Correction: Evaluation of p16INK4a expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation

Wagner, Steffen; Prigge, Elena-Sophie; Wuerdemann, Nora; Reder, Henrike; Bushnak, Ayman; Sharma, Shachi Jenny; Obermueller, Theresa; Doeberitz, Magnus von Knebel; Dreyer, Thomas; Gattenlöhner, Stefan; Wolf, Gregor; Pons-Kühnemann, Jörn; Wittekindt, Claus; Klußmann, Jens Peter

doi:10.1038/s41416-021-01457-z

Cited by 3 publications

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“…An important issue is whether these two discordant subsets -particularly those that are HPV-/p16+ and therefore assigned as 'HPV-positive' by routine testing -share the improved treatment response and survival outcomes of HPV+/p16+ cases, or whether outcomes are more closely aligned with HPV-/p16tumours. Multiple studies suggested differential prognosis but were limited by sample size or restricted geographical sampling [15][16][17][18][19] . A recent large multicentre study (n = 7,654) provided strong evidence that patients with discordant OPC (HPV+/p16-or HPV-/p16+) have significantly worse prognosis compared with HPV+/p16+ OPC patients, although significantly better than HPV-/p16patients 20 .…”

Section: Introductionmentioning

confidence: 99%

Using digital spatial profiling to analyse onco-immune-related gene expression within oropharyngeal tumours in relation to HPV and p16 status

Brooks,

Zheng,

Hunter

et al. 2023

Preprint

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Human Papilloma virus (HPV)-mediated oropharyngeal cancer (OPC) has significantly better prognosis compared with HPV-negative, stimulating interest in treatment de-intensification approaches to reduce long-term sequelae. Routine clinical testing frequently utilises immunohistochemistry to detect upregulation of p16 protein as a surrogate marker of HPV-mediation. However, this does not detect discordant HPV+/p16-cases and incorrectly assigns HPV-/p16+ cases, which, given their inferior prognosis compared to HPV+/p16+, may have important clinical implications. The biology underlying poorer prognosis of HPV/p16 discordant OPC requires exploration. Here, we utilised digital spatial profiling to compare the expression patterns of selected immuno-oncology-related genes within the tumour and stromal compartments of HPV+/p16+, HPV-/p16+ and HPV-/p16-OPC tumour tissues (n=12). KRT andHIF1Awere upregulated in HPV-/p16+ and HPV-/p16-tumours relative to HPV+/p16+. Conversely, multiple genes associated with antitumour immune responses (such asCXCL9, CXCL10, CD74) were upregulated in HPV+/p16+ tumours. Of note, HPV-/p16+ and HPV-/p16-tumours displayed highly similar gene expression profiles, with only CXCL9 showing differential expression in stromal regions. These results are consistent with described prognostic patterns (HPV+p16+ > HPV-/p16+ > HPV-/p16-) and underline the need for dual HPV and p16 testing to guide clinical decision making.

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Section: Introductionmentioning

confidence: 99%

Using digital spatial profiling to analyse onco-immune-related gene expression within oropharyngeal tumours in relation to HPV and p16 status

Brooks,

Zheng,

Hunter

et al. 2023

Preprint

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Das multizentrische Register „Oropharynxkarzinom“ des Deutschen Studienzentrums für HNO – erste Ergebnisse

2024

Laryngorhinootologie

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Hintergrund Die Zahl der durch humane Papillomaviren (HPV) verursachten oropharyngealen Plattenepithelkarzinome (OPSCC) hat in den letzten Jahrzehnten deutlich zugenommen. Es gibt bislang jedoch keine belastbaren Daten über die Häufigkeit von HPV-assoziiertem OPSCC in Mitteleuropa und dessen Behandlung. Ziel der Arbeit Die epidemiologische Erfassung von Patienten mit OPSCC und des Anteils der p16-positiven Tumoren in der Deutschen Krebsgesellschaft (DKG) zertifizierten Kopf-Hals-Tumorzentren. Material und Methoden Um die Evidenzlücke der Häufigkeit von p16-positiven OPSCC zu schließen, wurde ein multizentrisches Register eingerichtet, das Patienten mit OPSCC im deutschsprachigen Raum pseudonymisiert erfasst. Die Datenerfassung erfolgt prospektiv mit Research Electronic Data Capture (REDCap). Ergebnisse Insgesamt wurden in den Jahren 2022–2023 1312 Patienten mit einem OPSCC aus 34 Zentren eingeschlossen. Bei 720 Patienten (58,2 %) konnte p16 im Tumor nachgewiesen werden. Die häufigsten Lokalisationen der p16-positiven OPSCC waren mit 49,9 % die Tonsille und mit 28,7 % der Zungengrund. 63,1 % der p16-positiven OPSCC wurden primär chirurgisch behandelt, wohingegen nur 48,0 % der p16-negativen Tumoren primär operiert wurden. Bei der adjuvanten Therapie von OPSCC zeigen sich ebenfalls deutliche Unterschiede: 58 % der p16-negativen OPSCC erhielten keine adjuvante Therapie nach Operation, verglichen mit nur 37,1 % der p16-positiven OPSCC. Schlussfolgerung Der Start der Oropharynx-Registerstudie verlief reibungslos. Dieses Register gibt bereits jetzt einen Einblick in die aktuelle Versorgungssituation von OPSCC im deutschsprachigen Raum und wird durch die Teilnahme weiterer Zentren an Bedeutung gewinnen.

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

Brooks,

Zheng,

Hunter

et al. 2024

Front. Oncol.

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BackgroundThe 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.MethodsGeoMx 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-.ResultsKeratin (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.ConclusionsIn 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.

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Correction: Evaluation of p16INK4a expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation

Cited by 3 publications

References 0 publications

Using digital spatial profiling to analyse onco-immune-related gene expression within oropharyngeal tumours in relation to HPV and p16 status

Using digital spatial profiling to analyse onco-immune-related gene expression within oropharyngeal tumours in relation to HPV and p16 status

Das multizentrische Register „Oropharynxkarzinom“ des Deutschen Studienzentrums für HNO – erste Ergebnisse

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

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