Tuesday, February 23, 2021

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

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Histopathology. 2021 Feb 9. doi: 10.1111/his.14350. Online ahead of print.

ABSTRACT

AIMS: Oropharyngeal squamous cell carcinomas (OPSCC) related to human papillomavirus (HPV) infection have a better prognosis than those without HPV infection. Although p16INK4a 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 as HPV-driven because of p16 positivity. TP53 mutations are highly prevalent in OPSCC driven by mutagens in tobacco and alcohol. We describe herein a combined p16/p53 algorithm to predict HPV tumor status in OPSCC.

METHODS AND RESULTS: 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 (n = 63), DNA in-situ hybridization for high-risk HPV was performed and if negative, the HPV status was controlled by HPV DNA PCR (n=19). A significant association between TP53 mutation and pattern of p53 expression was found (WT-p53, 7/16, P<0.001). The p16-positive/WT-p53 was significantly associated with HPV+ tumor status (p16-positive/WT-p53, 50/110, P<0.001). Interestingly, a subset of p16-positive OPSCC was unrelated to HPV (13.5%, 8/59) and showed mutant-type staining of p53 expression.

CONCLUSIONS: 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.

PMID:33560536 | DOI:10.1111/his.14350

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