Correlation of morphologic and molecular criteria – Identifcation of a subtype in HPV-positive oropharyngeal carcinoma

Introduction Subgroups with a reduced prognosis exist patients with HPV-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC). The aim of this study is to identify morphological and genetic differences within HPV+ OPSCC. These will subsequently be analyzed in relation to prognosis to detect possible correlation between morphology and survival.

Material and methods This study included 108 patients with HPV+ OPSCC (Cologne, Giessen). Morphological classification was based on HE section in forms of a prediction score (PS) divided into HPV-typical morphology (HPV+/PS+) and HPV-untypical morphology (HPV+/PS-). Next generation sequencing of selected genes (including TP53) was performed on 57 tumor samples and results were correlated with morphological status and survival.

Results Significantly improved overall survival of the HPV+/PS+ subgroup (n=53) was demonstrated in the overall cohort (n=108, p=0.001). By NGS, four loss-of-function (LOF-) mutations in TP53 (n=4) could be detected, all of which occurred in the HPV+/PS- OPSCC subgroup. Likewise, the cumulative burden of gene mutations was increased in HPV+/PS- compared to HPV+/PS+ (n=57, p=0.057).

Conclusion/Discussion These results identify a subgroup within HPV+ OPSCC that resembles HPV- OPSCC by morphologic criteria and display poorer overall survival. At the same time, gene mutations and specifically a higher number of LOF-TP53 mutations were detected more frequently in HPV+/PS-, whose function as a biomarker should be further evaluated.

Publication History

Article published online:
12 May 2023