Anal intraepithelial neoplasia: A review of diagnosis and management

Abstract

Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.

Keywords: Anal cancer; Anal intraepithelial neoplasia; Anal squamous cell carcinoma; Human papillomavirus; Human papillomavirus vaccine.

Figure 1

Cytology of anal intraepithelial lesions. A: LSIL, with representative binucleate hyperchromatic cells (koilocytes) and nuclear enlargement (Papanicolaou stain, original magnification × 400); B: HSIL, with representative markedly increased nuclear to cytoplasmis ratio as comparted to LSIL at left (Papanicolaou stain, oil immersion, original magnification × 1000). Reproduced with permission[85]. LSIL: Low grade squamous intraepithelial lesions; HSIL: High grade squamous intraepithelial lesions.

Figure 2

High-resolution anoscopy of representative examples of anal intraepithelial lesions. A: Low grade AIN lesion after acetic acid application with representative acetowhitening; B: Low grade AIN lesion after application of Lugol’s iodine with brown area representing normal uptake by glycogenated cells, and “mustard” colored area representing negative uptake and suggestive of dysplasia; C: High grade AIN seen after application of acetic acid and the dense acetowhite change; D: High grade AIN with concern for invasion; E: External/perianal high grade AIN after application of acetic acid; F: High grade AIN with concern for invasion. Reproduced with permission[85]. AIN: Anal intraepithelial neoplasia.

Figure 3

Histologic examples of high grade anal intraepithelial neoplasia, hematoxylin and eosin stain. A: High grade AIN as demonstrated by nuclear pleomorphism, numerous mitoses and no maturation of the epithelium (original magnification × 400); B: Microinvasion of a high grade AIN demonstrated by a budding off of atypical cells with paradoxical maturation and a marked inflammatory response (original magnification × 200). Reproduced with permission[85]. AIN: Anal intraepithelial neoplasia.

Figure 4

Algorithm for diagnosis, treatment and surveillance of anal intraepithelial neoplasia. Adapted from Palefsky and Rubin, 2009[86]. ASCUS: Atypical squamous cells of undetermined significance; LSIL: Low-grade squamous intraepithelial lesion; HSIL: High-grade squamous intraepithelial lesion; AIN: Anal intraepithelial neoplasia.