Posted January 1, 2005
The use of anal-rectal cytology is a relatively new method of screening
for human papillomavirus (HPV) associated anal dysplasia. Its effectiveness
as a diagnostic and screening tool is still being investigated, especially
in high-risk populations, such as those infected with the human immunodeficiency
virus (HIV) and men who practice receptive anal intercourse. It is
important to note, though, that anal intraepithelial neoplasia (AIN)
and peri-anal intraepithelial neoplasia (PAIN) are also common in
women, especially those with cervical dysplasia. In the 2001 Bethesda
System for Reporting Cervical Cytology, the editors acknowledged
that Bethesda System terminology has been used for reporting anal-rectal
cytology, since there are many parallels between cervical-vaginal
and anal-rectal screening.
Cytologic sampling is generally done under direct visualization,
although some have reported using methods similar to colposcopy or
using a small anoscope to introduce the collection device. It is
important, as with the cervix, to sample the transformation zone,
which in the anus is the zone between the keratinized and non-keratinized
epithelia. There is no specific evidence to support one collection
device over another, although both Dacron fiber swabs and cytobrushes
have been used. While both conventional smears and liquid-based cytologic
preparations have been used, liquid samples have been shown to increase
Although the literature regarding what constitutes an adequate sample
is sparse, the editors of the Bethesda System endorse a minimum adequacy
cellularity of approximately 2,000-3,000 nucleated, unobscured squamous
cells for conventional smears. For liquid-based specimens, this would
be equivalent to 1-2 nucleated squamous cells per high-power field
(hpf) for ThinPreps TM and 3-6 nucleated squamous cells per hpf for
SurePath TM. Anucleate squamous cells are not considered to be adequate
for diagnosis. The presence of squamous metaplastic cells and/or
rectal columnar cells indicates that the transformation zone has
been sampled. Although many consider the presence of the anal-rectal
transformation zone necessary for adequacy, it is not clearly stated
as a requirement for an adequate sample per the Bethesda System 2001.
The cytomorphologic criteria used for the evaluation of anal-rectal
smears are analogous to those for cervical-vaginal cytology. The
major differences include (1) koilocytic or HPV-related changes may
not be as pronounced even in low-grade dysplasia of the anal canal,
although binucleation and multinucleation may be prominent, and (2)
anal-rectal dysplasia often displays more cytoplasmic keratinization
compared with cervical lesions (e.g. widespread parakeratosis and
Detection of HPV DNA in anal-rectal cytology specimens has been
shown to be significantly associated with AIN. The majority of AIN
lesions are positive for HPV types 6 and 11, and HPV type 16 has
been shown to be associated with a higher risk of progression to
carcinoma. Most studies have used a polymerase chain reaction (PCR)
based method for HPV detection, so it is unclear if hybrid capture
will be as useful in these specimens as in cervical cytology.
Although anal cytology seems to be a sensitive technique for identifying
patients with HPV-related anal disease, on its own it is often unable
to differentiate between those patients who simply have anal condylomata
and those who also have AIN. A biopsy is usually necessary to make
the latter diagnosis. This has important implications for use of
anal cytology as a screening test. The pathogenesis of anal carcinoma
and the natural history of AIN are unknown. While it is likely that
anal tumors develop from AIN in a manner resembling the development
of cervical carcinoma from cervical intraepithelial neoplasia, the
regression rate of anal condylomata and AIN is not well established.
Thus, anal cytology may be insufficient for triaging patients for
anoscopy and biopsy.
At present, anal cytology seems to be a more useful technique for
screening, diagnosis and follow-up of high-risk individuals, and
detecting occult AIN may represent an effective cancer prevention
strategy. However, using cytologic screening for AIN and guidelines
for interpreting anal cytology have not been well established.
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NewsPath® Editor: Megan
J. DiFurio, MD, FCAP
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