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

Oral Oncol. 2020 Jan:100:104488. doi: 10.1016/j.oraloncology.2019.104488. Epub 2019 Dec 10.

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.

Keywords: APOBEC; Aneuploidy; Head and neck cancer; Human papillomavirus; Immunotherapy; Oropharyngeal cancer; T-cells; Transforming growth factor receptor; Tumor immunology.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Genetic
  • Exome Sequencing
  • Female
  • Gene Expression Profiling
  • Genotype
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / virology*
  • Human papillomavirus 16 / classification
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / immunology
  • Humans
  • Male
  • Multivariate Analysis
  • Mutation*
  • Papillomaviridae / classification*
  • Papillomaviridae / genetics
  • Papillomaviridae / immunology
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / mortality*
  • Prognosis
  • Retrospective Studies
  • Sequence Analysis, RNA
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / immunology
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / virology*
  • Survival Analysis