Oropharyngeal squamous cell carcinoma: p16/p53 immunohistochemistry as a strong predictor of HPV tumour status

<jats:sec><jats:title>Aims</jats:title><jats:p>Oropharyngeal squamous cell carcinomas (OPSCC) related to human papillomavirus (HPV) infection have a better prognosis than those without HPV infection. Although p16<jats:sup>INK4a</jats:sup> overexpression is used as a surrogate marker for HPV infection, 5–20% of p16‐positive OPSCC are described as being unrelated to HPV infection, with worse overall survival compared to OPSCC‐related HPV. There is therefore a risk of undertreating a proportion of OPSCC patients falsely considered to be HPV‐driven because of p16 positivity. <jats:italic>TP53</jats:italic> mutations are highly prevalent in OPSCC driven by mutagens in tobacco and alcohol. We describe herein a combined p16/p53 algorithm to predict HPV tumour status in OPSCC.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>A total of 110 OPSCC were identified in the database of the pathology department and were studied using p16 and p53 immunohistochemistry. For p16‐positive or p16‐negative/wild‐type patterns‐p53 (WT‐p53) cases (<jats:italic>n</jats:italic> = 63), DNA <jats:italic>in‐situ</jats:italic> hybridisation for high‐risk HPV was performed, and if negative the HPV status was controlled by HPV DNA polymerase chain reaction (PCR) (<jats:italic>n</jats:italic> = 19). A significant association between <jats:italic>TP53</jats:italic> mutation and pattern of p53 expression was found (WT‐p53, seven of 16, <jats:italic>P</jats:italic> < 0.001). The p16‐positive/WT‐p53 was significantly associated with HPV<jats:sup>+</jats:sup> tumour status (p16‐positive/WT‐p53, 50 of 110, <jats:italic>P</jats:italic> < 0.001). Interestingly, a subset of p16‐positive OPSCC was unrelated to HPV (13.5%, eight of 59), and showed mutant‐type staining of p53 expression.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The p16 protein immunopositivity in conjunction with the mutant‐type pattern of p53 staining helped to reclassify a subset of p16‐positive OPSCC as OPSCC‐unrelated HPV. This approach could be routinely applied by pathologists involved in the management of OPSCC, because of their potential therapeutic implications.</jats:p></jats:sec>