A sexually active woman was seen for a routine gynecologic exam that included a Pap smear. The report indicated cervical intraepithelial neoplasia. In situ hybridization showed the presence of human papillomavirus (HPV) type 16 genomes within the neoplastic cells. Which of the following processes is required for HPV to lead to the development of cancer?
HPVs cause non-genital cutaneous and anogenital or mucosal syndromes. Mucosal and anogenital syndromes include cervical intraepithelial neoplasia (CIN) and cancer; conjunctival, oral, and laryngeal papillomas, and anogenital warts or condyloma accuminatum. HPV types 16, 18, 31, and 45 are high-risk strains associated with CIN and cancer, although additional types have also been found in such lesions. HPV types 6 and 11 cause the majority of papillomas and condyloma accuminatum. HPV infect the basal keratinocytes of the epithelial layer of skin and mucous membranes. Expression of viral proteins E5, E6, and E7 stimulates cell growth and results in thickening of the layers. As the cells mature, genome replication takes place and mature virions are released at the epithelial surface. The oncogenic mechanism of HPV involves integration of the viral genome (a) into the host chromosome. This results in inactivation of genes required for viral replication (d), which does not occur in these cells, and overexpression of HPV E6 and E7 proteins, which bind p53 and p105RB cellular growth suppressor proteins, a production of a clone of replicating cells with possible progression to neoplasia. Loss of HPV E6 and E7 (b) would forestall oncogenic changes; mutation of the virus (c) is not part of the process.
Integration of the viral genome
Loss of HPV E6 and E7 genes
Mutation of the virus
Viral replication
Virology