HPV disease transmission protection and control

Abstract

Human papillomaviruses (HPVs) represent a large collection of viral types associated with significant clinical disease of cutaneous and mucosal epithelium. HPV-associated cancers are found in anogenital and oral mucosa, and at various cutaneous sites. Papillomaviruses are highly species and tissue restricted, and these viruses display both mucosotropic, cutaneotropic or dual tropism for epithelial tissues. A subset of HPV types, predominantly mucosal, are also oncogenic and cancers with these HPV types account for more than 200,000 deaths world-wide. Host control of HPV infections requires both innate and adaptive immunity, but the viruses have developed strategies to escape immune detection. Viral proteins can disrupt both innate pathogen-sensing pathways and T-cell based recognition and subsequent destruction of infected tissues. Current treatments to manage HPV infections include mostly ablative strategies in which recurrences are common and only active disease is treated. Although much is known about the papillomavirus life cycle, viral protein functions, and immune responsiveness, we still lack knowledge in a number of key areas of PV biology including tissue tropism, site-specific cancer progression, codon usage profiles, and what are the best strategies to mount an effective immune response to the carcinogenic stages of PV disease. In this review, disease transmission, protection and control are discussed together with questions related to areas in PV biology that will continue to provide productive opportunities of discovery and to further our understanding of this diverse set of human viral pathogens.

Keywords: HPV; animal papillomaviruses; codon modification; immunotherapy; pathogenesis; vaccines; viral oncogenesis.

Figure 1. FIGURE 1: HPV16 genome showing viral open reading frames coding for known viral proteins.

The Upstream Regulatory Region (URR) is shown in grey. Map constructed using SnapGene software.

Figure 2. FIGURE 2: MmuPV1 secondary infections of the mouse oral cavity.

(A) (H&E), (B) (in situ hybridization using MmuPV1 DNA probe) and (C) (immunohistochemical staining using a monoclonal antibody to MmuPV-1 L1 protein) detecting an infection localized to the base of the tongue at the circumvallate papilla. (A), (B) and (C) are successive 4 μm sections from formalin-fixed paraffin-embedded tissues from athymic mice. One of several examples of MmuPV-1 infection of the circumvallate papilla of the mouse tongue.