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Defining the Young Patient with Oral Cavity Cancer: Phenotypic and Genotypic Analysis
30 Pages Posted: 25 Jun 2021More...
Background: Oral cavity squamous cell carcinoma (OCSCC) is a deadly and morbid disease typically affecting older, male smokers. Emerging data suggests an increasing incidence of OCSCC in younger patients without traditional risk factors. However, these patients remain rare and difficult to study. One significant challenge is defining “young” OCSCC as prior determinations have been arbitrary leading to conflicting results. Hereupon we sought to characterize the young OCSCC through integration of clinical and genomic databases using mathematical modeling to optimally define the young OCSCC cohort to assess risk stratification.
Methods: Case-control analyses integrating the Surveillance, Epidemiology, and End Results (SEER) and The Cancer Genome Atlas databases; results were validated with an institutional database. Cases of OCSCC were matched by subsite, age and stage. Mathematical modeling of clinical and genomic features was integrated and analyzed to characterize the young phenotype and objectively define the optimal age cutoff between young and traditional OCSCC patients. Secondary outcomes were survival and prevalence of young OCSCC patients using our mathematically derived age cutoff.
Findings: There is a significant phenotypic shift of sex and tumor subsite as a function of age with an inflection point coalescing at 40-years. Genomic analysis assessing total mutational burden (TMB) confirmed the phenotypic inflection points at 40-years. Utilizing this age cutoff, we confirmed a rising incidence of OCSCC in both young women and men, improved overall survival, equivalent disease-specific survival, lower proportion of tobacco and alcohol exposure, and lower TMB. Interpretation Phenotypic and genotypic analysis of a rare subset of OCSCC identified 40-years as an objective age cutoff to define young OCSCC patients. These patients comprise a unique cohort given their lack of traditional risk factors yet similarly suboptimal oncologic outcomes. Defining an objective age cutoff allows for further investigation to optimally characterize their tumor biology and risk factors.
Funding: NIH/NCI grant K08 17-PAF07511 and UM MICHR 1KL2TR002241
Declaration of Interest: None to declare.
Ethical Approval: This study was approved by the University of Michigan Medical School Institutional Review Board (IRB).
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