The combined assessment of p16^INK4a and Mib/Ki-67 in oral squamous cell carcinoma

Objective: Despite numerous studies addressing the impact of p16^INK4a in oral squamous cell carcinoma (OSCC), consistent data regarding survival and tumor proliferation behavior are lacking. Although some authors investigate both p16^INK4a and Mib/Ki-67 in their cohorts, direct correlations are consistently missing. The aim of this study was to investigate the combined influence of p16^INK4a and Mib/Ki-67 status on prognosis in OSCC.

Materials and methods: Clinical data of all patients diagnosed with OSCC and treated curatively between 2005 and 2011 were collected retrospectively. Tissue microarrays of formalin-fixed paraffin-embedded specimens were stained for p16^INK4a and Mib/Ki-67 using the CINtec Histology V-Kit or MIB-1 antibody and correlated with the clinical outcome.

Results: A total of 316 patients, with a mean age of 61.7 years were included. Tumor tissues that were tested p16^INK4a positive with low Mib/Ki-67 expression demonstrated a remarkable 5-year survival rate of 83% with an improved RFS compared to all other subgroups (p=0.034; p=0.017; p=0.026) and an improved OS compared to those with high Mib/Ki-67 expression (p=0.026; p=0.020). Cox regression identified the combined p16^INK4a and Mib/Ki-67 status as a risk factor on OS (HR 6.25; CI1.26-31.0; p=0.025) and RFS (HR 5.88; CI1.19-29.20; p=0.030).

Conclusion: These results underscore the importance of a combined assessment of p16^INK4a and Mib/Ki-67 in evaluating the prognosis of OSCC, leading to the identification of distinct subgroups that may serve as risk factors for treatment stratification.