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

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.