INTRODUCTION Increasing incidence of head and neck cancer are reported worldwide, especially for oropharyngeal squamous cell carcinomas (OPSCC) induced by human papillomavirus (HPV). Due to a remarkably better prognosis, a de-escalation of the standard treatment for patients with HPV-driven OPSCC has been proposed. p16INK4a (p16) is currently accepted as a surrogate for HPV in OPSCC staging. However, the specificity rates have raised concerns about de-escalation when based solely on p16 expression, and experimental data on HPV prevalence in OPSCC are still insufficient.
MATERIAL AND METHODS We investigated HPV-DNA status, p16 expression and multiple tumor- and patient-related risk factors in a consecutive cohort of OPSCC diagnosed between 2000 and 2017 and compared our data with cancer registry databases.
RESULTS The HPV-attributable fraction comprises n=192 (27 % ) OPSCC with p16-expression and positivity for high-risk HPV-DNA, in most cases (95 % ) HPV-type 16. The incidence significantly increased in the oropharyngeal sub-sites tonsils and oropharynx, while others did not change. This is reflected in cancer registry data, although there are national differences.
In n=39 OPSCC, p16-expression without detectable HPV DNA was found. According to principal component and survival analyses, 61 % of these cases, which represented 11 % of total p16-positive cases, were not comparable to HPV-driven OPSCC in terms of risk factor profile and overall survival.
Discussion The increasing incidence of HPV-driven OPSCC is undeniable in several countries. Nevertheless, population-based studies of spatial heterogeneity and the role of HPV in subpopulations, such as p16-positive but HPV-DNA negative OPSCC, which appear unsuitable for treatment de-escalation, remain essential.
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Teile dieser Arbeit wurde durch das Investigator Studies Program (MISP, Fördernummer: 56606) von MSD Sharp & Dohme GmbH unterstützt.
