5.45 (95 CI% 1.09-27.55, p=0.039), and HR 4.87 (95CI% 1.21-19.6, p=0.025)].
Conclusions
In smokers with OSCC, we found increased frequency of alterations in PI3K pathway in p16+ patients, as has been previously described for HPV+ non-smokers. The presence of any mutation as well as alterations in TP53, DNA repair and cell cycle pathways in peripheral blood were inversely correlated with survival.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Hellenic Society of Medical Oncology.
Disclosure
A. Psyrri: Financial Interests, Personal, Invited Speaker: MSD. All other authors have declared no conflicts of interest.