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  • Title: p16 overexpression and Rb loss correlate with high-risk HPV infection in oropharyngeal squamous cell carcinoma.
    Author: Jiromaru R, Yamamoto H, Yasumatsu R, Hongo T, Nozaki Y, Nakano T, Hashimoto K, Nakagawa T, Oda Y.
    Journal: Histopathology; 2021 Sep; 79(3):358-369. PubMed ID: 33450095.
    Abstract:
    AIMS: p16 is a sensitive surrogate marker for transcriptionally active high-risk human papillomavirus (HR-HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC), but it is not sufficient in all clinical settings. METHODS AND RESULTS: We examined the p16 and Rb expression status in 177 OPSCC cases by immunohistochemistry and the presence of transcriptionally active HR-HPV infection by mRNA in-situ hybridisation. The 177 cases were divided into p16+ /HPV+ (n = 105, 59.3%), p16+ /HPV- (n = 8, 4.5%) and p16- /HPV- (n = 64, 36.2%) groups. The p16+ /HPV- and p16- /HPV- groups had a trend towards worse overall survival (OS) or significantly worse OS than the p16+ /HPV+ group (n = 105) (P = 0.0610, P = 0.0004, respectively). We divided the Rb status into preserved expression (> 90%, n = 68), partial loss (PL) (10-90%, n = 97) and complete loss (CL) (< 10%, n = 12). Among the HPV-positive cases (n = 105), the Rb pattern was typically PL (n = 97, 92.4%) and rarely CL (n = 8, 7.6%), but never preserved expression (0%). In contrast, among the HPV-negative cases (n = 72), the Rb pattern was typically preserved expression (n = 68, 94.4%) and rarely CL (n = 4, 5.6%), but never PL (0%). Compared to p16 alone, the combination of p16 overexpression and Rb-PL/CL showed equally excellent sensitivity (each 100%) and improved specificity (97.2 versus 88.9%) and positive predictive values (98.1 versus 92.9%). CONCLUSIONS: These results suggest that the combined use of p16 and Rb immunohistochemistry could be a reliable, cost-effective method to predict HR-HPV infection in OPSCCs; however, HPV specific testing is necessary on inconclusive cases. We propose a diagnostic algorithm for practical use of these markers.
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