Tumor molecular differences associated with outcome disparities of Black patients with head and neck cancer

Abstract

Background Numerous studies of head and neck squamous cell carcinoma (HNSCC) have demonstrated disparate outcomes by race and ethnicity. Beyond known associations with socioeconomic variables, whether these are also associated with differences in tumor molecular composition has thus far been poorly explored. Methods We downloaded clinical and multiplatform molecular data from The Cancer Genome Atlas and other published studies. These were compared between non‐Hispanic Black (n = 43) and White (n = 354) patients with non‐HPV‐related tumors, using multivariable models. Publicly available validation cohorts were used. Results Black patients had poorer progression‐free survival than White patients. Tumors of Black patients had greater copy number aberrations, and increased SFRP1 methylation and miRNA‐mediated PRG4 silencing associated with poor survival. PI3K/AkT/mTOR pathway proteins were differentially expressed. Conclusions There are molecular differences between tumors of Black and White patients that may partially account for differences in survival. These may inform targeted treatment decisions to achieve equitable outcomes.

HPV‐negative head and neck cancers with adverse pathological features carry specific molecular changes that are associated with survival

“…We selected covariates that were identical to those use in our previous peer reviewed analyses. This allows us to directly compare the model estimates with our prior work 18–21 . As a final note, our findings of molecular and survival differences are associative, and in some cases the significance is unclear.…”

“…The mRNA abundance profiles of tumors positive and negative for each pathological feature were modeled as negative binomial generalized linear distributions and compared using a Wald test with shrinking of log 2 fold‐change values within the DESeq2 program. FDR adjustment was done as previously described 16–21 . Genes with significantly different mRNA expression were analyzed for pathway over‐representation using Reactome Pathway Analysis 30 …”

“…Fisher, χ 2 Goodness of fit, and Mann–Whitney U tests were performed to compare clinical variables by pathological feature in the HPV‐negative group. Smoking history was defined as never smokers, light smokers (<20 pack year history), or heavy smokers (>20 pack year history) as in our previous research 17–23 …”

“…All p values from multiple testing for each analysis were adjusted for false discovery rate (FDR) using the Benjamini-Hochberg method, and the FDR significance threshold was set at 0.1 as in our previous studies. [16][17][18][19][20][21]…”

Disparities in Survival Outcomes among Racial/Ethnic Minorities with Head and Neck Squamous Cell Cancer in the United States

“…Chaudhary and colleagues used the cancer genome atlas and cancer digital archive of HNSCC patient and showed that Black patients had a higher frequency of mutations in several genes such as P53 and FATI, and showed less intra-tumoral infiltration of the effector immune cells [ 31 ]. Another study comparing mutational differences between Black and White HNSCC patients showed a greater number of copy aberrations and increased miRNA-mediated PRG4 silencing [ 32 ]. Future studies should continue to investigate the biological markers and drivers of disease in R/E minorities, which may elucidate opportunities for personalized medicine in these specific populations.…”