| “Abnormal” is the word women dread when waiting
for their Pap test result. Many mistake “abnormal Pap” for
“will get cancer,” and most US women have up to a 30 percent
chance of receiving an abnormal Pap test result at least once in their
lives. Today, however, cancer of the cervix is one of the most preventable
and curable cancers in the country, thanks to widespread use of the Pap
test and improved screening technologies for early detection. And in the
near future cervical cancer may be controlled with a vaccine that arrests
its cause—persistent infection with human papillomavirus (HPV).
What Is an Abnormal
Pap Test?
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| Results from 5–10 percent
of Pap tests performed each year on women in the United States are
reported as abnormal. Abnormal cell types include:
- ASC-US: atypical squamous cells of undetermined significance.
Squamous cells are the thin flat cells that form the surface of
the cervix.
- LSIL: low-grade (early changes in the size, shape, and number
of abnormal cells) squamous intraepithelial lesion. The word lesion
refers to an area of abnormal tissue; intraepithelial means that
the abnormal cells are present only in the surface layer of cells.
- HSIL: high-grade squamous intraepithelial lesion. High-grade
means that there are precancerous cells that look the most different
from normal cells. (There may be many or very few abnormal cells
on an HSIL Pap result.)
ASC-US and LSIL are considered mild abnormalities. HSIL is more
severe and has a higher likelihood of progressing to invasive cancer.
If the Pap test abnormality is unclear or minor, the doctor may
repeat the test or do an HPV test. If the Pap test shows a significant
abnormality, the clinician may proceed to additional tests:
- Colposcopy. The clinician uses a magnifying instrument to view
the cervix and the area surrounding the vagina to check for any
abnormalities.
- Schiller test. The clinician coats the cervix with an iodine
solution. Healthy cells turn brown, whereas abnormal cells do
not stain or partially stain yellow.
- Biopsy. The clinician also may remove a small amount of cervical
tissue for examination. This is the only sure way to know whether
the abnormal cells indicate precancer, or very rarely, cancer.
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HPV is an extremely common, sexually transmitted virus that can appear
in more than 100 different strains or “types.” Some types
linger on the skin, then simply disappear. Some types can cause warts
(papillomas) that grow on hands and feet, whereas other types can cause
warts in the throat (rare) and anus and on genitals. A few HPV strains
are the primary cause of cervical cancer; these are considered the “high-risk”
types (see boxes, “What Is an Abnormal Pap
Test?” and “Making
the Link: HPV and Cervical Cancer”).
Of the small percentage of women who develop persistent infections with
high-risk HPV, fewer will develop the lesions that can lead to cervical
cancer. Preventable though it is, cervical cancer will be detected in
an estimated 14,000 new cases and will kill more than 4,000 women in the
United States this year.1 Two major developments
may help to reduce these numbers further: the liquid-based Pap test and
HPV DNA testing. Both aim to overcome the inherent weaknesses in traditional
Pap technology and afford improved ways to manage abnormal Pap test results.
The availability of better testing alone will not be enough to reduce
rates
of cervical cancer, however; women and their health care providers need
more education about the link between HPV and cervical cancer, which
will allow for informed, shared decision making, and more women need
access to screening.
“The vast majority of sexually active adults in this country have
been
infected with HPV at one point or another,” says Diane Solomon,
MD, a
senior investigator in the Breast and Gynecologic Cancer Research Group
at the National Cancer Institute (NCI). “The main thing is finding
and
screening the women who have been underscreened.”
