{
  "abstract": "Background Human papillomavirus (HPV)-associated head and neck cancers (HNC), mainly non-nasopharyngeal HNC, can have distinct clinical and molecular characteristics compared to HPV-negative tumors. HPV-positive cancers are often associated with a better prognosis, which may be influenced by differences in the tumor immune microenvironment (TME), including immune cell infiltration and immune responses. Recent studies suggest that HPV infection alters the expression of key immune-related genes, potentially enhancing T cell-mediated immune responses. Understanding how immune gene expression differs between HPV-positive and negative tumors could provide insights into the mechanisms underlying tumor immune evasion and aid in developing more targeted immunotherapies for HNCs.Methods We retrospectively analyzed immune profiling data from two cohorts encompassing 64 patients with non-nasopharyngeal HNC whose tumors were tested for HPV positivity and subjected to comprehensive immune profiling as part of their routine clinical care. HPV positivity was determined using p16 immunohistochemistry. Gene expression was assessed using targeted sequencing of 395 immune-related genes (N=27) or whole transcriptome sequencing (N=37). Differences in immune gene expression between HPV-positive vs -negative tumors were assessed across the two cohorts using linear regression and a random effects meta-analysis. Differentially expressed genes (DEGs) were used as input for unsupervised clustering to determine their ability to discriminate HPV-positive from negative tumors in each cohort.Results Out of 395 tested immune genes, 35 (9%) were differentially expressed between HPV-positive and negative tumors (corrected P<0.05). Most DEGs (29, 83%) were enriched in HPV-positive tumors and were overrepresented in CD8-positive, alpha-beta T cell activation and other T cell differentiation pathways (corrected P<0.05) ( figure 1, figure 2). Using expression values of the 35 DEGs, tumors of both cohorts clustered into two main groups characterized by the predominance of either p16-positive or -negative tumors.Conclusions These findings reveal distinct immune profiles in HPV-positive non-nasopharyngeal HNCs, characterized by higher T cell differentiation, and demonstrate the potential of immune profiling in distinguishing HPV-positive from HPV-negative tumors. These results have important implications for understanding differences in the TME between HPV-positive vs negative HNC and detecting HPV immune signatures to inform patient treatment strategies.Ethics Approval Ethics approval for this study, including waiver of informed consent, was obtained from WCG IRB (Study #1340120), an independent institutional review board.Abstract 1278 Figure 1Volcano plot of differentially expressed immune-related genes between HPV-positive vs -negative head and neck tumors. Results are derived from meta-analysis between two datasets assessed with targeted (N=27) or whole transcriptome (N=37) RNA-seqAbstract 1278 Figure 2Unsupervised hierarchical clustering of HPV-positive and -negative head and neck tumors in the (A) targeted (N=27) and (B) whole transcriptome (N=37) RNA-seq cohort. Clustering was visualized via heatmap along with normalized gene expression values",
  "authors": [
    {
      "affiliations": [
        "Labcorp Oncology, Raleigh, NC, USA"
      ],
      "name": "Zachary D Wallen"
    },
    {
      "affiliations": [
        "Avera Cancer Institute, Sioux Falls, SD, USA"
      ],
      "name": "Tobias Meissner"
    },
    {
      "affiliations": [
        "Labcorp, Durham, NC, USA"
      ],
      "name": "Stephanie B Hastings"
    },
    {
      "affiliations": [
        "Labcorp, Durham, NC, USA"
      ],
      "name": "Heidi Ko"
    },
    {
      "affiliations": [
        "Labcorp, Durham, NC, USA",
        "Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA"
      ],
      "name": "Rebecca A Previs"
    },
    {
      "affiliations": [
        "Labcorp, Durham, NC, USA",
        "Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA"
      ],
      "name": "Kyle C Strickland"
    },
    {
      "affiliations": [
        "Labcorp, Durham, NC, USA"
      ],
      "name": "Eric A Severson"
    },
    {
      "affiliations": [
        "Avera Cancer Institute, Sioux Falls, SD, USA"
      ],
      "name": "Benjamin M Solomon"
    },
    {
      "affiliations": [
        "Avera Cancer Institute, Sioux Falls, SD, USA"
      ],
      "name": "William C Spanos"
    },
    {
      "affiliations": [
        "Avera Cancer Institute, Sioux Falls, SD, USA"
      ],
      "name": "Rachel J Elsey"
    }
  ],
  "title": "1278 Immune gene expression differences in HPV-positive and HPV-negative non-nasopharyngeal head and neck cancer offer potential for tumor classification by HPV status",
  "uid": "42ccbc25-0d03-5e8e-b49d-02e133eb8b16"
}