Screening to prevent anal cancer: Current thinking and future directions

Anal cancer is biologically similar to cervical cancer in its relationship to human papillomavirus (HPV) and, like cervical cancer, is preceded by high-grade squamous intraepithelial lesion (HSIL). Using techniques adapted from cervical cancer prevention programs, anal HSIL can readily be identified using high-resolution anoscopy (HRA), with the goal of providing histopathologic confirmation of the level of disease and guiding therapy. The incidence of anal cancer in the general population is rather low, at approximately 2 per 100,000 population.1 However, the incidence of this disease has been increasing in the general population by about 2% per year in both men and women for the last several decades. Unlike cervical cancer, for which nearly all sexually active women may be at risk, the risk of anal cancer is not evenly distributed in the population. By far the highest risk of anal cancer is among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), with an incidence of 131 per 100,000),2 followed by HIV-infected women (30 per 100,000), and men who have sex with women (46 per 100,000). HIV-negative MSM are also at high risk as are women with a history of vulvar/cervical cancer or vulvar/cervical intraepithelial neoplasia grade 3.3 Also at increased risk are men and women who are immunosuppressed for reasons other than HIV infection, such as solid organ transplantation. Each of these groups could be potentially attractive screening populations (Table 1). Screening approaches to identify anal HSIL are not yet optimized. Like cervical screening, the most specific test to identify HSIL is direct visualization with 5% acetic acid and magnification using a colposcope. In the anus, this is HRA. However, like colposcopy, HRA is too expensive to be used as a screening tool, and there is also a paucity of clinicians well trained in HRA. Therefore, as in many cervical cancer screening programs, the initial step in screening is cytology (Fig. 1). Like cervical cytology, anal cytology has limited sensitivity for the detection of anal HSIL.4 Although the detection of anal HSIL on cytology is very specific, the grade of disease is often underestimated on cytology compared with HRA-guided biopsy. This is the screening algorithm for anal high-grade squamous intraepithelial lesions recommended by the University of California San Francisco Anal Neoplasia Clinic, Research, and Education Center. ASC-H indicates atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion; ASC-US, atypical squamous cells of undetermined significance; HIV−, human immunodeficiency virus-negative; HIV+, human immunodeficiency virus-positive; HRA, high-resolution anoscopy; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion. Despite these challenges, screening for anal HSIL is recommended by some experts around the United States.6 A growing number of clinics around the United States are offering anal cancer prevention services, and permanent International Classification of Diseases-9th Revision billing codes recently were approved for HRA. Because results from the ANCHOR study may not be available for up to 8 years, we choose to actively treat anal HSIL in patients who are not in the ANCHOR study whenever possible, until and unless the ANCHOR results demonstrate that doing so is not warranted. In addition, anal cancer screening is recommended as standard of care for HIV-infected men and women in the State of New York. State officials also recognized the challenges in implementing screening on a state-wide basis, including the paucity of clinicians trained in HRA and office based anal HSIL treatment techniques. In summary, the implementation of anal cancer prevention services should be strongly considered in locations where there are sufficient numbers of men and women at risk of anal cancer. Screening with anal cytology is currently the most common approach, but adoption of other techniques may occur in the future. We do not recommend anal screening at locations where there is an absence of clinicians who are trained to follow up on the results of an abnormal cytology, ie, trained in HRA and office-based treatment of anal HSIL. For patients who are at risk of anal cancer but who do not have access to HRA-trained clinicians, we strongly recommend an annual digital anorectal examination to palpate hard masses that might indicate the presence of anal cancer—early detection and treatment lead to better outcomes. No specific funding was disclosed. The author made no disclosures. Joel M. Palefsky, MD, CM, FRCP(C), is Professor of Medicine at the University of California San Francisco. He is an internationally recognized expert on the molecular biology, treatment, pathogenesis, and natural history of anogenital human papillomavirus (HPV) infections, particularly in the setting of human immunodeficiency virus (HIV) infection. He is director of the world's first clinic devoted to the prevention of anal cancer: the University of California San Francisco Anal Neoplasia Clinic, Research, and Education Center. He has pioneered diagnostic and treatment methods for anal squamous intraepithelial lesions. He is also chair of the HPV Working Group of the US National Cancer Institute-supported AIDS Malignancy Consortium and Principal Investigator of the ANal Cancer/HSIL Outcomes Research (ANCHOR) study. He is founder of the International Anal Neoplasia Society and president of the International Papillomavirus Society.