Women and AIDS: Cervical Cancer
Screening Issues for HIV Positive Women: A Physician's Perspective
by Lisa Bardaro, MD
There is a general lack of consensus regarding how best to screen for,
diagnose and manage cervical neoplasia (abnormal, precancerous cells)
and cervical cancer for the general population. Since the scientific evidence
confirms that women with HIV infection have higher rates of cervical neoplasia
and more aggressive cervical cancers, these issues have particular importance
for women with HIV. Many clinicians agree that women with HIV should probably
have frequent Pap smears, but we cannot yet agree on a definitive answer
to the crucial question: how often?
Terminology
Cervical intraepithelial neoplasia (CIN) is now used to describe what
was once called dysplasia:
- CIN I = minimal dysplasia
- CIN II = moderate dysplasia
- CIN III = severe dysplasia or carcinoma in situ
CIN III, severe dysplasia and carcinoma in situ are all different names
for the same thing--early cervical cancer. While approximately one-third
of all cases of CIN I will resolve in time, the rest will progress. All
degrees of CIN, however, require immediate colposcopy.
Medical Historical Background
The Pap smear came into widespread use in the 1960s, although the test
was available to women in major urban centers in the 1950s. The advent
of the Pap smear revolutionized one aspect of women's healthcare. Widespread
availability of this simple, low-cost, easily performed test has saved
countless lives. Before the Pap smear came into use, cervical cancer was
virtually never diagnosed before a woman had entered the terminal stages,
when cancerous growths had become sufficiently large to cause obvious
symptoms. A symptom such as bleeding after intercourse might bring a woman
in to see her doctor; examination might reveal a large tumor and necrosing
(dying) tissue, and ultimately result in a diagnosis of stage IV cancer.
(Cervical cancer is classified into 4 stages--see chart of FIGO staging.)
In 1988, a coalition of organizations (the American College of Obstetrics
and Gynecology, the American Academy of Family Practice, the American
Cancer Society, the National Cancer Institute, the American Medical Association,
the American Nursing Association and the American Medical Women's Association)
developed a consensus statement regarding cervical Pap smears. The statement
recommended annual Pap smears for all women who were or had been sexually
active, or were at least 18 years of age. However, just 1 year later,
the United States Preventive Services Task Force issued a very different
statement, recommending Pap smears every 1-3 years, depending on risk
factors. In addition to HIV infection, other established risk factors
for cervical cancer are infection with human papillomavirus (HPV), especially
types 16 and 18, immunosuppression due to any cause and cigarette smoking.
Current evidence suggests that low dietary levels of folate, vitamin C
and beta carotene may also predispose women to cervical neoplasia.
Another crucial question then arises: what is the cost of a Pap smear
versus the cost of treating invasive cervical cancer?
Pap Smear and Colposcopy
The Pap smear and colposcopy are the 2 basic tools used for screening
and follow-up for CIN. A Pap smear is a simple test performed as part
of a regular, simple pelvic examination. Cells are removed from the cervix
and vagina with a small flat stick and a cervical brush, and smeared on
a glass slide. The slide is sent to a laboratory for analysis. A Pap smear
allows a technician to look at cells but not to make a diagnosis, since
it only includes cells but not the entire tissue. To make a definitive
diagnosis, it is extremely important to be able to view the entire tissue,
which is what colposcopy and biopsy allow. Only then can an appropriate
treatment plan be devised.
Colposcopy is a diagnostic procedure that entails magnified examination
of the vulva, vagina and cervix, with what is essentially a very high-powered
microscope. A somewhat involved although not painful procedure, colposcopy
must be performed by a trained healthcare provider. Any suspicious areas
seen under the lens are biopsied (sampled). A complete colposcopy also
entails biopsy of the cervical canal, a procedure known as endocervical
curettage (ECC). This step is especially important because many cancers
arise from the cervical canal. ECC is contraindicated only during pregnancy.
False-Negative Smears
A very significant issue is the high rate of false-negative Pap smears.
A false-negative Pap smear is one that fails to detect existing neoplasia.
False-negative Pap smears generally result from either incorrect performance
of the Pap smear test (i.e., abnormal cells actually present in the cervix
were not gathered, due to poor technique on the part of the health professional)
or incorrect reading of the test slide by the laboratory technicians,
who view the smear under a microscope. Adequately performed and adequately
read smears have a false-negative rate of up to 25%. Clearly, under less
than optimal conditions, this rate is even higher.
The inherently high rate of false-negative smears must be offset; one
of the best ways is to have Pap smears on a regular basis.
Slow and Rapid Disease
Cervical cancer generally takes either a slowly progressive or a rapidly
progressive course. The former refers to cases that progress from a normal
Pap smear to invasive cervical cancer over a period of about 20 years.
The latter describes cases that traverse that journey in 1-3 years, with
10% developing invasive cervical cancer in the first year. While it is
generally believed that rapidly progressive disease occurs primarily in
high-risk groups, there is no practical way to determine before the development
of neoplasia into which group a woman will fall. The strain or type of
HPV may be most predictive of the group in which a woman will be classified,
but this is of limited utility because 1) tests of HPV type are not routinely
performed, except in research settings and 2) typing is not conducted
until after the development of neoplasia.
Besides HPV, immunosuppression is also associated with more rapidly progressive
disease. Therefore, it is particularly important for women with HIV to
have regular Pap smears to diagnose neoplasia early enough for potential
cure. Cure rates are high for cervical cancer detected early (stage I
and most stage II), but the chance for cure decreases with increasing
stage at time of diagnosis.
What Next?
