HPV-incidence and the role of p16^INK4a expression in squamous cell carcinomas of the oropharynx

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. p16^INK4a (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.

Conflict of interest

Der Erstautor gibt keinen Interessenskonflikt an.

Publication History

Article published online:
13 May 2021