Advances in virology during the 1970s established the existence of multiple distinct types of human papillomavirus (HPV). These virologic discoveries, when combined with epidemiologic studies, and the recognition that viral DNA can be integrated into the host genome, enabled the eventual identification of the causal role of specific HPV types in cervical cancers and later other cancers, as well as anogenital warts and recurrent respiratory papillomatosis (RRP).1,2 These advances and the identification of HPV types 16 and 18 in the majority of cervical cancers, as well as in precancers, later led to the development of prophylactic HPV vaccines; this work was recognized with a portion of the 2008 Nobel Prize in Physiology or Medicine for Harald zur Hausen.1,3
Genital HPV infection is the most common sexually transmitted infection worldwide4,5 Studies have shown that HPV is prevalent in all regions of the world, with an average prevalence of 11% in females with normal cervical cytology, a correlation between prevalence in females and males, and variation by geographic region.4 An estimated 4.5% of all cancers worldwide, 630,000 cancers annually, are attributable to HPV.6 In the United States, an estimated 14 million persons are newly infected every year, resulting in an estimated U.S.$1.7 (U.S.$0.8–U.S.$2.9) billion in direct medical costs.7 HPV infections are commonly acquired soon after initiation of sexual activity.8,9 Although the vast majority of HPV infections cause no symptoms and are self-limited, persistent HPV infection can cause cervical cancer as well as other anogenital cancers in women, penile cancer in men, and oropharyngeal and anal cancers in men and women6,10 HPV is also the cause of anogenital warts and RRP.11
NOMENCLATURE AND CLASSIFICATION
HPVs are in the family Papillomaviridae.12 All are double-stranded DNA viruses, with a small (8 kb) circular genome, share a common organization, and encode two late (L) and several early (E) proteins. HPVs have two capsid proteins, L1 and L2. L1 is the major capsid protein. The L1 capsid proteins can self-assemble to form virus-like particles (VLPs), with type-specific conformational epitopes; these are the basis of currently available prophylactic vaccines.13 The early proteins are responsible for viral DNA replication and transcriptional regulation (E1 and E2), virus assembly and virion release (E4), and transformation (E5, E6, and E7).12,14 Not all early genes are present in all HPV types; E6 and E7 are the primary oncoproteins in oncogenic HPV types.12,15
More than 200 HPV types have been identified.12,15,16 These are classified into five genera (evolutionary groups) based on the degree of L1 sequence homology12,15: alpha, beta, gamma, mu, and nu. All five genera include cutaneous types, and the alpha genus also includes all mucosal types.15 Within genera, species are denoted with numbers (e.g., alpha-1, alpha-2, beta-3, gamma-10). HPV types were numbered in order of discovery, therefore the type numbers bear no ...