Anal Pre-Cancer: Squamous Intraepithelial Lesions

Human papillomaviruses (HPV)

Human papillomaviruses (HPV) are a family of viruses that infect cells lining the surfaces of the body. Anogenital HPV types infect the anogenital and upper digestive tract and are sexually transmitted. Infection with anal HPV is very common; the lifetime risk of anogenital HPV is at least 80-90% in sexually active people[1]. 

Of about 40 anogenital HPV types, 15-20 are considered "high-risk" (hr-HPV) due to their potential to cause invasive cancer[2]. The hr-HPV type 16 carries the strongest association with invasive anal cancer. While 90% of anal cancers are caused by infection with hr-HPV, it is important to remember that only a small fraction of people with anal hr-HPV infection ever develop anal cancer. Infection with low-risk HPV (lr-HPV) anogenital types is associated with genital warts, also known as condyloma acuminata. Lr-HPV types 6 and 11 cause 90% of genital warts. 

Squamous intraepithelial lesions

HPV infection of the anal canal and perianus leads to the formation of anal squamous intraepithelial lesions (SIL). Persistent hr-HPV infection can lead to the cancer precursor anal high-grade SIL (HSIL). A small proportion of anal HSIL, in turn, will progress to invasive anal squamous cell carcinoma. It is important to remember that anal HSIL is not invasive cancer and that only a small number of people with anal HSIL develop anal cancer. Infection with low-risk HPV (lr-HPV) anogenital types is associated primarily with low-grade squamous intraepithelial lesions (LSIL), which include genital warts or condyloma acuminata. Anal LSIL does not result in anal cancer,  but can cause significant discomfort and psychological distress. 


We use the terms anal HSIL and anal LSIL to describe HPV-associated lesions of the anus according to recommendations from the Lower Anogenital Squamous Terminology (LAST) project[3]. This two-tiered nomenclature system is intended to reflect the biological distinction between precancerous (anal HSIL) and benign (anal LSIL) changes. Previously, HPV-associated changes were termed anal intraepithelial neoplasia (AIN) grades 1, 2, or 3 with a larger number indicating increased severity of the lesions. Per the LAST project, lesions that were previously classified as AIN 1 now correspond to anal LSIL and AIN 2 or 3 correspond to anal HSIL. Additional older terms like “carcinoma-in-situ”, “Bowen disease” and “Bowenoid papulosis” are also classified as anal HSIL.

Older terminology is still seen on pathology reports today. In addition, it is possible for anal LSIL and HSIL to be further classified by the applicable AIN subcategorization (eg, HSIL[AIN2] or HSIL[AIN3]). It is important to emphasize that the various terms used to describe anal HSIL describe the presence of a precancerous lesion and NOT invasive cancer. Only a small proportion of people with anal HSIL develop anal cancer. 

Schematic Representation of Anal Squamous Intraepithelial Lesions

Treatment of squamous intraepithelial lesions

Following publication of the ANCHOR study, we now have good evidence that the use of HRA to identify and treat anal HSIL significantly decreases the risk of anal cancer in people living with HIV[4]. Our goal at the Anal Neoplasia Clinic, Research and Education Center is to prevent as many cases of anal cancer as possible by treating anal HSIL before it progresses to cancer. We also offer treatment for symptomatic anal LSIL.


1. Chesson HW et al. Sex Transm Dis 2014; 41(11): 660-4.

2. Schiffman M et al. Lancet 2007; 370(9590): 890-907.

3. Darragh TM et al. Int J Gynecol Pathol 2013; 32-76.

4. Palefsky JM et al. NEJM; 386: 2273-82.