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. Author manuscript; available in PMC: 2023 Dec 2.
Published in final edited form as: Cancer Res. 2023 Jun 2;83(11):1768–1781. doi: 10.1158/0008-5472.CAN-22-3030

Figure 7. Mechanisms of HPV carcinogenesis.

Figure 7.

An HPV episome can undergo a simple integration, deleting the E1 and E2 genes, inhibiting DNA synthesis at the HPV origin of replication (ORI) and upregulating E6 and E7. If during integration E1 and E2 are not suppressed, a local amplification can case a complex integration leading to multiple copies of HPV and flanking DNA, resulting in higher expression of E6 and E7, formation of a super-enhancer activating flanking genes (23), and potentially amplifying a carcinogenic host gene. Monomer episomal cancer occurs when the genome remains an episome but undergoes an epigenetic switch to upregulate E6/E7. Aberrant episome replication can lead to Multimer episomal cancer in which deletions and rearrangements in the E1/E2 genes or URR lead to high E6/E7 and low E1/E2 expression. Insertion of multimer episomes into multiple genomic locations give rise to HPV superspreading cancer.