Anal intraepithelial neoplasia (AIN) in the antiretroviral therapy era

Anal intraepithelial neoplasia (AIN) as a precursor for invasive SCCA has emerged from the recent literature as one of the most important contributions to the field of anal cancer. HIV positive women are more likely to demonstrate abnormal Papanicolaou smears, as well as persistence of cervical infection with HPV over time [50]. Thus, invasive cervical cancer was added to the list of AIDS-defining conditions in 1993.  Not surprisingly,  AIN is common among HIV-positive homosexuals, in this population, more than 50% of individuals with a CD4+  count <500, and 33% of those who had a CD4+ count >500 developed AIN within 4 years of follow-up [51]. Anal colposcopy is a specialised procedure,  which should be performed by a trained coloproctologist,  using 5% acetic acid epithelial staining in accordance with the techniques used for cervical colposcopy. The rationale for screening this high-risk population with anal Papanicolaou smears is currently under investigation. It appears, however, that AIN does not always progress to SCCA, and that a significant percentage of these lesions undergo spontaneous regression.

In theory, highly active antiretroviral therapy (HAART),  which results in improved immune function,  may subsequently reduce the risk of HIV-positive homosexuals developing persistent HPV infection in the anal canal. Alternatively, the incidence of AIN may increase over time, since AIDS patients now live longer in the setting of imperfect immune reconstitution. Indeed, recent data regarding AIN and SCCA in the era of HAART give cause for concern. Despite prolonged response to anti-retroviral therapy, HIV-positive homosexuals have persistent HPV infection, and HAART had no effect on the incidence and progression of AIN [52].

The current consensus is that HAART will probably not be associated with a reversal of high-grade dysplasia, since these lesions have already acquired irreversible chromosomal alterations.  Furthermore,  epidemiological data from the San Francisco area indicate that the incidence of anal cancer continues to increase substantially despite the widespread use of HAART in this population.

Pascal Gervaz, MD
Clinique de Chirurgie Viscerale
Hopital Cantonal Universitaire de Geneve
Rue Micheli-du-Crest 24
CH-1211 Geneve
E-Mail: .(JavaScript must be enabled to view this email address)


  •   Xi LF, Critchlow CW, Wheeler CM, Koutsky LA, Galloway DA, et al. Risk of anal carcinoma in situ in relation to human papillomavirus type 16 variants. Cancer Res 1998; 58:3839–44.
  •   Chen T, Pecaro G, Defendi V. Genetic analysis of in vitro progression of human papillomavirus transfected human cervical cells. Cancer Res 1993; 53:1167–71.
  •   Critchlow CW, Hawes SE, Kuypers J, Goldbaum G, Holmes K, et al. Effect of HIV infection on the natural history of anal human papillomavirus infection. AIDS 1998; 12:1177–84.
  •   Tilston P. Anal human papillomavirus and anal cancer. J Clin Pathol 1997; 50:625–34.
  •   Palefsky JM, Holly EA, Ralston ML, Jay N. Prevalence and risk factors for human papillomavirus infection of the anal canal in human immunodeficiency virus (HIV)-positive and HIV-negative homosexual men. J Infect Dis 1998; 177:361–7.
  •   Palefsky JM, Holly EA, Ralston ML, Arthur SP, Jay N, et al. Anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual and bisexual men: prevalence and risk factors.  J Acquir Immune Def Syndr Hum Retrovirol 1998; 17:320–6.
  •   Rader JS, Kamarasova T, Huettner PC, Li L, et al. Allelotyping of all chromosomal arms in invasive cervical cancer.  Oncogene1996;13:2737–41.
  •   Muleris M, Salmon RJ, Girodet J, Zafrani B, Dutrillaux B. Recurrent deletions of chromosomes 11q and 3p in anal canal carcinoma. Int J Cancer 1987; 39:595–8.
  •   Vatra B, Sobhani I. Aparicio T, Girard PM, Puy Montbrun TD, et al. Anal canal squamous-cell carcinomas in HIV positive patients:  clinical features,  treatments and prognosis.  Gastroenterol Clin Biol 2002; 26:147–9.
  •   Place RJ, Gregorcyk SG, Huber PJ, Simmang CL. Outcome analysis of HIV-positive patients with anal squamous cell carcinoma. Dis Colon Rectum 2001; 44:506–12.
  •   Goldie SJ, Kuntz KM, Weinstein MC, Freedberg KA, Welton ML, Palefsky JM. The clinical effectiveness and cost-effectiveness of screening for anal squamous intraepithelial lesions in homosexual and bisexual HIV-positive men.  JAMA 1999;  281: 1822–9.
  •   Massad LS, Riester KA, Anastos KM, Fruchter RG, Palefsky JM, et al. Prevalence and predictors of squamous cell abnormalities in Papanicolaou smears from women infected with HIV-1. J Acquir Immune Defic Syndr 1999; 21:33–41.
  •   Palefsky JM, Holly EA, Ralston ML, et al. High incidence of anal high grade squamous intraepithelial lesions among HIV positive and HIV negative homosexual and bisexual men. AIDS 1998; 12:495–503.
  •   Palefsky JM, Holly EA, Ralston ML, et al. The effect of highly active antiretroviral therapy on the natural history of anal squamous intraepithelial lesions and anal HPV infection. J Acquir Immune Defic Syndr 2001; 28:422–8.

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