Multivariable Cox analysis including age (cut-off = 70 years), tobacco consumption, WHO histological classification, PIK3CA amplification, and SOX2 amplification showed that PIK3CA amplification was the only significant independent predictor of laryngeal cancer development (HR = 2.64, 95% CI 1.09–6.37, p = 0.031). This evidence concerns the gene PIK3CA and laryngeal carcinoma.