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Defining the Young Patient with Oral Cavity Cancer: Phenotypic and Genotypic Analysis

30 Pages Posted: 25 Jun 2021

See all articles by Emily Marchiano

Emily Marchiano

University of Michigan at Ann Arbor - University of Michigan Health System

Illona Argirion

University of Michigan at Ann Arbor

Taylor Vandenberg

University of Michigan at Ann Arbor

Apurva D. Bhangale

University of Michigan at Ann Arbor

Andrew C. Birkeland

University of California, Davis

Mark E.P. Prince

University of Michigan at Ann Arbor

Carol R. Bradford

Ohio State University (OSU)

Jonathan B. McHugh

University of Michigan at Ann Arbor

Douglas B. Chepeha

University of Michigan at Ann Arbor

Maureen A. Sartor

University of Michigan Medical School - Department of Computational Medicine and Bioinformatics

Laura S. Rozek

University of Michigan at Ann Arbor

Andrew G. Shuman

University of Michigan Hospitals - Department of Otalaryngology

J. Chad Brenner

University of Michigan at Ann Arbor

Matthew E. Spector

University of Michigan at Ann Arbor

Steven B. Chinn

University of Michigan at Ann Arbor - Department of Otolaryngology - Head and Neck Surgery; University of Michigan at Ann Arbor - Rogel Cancer Center

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Abstract

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).

Suggested Citation

Marchiano, Emily and Argirion, Illona and Vandenberg, Taylor and Bhangale, Apurva D. and Birkeland, Andrew C. and Prince, Mark E.P. and Bradford, Carol R. and McHugh, Jonathan B. and Chepeha, Douglas B. and Sartor, Maureen A. and Rozek, Laura S. and Shuman, Andrew G. and Brenner, J. Chad and Spector, Matthew E. and Chinn, Steven B., Defining the Young Patient with Oral Cavity Cancer: Phenotypic and Genotypic Analysis (6/24/2021). Available at SSRN: https://ssrn.com/abstract=3874126 or http://dx.doi.org/10.2139/ssrn.3874126

Emily Marchiano

University of Michigan at Ann Arbor - University of Michigan Health System

Ann Arbor, MI 48109
United States

Illona Argirion

University of Michigan at Ann Arbor

500 S. State Street
Ann Arbor, MI 48109
United States

Taylor Vandenberg

University of Michigan at Ann Arbor

500 S. State Street
Ann Arbor, MI 48109
United States

Apurva D. Bhangale

University of Michigan at Ann Arbor

500 S. State Street
Ann Arbor, MI 48109
United States

Andrew C. Birkeland

University of California, Davis

One Shields Avenue
Apt 153
Davis, CA 95616
United States

Mark E.P. Prince

University of Michigan at Ann Arbor

500 S. State Street
Ann Arbor, MI 48109
United States

Carol R. Bradford

Ohio State University (OSU)

Blankenship Hall-2010
901 Woody Hayes Drive
Columbus, OH OH 43210
United States

Jonathan B. McHugh

University of Michigan at Ann Arbor

500 S. State Street
Ann Arbor, MI 48109
United States

Douglas B. Chepeha

University of Michigan at Ann Arbor

500 S. State Street
Ann Arbor, MI 48109
United States

Maureen A. Sartor

University of Michigan Medical School - Department of Computational Medicine and Bioinformatics ( email )

Ann Arbor, MI 48109
United States

Laura S. Rozek

University of Michigan at Ann Arbor ( email )

500 S. State Street
Ann Arbor, MI 48109
United States

Andrew G. Shuman

University of Michigan Hospitals - Department of Otalaryngology ( email )

1500 E. Medical Center Drive
Ann Arbor, MI 48109
United States

J. Chad Brenner

University of Michigan at Ann Arbor

500 S. State Street
Ann Arbor, MI 48109
United States

Matthew E. Spector

University of Michigan at Ann Arbor

500 S. State Street
Ann Arbor, MI 48109
United States

Steven B. Chinn (Contact Author)

University of Michigan at Ann Arbor - Department of Otolaryngology - Head and Neck Surgery ( email )

1500 East Medical Center Drive
Ann Arbor, MI 48109
United States
(734) 232-0120 (Phone)
(734) 936 - 9625 (Fax)

University of Michigan at Ann Arbor - Rogel Cancer Center

1500 East Medical Center Drive
Ann Arbor, MI 48109
United States

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