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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Head and Neck Cancer
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1428741

Digital Spatial Profiling identifies distinct patterns of immuno-oncology-related gene expression within oropharyngeal tumours in relation to HPV and p16 status

Provisionally accepted
Jill M. Brooks Jill M. Brooks 1*Yuanning Zheng Yuanning Zheng 2Kelly Hunter Kelly Hunter 3Benjamin E. Willcox Benjamin E. Willcox 4Janet Dunn Janet Dunn 5Paul Nankivell Paul Nankivell 1Olivier Gevaert Olivier Gevaert 2Hisham Mehanna Hisham Mehanna 6*
  • 1 Institute of Head and Neck Studies and Education, University of Birmingham, Birmingham, England, United Kingdom
  • 2 Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, Stanford, California, United States
  • 3 Other, Hereford, United Kingdom
  • 4 Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
  • 5 Clinical Trials Unit, Warwick Medical School, Faculty of Science, Engineering and Medicine, University of Warwick, Coventry, West Midlands, United Kingdom
  • 6 Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, England, United Kingdom

The final, formatted version of the article will be published soon.

    Background: The incidence of oropharyngeal cancer (OPC) is increasing, due mainly to a rise in Human Papilloma Virus (HPV)-mediated disease. HPV-mediated OPC has significantly better prognosis compared with HPV-negative OPC, stimulating interest in treatment de-intensification approaches to reduce long-term sequelae. Routine clinical testing frequently utilises immunohistochemistry to detect upregulation of p16 as a surrogate marker of HPV-mediation. However, this does not detect discordant p16-/HPV+ cases and incorrectly assigns p16+/HPV- cases, which, given their inferior prognosis compared to p16+/HPV+, may have important clinical implications. The biology underlying poorer prognosis of p16/HPV discordant OPC requires exploration. Methods: GeoMx digital spatial profiling was used to compare the expression patterns of selected immuno-oncology-related genes/gene families (n=73) within the tumour and stromal compartments of formalin-fixed, paraffin-embedded OPC tumour tissues (n=12) representing the three subgroups, p16+/HPV+, p16+/HPV- and p16-/HPV-. Results: Keratin (multi KRT) and HIF1A, a key regulator of hypoxia adaptation, were upregulated in both p16+/HPV- and p16-/HPV- tumours relative to p16+/HPV+. Several genes associated with tumour cell proliferation and survival (CCND1, AKT1 and CD44) were more highly expressed in p16-/HPV- tumours relative to p16+/HPV+. Conversely, multiple genes with potential roles in anti-tumour immune responses (immune cell recruitment/trafficking, antigen processing and presentation), such as CXCL9, CXCL10, ITGB2, PSMB10, CD74, HLA-DRB and B2M, were more highly expressed in the tumour and stromal compartments of p16+/HPV+ OPC versus p16-/HPV- and p16+/HPV-. CXCL9 was the only gene showing significant differential expression between p16+/HPV- and p16-/HPV- tumours being upregulated within the stromal compartment of the former. Conclusions: In terms of immune-oncology-related gene expression, discordant p16+/HPV- OPCs are much more closely aligned with p16-/HPV-OPCs and quite distinct from p16+/HPV+ tumours. This is consistent with previously described prognostic patterns (p16+/HPV+>> p16+/HPV- > p16-/HPV-) and underlines the need for dual p16 and HPV testing to guide clinical decision making.

    Keywords: oropharyngeal cancer, Human Papilloma Virus (HPV), p16, dual p16/HPV testing, Treatment de-intensification, Digital spatial profiling, tumour microenvironment

    Received: 06 May 2024; Accepted: 08 Aug 2024.

    Copyright: © 2024 Brooks, Zheng, Hunter, Willcox, Dunn, Nankivell, Gevaert and Mehanna. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jill M. Brooks, Institute of Head and Neck Studies and Education, University of Birmingham, Birmingham, B15 2TT, England, United Kingdom
    Hisham Mehanna, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, England, United Kingdom

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