Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status

Abstract

There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)‐positive and HPV‐negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue‐saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV‐positive and HPV‐negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer‐testis antigens, 5 cancer‐retina antigens and 8 oncogenes) and 29 HPV‐antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV‐positive and 209 HPV‐negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c‐myc, LAGE‐1, MAGE‐A1, ‐A3, ‐A4, NY‐ESO‐1, SpanX‐a1 and p53. AR to MAGE‐A3, MAGE‐A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with ≤10 AR, multiobjective optimization revealed distinct antigen selections by HPV status. We identified that AR to nonviral antigens differ by HPV status indicating differential antigen expression. Multiplex serology may be used to characterize antigen expression using serum or plasma as a tissue‐sparing liquid biopsy. Cancer antigen panels should address the distinct antigen repertoire of HPV‐positive and HPV‐negative HNSCC.

Analysis, identification and visualization of subgroups in genomics

“…Here, finding optimal gene subsets such as target selection for semi-personalized vaccination is formulated as a multi-objective optimization task. We further presented a walkthrough for the use of AVAtar by showing a real case scenario already applied in medical research [ 29 ]. The analysis of HNSCC expression data demonstrates the capabilities of AVAtar focusing on data import, visualization and optimization.…”

“…In the following sections, we will further guide through the features of AVAtar by presenting the use case also available on the tutorial of the software. An in-depth medical description of the analysis performed on AVAtar can be found in [ 29 ]. The HNSCC analysis aims is to compare promising vaccination target sets for different subgroups of patients with HNSCC.…”

“…The five-gene selection found for the HPV-positive patients contains completely distinct genes compared to all-patients selection and has only one common gene with the HPV-negative selection. An in-depth medical discussion of the obtained results can be found in [ 29 ].…”

“…To explore the possibilities provided by AVAtar, we first compared its features to available tools for both visualization and analysis. Second, we summarized a use case from an already published study [ 29 ] regarding semi-personalized selection of candidate vaccination targets for head and neck squamous cell carcinomas (HNSCC).…”

Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

“…Evidence from some studies suggests that CT antigens are present and recognized by the immune system in HPVpositive HNSCC patients and may serve as prognostic biomarkers. One study examining antibody responses to 16 CT antigens in HNSCC patients identified a subset of HPV-positive patients who exhibited responses, although there was considerable heterogeneity in the target signatures [136]. A related study examined prognostic trends in HNSCC patient antibody responses to 16 CT antigens, stratified by HPV status.…”