If biopsy reveals CIN I, women should get a repeat Pap smear and colposcopy
in 3-6 months. An upcoming trial, AIDS Clinical Trials Group (ACTG) 293,
will evaluate a possible treatment regimen for women with HIV and CIN
I. Participants will be randomized to receive either oral isotretinoin
(Accutane) or observation (no treatment) for 6 months, with an additional
follow-up period of 1 year.
If biopsy reports confirm CIN II or CIN III, the next step is a biopsy
of the cervix called conization or a cone biopsy, so named because it
describes the shape of tissue removed. This can be done by scalpel (cold-knife
cone), by laser or, most commonly, by loop electrosurgical excision procedure
(LEEP). Essentially, LEEP uses an electric scalpel. The cone biopsy allows
a pathologist to stage disease by determining the depth of invasion of
cancerous cells. It also can be curative, if all margins of the removed
tissue are free of cancer.
Regardless of biopsy results, most authorities recommend cone biopsy
or LEEP if:
- 1) the ECC reveals CIN,
- 2) any biopsy reveals glandular CIN, or
- 3) the transformation zone has retracted within the cervical canal
and cannot be fully visualized.
Squamous cell cancers account for about 80% of all cases, with the remainder
being adenocarcinoma, adenosquamous or undifferentiated cancer.
Staging and Treatment of Cervical Cancer
Treatment of cervical cancer or CIN III depends on the International
Federation of Gynecology and Obstetrics (FIGO) stage at the time of diagnosis.
This system is used by physicians worldwide to devise treatment plans
and to provide consistency in reporting diagnoses to public health authorities.
Four possible FIGO stages are determined by 2 factors: the depth of invasion
on the biopsy report and careful pelvic examination. In developed nations,
frequently intravenous pyelograms (IVP), computerized axial tomography
(CAT) scans and magnetic resonance imaging (MRI) can help to define the
stage of disease. In general, FIGO stages I and II are treated with radical
hysterectomy (removal of the cervix, upper vagina, fallopian tubes, ovaries,
pelvic lymph nodes and supporting ligaments). In younger women, the ovaries
may be left intact.
After stage II, the cancer cannot be entirely removed by surgery alone.
The surrounding abdominal region is now involved, including the lymph
nodes and muscles. More advanced stages--stages III-IV, although some
physicians recommend the following for stage IIB as well--are treated
with radiation therapy using both external beam (a machine is used to
radiate the external pelvic region and any other areas where the cancer
might be present) and intracavitary radiation (radium pellets are surgically
implanted into the tissue of the vagina and cervix).
Chemotherapy with anticancer drugs is no longer used to treat cervical
cancer.
Cryotherapy and its Legacy
Cryotherapy involves the use of liquid nitrogen to freeze and thereby
destroy abnormal tissue. For many years and until recently, cryotherapy
was regularly used to treat CIN. Its benefits were ease of use, low cost
and the fact that it was a non-surgical approach. Now the bad news: cryotherapy
can cause scarring and narrowing of the cervical canal (cervical stenosis).
It can also cause the transformation zone (where squamous and columnar
tissues meet) to retract upward as it heals, which makes future visualization
and biopsy of this area impossible.
However, the worst legacy of this procedure is still more ominous. Cryotherapy
can cause normal tissue to heal over a deeper area of neoplasia, causing
future Pap smears to appear normal while abnormal tissue continues to
grow undetected underneath. For these reasons, gynecological oncologists
(specialists in the treatment of reproductive cancers) now recommend against
cryotherapy. Women who have been treated with cryotherapy in the past
should be examined regularly and carefully.
Previous Hysterectomy
There is no general consensus about the frequency of Pap smears for women
who have had hysterectomies for benign conditions. However, women with
a history of cervical cancer have a higher rate of subsequent vaginal
neoplasia and should have yearly vaginal Pap smears.
Conclusion
When cervical cancer is undiagnosed, untreated or fails to respond to
treatment, 95% of women will die within 2 years. Given these facts, and
the high rates of cervical neoplasia in women with HIV infection, increasing
survival should be the top priority. This author strongly recommends that
all women with HIV infection have Pap smears every 6 months.
International Federation of Gynecology and Obstetrics (FIGO) Staging of
Cervial Cancer
- Stage I -- The cancer is confined to the cervix
- Stage IA -- Microinvasive disease
- Stage IA1 -- Stromal (connective tissue) invasion less than
3 mm
- Stage IA2 -- Stromal invasion 3-5 mm, not in excess of 7 mm
in horizontal spread
- Stage IB -- Lesions greater than 7 mm in horizontal spread
- Stage II -- Involvement extends beyond the cervix, including the vagina
except for the lowest third, or infiltration of the parametrium (connective
tissue near the uterus) but not out to the pelvic sidewall.
- Stage IIA -- Involvement of the upper two-thirds of the vagina,
without lateral extension into the parametrium
- Stage IIB -- Lateral extension into the parametrial tissue but
not out to the pelvic sidewall
- Stage III -- Involvement of the lowest third of the vagina or the
pelvic sidewall or causes hydronephrosis (nonfunctioning kidney)
- Stage IIIA -- Involvement of the lowest third of the vagina
- Stage IIIB -- Involvement of the pelvic sidewall or hydronephrosis
- Stage IV -- Cancer extends beyond the reproductive tract
- Stage IVA -- Involvement of the bladder or rectal mucosa
- Stage IVB -- Distant metastasis (cancer that spreads to other
parts of the body away from the original, primary site) or disease
outside the true pelvis.
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Page last updated 30 July 1996
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