Conversely, in lesions related with high risk HPV (cancers or intra-epithelial neoplasia), there is an overexpression of the p16 protein, resulting in intense cytoplasmic and nuclear staining of the majority of tumors cells (>70%); this has mainly been studied in the female genital tract and the anus [43,44,45]. The gene discussed is CDKN2A; the disease is cancer.