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Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status
Author(s) -
Gangkofner Dominik S.,
Holzinger Dana,
Schroeder Lea,
Eichmüller Stefan B.,
Zörnig Inka,
Jäger Dirk,
Wichmann Gunnar,
Dietz Andreas,
Broglie Martina A.,
HeroldMende Christel,
Dyckhoff Gerhard,
BoscoloRizzo Paolo,
Ezic Jasmin,
Marienfeld Ralf B.,
Möller Peter,
Völkel Gunnar,
Kraus Johann M.,
Kestler Hans A.,
Brunner Cornelia,
Schuler Patrick J.,
Wigand Marlene,
Theodoraki Marie N.,
Doescher Johannes,
Hoffmann Thomas K.,
Pawlita Michael,
Butt Julia,
Waterboer Tim,
Laban Simon
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32623
Subject(s) - antigen , head and neck squamous cell carcinoma , cancer , multiplex , head and neck cancer , serology , antibody , medicine , cervical cancer , cancer research , immunology , pathology , biology , bioinformatics
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.