By Kenneth E. Youens, M.D.
Squamous cell carcinoma (SCC) of the anus is a human papillomavirus (HPV)-related disease that represents about 1.5% of cancers of the digestive tract. Though uncommon compared to cervical cancer or other digestive cancers, the incidence of anal SCC in patients at highest risk is rising, and is currently more than double that of cervical cancer prior to the initiation of Pap screening1.
The most significant risk factor for anal SCC is anogenital HPV infection. Other risk factors include immunosuppression, a history of anal receptive intercourse, multiple sexual partners, cigarette smoking, and a history of sexually transmitted disease. Women with anal SCC are likely to have a prior history of cervical or vulvar dysplasia or carcinoma.3
Given the many parallels between cervical and anal cancer, the success of cervical cancer screening suggests that it could be a valuable template for anal cancer screening. Like cervical cytology, the purpose of anal-rectal cytology is to detect and treat dysplastic precursor lesions before cancer develops.
The question of who should be screened is controversial, and formal guidelines recommending anal cytology screening have not been widely adopted. Most authors would agree that yearly screening of HIV-positive homosexual and bisexual men is preferred, and screening every two or three years would produce life-expectancy benefits in HIV-negative homosexual and bisexual men.2 The prevalence of anal dysplasia in women with cervical, vulvar, and vaginal dysplasia is approximately 12%, and some authors recommend anal cancer screening in this population as well.3
The Role of Human Papillomavirus Testing
The value of high-risk HPV DNA testing is well-established for cervical cancer screening, but its utility in anal cancer screening is less clear. HPV testing of anal samples is highly sensitive for anal dysplasia (84-100%), but suffers from very poor specificity (16-18%). Given the high prevalence of anal HPV infection in HIV-positive homosexual and bisexual men, HPV testing should probably not be used for primary screening in this population. Anal HPV testing may be useful in other at-risk populations with a lower prevalence of anal HPV infection because of its excellent negative predictive value.1 Type-specific HPV testing and other HPV-related biomarker testing may play a useful role in some specific clinical scenarios.
Anal cytology collection should sample the entire anal canal, including the anorectal transformation zone. One method is described below:
Label a cytology preservative container (e.g. PreservCyt™, CytoLyt™, or CytoRich™ Red) or a frosted glass slide with two unique identifiers (e.g. name and date of birth).
Position the patient in the lateral recumbent or dorsal lithotomy position.
Moisten a Dacron swab with water.
Blindly insert the swab 5-6 cm into the anal canal.
Applying firm lateral pressure, slowly rotate the swab and withdraw until the swab exits the anal verge.
Place the sample in liquid-based cytology preservative or immediately smear the specimen on a slide and spray fix.
Screening Results and Follow-up
Anal-rectal cytology results are reported using a modified version of the 2001 Bethesda System for reporting results of cervical cytology. Follow-up protocols for abnormal anal cytology results are less well-established than for cervical cytology. One proposal is to refer all patients with abnormal anal cytology results (i.e. ASC-US, ASC-H, LSIL, or HSIL) to high-resolution anoscopy with biopsy. 4 In settings where high-resolution anoscopy is not widely available, some recommend limiting anoscopic referrals to patients with high-grade cytological abnormalities, with follow up of lesser abnormalities by serial digital anal-rectal examination and repeat cytology.1
If anal dysplasia is identified at biopsy, topical therapies or a variety of ablative or excisional treatment modalities can be considered, with the goal of removing precursor lesions and reducing the risk of invasive anal cancer.
- Darragh TM, Winkler B. Anal cancer and cervical cancer screening: key differences. Cancer cytopathology. 2011;119(1):5-19. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21319310 .
- Bean SM. Anal – Rectal Cytology : A Review. Diagnostic Cytopathology. 2009;38(7).
- Santoso JT, Long M, Crigger M, Wan JY, Haefner HK. Anal intraepithelial neoplasia in women with genital intraepithelial neoplasia. Obstetrics and gynecology. 2010;116(3):578-82. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20733438
- Park IU, Palefsky JM. Evaluation and Management of Anal Intraepithelial Neoplasia in HIV-Negative and HIV-Positive Men Who Have Sex with Men. Current infectious disease reports. 2010;12(2):126-33. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2860554