Faculty Peer Reviewed
A 56 year-old homosexual male presents to your clinic to ask whether or not he should have an anal Pap smear. The patient is HIV positive, has been on HAART for five years, and has no history of opportunistic infections. He denies any anal pain, bleeding or masses.
While efforts to improve knowledge about colorectal cancer in various communities continues to grow, awareness of and misconceptions about anal cancer remain. Over the past couple of years there has been more discussion about anal cancer in large part because it was the seemingly unlikely cause of death of the actress Farrah Fawcett. The danger with the way in which this issue has come to light is that it might be dismissed as a curious anomaly not likely to affect anyone and with no screening modality for early detection.
A good screening test should meet certain criteria for its recommended use: early diagnosis of a common disease, a treatable condition, a high sensitivity and specificity, and ease of use. For example, cervical cancer has no symptoms early on, but a cervical pap smear can detect dysplastic cells or early stage cancer. Early detection can lead to complete cure, and the cervical pap smear is both reliable and easy to use.
Anal cancer remains an uncommon cancer with a slowly rising national incidence rate. The current age-adjusted incidence rate for anorectal cancer is 1.6 per 100,000 men and women per year and it is estimated that approximately 2,000 men and 3,260 women were diagnosed with cancer of the anus, anal canal and anorectum in 2010 . The median age at diagnosis for cancer of the anus is 60 years of age. Among men, blacks have the highest incidence rates (1.9), and among women, whites have the highest incidence (2.0). The age-adjusted death rate is 0.2 per 100,000 per year. The overall 5-year mortality rate from 2001-2007 of 35.1% was either on par or better than more well-recognized malignancies with poor outcomes such as acute myeloid leukemia, multiple myeloma, gastric cancer, and ovarian cancer .
Cancer of the anus develops in the canal’s transition zone or linea pectinea . Anal cancer is preceded by the development of anal squamous intraepithelial lesions (ASIL) . Human papilloma virus (HPV) infection is responsible for 90% of ASIL’s . Other risk factors for ASIL’s include multiple sexual partners, tobacco use, and immunosuppression. ASIL’s are further classified into low-grade anal intraepithelial lesions (LSIL) and high-grade anal intraepithelial lesions (HSIL). LSIL’s have spontaneous resolution in the majority of cases, while HSIL’s are a more likely precursor of invasive tumor .
The anal pap smear is an underutilized available screening tool for anal cancer with a sensitivity of 50-75% for detection of ASIL and specificity of 50% [6,7]. Similar to a cervical pap smear the anal pap test evaluates the morphology of epithelial cells from the respective region. Unlike a cervical pap smear a cavity scope is not required; rather only a small brush (measuring 3 millimeters) is inserted in the anal canal. Although the test is easily performed, there are numerous barriers to its widespread usage. One obstacle is the limited number of physicians who are aware of the test and are trained to perform it. Primary care doctors, gastroenterologists, gynecologists, and general surgeons could all potentially perform the anal pap smear. However, there is no training requirement for anal pap screening in residency programs. Discomfort with discussion of sexual behaviors and testing may pose a significant barrier that dissuades clinical discussion of the test. In addition, insurance coverage for anal pap smears is very limited.
Another issue that arises from anal cancer screening is the question of treatment. Unlike cervical dysplasia and localized cervical cancer, where large excisions or complete resections have high cure rates (eg: 90.9% 5-year survival rate for localized cervical cancer) , anal dysplasia and cancer does not have comparable treatment capability or success. Current treatment modalities for anal dysplasia include topical agents, immune modulation, cryotherapy, laser therapy and surgery. These treatments often don’t lead to a cure and are associated with recurrence rates as high as 50-85% . Anal cancer is currently treated with chemoradiation and surgery, depending on oncologic staging, with an overall 5-year mortality rate of 35.1% .
