p16^INK4 expression is of prognostic and predictive value in oropharyngeal cancers independent of human papillomavirus status: a Hungarian study

Head and neck cancer treatment protocols still lack well-established biomarkers of prognostic and predictive value. It is well known that human papillomavirus (HPV)-related and non-HPV-related oropharyngeal cancers are distinct entities concerning tumor biology and clinical outcome. However, there is an ongoing debate whether tumor suppressor p16^INK4 status alone or both p16^INK4 and HPV detection should be used in clinical settings. The aim of this study was to investigate p16^INK4-immunolabelled and HPV-induced rates and determine their clinical significance in 110 primary head and neck squamous cell carcinomas. The expression of p16^INK4 protein was assessed with immunohistochemistry, while high-risk HPV detection was performed using DNA PCR method. P16^INK4 immunolabelling was detected in 17.3% of all tumor samples, and in 38.1% of oropharyngeal malignancies. Oropharyngeal, p16^INK4-immunolabelled tumors showed an improved disease-specific survival compared to the non-p16^INK4-immunolabelled group (median survival: 30.3 vs. 8.8 months, p < 0.001 with the log-rank test). Furthermore, 56% of p16^INK4-immunolabelled cases were tested positive for HPV-DNA. The HPV-induced group presented better disease-specific survival compared to the non-HPV-induced cases (median survival: 25.9 vs. 9.5 months, p = 0.024 with the log-rank test). Improved response rates to neoadjuvant chemotherapy were observed both in p16^INK4-immunolabelled and p16^INK4- immunolabelled/HPV DNA- containing groups (Fisher’s exact test: p = 0.025 and p = 0.009). In conclusion, p16^INK4 immunohistochemistry proved to be a reliable and affordable tool for prognostic and predictive testing of head and neck squamous cell cancers. The p16^INK4 immunopositivity status alone was confirmed to be an equally precise indicator of clinical outcome as p16^INK4/HPV DNA PCR double testing.