Supplementary Figure S4 from Antibody Responses to Cancer Antigens Identify Patients with a Poor Prognosis among HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma Patients

Laban, Simon; Gangkofner, Dominik S.; Holzinger, Dana; Schroeder, Lea; Eichmüller, Stefan B.; Zörnig, Inka; Jäger, Dirk; Wichmann, Gunnar; Dietz, Andreas; Broglie, Martina A.; Herold-Mende, Christel C.; Dyckhoff, Gerhard; Boscolo-Rizzo, Paolo; Ezić, Jasmin; Marienfeld, Ralf; Möller, Peter; Kraus, Johann M.; Völkel, Gunnar; Kestler, Hans A.; Brunner, Cornelia; Schuler, Patrick J.; Wigand, Marlene C.; Theodoraki, Marie-Nicole; Doescher, Johannes; Hoffmann, Thomas K.; Pawlita, Michael; Waterboer, Tim; Butt, Julia

doi:10.1158/1078-0432.22470926.v1

10780432ccr191490-sup-221869_3_supp_5678089_pvf7nr.pdf (264.66 kB)

Supplementary Figure S4 from Antibody Responses to Cancer Antigens Identify Patients with a Poor Prognosis among HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma Patients

journal contribution

posted on 2023-03-31, 21:00 authored by Simon Laban, Dominik S. Gangkofner, Dana Holzinger, Lea Schroeder, Stefan B. Eichmüller, Inka Zörnig, Dirk Jäger, Gunnar Wichmann, Andreas Dietz, Martina A. Broglie, Christel C. Herold-Mende, Gerhard Dyckhoff, Paolo Boscolo-Rizzo, Jasmin Ezić, Ralf Marienfeld, Peter Möller, Johann M. Kraus, Gunnar Völkel, Hans A. Kestler, Cornelia Brunner, Patrick J. Schuler, Marlene C. Wigand, Marie-Nicole Theodoraki, Johannes Doescher, Thomas K. Hoffmann, Michael Pawlita, Tim Waterboer, Julia Butt

Prognostic impact of antibody responses to cancer antigens stratified by HPV-status. Overall survival was significantly shorter for patients with {greater than or equal to}2 AR, AR to c-myc, MAGåE-A1, MAGE-A4 and Rhodopsin E2 in the HPV-negative cohort and IMP-1 in the HPV-positive cohort. Overall survival was calculated using the Kaplan-Meier method and p-values were determined using logrank tests. Results were corrected for multiple testing with a false discovery rate of 15%.

Funding

Deutsche Forschungsgemeinschaft

History

ARTICLE ABSTRACT

The identification of high-risk patients within human papillomavirus (HPV)-positive and -negative head and neck squamous cell carcinoma (HNSCC) is needed for improved treatment and surveillance strategies. In this study, we set out to discover antibody responses (AR) with prognostic impact in HNSCC stratified by HPV status. A fluorescent bead–based multiplex serology assay on 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens, and 8 oncogenes) and 29 HPV antigens was performed in samples of 362 patients with HNSCC from five independent cohorts (153 HPV positive, 209 HPV negative). A multivariable Cox proportional hazard model with bootstrapping (M = 1000) was used for validation of prognostic antibody responses. Antibody response to any of the cancer antigens was found in 257 of 362 patients (71%). In HPV-negative patients, antibody responses to c-myc, MAGE-A1, -A4, and Rhodopsin E2 (combined as ARhigh risk) were significantly associated with shorter overall survival. In HPV-positive patients, antibody responses to IMP-1 were discovered as a negative prognostic factor. ARhigh risk (HR = 1.76) and antibody responses to IMP-1 (HR = 3.28) were confirmed as independent markers for a poor prognosis in a multivariable Cox proportional hazard model with bootstrapping (M = 1000). We identified antibody responses to cancer antigens that associate with a dismal prognosis in patients with HNSCC beyond HPV-positive status. ARhigh risk may be used to detect HPV-negative patients with an extraordinarily bad prognosis. Most importantly, antibody response to IMP-1 may serve as a marker for a subgroup of HPV-positive patients who present with a poor prognosis similar to that in HPV-negative patients.