The role of protein p16INK4a in non-oropharyngeal head and neck squamous cell carcinoma in Southern China

Abstract

Cyclin-dependent kinase inhibitor 2A (p16^INK4a) protein is a surrogate immunohistochemical marker of human papillomavirus infection in oropharynx squamous cell carcinoma (OPSCC). However, the effects of p16^INK4a in non-OPSCC require additional analysis. In addition, major gaps remain in the literature, including small volumes of data for China. Therefore, the present study evaluated the frequency of p16^INK4a positivity in patients with non-OPSCC in Southern China, and assessed its prognostic value. p16^INK4a expression status in patients with non-OPSCC was determined by immunohistochemistry. p16^INK4a-positive expression was defined as a strong and diffuse staining in ≥70% of the tumor cells. Then, the diagnostic value of p16^INK4a in predicting overall survival (OS) and disease-free survival (DFS) rate was determined. The positive rate of p16^INK4a was 26.3% in larynx cancer and 24.8% in oral cavity cancer. Multivariate analysis revealed that the protein status independently predicted improved OS rate, but not DFS rate (P=0.096). Comparing different disease stages, patients at an early stage with p16^INK4a-positive non-OPSCC exhibited improved DFS and OS rates compared with those exhibited by patients who were negative. The p16^INK4a-positive rate in patients with non-OPSCC was 25.1% [26.3% in Laryngeal squamous cell carcinoma (LSCC) and 24.8% in Oropharyngeal squamous cell carcinomas (OSCC)] in the present cohort from South China. The present study suggested that p16^INK4a expression in non-OPSCC predicts favorable clinical outcomes, particularly in early stage non-OPSCC and oral cancer.

Keywords: cyclin-dependent kinase inhibitor 2A expression; human papillomavirus infection; immunohistochemical marker; non-oropharynx squamous cell carcinoma; prognosis.

Figure 1.

Representative p16^INK4a immunohistochemistry results. Lack of brown staining in p16^INK4a negative carcinoma at a magnification of (A) ×100 and (B) ×200. p16^INK4a exhibiting diffuse nuclear and cytoplasmic brown staining in ≥70% of the tumor cells at (C) a magnification of ×100 and (D) ×200. p16^INK4a, cyclin-dependent kinase inhibitor 2A.

Figure 2.

Survival curves of 183 patients with non-oropharynx squamous cell carcinoma, stratified by p16^INK4a expression status. (A) Overall survival rate. (B) Disease-free survival rate. p16^INK4a, cyclin-dependent kinase inhibitor 2A.

Figure 3.

Survival curves of patients with OSCC and LSCC. Overall survival rates are presented according to the primary tumor site and p16^INK4a status of (A) OSCC and (C) LSCC. Disease-free survival rates are presented according to the primary tumor site and p16^INK4a status of (B) OSCC and (D) LSCC. OSCC, oral cavity squamous cell carcinoma; LSCC, larynx squamous cell carcinoma; p16^INK4a, cyclin-dependent kinase inhibitor 2A.

Figure 4.

Survival curves of patients with different tumor stages. Overall survival rates are presented according to the disease stage and p16^INK4a status in (A) stage I/II tumor types and (C) stage III/IV tumor types. Disease-free survival rates are presented according to the disease stage and p16^INK4a status in (B) stage I/II tumor types and (D) stage III/IV tumor types. p16^INK4a, cyclin-dependent kinase inhibitor 2A.