Comparison of 2 anal cytology protocols to predict high-grade anal intraepithelial neoplasia.

Invasive anal squamous cell cancer (IAC) is a health crisis for gay, bisexual, and other men who have sex with men (MSM), and for male-to-female transgendered women who have had sex with men (TWSM), especially within the context of HIV-coinfection where risk for invasive malignancy is greatest (1-6). Currently, experts recommend using the Dacron swab for anal cytology (Pap test) specimen collection at annual and semi-annual intervals for HIV-infected and -uninfected MSM, respectively (7, 8). Dacron-swab anal cytology poorly correlates with histological evaluation of disease (9) and while cervical-cytology sampling has informed anal-cytology specimen collection, cervical screening tools may not be appropriate for analcancer screening. For example, cytobrushes with and without spatulas, cytopicks; and cotton, Dacron, rayon, and nylon-flocked (NF)-swab have been evaluated in genital sampling for pathogens, including HPV, and for cervical cytology (10-14). Cytobrushes improved cervical sampling over cotton swabs by 58-76% for detecting endocervical cells in a sample of >800 adult females >29 years of age (14) and are shown superior to Ayers spatulas (10). One report suggests the cytobrush may be effective in anal cytology,(15) but may be uncomfortable in blind sampling (16). The NF-swab is evaluated extensively for respiratory-pathogen and -cytology sampling, yielding more cells and pathogens than other collection protocols (17-20). For example, Daley et al. report >2-fold cell yield of respiratory epithelial cells using NF-over Dacron swabs, and Krech et al. report a 5-fold greater yield of Chlamydia trachomatis, as well as greater HPV yield using NF-over rayon-wrapped swabs in cervicovaginal tissues (17, 21). Further, unsatisfactory cervical cytology findings range from 0.3-10.9% and 0.17-2.7% for specimens preserved using PreservCyt® (Hologic, Inc., Marlborough, Massachusetts) and SurePath™ (TriPath Imaging, Inc., Burlington, N.C.) preservatives, respectively (22-25), whereas the prevalence of unsatisfactory anal cytology specimens may range from 1% to upwards of 14% (26-33). The cervix and the anal canal are distinct anatomical targets that might easily require different sampling tools. The cervix is firm and sampling is more akin to hitting the bulls-eye on a target while the anal canal is soft and folds much like the surface of a deflated balloon. Cervical cytology uses a speculum to visually guide sample collection and the transformation zone (TZ) of the cervix closely approximates the cervical os. The dentate line lies approximately ~5 centimeters proximal to the anal verge, and the anal TZ immediately adjoins it about ~0.5-1 cm, just cephalad (34). Current anal cytology recommendations are to blindly insert a Dacron swab through the anal verge ~5 cm, approximate it to the anal wall, and rotate the swab using lateral pressure to sample the canal circumferentially as it is withdrawn over 10-20 seconds and stored in liquid preservative for laboratory examination (35). Although experts suggest screening in high-risk populations is important and data show it is cost-effective, there is no current national consensus for screening methods or frequency for anal cancer screening using Papanicolaou staining (Pap test) (8, 36-38). To date, no large studies evaluate the risks or benefits of early detection and treatment for preventing anal cancer and general reluctance among clinicians for anal cytology screening may be due to the imprecision of the test, the rarity of malignancy, and the limited success of available treatments, especially within the context of HIV infection where there is poor control over HPV infections (39-41). Developing a screening strategy with modest-to-high sensitivity and specificity for anal precancers, high-grade anal intraepithelial neoplasia (HG-AIN), is an important public health goal. Thus, to evaluate the sensitivity and specificity for two cytology collection procedures and compare their efficacy for predicting HG-AIN, we evaluated a protocol using an NF-swab (Copan Diagnostics Inc., Murrieta, CA) and the Dacron swab (Thermo Fisher Scientific, Miami, OK), each with preservative, for anal cytology.