Integrative genomic analysis reveals low T-cell infiltration as the primary feature of tobacco use in HPV-positive oropharyngeal cancer
Benjamin M. Wahle,
Paul Zolkind,
Ricardo J. Ramirez,
Zachary L. Skidmore,
Sydney R. Anderson,
Angela Mazul,
D. Neil Hayes,
Vlad C. Sandulache,
Wade L. Thorstad,
Douglas Adkins,
Obi L. Griffith,
Malachi Griffith,
Jose P. Zevallos
Affiliations
Benjamin M. Wahle
Department of Otolaryngology – Head and Neck Surgery, Washington University School of Medicine, Campus Box 8115, 660 South Euclid Avenue, St. Louis, MO 63110, USA
Paul Zolkind
Department of Otolaryngology – Head and Neck Surgery, Washington University School of Medicine, Campus Box 8115, 660 South Euclid Avenue, St. Louis, MO 63110, USA
Ricardo J. Ramirez
Department of Otolaryngology – Head and Neck Surgery, Washington University School of Medicine, Campus Box 8115, 660 South Euclid Avenue, St. Louis, MO 63110, USA
Zachary L. Skidmore
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA
Sydney R. Anderson
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA
Angela Mazul
Department of Otolaryngology – Head and Neck Surgery, Washington University School of Medicine, Campus Box 8115, 660 South Euclid Avenue, St. Louis, MO 63110, USA
D. Neil Hayes
Department of Medicine, Division of Hematology-Oncology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Vlad C. Sandulache
Bobby R. Alford Department of Otolaryngology Head and Neck Surgery, Baylor College of Medicine, Houston, TX 77030, USA; ENT Section, Operative Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030; Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030
Wade L. Thorstad
Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO 63108, USA
Douglas Adkins
Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110 USA
Obi L. Griffith
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110 USA; Department of Genetics, Washington University School of Medicine, St Louis, Missouri
Malachi Griffith
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110 USA; Department of Genetics, Washington University School of Medicine, St Louis, Missouri
Jose P. Zevallos
Department of Otolaryngology – Head and Neck Surgery, Washington University School of Medicine, Campus Box 8115, 660 South Euclid Avenue, St. Louis, MO 63110, USA; Corresponding author
Summary: Although tobacco use is an independent adverse prognostic feature in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC), the biologic features associated with tobacco use have not been systematically investigated. We characterized genomic and immunologic features associated with tobacco use through whole exome sequencing, mRNA hybridization, and immunohistochemical staining in 47 HPV(+) OPSCC tumors. Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T > C substitutions and a lower proportion of expected mutational signatures, but not with increases in mutational burden or recurrent oncogenic mutations. Our findings suggest that rather than increased mutational burden, tobacco’s primary and clinically relevant association in HPV(+) OPSCC is immunosuppression of the tumor immune microenvironment. Quantitative assays of T cell infiltration merit further study as prognostic markers in HPV(+) OPSCC.
