Anal Intraepithelial Neoplasia and Squamous Cell Carcinoma in HIV-Infected Adults

WWY Tong; RJ Hillman; AD Kelleher; AE Grulich; A Carr


HIV Medicine. 2014;15(2):65-76. 

In This Article

Abstract and Introduction


Anal cancer is one of the most common non-AIDS-defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV-infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV-related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV-infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV-infected adults.


HIV infection coupled with oncogenic human papilloma virus (HPV) infection is a strong risk factor for anal squamous cell carcinoma (SCC)[1] and its precursor lesion, high-grade anal intraepithelial neoplasia (HGAIN). Similar to cervical cancer, > 90% of anal cancers are attributable to persistent infection with HPV.[2] However, unlike invasive cervical cancer, anal cancer is not an AIDS-defining malignancy, although in many ways it behaves like one (e.g. is caused by infection and has a higher incidence in individuals with immunodeficiency). In the era of combination antiretroviral therapy (cART), it has become the most common non-AIDS-defining malignancy in HIV-infected adults in some settings.[3] The terminology used for diagnosis of anal intraepithelial neoplasia (AIN) parallels that for cervical intraepithelial neoplasia (Table 1).[4]

Human Papillomavirus

Papillomaviruses are host-specific, strictly epitheliotropic, small (40–55 nm), nonenveloped, double-stranded DNA viruses (approximately 8000 bases).[5] An icosahedral capsid is formed by their major (L1) and minor (L2) structural proteins, and there are six nonstructural proteins, of which E6 and E7 are the major oncoproteins.[5] The 120 types[6] of HPV are classified by their L1 open-reading frame DNA sequence, each type differing by more than 10% in this conserved region.[7] Genitally transmitted, disease-causing types belong to the genus Alphapapillomavirus.[8] HPVs are also classified according to their carcinogenicity as high risk (having a strong epidemiological association with anogenital cancer) or low risk (causing benign genital warts).[9] Most HPV-positive anal cancers are attributed to high-risk HPV type 16 (85%) or 18 (7%);[10,11] these account for 70% of all cervical cancers.[12]