Human papillomavirus in cancer: Pathogenesis and vaccination approaches

Abstract

Human papillomavirus (HPV) is a small, non-enveloped virus that infects cutaneous and mucosal epithelium. It is sexually transmitted, and persistent infections with high-risk strains, such as HPV-16 and HPV-18, have been identified as contributing factors to 70% of global cervical cancer cases. Cervical cancer is a serious problem in developing countries such as South Africa, where early detection of precancerous lesions and comorbidities remains a challenge. The oncogenic activity of high-risk HPV strains is driven by the overexpression of E6 and E7 oncoproteins that bind to and inactivate key cell cycle regulators in host cells, such as tumour suppressor protein p53 and retinoblastoma protein (pRb), resulting in the transformation of normal cells into cancerous cells. Since cervical cancer is a global health problem, vaccines that prevent and target HPV infections have been developed to eliminate HPV-related cancers. Prophylactic vaccines are based on virus-like particles derived from genotype-specific L1 proteins and are essential for preventing HPV infections by inducing neutralising antibodies. School-based vaccination programmes in South Africa provide a single-dose of a L1 based bivalent vaccine, Cervarix, to girls over 9 years of age. While prophylactic vaccines prevent HPV infections, they have no therapeutic effect in patients with established infections. Therefore, therapeutic vaccines, such as ADXS11-001 and MVA-E2, which induce cell-mediated immune responses against viral oncoproteins E6 and E7 in HPV-related cancer, are currently under clinical investigation worldwide. The types of therapeutic vaccines that have been developed and evaluated in clinical trials include vector-, peptide- and protein-, whole-cell-, and nucleic acid-based vaccines; however, none have been approved for clinical use. Improving the efficacy of prophylactic and therapeutic vaccines remains critical for targeting HPV-related cancers.