HPV33+ HNSCC is associated with poor prognosis and has unique genomic and immunologic landscapes.

ABSTRACT:

Objective

To determine the influence of high-risk HPV genotype on outcomes in HNSCC patients.

Materials and methods

This is a retrospective analysis of The Cancer Genome Atlas HNSCC cohort.

Results

Using multivariate Cox regression analysis, we revealed that HPV33+ HNSCC patients have inferior overall survival compared to HPV16+ HNSCC patients independent of anatomical site (HR 3.59, 95% CI 1.58-8.12; p = 0.002). A host anti-viral immune response, apolipoprotein B mRNA editing enzyme, and catalytic polypeptide-like mutational signature, was under represented and, aneuploidy and 3p loss were more frequent in HPV33+ tumors. A deconvolution RNA-Seq algorithm to infer immune cell fractions revealed that CD8+ cytotoxic T-cell infiltration was reduced in HPV33+ compared to HPV16+ tumors (1.3% vs. 2.7%, p = 0.007). TGFB1, a negative modulator of T-cell infiltration and function, showed expression and pathway enrichment in HPV33+ tumors.

Conclusions

Our work reveals that HPV genotype, in particular HPV33, has a powerful impact on HNSCC patient survival. We argue that p16 immunohistochemistry as a surrogate biomarker for HPV+ status will lead to sub-optimal risk stratification and advocate HPV genotype testing as standard of care.

SUBMITTER: Chatfield-Reed K 

PROVIDER: S-EPMC7897465 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature