The pathology and molecular biology of anal intraepithelial neoplasia: Comparisons with cervical and vulvar intraepithelial carcinoma

Background: Anal intraepithelial neoplasia (AIN) is a well-described pathological precursor of invasive squamous cell carcinoma which has recently been detected with increasing frequency in immunocompromised patients, particularly those with seropositivity for human immunodeficiency virus (HIV). The epidemiology and natural history of this entity is somewhat unclear, since the overall prevalence in the HIV seronegative population is unknown. Discussion: There is a clear etiological association between AIN and high-risk human papillomavirus (HPV) subtype infection although there is great variability in HPV DNA detection of cytological and histological material in these patients. It appears that there is an antigen-specific hyporesponsiveness by cytotoxic lymphocytes against HPV peptide sequences or recombinant proteins encoded by oncogenic HPV subtypes in these patients, which is dependent upon the stage of their HIV-associated disease. Although the molecular biology of AIN and cervical or vulvar intraepithelial neoplasia are comparable, in AIN there is less significance of tumor suppressor gene mutations, proto-oncogenic growth factor activation, and genomic instability. Conclusion: Current concepts in the epidemiology and etiology of AIN are discussed, as well as its immunological response in the HIV-positive population, drawing parallels where possible between other HPV-related preinvasive disorders, and concluding with a suggested management protocol.