Specifically, hotspot were detected in 33.3% of SCC, 21.4% of ADC, 4.5% of CIN3, 10.2% of AIS, 3.1% of CIN2, and 2.6% of controls. Of the hotspot mutations detected in the ICC samples, the most common was PIK3CA E545K (15.2% of all ICC), for each histology (11.4% of ADC, 20.6% of SCC), and by HPV type (16.5% of HPV16-positive ICC, 11.1% of HPV18-positive, 9.1% of HPV45-positive). This evidence concerns the gene PIK3CA and intrahepatic cholangiocarcinoma.