Clinical significance of P16-positive status and high index of proliferative activity in patients with oropharyngeal squamous cell carcinoma

Abstract

Introduction. In accordance with uICC and AJCC 8th edition TNM classifications, there is a strong evidence for division of oropharyngeal squamous cell carcinoma (OPSCC) into 2 molecular subtypes by HPV-status with distinct prognosis depending on biological differences. Such a division leads to differences in staging OPSCC and in future it will lead to implementation of preventive measures and new therapeutic strategies against HPV-positive cancer. Aim of the study : to assess the clinical and prognostic significance of the combination of P16, a surrogate marker for HPV-positivity, and high proliferative activity in patients with oropharyngeal carcinoma. Material and Methods . Immunohistochemical (ICH) analysis with monoclonal antibodies specific for P16 and Ki67 proteins was used to detect expression patterns in the formalin-fixed, paraffin-embedded tumor samples obtained from 104 patients with squamous cell carcinoma of the tongue and oropharynx, treated at Oncological Dispencery № 1 in Krasnodar from 2011 to 2016. HPV-positive status was determined if more than 70 % of tumor cells had moderate or strong nuclear and cytoplasmic P16-staining. High index of proliferative activity (PA) was detected if more than 50 % tumor cells expressed Ki67 nuclear antigen. Results. P16-positivie status was associated with tonsillar cancer ( р =0.002), female gender ( р =0.015), age <60 years ( р <0.001), non - keratinizing morphology ( р =0.022), and high index of PA (p=0.01).The combination of P16>70 % with high PA demonstrated correlation with tonsillar cancer ( р <0.001), female gander ( р =0.015), age under 60 years ( р <0.001) and non - keratinizing morphology ( р =0.012). HPV-positive patients and patients with a combination of P16>70 % and high index of PA at N1-2 had an overall survival benefit (p=0.021). Conclusion. The correlation between IHC-complex for P16>70 %/Ki67>50 % and clinicopathologicl parameters and overall survival confirms the biological features of HPV-associated cancer. The evaluation of this IHC-complex can increase the diagnostic accuracy of IHC-analysis of HPV-status and predict the prognosis of patients with OPSCC.