According to the studies from Heidelberg University group, most HPV++ designated OPSCCs (cancers with high viral load of HPV16 mRNA) showed reduced pRb, low cyclin-D1 and p-53 and up-regulated p16INK4a; in contrast, HPV+ designated tumors (cancers with low viral load of HPV16 mRNA showed normal pRb, increased Cyclin D1 and p-53, and reduced p16INK4a, a pattern typical for HPV-negative tumors; LSCCs showed only the pattern for HPV negative tumors [78]. Here, CCND1 is linked to cancer.