Additionally, the cost-effectiveness of anal cancer screening is questionable. In the United States, a cost-effective screening program is determined to be one that has a treatment cost of under $30,000-50,000 per year of life saved (PYLS) . Taking cervical cancer as an example, pap smears every three years for HIV-negative women incur a treatment cost of approximately $11,800 PYLS . In HIV+ women with yearly cervical Pap smears, the treatment cost would be $13,000 PYLS . Estimates for Pap screening in anal cancer showed that the costs of screening in HIV+ men with annual testing amounted to $11,000 PYLS, a cost similar to that of cervical cancer screening . A three-yearly testing regimen in HIV- men was estimated to cost about $7,800 PYLS .
However, in the United Kingdom, a cost-effective analysis of anal pap screening did not reveal promising results . The UK study examined the cost-effectiveness of screening high-risk HIV+ men who have sex with men (MSM). Researchers concluded that screening of this high-risk group would not generate health improvements at a reasonable cost. The estimated economic burden of screening HIV+ MSM was calculated at £66,000 ($102,227) per quality-adjusted life-year (QALY) gained, well above accepted cost-effectiveness thresholds. The authors of this research suggest that the main difference in this cost-effectiveness model when compared to the U.S. study is that the UK model combines HIV-, undiagnosed HIV+, and diagnosed HIV+ MSM. This explanation does not completely account for the large discrepancy in cost analysis.
Currently there are no national recommendations for anal pap screening. The test is best suited for specific high-risk populations: multiple sexual partners, a history of sexually transmitted disease, and HIV infection or other chronically immunosuppressed states. Among men who have sex with men, the incidence rate of anal cancer among HIV+ patients is 69/100,000 person-years . Rates of anal cancer among HIV+ patients have risen during the HAART era because patients are living longer with their HIV disease, allowing time for anal dysplasia to progress to cancer . Screening for these patients may yield significant health benefits.
Based on our patient’s HIV status, his increased risk for the development of anal cancer, ease of use of the screening test, and the potential for life-saving treatment if cancer is diagnosed, the anal pap should be recommended. The patient should be advised that any abnormal pap findings will result in anoscopy and biopsy. If the baseline screening is negative, annual surveillance screening should be discussed with a physician to review the risks and benefits of testing. Testing is also recommended if pain, bleeding or palpable masses develop in the anorectal region.
More research is needed to clarify the controversies surrounding anal cancer screening. Large population-based randomized controlled trials (RCT) are needed to further examine the survival benefit and cost-effectiveness to the screening and treatment of anal cancer in high-risk populations. Currently, there is a lack of RCT’s to conclusively support or refute the use of anal pap smears, and it remains unknown when this data will become available. In addition, clinician training and insurance policy modifications are needed for more widespread application of this screening modality.
Commentary by Michelle Cespedes MD Assistant Professor Department of Medicine (Infectious Disease and Immunology)
This commentary on the benefit of anal PAP screening in HIV infected populations is timely and will familiarize health care providers on the benefit of this simple but underutilized tool that can improve the health outcomes of our patients. Investigators from the North American AIDS Cohort Collaboration on Research and Design recently analyzed findings from 13 US and Canadian studies. Recent data suggest that 3% of all HIV infected adults (including non-gay HIV infected men, HIV infected women, and HIV infected men who have sex with men (MSM)) will develop anal cancer by age 60. HIV infected MSM are 80 times more likely to develop anal cancer compared to HIV negative men. HIV infected non gay men are 27 times more likely to develop anal cancer compared to HIV negative men.
This study suggests that anal cancer screening for HIV infected patients is likely to be cost effective. The current New York State AIDS Institute guidelines now recommends targeted anal PAP for HIV infected MSM, individuals with a history of anogenital warts, and for women with a history of abnormal cervical or vulvar histology.
Silverberg MJ, Lau B, Justice AC, et al. Risk of anal cancer in HIV-infected and HIV-uninfected individuals in North America. Clin Infect Dis. 2012 Apr; 54(7):1026-34.
Dr. Nelson Sanchez is a former resident at NYU Langone Medical Center and a current Instructor, Clinical Medicine at Memorial Sloan Kettering Hospital
Peer reviewed by Dr. Francois, Assistant Professor of Medicine (Gastroenterology) NYU Langone Medicacl Center
Image Courtesy of Wikimedia Commons
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