College of American Pathologists
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  Anal cancer screening


CAP Today




August 2011
Cytopathology And More

Teresa M. Darragh, MD
Barbara A. Winkler, MD

Q. What is the role of human papillomavirus DNA testing in screening for anal squamous cell carcinoma?

A. Because the role of screening for anal cancer is still developing, there are no national guidelines to screen for this disease. However, with the rising incidence of anal cancer in high-risk populations, anal cytology is more frequently being used as a screening test in a manner similar to the Pap test in cervical cancer screening. As HPV DNA testing becomes an increasingly important part of cervical cancer screening protocols, the question can be asked whether or not HPV DNA testing has a parallel role in anal cancer screening.

At present, HPV DNA testing has not been incorporated into any proposed screening or clinical management algorithms for anal cancer precursors. HPV DNA testing is not recommended as a primary anal cancer screening test, as an adjunct to anal cytology, or as a reflex test for atypical squamous cells on anal cytology. Furthermore, there are no FDA-approved HPV DNA tests for use on anal cytology or direct anal cellular samples. Some laboratories will perform HPV DNA testing on these specimens after an internal validation or with a disclaimer that the test has not been validated for this site. Typically, these are the same tests used in cervical cancer screening: Qiagen’s Hybrid Capture 2 and Hologic’s Cervista HPV test. Most of the published literature on anal cancer and anal cancer screening report the research results of PCR-based HPV DNA testing and that these results may not be reproducible with commercial kits. No studies using the newly FDA-approved Roche Cobas 4800 HPV test on anal cytology have been published yet.

The role of HPV DNA testing in screening and triage of anal intraepithelial neoplasia (AIN) has further absolute limitations. Those at highest risk for anal cancer—men who have sex with men, especially if they are HIV positive—have a very high prevalence of anal HPV—well over 80 percent in most studies. This high background prevalence mitigates any benefit from the use of HPV DNA testing for primary screening or triage of ASC-US results. HPV DNA testing in groups with lower HPV prevalence but who are still at higher risk for anal cancer, such as organ transplant recipients and women with a history of multicentric HPV-related lower genital tract neoplasia, may prove useful but its value has not been studied sufficiently.

In clinical management, the excellent negative predictive value of high-risk HPV DNA testing may be of value in post-treatment followup, but this awaits further investigation. Another plausible strategy for the use of HPV DNA tests in anal disease management includes the use of type-specific HPV 16 DNA testing. HPV type 16 plays a dominant role in anal cancer development, and its presence may highlight individuals most at risk to develop high-grade precursors and invasive anal squamous cell carcinoma. Its use in clinical management algorithms is under study. Stay tuned.


1. Bean SM, Chhieng DC. Anal-rectal cytology: a review. Diagn Cytopathol. 2010;38(7):538–546.

2. Park IU, Palefsky JM. Evaluation and management of anal intraepithelial neoplasia in HIV-negative and HIV-positive men who have sex with men. Curr Infect Dis Rep. 2010. Mar; 12(2):126–133. Epub Feb. 24, 2010.

3. Darragh TM, Winkler BW. Anal cancer and cervical cancer screening: key differences. Cancer (Cancer Cytopathol). 2011; 119:5–19.

Drs. Darragh and Winkler are members of the CAP Cytopathology Committee. Dr. Darragh is in the Department of Pathology, University of California San Francisco Medical Center, and Dr. Winkler is in the Department of Pathology, Mount Kisco (NY) Medical Group.