HPV infection in the genital tract is common in young sexually active individuals, the majority of whom clear the
infection without overt clinical disease. However most of those who develop benign lesions eventually mount an effective cell mediated immune response and the lesions regress. Regression of ano-
genital warts is accompanied histologically by a CD4+ T cell dominated Th1 response; animal models support this and provide evidence that the response is modulated by CD4+ T cell dependent mechanisms. Failure to develop effective CMI to clear or control infection results in
persistent infection and, in the case of the oncogenic HPVs, an increased probability of progression to CIN3 and invasive
carcinoma. The central importance of the CD4+ T cell population in the control of
HPV infection is shown by the increased prevalence of
HPV infections and HGSIL in individuals immunosuppressed as a consequence of
HIV infection. The prolonged duration of
infection associated with HPV seems to be associated with effective evasion of innate immunity as reflected in the absence of
inflammation during virus replication, assembly and release, and down regulation of
interferon secretion and response thus delaying the activation of adaptive immunity. Serum neutralising antibody to the major
capsid protein L1 usually develops after the induction of successful cell mediated immunity and these antibody and cell mediated responses are protective against subsequent viral challenge in natural
infections in animals. Prophylactic
vaccines consisting of HPV L1 VLPs generate high anti L1 serum
neutralizing antibody concentrations and in clinical trials have shown greater than 95 per cent efficacy against both benign and neoplastic genital HPV associated disease. These
vaccines are delivered intramuscularly and therefore circumvent the immune evasion strategies of the virus.