Human papillomaviruses (HPVs) are associated with various benign and malignant epithelial proliferative diseases. Over 100 genotypes of HPV are recognized.
An HPV isolate is described as a novel type if the nucleotide sequence of its E6, E7, and L1 genes differs more than 10% from that of any other HPV type. Based on tropism, a distinction can be made between cutaneous HPV types that infect the epidermis and mucosal HPV types that infect the epithelia of the anogenital or the aerodigestive tract.
In vitro studies showed that a group of phylogeneti-cally related mucosal HPV types has oncogenic potential: their E6 and E7 proteins interfere with cell cycle regulation by mediating degradation of p53 and pRb proteins, respectively. These oncogenic HPVs, designated high-risk (HR) HPVs, are an important causal factor in carcino-genesis of the uterine cervix. Epidemiological studies have shown that HR-HPVs include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 and probably also types 26, 53, and 66. Nononcogenic or low-risk (LR) genital HPVs are phylogenetically distant from the HR-HPVs. They include HPV 6, 11,40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108. Their E6 and E7 proteins are less competent in interfering with p53 and pRb functions, and they can cause benign proliferations such as condylomata acuminata (genital warts). For a number of mucosal HPV types, the risk has not been determined yet.
Cutaneous HPVs belong to other phylogenetic subgroups than mucosal HPVs. Some of them play a role in benign epidermal proliferation, e.g., HPV 1 which is causally related to verruca vulgaris (warts). In addition, associations between cutaneous HPVs and malignant skin diseases were discovered (reviewed in Ref. ). For example, squamous cell carcinomas (SCCs) from patients with the rare hereditary disorder epidermodys-plasia verruciformis (EV) are associated with a particular group of 22 phylogenetically related cutaneous HPVs which are therefore designed EV-HPVs. They include HPV 5, 8, 9, 12, 14, 15, 17, and 19-25. These types were also detected in other cutaneous malignancies such as SCC in individuals without EV and basal cell carcinomas (BCC). The prevalence of HPV in skin tumors is especially high in immunosuppressed individuals.
Human papillomavirus typing methods can be divided in target-amplification methods, i.e., methods involving polymerase chain reaction (PCR), and non-PCR techniques. In the following section, technical aspects of the different currently available HPV typing methods are
Table 1 HPV typing methods and their applications
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