In order to assess and compare the tumorigenic effects of single versus multiple infections with high‐risk HPVs (HPV16 and HPV18), across diverse mutational classes of CRC (KRAS and TP53 mutants), we transfected CRC cell models (HCT 116 and HT‐29) with E6/E7 of HPV16 and HPV18 alone and in combination (1:1). This evidence concerns the gene TP53 and colorectal carcinoma.