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.

Correlation between microvessel density (MVD) and multi-spiral CT (MSCT) perfusion parameters of esophageal cancer lesions and the diagnostic value of combined CtBP2 and P16INK4A

“…At present, a large number of foreign studies have shown that the sensitivity and specificity of a single test cannot be used to qualitatively diagnose malignant tumors. The main reason is that tumor cells and normal tissues can express certain genes (23). Studies have suggested that the combined detection of imaging and molecular biology can improve the diagnosis of malignant diseases, but there is no final conclusion (24).…”

Long-Term Survival and Recurrence in Oropharyngeal Squamous Cell Carcinoma in Relation to Subsites, HPV, and p16-Status

“…The overexpression of p16 Ink4a (p16 + ) has, similar to the presence of HPV-DNA (HPVDNA + ), been shown to have a strong correlation to active HPV infection (i.e., expression of HPV E6 mRNA) in OPSCC, although the combined presence of both p16 + and HPVDNA + is superior to using these markers separately [ 13 ]. Because p16 + is easier to determine by immunohistochemistry (IHC), it was therefore suggested as a possible surrogate marker for HPV infection, and thereby also shown to be associated with a better prognosis in OPSCC [ 14 , 15 ]. In addition, p16 + as a marker of HPV infection is now used in the 8th version of the American Joint Committee of Cancer (AJCC) AJCC Staging manual (TNM-8) to separate HPV-related from HPV-unrelated OPSCC [ 16 ].…”

Mutation patterns in recurrent and/or metastatic oropharyngeal squamous cell carcinomas in relation to human papillomavirus status

“…In contrast to other head and neck cancers, the incidence of OPSCC is increasing and in many countries a growing number of cases are attributed to high‐risk human papillomavirus (HPV) 2–4 . These patients are characterized by a specific risk profile, comparatively good response to therapy, and superior overall survival (OS) rates 5,6 . Consequently, strategies to de‐escalate the treatment of patients with HPV‐driven (HPV+) OPSCC are investigated.…”