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INTRODUCTION

Interest in human papillomavirus (HPV) infection began in earnest in the 1980s after Harold zur Hausen postulated that infection with these viruses was associated with cervical cancer. It is now recognized that HPV infection of the human genital tract is extremely common and causes clinical conditions ranging from asymptomatic infection to genital warts (condylomata acuminata); dysplastic lesions and invasive cancers of the anus, penis, vulva, vagina, and cervix; and a subset of oropharyngeal cancers. This chapter describes the epidemiology of HPV as a virus and a pathogen, the natural history of HPV infections and associated cancers, strategies to prevent infection and HPV-associated disease, and treatment modalities for some conditions caused by HPV.

PATHOGENESIS

Overview

Image not available. HPV is an icosahedral, nonenveloped, 8000-base-pair, double-stranded DNA virus with a diameter of 55 nm. Like the genomes of other papillomaviruses, HPV’s genome consists of an early (E) gene region, a late (L) gene region, and a noncoding region, which contains regulatory elements. The E1, E2, E5, E6, and E7 proteins are expressed early in the growth cycle and are necessary for viral replication and cellular transformation. The E6 and E7 proteins are responsible for malignant transformation, targeting the human cell-cycle regulatory molecules p53 and Rb (retinoblastoma protein) for degradation, respectively. Translation of the L1 and L2 transcripts and splicing of an E1^E4 transcript occur later. The L1 gene encodes the 54-kDa major capsid protein that makes up the majority of the virus shell; the 77-kDa L2 minor protein contributes a smaller percentage of the capsid mass.

More than 125 HPV types have been identified and are numerically designated on the basis of a unique L1 gene sequence. Approximately 40 HPV types are regularly identified in the anogenital tract; these types are subdivided into high-risk and low-risk categories depending on the associated risk of cervical cancer. For example, HPV types 6 and 11 cause genital warts and ~10% of low-grade cervical lesions and are thus designated low risk. HPV types 16 and 18 cause dysplastic lesions and a high percentage of invasive cancers of the cervix and are therefore considered high risk.

HPV targets basal keratinocytes after microtrauma allows exposure of these cells to the virus. The HPV replication cycle is completed as keratinocytes undergo differentiation. Virions are assembled in the nuclei of differentiated keratinocytes and can be detected by electron microscopy. Infection is transmitted by contact with virus contained in these desquamated keratinocytes (or with free virus) from an infected individual.

The Immune Response to HPV Infection

Unlike many viral infections, HPV infection has no viremic phase. This lack of viremia may account for the incomplete antibody response to HPV infection. Natural HPV infection of the genital tract gives rise to a serum antibody response in 60–70% of individuals. Significant, although incomplete, protection against type-specific reinfection is associated with the presence of neutralizing ...

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