Advances In Screening For Cervical Cancer
Less than a century ago, cervical cancer was the number one cancer killer
of US women. Although its impact has been dramatically reduced in the
United States, cervical cancer remains the second most common cancer among
women worldwide and kills more than a quarter of a million women each
year.2–3
Introduced in 1943, the Papanicolaou (Pap) test was designed to detect
cervical abnormalities that could be treated, thereby preventing progression
to invasive cervical cancer, and also to detect invasive cervical cancer
at a very early stage. Widespread use of the Pap test has helped to reduce
cervical cancer deaths by more than 70 percent in the United States.3–4
More than half the new cases of cervical cancer will be diagnosed in women
who have not received proper screening.5
Nevertheless, the conventional Pap test is associated with a significant
false-negative rate and a sensitivity of only 70–80 percent for
the abnormal cell growth on the cervix that is most likely to lead to
cancer, high-grade cervical intraepithelial neoplasia (CIN, grades 2 and
3).6–7
Progression from abnormal cell growth that might become cancer (precancer)
to cervical cancer is a slow process, estimated to take 10–15 years.
If abnormal cervical cells are detected early, progression to cervical
cancer can be stopped. Women with lesions that have not invaded surrounding
tissue (pre-invasive) have a five-year survival rate of close to 100 percent.
For those whose lesions are caught at an early invasive stage, the five-year
survival rate is 92 percent.1
Nancy Roach
Nancy Roach, 49, a colorectal cancer advocate with the Marti Nelson
Cancer Foundation, was diagnosed with cervical cancer in October
2001. She had a radical hysterectomy and extensive lymph node dissection
and was treated with pelvic radiation plus chemotherapy. She is
currently cancer free.
“My experience with cervical cancer shows that no screening
is perfect,” Roach said. “I have been in a mutually
monogamous relationship for 20-plus years, and I had regular, negative
Pap smears at an excellent health facility during most of that time.
And I was diagnosed with locally invasive cervical cancer. If it
can happen to me, it can happen to anyone.”
In her work as a health advocate, Roach has met many women who
are ashamed about cervical lesions or cancer. She has also experienced
firsthand the stigma and assumptions behind an HPV diagnosis. Reporters
have asked who she blames for her cancer diagnosis, or if she feels
responsible for her cancer. Others have asked why she assumes that
her relationship is monogamous.
“Ignorance frequently leads to misjudgments,” she said.
“Some people hear ‘sexually transmitted’ and immediately
assume that HPV is due to promiscuity.”
The sexually transmitted aspect of HPV is only part of the HPV
story, Roach said. She emphasizes that although most people will
have HPV at some point in their life, very few cases will progress
to cervical cancer. She feels that the shame and embarrassment behind
a diagnosis of HPV reflect a lack of understanding about the prevalence
and etiology of HPV, and she is concerned that women may be reluctant
to use appropriate HPV testing as a way to minimize their risk of
cervical cancer.
“While I’m embarrassed by the thought of people who
don’t understand HPV making judgments about my sexual history
and my relationship with my husband, I also know that if I’m
not willing to speak out about it, who will?” she said. |
Screening remains the paradigm of successful cervical cancer prevention,
according to NCI’s Solomon. “This is not to say that cervical
cancer screening technology is 100 percent effective, or 100 percent sensitive,
or that we are ever going to completely eradicate cervical cancer,”
she says. “But cervical cancer screening is still a very powerful
means of cancer prevention.”
Pap Accuracy: Impact of False-Negatives
Every screening test has an error rate. The false-negative rate of the
conventional Pap smear has often been underestimated at 5–10 percent,
even though most reports now estimate the false-negative rate of the Pap
smear to be between 25 and 49 percent and of the liquid-based Pap test
to be between 15 and 25 percent. Frequent repetition of the Pap test usually
compensates for this high false-negative rate. If an abnormality is missed
on one test, it will generally be detected with the next Pap test, while
it is still in a precancerous stage.
False-negative results may occur when insufficient cells are collected,
when the cells that are collected are examined under the microscope (screening),
or during interpretation of examined cells. The average Pap smear consists
of up to 300,000 cells. When only a few abnormal cells are scattered throughout
the sample, they may not be detected. In rare instances (about 1 percent),
cells may be interpreted as benign or normal when they are precancerous.8–9
The accuracy of Pap test results depends in part on how well the cervical
tissue is sampled and how well the slide is prepared. Sometimes the samples
of cells collected from the surface of the cervix do not include abnormal
cells, which means that abnormalities cannot be detected. For example,
the sample may not contain enough cervical cells. Abnormal cells also
may be hard to see if they are “hidden” by mucus or inflammation
in the cervix, or signs of abnormal cells may simply be missed by the
laboratory technician looking through the microscope. Each of these cases
represents a false-negative result.
