Fig. 1

The genetic makeup and organization of HPV. An illustration of the genetic map of HPV-16 is shown. Open reading frames (ORFs) are denoted by solid bars. The six initial ORFs (E1, E2, E4, E5, E6, and E7) are expressed at distinct phases of epithelial development. The L1 and L2 ORFs are actively transcribed in cells undergoing viral DNA replication in highly differentiated epithelial cells [53]. Three sense-strand trinucleotide (codon) reading frames represent the approximately 7.9 kb circular double-stranded DNA genome of HPV16. Rectangles of color in the appropriate reading frame represent protein-coding ORFs. The three primary parts of the HPV genome are the long control region (LCR), the early and late regions, and the timing of viral protein production after viral entrance into the host cell. The early section primarily encodes regulatory proteins that are necessary for the transcription and replication of the virus as well as cell cycle regulation, which supports HPV’s ability to transform and become immortal. The two viral structural proteins, L1 and L2, required for capsid formation, are encoded in the late region. The majority of the regulatory DNA sequences, including the origin of DNA replication and enhancer and promoter regions, that are required for both viral gene expression and genome replication are found in the LCR [54]. E8 is completely encoded within E1, while E4 is completely encoded within E2. The E4 protein is classified as a regulatory protein, which is produced by the genes of early viruses. E1, E2, E4, E5, E6, and E7 proteins are responsible for viral genome replication and maintenance in infected cells. The designations for early and late promoters (p) are p97 and p670, whereas the designations for early and late polyadenylation sites (polyA) are polyAE and polyAL, respectively [45, 55]