Evidence for different molecular parameters in head and neck squamous cell carcinoma of nonsmokers and nondrinkers: Systematic review and meta‐analysis on <scp>HPV</scp> , <scp>p16</scp> , and <scp> TP53 </scp>

BACKGROUND The goal of this review was to present an overview of the currently identified molecular parameters in head and neck squamous cell carcinoma (HNSCC) of nonsmokers and nondrinkers (NSND). METHODS Following the PRISMA guidelines, a systematic search was performed using the electronic databases PubMed, Embase, and Google Scholar. RESULTS Of the 902 analyzed unique studies, 74 were included in a quantitative synthesis and 24 in a meta-analysis. Human papillomavirus (HPV) was reported as a molecular parameter in 38 studies, followed by p16 and TP53 (23 and 14 studies, respectively). The variety of other molecular parameters concerned sporadic findings in small numbers of NSND. CONCLUSIONS HNSCC in NSND is more often related to HPV and p16 overexpression compared to tumors of smokers-drinkers. In a third of virus-negative tumors, TP53 mutations were detected with a mutational profile associated with aging and ultraviolet light exposure rather than to tobacco consumption.