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

Abstract:

BACKGROUND:A remarkably better prognosis is associated with oropharyngeal squamous cell carcinomas (OPSCC) driven by human papillomaviruses (HPV) compared with HPV-negative OPSCC. Consequently, de-escalation of standard treatment has been suggested. Due to modest specificity rates, debates are ongoing, whether p16INK4a, a surrogate marker for HPV-driven OPSCC, is sufficient to correctly identify those tumours and avoid substantial HPV misattribution and thus undertreatment of patients by de-escalation. Robust data estimating the proportion of potentially undertreated patients are missing. METHODS:We assessed a large-scale cohort of consecutively included OPSCC diagnosed between 2000 and 2017 for HPV-DNA, HPV genotypes, p16INK4a expression and multiple tumour- and patient-related risk factors, and investigated their impact on patients' survival in comprehensive uni- and multivariate analyses. RESULTS:Aetiological relevance of HPV (p16INK4a- and high-risk HPV-DNA-positivity) was detected in 27.1% (n = 192) of OPSCC, with HPV16 being the most abundant HPV type (94.6%). In 5.5% patients (n = 39), p16INK4a overexpression but no HPV-DNA was detected. Principal component and survival analyses revealed that 60.6% of these p16INK4a-positive OPSCC lacking HPV-DNA did not resemble HPV16-driven but HPV-negative OPSCC regarding risk-factor profile and overall survival. Notably, this group represented 10.6% of all p16INK4a-overexpressing OPSCC. CONCLUSIONS:p16INK4a as a single marker appears insufficient to indicate OPSCC patients suitable for treatment de-escalation.

journal_name

Br J Cancer

authors

Wagner S,Prigge ES,Wuerdemann N,Reder H,Bushnak A,Sharma SJ,Obermueller T,von Knebel Doeberitz M,Dreyer T,Gattenlöhner S,Wolf G,Pons-Kühnemann J,Wittekindt C,Klussmann JP

doi

10.1038/s41416-020-0964-x

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

1114-1122

issue

7

eissn

0007-0920

issn

1532-1827

pii

10.1038/s41416-020-0964-x

journal_volume

123

pub_type

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