Human Papillomavirus Infections: Warts or Cancer?

Abstract

Human papillomaviruses (HPVs) are prevalent pathogens of mucosal and cutaneous epithe-lia. Productive infections of squamous epithelia lead to benign hyperproliferative warts, condylomata, or papillomas. Persistent infections of the anogenital mucosa by high-risk HPV genotypes 16 and 18 and closely related types can infrequently progress to high-grade intraepithelial neoplasias, carcinomas-in-situ, and invasive cancers in women and men. HPV-16 is also associated with a fraction of head and neck cancers. We discuss the interactions of the mucosotropic HPVs with the host regulatory proteins and pathways that lead to benign coexistence and enable HPV DNA amplification or, alternatively, to cancers that no longer support viral production. H uman papillomaviruses (HPVs) are ubiquitous small DNA viruses that comprise a family of more than 150 genotypes. Closely related types show a predilection for particular epithelial tissues and have similar pathogenic properties (de Villiers et al. 2004; Bravo et al. 2010). The mucosotropic HPVs can be sexually transmitted. Infections are frequently asymp-tomatic and are cleared by the immune systems. Active cases are manifested as hyperproliferative lesions but often regress into subclinical persis-tency within a year. Latent infections can reactivate following immunosuppression or upon undergoing repeated cycles of wounding and healing (Fig. 1). A small fraction of persistent infections by the high-risk (HR) HPV genotypes leads to cancers (reviewed by zur Hausen 2009). Worldwide, each year there are about 500,000 new cases of cervical cancer and 275,000 deaths. More than 99% of cervical cancers are caused by high-risk (HR) HPVs, and types 16 and 18 are responsible for about 70% of the cases (Wal-boomers et al. 1999). The HR HPVs are also responsible for a high percentage of cancers of other anogenital sites in men and women. Moreover, HPV-16 is associated with a fraction of the head and neck neoplasias, in particular tonsillar and oro-pharyngeal cancers (reviewed by Syrjänen 2010). In contrast, infections by the low-risk (LR) types 6 and 11 cause 90% of genital warts and essentially all laryngeal papillomas (recurrent respiratory papillomatosis or RRP) (reviewed by Derkay and Wiatrak 2008) but they rarely result in carcinomas. Juvenile-onset RRP results from transmission in utero or during passage through the birth canal of mothers with active condylomata, yet infections may become symptomatic years later. Recent studies

A randomized controlled proof‐of‐concept trial of digoxin and furosemide in adults with cutaneous warts

“…Ki‐67 is a biomarker for cell proliferation, and in normal epithelium the Ki‐67 signals are restricted to the basal layer. By reactive change, the Ki‐67 positivity is also observed in the other layers of the epithelium (scattered staining) . From this we can conclude that there is a clear correlation between the histopathological diagnoses, presence of E4 and Ki‐67 pattern and HPV load.…”

Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia

“…(B) Initiation of HPV DNA replication. Replication begins with the recruitment of E1 by E2 to the Ori (which contains of a cluster of three E2 binding sites flanking a series of overlapping E1 binding sites) (Chow and Broker, 2013). This recruitment step involves an essential protein-protein interaction between the E2 transactivating domain (i.e.…”

Transcriptome analysis of HPV-induced warts and healthy skin in humans

“…Although warts are themselves benign, HPV infection has been identified as the definitive cause of cervical cancer and has been associated with a number of other cancers and diseases [16]. As a result, the majority of peer-reviewed studies conducted on HPV infection have been in the context of cancer research.…”