According to one recent study, some women may be getting false-negative
results as a result of tissue changes that keep abnormal cells from being
picked up during the exam.10
The liquid-based Pap test was designed to overcome the inherent weaknesses
in traditional Pap smear technology.1
Liquid-Based Pap
In traditional Pap cytology, cells are scraped from the cervix and placed
directly on a slide for examination in a laboratory. With the liquid-based
technique, cells collected by the clinician are suspended in liquid then
applied to a glass slide in a laboratory as a thin cellular layer, removing
much of the mucus, blood, and inflammatory cells. Liquid-based methods
are more expensive than conventional Pap tests but have been shown to
miss less disease, probably because they reduce problems with preparation
of the sample.12
The US Food and Drug Administration (FDA) has approved two liquidbased
cytology methods: the Sure-Path®
system and the ThinPrep® Pap Test™.
| Christine Baze
Christine Baze was a 31-year-old rock musician when she was diagnosed
with invasive cervical cancer. Treatment devastated her body and
mind: radical hysterectomy, chemotherapy, and radiation. She had
never heard of HPV but was told after the hysterectomy that she’d
had it. She’ll never have children.
“I was shocked, devastated, scared, angry, and confused.
I had been married eight years, was a non-smoker, had a history
of normal Pap tests, was a vegetarian for 10 years, do yoga, and
run,” she said. “I didn’t understand how this
could happen to someone like me. But obviously I had been carrying
the HPV virus for years and didn’t know it.”
Baze created a non-profit organization to raise awareness about
cervical cancer (www.popsmear.org). And now, four years after Baze’s
diagnosis and treatment, her band, Skills of Ortega, gives benefit
concerts to raise research money and spread the word about cervical
cancer, HPV, and modern screening technologies. Ms. Magazine named
Baze one of “50 women who made a difference in 2003.”
“My advice to women is to be proactive about your gynecological
health—have a conversation with your doctor, know what she
or he is doing ‘down there,’ ” Baze said. “And
above all else, make sure you are getting an HPV test with a liquid-based
Pap test. The standard Pap test is not enough; it wasn’t enough
for me.” |
The Pap test identifies many women in need of treatment, especially when
it is repeated regularly. However, no Pap technology is foolproof, because
the test, whether it is the conventional technique or the newer liquidbased
approach, inherently is not very precise and is subject to human error.
“The major reason for screened women getting squamous cell cervical
cancer is a poor sample taken during the speculum exam,” says Debbie
Saslow, PhD, director of Breast and Cervical Cancer Control for the
American Cancer Society. “The newer, liquid-based Pap tests have
overcome
a lot of this—it is easier to get an adequate sample.”
Pap results also may be “false-positive,” meaning
that a woman is told that her cervical cells look
abnormal when they are actually healthy. This
can cause anxiety and lead to unnecessary tests
and procedures.
Like false-negative results, false-positive results
can happen with liquid-based technology as well
as traditional Pap tests.
“Liquid-based cytology has a higher sensitivity for detection
of SIL [squamous intraepithelial lesions] and can facilitate HPV-DNA testing
in women with ASC-US Pap test results,” says Herschel Lawson, MD,
senior medical advisor in the Division of Cancer Prevention and Control
at the Centers for Disease Control and Prevention (CDC). “However,
it may also have a lower specificity, resulting in more false-positive
tests and more administrative and patient-related costs, which could reduce
the cost-effectiveness of cervical cancer screening and potentially increase
the harms to women due to the additional need for diagnostic testing.
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