CUL2 and cancer: Similar to mRNA detection, the expression of CUL2 protein by IHC analysis was negative or weak in HPV negative cervical normal epithelium, slightly increased in HPV16 positive cervical normal tissues with the localization in the cytoplasm in the upper layers of epithelium, while greatly increased and located both in nucleus and cytoplasm in the midzone and basal layer of the infected epithelium in HPV16 positive CIN2-3, as well as invasive cancer tissues (Figure 1D).