Evaluation of p16^INK4a 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 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 HPV₁₆ 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 HPV₁₆-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.

SUBMITTER: Wagner S 

PROVIDER: S-EPMC7525437 | biostudies-literature |

REPOSITORIES: biostudies-literature