The recently published data [11,15] highlighted an interesting phenomenon that even though HPV-positive SCC harbored fewer mutations on average, as high as 20% of HPV-positive SCC (3/15 cases [15]) harbored PIK3CA mutation as the only cancer gene mutation, indicating that PI3K pathway mutations are enriched in HPV-positive tumors despite the lower rate of gene mutations in general. Here, PIK3CA is linked to cancer.