Abstract 892P
Background
Oropharyngeal squamous cell carcinomas (OPSCC) caused by human-papillomaviruses (HPV) have a different epidemiology, prognosis, response to treatment when compared to HPV-negative OPSCC. However, the distribution of genomic alterations of Chinese OPSCC patients remains unknown.
Methods
50 Chinese OPSCC patients were enrolled in this study. Next-generation sequencing targeting 450 cancer genes was performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissues. Genomic alterations included single base substitution, short and long insertion/deletion (Indel). Tumor mutational burden (TMB) and microsatellite instability (MSI) were assessed.
Results
This cohort contained 36 male and 14 female patients, including 37 HPV-positive OPSCCs and 13 HPV-negative OPSCCs. The genomic features of Chinese HPV-positive OPSCCs showed a mutational signature distinct from The Cancer Genome Atlas (TCGA). MUC16 (35.1%) was the most frequently mutated gene among HPV-positive OPSCCs of Chinese patients and other high mutation genes included TP53 (32.4%), FGF3 (24.3%), and PIK3CA (24.3%), whereas Top3 high frequency mutation genes of HPV-positive OPCSSs as reported in TCGA (n=46) were PIK3CA (28%), LRP1B (19%) and CASZ1 (13%). Otherwise, mutational frequencies of TP53 were significantly higher in HPV-negative OPSCCs compared with HPV-positive OPSCCs (84.6% vs. 32.4%, P<0.01). In addition, only 7.7% of the HPV-negative OPSCCs exhibited TMB value greater than 10muts/Mb compared with 25% of the HPV-positive OPSCCs. Moreover, the gene mutation of Chinese HPV-positive OPSCC were notably enriched in the RTK/RAS (67.6%), NOTCH (62.2%) and PI3K (56.8%) signaling pathway, while HPV-negative OPSCC in TP53 (84.6%), PI3K (69.2%) and DDR (61.5%) signaling pathway.
Conclusions
This is the largest cohort studying the variation information of Chinese OPSCC patients, implying that Chinese HPV-associated OPSCC show a different genomic landscape compared with HPV-positive OPSCCs from TCGA. Furthermore, we noted an extremely high mutational frequency of TP53 (84.6%) in HPV-negative OPSCC. We also observed activating mutations in PI3K signaling pathway both in HPV-positive and HPV-negative OPSCC, which might be a therapeutic target for OPSCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Sun Yat-sen Memorial Hospital, Sun Yat-sen University.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.