Stanley et al. BMC Cancer 2012, 12:398 http://www.biomedcentral.com/1471-2407/12/398 C O R R E S P O N D E N C E Open Access HPV infection, anal intra-epithelial neoplasia (AIN) and anal cancer: current issues Margaret A Stanley, David M Winder, Jane C Sterling and Peter KC Goon* Abstract Background: Human papillomavirus (HPV) is well known as the major etiological agent for ano-genital cancer. In contrast to cervical cancer, anal cancer is uncommon, but is increasing steadily in the community over the last few decades. However, it has undergone an exponential rise in the men who have sex with men (MSM) and HIV + groups. HIV + MSM in particular, have anal cancer incidences about three times that of the highest worldwide reported cervical cancer incidences. Discussion: There has therefore traditionally been a lack of data from studies focused on heterosexual men and non-HIV + women. There is also less evidence reporting on the putative precursor lesion to anal cancer (AIN – anal intraepithelial neoplasia), when compared to cervical cancer and CIN (cervical intraepithelial neoplasia). This review summarises the available biological and epidemiological evidence for HPV in the anal site and the pathogenesis of AIN and anal cancer amongst traditionally non-high risk groups. Summary: There is strong evidence to conclude that high-grade AIN is a precursor to anal cancer, and some data on the progression of AIN to invasive cancer. Keywords: Anal cancer, Anal intraepithelial neoplasia, AIN, Progression, Human papillomavirus Background Approximately 15 of the 30–40 human papillomavirus (HPV) types infecting the ano-genital mucosae (cervix, vagina, vulva, anus and penis) are oncogenic viruses causing ~ 5.2% of total human cancers [1]. Like cervical cancer, squamous cell carcinoma of the anus (anal SCC) is thought to be preceded by a spectrum of intra- epithelial changes, anal intra-epithelial neoplasia (AIN), of varying cytological and histological severity AIN 1 - mild, AIN 2 - moderate, AIN 3 - severe, similar to cer- vical intra-epithelial neoplasia (CIN), that correspond to the CIN spectrum CIN 1, CIN 2/3 [2-4]. The success of current HPV L1 prophylactic vaccines in preventing high-grade dysplasia of the cervix (and consequently the end-result of cancer) has raised the questions of whether these vaccines will be successful in preventing other HPV-related cancers, and whether subsequent licensing of vaccine for non-cervical cancers is merited. * Correspondence: pg336@cam.ac.uk Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK In this context, we will summarise the available evi- dence that seeks to answer three questions which are currently discussed for anal cancer and pre-cancers. 1) The lack of data on AIN and anal cancer from the larger percentage of the community i.e. heterosexual males and non-HIV-positive or non-high risk women, which has meant that the majority of the inferences are therefore extrapolated from MSM data. 2) That AIN is a precursor lesion to invasive anal cancer. 3) The rate of progression of AIN 3 to invasive anal cancer. Discussion Epidemiology and biology Anal SCC is an uncommon cancer but the incidence worldwide is increasing in men and women [3]. Women have a higher incidence rate in age groups greater than 50 years but men dominate the 20–49 year old age group. In men and women, common risk factors are re- ceptive anal sex, lifetime number of sexual partners, a © 2012 Stanley et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.