Human Papillomavirus (HPV)

Abstract

DefinitionHuman papillomaviruses (HPV) are a family of small DNA tumor viruses with a size of 52-55 nm. The family consists of 200 different genotypes; many of the types cause benign warts or papilloma, while a small fraction of oncogenic or "high-risk" types can cause invasive cervical cancer or other tumors. HPV infects keratinocytes in the basal layer of stratified squamous epithelia and replicates in the nucleus of infected keratinocytes along with keratinocyte differentiation. The viral genome in size of 7.9 kb encodes six early, nonstructural regulatory proteins (E1, E2, E4, E5, E6, and E7) and two late structural proteins (L1 and L2). E6 and E7 are two oncoproteins responsible for the viral oncogenesis of high-risk HPVs, including HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, HPV59, HPV68, HPV73, and HPV82. L1 is a major structural component of viral capsid, and its self-assembly in vitro into a viral-like particle (VLP) provides the basis of prophylactic vaccines against infections of several HPV types. In addition to cervical cancer, high-risk HPVs are associated with the development of various anogenital cancers and certain head and neck cancers. Classification of Human PapillomavirusesHPVs are a family of 200 different genotypes, with 155 genotypes being completely sequenced. Papillomaviruses were originally classified as members of the family Papovaviridae, but reclassified in 2002 as an independent family, Papillomaviridae. The family Papillomaviridae currently contains at least 29 genera, and human papillomaviruses are grouped into five (alpha, beta, gamma, mu, and nu) genera (Fig. 1). The classification of papillomaviruses depends on the most conserved L1 open reading frame (ORF) by genotyping. Different genera share less than 60 % nucleotide sequence identity in the L1 ORF. A new type of papillomavirus is given when its DNA sequence of L1 ORF differs by more than 10 % from the closest known HPV type. Otherwise, a subtype indicates the difference between 2 % and 10 % and a variant less than 2 %. HPV types are numbered in the order of their discovery. HPVs in the alpha genus cause mucosal and a fraction of cutaneous HPV lesions, while HPVs in the beta, gamma, mu, and nu genera cause cutaneous lesions.HPVs are also grouped clinically as high-risk (oncogenic) types, which are frequently associated with invasive cervical cancer, and low-risk (non-oncogenic) types, which are found mainly in genital warts. Fifteen HPV types (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82) are high risk. Twelve HPV types (types 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and 89) are low risk (Munoz et al. 2003). Among the high-risk HPVs, HPV16 and HPV18 are the principal causes of cervical cancer, with a combined, worldwide relative contribution of 70 % of invasive cervical cancer.