This model fits well with much of our data on the role of Beta HPV proteins and expression patterns, but still requires some confirmation, perhaps by the analysis of intermediate disease states during cancer progression. Although there are many similarities in genome organisation of HPVs, there are many differences, both in protein function and expression patterns that underlie disease phenotype.
The discovery of Gamma HPV types 101, 103 and 108 that lack an apparent E6 gene, and which are associated with cervical disease [199] and [200], emphasises the limitations of applying general principles across wider groupings. Such considerations should also be borne in mind when considering buy GSK J4 how HPV16 and 18 cause disease, and how even more closely related types, such see more as HPV16 and 31, function in infected epithelial tissue. Although high-risk HPV infection is common, with over 80% of women becoming infected at some stage in their life, cervical cancer arises only rarely as a result of infection. Most infections are cleared as a result of a cell-mediated immune response, and do not persist long enough for deregulated gene expression and the accumulation of secondary genetic
errors to occur. HPV16 has an average length of persistence that is longer than most other high-risk types, and this may contribute to its higher cancer risk [201] and [202]. Poorly understood differences in cell tropism and disease progression patterns associated with individual HPV types may underlie the higher association of HPV18 with adenocarcinoma (rather than squamous cell
carcinoma) and its relative infrequence in CIN2. Indeed, our current thinking suggests that HPV16, 18 and 45, which are the primary cause of adenocarcinomas, may infect cells with potential for glandular differentiation [203], and that an abortive Sodium butyrate or semi-permissive infection in these cells is important for the development of adenocarcinoma. Recent studies have suggested that the infection of specific cells in the junctional region between the endo and ectocervix may in fact underlie the development of many cervical cancers [204]. In general however, genital tract infections by HPV are common in young sexually active individuals, with the majority (80–90%) clearing the infection without overt clinical disease. Most of those who develop benign lesions eventually mount an effective cell mediated immune response and the lesions regress. Regression of anogenital warts is accompanied histologically by a CD4+ T cell-dominated Th1 response, which is also seen in animal models of PV-associated disease [205], [206], [207] and [208]. Such models provide evidence that the response is modulated by antigen-specific CD4+ T cell dependent mechanisms.
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