October 2005
ADVANCES IN CERVICAL CANCER DETECTION
The Pap smear is the most successful cancer
screening test ever developed. In 1928, Dr. Papanicolaou
was studying the effects of hormonal changes on cervical
and vaginal cells when he noticed abnormal cells in patients
with cervical carcinoma. A few years later Dr. Ayre developed
a simple test, eventually named the “Pap Smear”
which involved using a wooden spatula to scrape the cervix,
smear the cells onto a glass slide, stain them and then
look for abnormal cells using a microscope. It was not until
the 1950’s that the test was used routinely in the
United States. At that time there were over 35,000 cases
of cervical cancer in the United States each year. By 2002
this number had been reduced to 4,100. This marked decrease
in cervical cancer cases is mainly attributed to the success
of the Pap smear.
The beauty of the Pap smear is that it can
detect abnormal cells years before cancer develops. These
precancerous or dysplastic cells, when detected early, can
be surgically removed or destroyed by freezing or laser.
The detection of these cells is not easy and requires the
trained eyes of cytotechnologists and cytopathologists to
find the abnormal cells and then to classify them as cancer
cells, precancerous cells or simply normal cells that are
reacting to inflammation or trauma. Cytotechnologists must
search through hundreds of thousands of normal cells on
a slide to try to find any abnormal cells. If you can imagine
trying to find a single Canadian penny in a jar of thousands
of American pennies then you can see how difficult this
process can be. Since this test relies on human abilities,
it is not perfect.
Even in the best laboratories, the Pap Test
has a false negative fraction of 5-10%. This means that
no matter how hard a laboratory strives for perfection there
will still be cases in which abnormal cells are present
but are not detected by the Pap Test. Fortunately since
it takes years for dysplastic cells to change into cancer
cells there is a long window of opportunity to detect abnormal
cells in a patient before she has cervical cancer. Therefore
if a woman has an annual Pap Test even if abnormal cells
are not detected one year, they should be detected the next.
Studies of women with cervical cancer have
shown that the number one reason for failure of the Pap
Test screening program is the lack of regular pelvic examinations
and Pap Tests. Approximately 80% of women with cervical
cancer have not had a Pap Test in the five years prior to
their diagnosis and 50% have never had a Pap Test. Another
18% of these women had an abnormal Pap Test in the past
but failed to follow-up for treatment. However, in approximately
one percent of women with cervical cancer, at least one
Pap Test failed to detect abnormal cells.
There are multiple steps involved in the proper
collection, preparation and examination of a Pap Test. There
is the potential for error at each of these steps. During
the collection of the specimen, the sampling device must
actually scrape the abnormal area and dislodge abnormal
cells onto the device. The lining of the cervix is not completely
smooth and thus there are times when the abnormal cells
are present in a fold or groove within the lining and thus
are not sampled by the collection device. Once the sample
is collected the cells must be dislodged from the device
and transferred onto a glass slide. Once transferred onto
the slide, the abnormal cells must be visible and not hidden
under normal cells, blood, or inflammatory cells. Finally,
the abnormal cells, if visible, must be identified by the
cytotechnologist and then confirmed to be abnormal by a
cytopathologist. Over the past 15-20 years much time and
research has gone into ways of overcoming potential errors
in each of these steps.
New collection devices are continually being
developed. These include plastic spatulas rather than the
old wooden devices as well as broom and brush devices. These
have bristles of varying length and orientation. This
allows sampling of uneven folds and grooves in the lining
of the cervix and can help uncover abnormal cells hidden
in these areas. The old wooden spatulas used to absorb some
of the cells into the wood and prevent them from being dislodged
onto the slide. The new plastic devices do not have this
problem. Endocervical brushes allow sampling of difficult
to reach areas high up in the cervix. Unfortunately with
each of these devices if they are used to simply smear the
cells on a slide, there is a chance that the abnormal cells
will not make it to the slide but instead will be discarded
in the garbage along with the collection device.
Two liquid based, thin layer, Pap Tests have
recently received FDA approval. The first to be approved
is known as the ThinPrep® Pap Test and the second is
known as the SurePath™ Pap. Each of these techniques
involves placing the collection device into a liquid medium,
which is then processed to produce a thin layer of cells
on a slide. With the ThinPrep® method the collection
device is rinsed off in a liquid solution but the device
is then ultimately discarded. Studies have documented that
some abnormal cells are discarded with these devices. With
the SurePath™ method the device is not thrown away
and thus there is no danger of inadvertently discarding
diagnostic cells. Both the ThinPrep® and SurePath™
techniques ultimately produce a thin layer of cells on a
slide. This thin layer is easier to screen since abnormal
cells will not be hidden under normal cells or by blood
or inflammatory cells like they were on the old Pap smear.
Unfortunately in a some cases the ThinPrep® sample can
be unsatisfactory for screening if it contains blood, inflammation
or mucus and the patient will have to come back for a repeat
Pap Test. The SurePath™ method has overcome this obstacle
and thus has very few unsatisfactory samples.
Another advantage of liquid based Pap Tests
is that there is extra sample left over after the Pap slide
is prepared. This can be used for additional tests for human
papilloma virus (HPV), the agent responsible for most cases
of cervical cancer, or for Chlamydia, gonorrhea, or even
for cystic fibrosis genes.
Despite the advances made by utilizing liquid-based
Pap specimen technology, false negative Paps remain a problem.
Computer-assisted Pap screening systems directly address
the problem of human error in the screening of Pap slides.
These recently developed devices help to reduce both false
negative and false positive results when combined with human
Pap screening.
Keith V. Nance, MD
Medical Director of Cytology
Rex Hospital
