Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Hypothesis: We hypothesize that individual gene mutations in oral cavity squamous cell carcinoma (OCSCC) are associated with pathologic features of malignancy and disease-free survival (DFS).
Objective: With increasing accessibility of next generation sequencing (NGS), the utility of molecular analysis in guiding cancer treatment has become an area of interest. Molecular analysis has already been implemented into the decision-making process for lung cancer, melanoma, thyroid cancer, lymphoma, and other tumor types. Furthermore, investigating treatment responsiveness based on the presence of mutated TP53 in squamous cell carcinoma of the head and neck is central to the ongoing EA3132 clinical trial. Therefore, this study sought to explore the association between common gene mutations in OCSCC and pathologic features of malignancy, and to analyze the impact these gene mutations have on patient survival.
Methods: The cBioPortal database was queried for 4 head and neck cancer studies, isolating OCSCC cases with TP53, TTN, or FAT1 mutations. Patients with missing primary site data and duplicate patient data were excluded. In concordance with the KEYNOTE-158 trial, the TMB low group included genes with <10 mutations/megabase, while TMB high included those with ≥10 mutations/megabase. Univariate and multivariable analyses were performed using IBM SPSS v25.
Results: In our analysis of 320 OCSCC patients, the majority were male (66.6%), white (86.3%), and current/former smokers (69.4%). TP53 was the most common gene mutation (74.7%) followed by TTN and FAT1 (36.6% and 26.3%, respectively). Univariate analyses revealed that mutated TTN was associated with older age compared to wild-type (WT) TTN/other mutations (63.9 years vs. 60.5 years, p = 0.029). Comparing mutated TP53 to WT TP53/other gene mutations revealed that mutated TP53 was more commonly associated with microscopic extranodal extension (ENE) (22.1% vs. 11.9%), gross ENE (9.9% vs. 3.4%) (p = 0.040) and perineural invasion (PNI) (59.1% vs. 40.7%, p = 0.013). The relationship between mutated TP53 and presence of ENE remained consistent on multivariable analysis (OR 2.63, 95% CI 1.06 to 6.56, p = 0.038). Average nonsynonymous TMB in the cohort was 5.05 mutations/megabase and TMB high (>10) was rare (6.9%). There was no significant association between TMB and age, sex, smoking status, ENE, or PNI. On cox regression analysis of mutated TP53, there was no difference in overall survival (OS) (HR 0.77, 95% 0.44 to 1.35, p =0.36), nor DFS (HR 0.79, 95% CI 0.42 to 1.47, p = 0.45). Multivariable analyses controlling for age, sex, race, smoking status, ENE, and PNI demonstrated that mutated TTN was more commonly present in the TMB high group compared to WT TTN/other mutations (OR 6.46, 95% CI 1.64 to 25.51, p = 0.008).
Conclusion: In our cohort of 320 OCSCC patients, TP53 was the most common gene mutation and was associated with ENE and PNI on multivariable analysis. There was a statistically significant association between mutated TTN and the TMB high group. No significant difference in OS or DFS was seen based on the presence of individual gene mutations.