The Correlation between p16 Over Expression and Histological Grading Oforopharyngeal Squamous Cell Carcinoma at Muhimbili National Hospital

Abstract

Background: Oropharyngeal squamous cell carcinoma (OPSCC) is the most common type of cancer in the oropharynx and is commonly associated with high risk human papilloma virus (rHPV) infection predominantly HPV 16 and 18. HPV oncoproteins E6 and E7 which are encoded by (rHPV) DNA are primarily viral factors which are responsible for initiation and progression of human papilloma virus (HPV) related cancers by inactivation of p53 and Rb proteins, which results in a cascade of molecular events that induce the expression of a p16- related transcript. Subsequently, p16 have been used as a surrogate marker for high risk HPV lesions. About 50-70% HPV related OPSCC demonstratep16 immunostaining overexpression of which 71-90% are grade II &III (non-keratinizing) sub-types. Despite of a tendency to present at high histological grades, management outcome of HPV-related OPSCC is associated with better patient survival compared to the HPV negative and p16 overexpression appear to have implication in the diagnosis, prognosis and treatment of OPSCC. In economic constrained settings like in Tanzania where detection of rHPV and/or IHC assessment for p16 status cannot be ensured in every OPSCC case, it is important to identify the most likely rHPV related cases that can be subjected for testing in order to be practically cost effective. Objective: The aim of this study was to find out whether there is a correlation between histological grading of OPSCC and rHPV using p16 immunohistochemistry (IHC) overexpression. Methodology: The study was a retrospective hospital based study of OPSCC cases diagnosed at Histopathology Department of Muhimbili National hospital for a period of 2 years from January 2016 to December 2017. The H&E slides of oropharyngeal carcinoma were reviewed to confirm the diagnosis and assigned to histological grading according to Broder’s grading system. p16 IHC was performed in all cases using formalin fixed paraffin embedded tissue blocks. A case was considered to have p16 (IHC) overexpression if there was diffuse nuclear and cytoplasm stain in more than 75% of the cells. Data were recorded and analyzed by SPSS version 20 and demographic data were analyzed by frequency and percentages. The association between variables was calculated using chi square where the association was regarded to be significant if p value of < .001), furthermore about one third of OPSCC in this study showed p16 over-expression predominantly grade II and III (non keratinizing type of OPSCC) indicating good response after treatment therefore better prognosis in such group of patients. Recommendation: Routine p16 IHC should be adopted in our setting especially in lesions presenting with grade II and III OPSCC. This will assist in the management and prognostication of OPSCC. Furthermore, the results of this study recommend inclusion of both gender in preventive programs against HPV related tumors to reduce the rising trend of HPV related malignancies.