Evaluation of p16INK4a expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation
Steffen Wagner, Elena‐Sophie Prigge, Nora Wuerdemann, Henrike Reder, Ayman Bushnak, Shachi Jenny Sharma, Theresa Obermueller, Magnus von Knebel Doeberitz, Thomas Dreyer, Stefan Gattenlöhner, Gregor Wolf, Jörn Pons‐Kühnemann, Claus Wittekindt, Jens Peter Klußmann
Abstract
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 p16 INK4a , 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, p16 INK4a 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 (p16 INK4a - and high-risk HPV–DNA-positivity) was detected in 27.1% ( n = 192) of OPSCC, with HPV 16 being the most abundant HPV type (94.6%). In 5.5% patients ( n = 39), p16 INK4a overexpression but no HPV–DNA was detected. Principal component and survival analyses revealed that 60.6% of these p16 INK4a -positive OPSCC lacking HPV–DNA did not resemble HPV 16 -driven but HPV-negative OPSCC regarding risk-factor profile and overall survival. Notably, this group represented 10.6% of all p16 INK4a -overexpressing OPSCC. Conclusions p16 INK4a as a single marker appears insufficient to indicate OPSCC patients suitable for treatment de-escalation.