Abstract 2207: Genomic associations of biological sex and survival in head and neck squamous cell carcinoma

Approximately half of all head and neck squamous cell carcinoma patients die within five years of diagnosis despite treatment. Recent studies revealed that females have a worse overall prognosis; however, the genetic and molecular underpinnings have not yet been identified. We investigated the genetic characteristics of head and neck squamous cell carcinomas stratified by HPV status and biological sex. Within the HPV-negative cohort, female patients have worse survival outcomes compared to male patients, although tumors in female patients show lower levels of aneuploidy alterations and copy number changes. Specifically, chromosomes 4, 5, 6, and 20 were amplified at higher frequency in the tumors of male patients compared to female patients. Analysis of mRNA expression found that genes most highly expressed in females compared to males included sex-chromosome genes XIST and TISX. Interestingly, along with y chromosome gene PRKY, Notch signaling gene HES7 was also up-regulated in the tumors of male patients. In addition, tumors of female patients showed higher expression of immune pathway genes, even when potential confounding factors of age and tumor location are considered. This study provides new insight into possible gene expression biomarkers for HNSCC in female patients. Future research will incorporate these findings to better assess therapeutic response in women with HNSCC. Citation Format: Alexandria G. Yao, Nadia Mezghani, Alison M. Taylor, Fatemeh Momen-Heravi. Genomic associations of biological sex and survival in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2207.