30 Papillomavirus

Abstract

Human papillomaviruses (HPVs) comprise a family of small DNA tumor viruses that replicate as extrachromosomal nuclear plasmids. Closely related HPV genotypes exhibit a predilection for epithelial tissues at particular anatomic sites (de Villiers et al. 2004). The mucosotropic groups are the most thoroughly investigated because they are highly prevalent, can be sexually transmitted, and cause significant morbidity and mortality worldwide. HPV infections have alternative outcomes (Fig. 1). They can be asymptomatic or they may go into a productive phase. Productive infections often regress into subclinical latency after a year or so of activity, but overt symptoms may reappear years or decades later during periods of immune suppression. Persistent infection by the high-risk HPV genotypes such as HPV-16, HPV-18, and closely related types can lead to cancers at a low frequency and, conversely, more than 99% of the cervical cancers are caused by the high-risk HPVs (Walboomers 1999; for review, see zur Hausen 2002). In contrast, infections by the low-risk types 6 and 11 rarely result in carcinomas. To understand these alternative outcomes, one must first appreciate how the virus establishes a benign coexistence with the host. It is then evident why a loss of quasi-equilibrium can lead to deadly consequences for both parties.

PERMISSIVE HOST TISSUES
Regardless of their oncogenic potential, the productive phase of all human papillomaviruses takes place only in differentiated cells in a squamous epithelium (for review, see Longworth and Laimins 2004; Chow and Broker 2006a), which is a “conveyer belt” of keratinocytes that continuously stratify and...