SAN FRANCISCOWomen infected with the human immunodeficiency
virus (HIV) are at increased risk for cervical abnormalities,
including cervical intraepithelial neoplasia (CIN), and these
problems may not be eradicated by conventional approaches such as
Research reported at the 30th Annual Meeting of the Society of
Gynecologic Oncologists pointed to new approaches to managing CIN and
highlighted the inadequacy of conventional Pap smears for monitoring
potential problems in HIV-positive women.
Mitchell Maiman, MD, reported that HIV-infected women are at high
risk for recurrence of CIN after standard therapy, and this risk can
be significantly reduced by maintenance therapy with topical
5-fluorouracil (5-FU). Adjunctive vaginal 5-FU was particularly
effective in reducing the rate of high-grade CIN, he said.
Dr. Maiman and his colleagues at Staten Island University Hospital,
New York, conducted a phase III, randomized, non-blinded study
comparing topical vaginal 5-FU with observation in 101 HIV-positive
women after standard excisional or ablative cervical treatment of
grade II or III CIN.
Fluorouracil treatment consisted of 2 g of 5% cream biweekly. Pap
smears and colposcopy were done at regular intervals over 18 months
Dr. Maiman reported that, overall, 38% of women developed recurrence:
14 of 50 (28%) on the 5-FU arm vs 24 of 51 (47%) on the observation
arm. Treatment with 5-FU was significantly associated with prolonged
time to CIN (P = .04), and patients who did not receive 5-FU were
more likely to develop high-grade recurrences.
Patients with more profound immu-nosuppression (CD4 counts under
200/mm³) were significantly more likely to have a recurrence,
regardless of treatment (46% vs 33%, P = .04).
In an interview, Dr. Maiman said that multicovariate analysis with
patients stratified by CD4 count showed that the treatment effect was
significant at P = .08.
He noted that use of topical 5-FU could be easily incorporated into
ordinary clinical practice and that compliance was, in general, excellent.
False-Negative Pap Smears
Conventional Pap smears have false-negative rates of 20% to 37% in
women with high sexual risk factors and should probably be replaced
by regular colposcopic screening in women with atypical squamous
cells of undetermined significance (ASCUS) , according to data
presented by Annekathryn Goodman, MD, and her colleagues at
Massachusetts General Hospital, Boston.
HIV-positive women, especially those who have high sexual risk
factors such as multiple sexual partners, have a higher incidence of
cervical dysplasia and a higher rate of false-negative Pap smears.
They need to be screened carefully, perhaps more than once a year,
and those who have atypical squamous Pap smears probably need
colposcopy as opposed to just repeating the Pap smear, Dr.
Goodman said in an interview.
Dr. Goodman studied 184 women recruited from a sexually transmitted
disease (STD) clinic or a womens prison. Of these, 82 were
HIV-negative, and 102 were HIV-positive. All underwent Pap smear,
colposcopy-directed biopsies, and endocervical curettage.
False-negative Pap smear rates were 21% in HIV-negative and 37% in
HIV-positive women (P = NS), indicating that HIV infection did not
significantly increase the risk of false-negative Pap smears in this
already high-risk population. [The false-negative rate in women
without HIV who do not have other sexual risk factors is about 10%.]
Dr. Goodman said that women with patches of ASCUS comprised the
majority of false negatives among HIV-positive women. That is a
very important category in HIV-positive women but much less so in
HIV-negative women, she concluded.
Kevin M. Holcomb, MD, and his associates at the State University of
New York Health Science Center, Brooklyn, also studied ASCUS in
HIV-infected women and concluded that given the 29% risk of
associated CIN, all HIV-positive women with ASCUS cytology should
undergo colposcopic evaluation.
This study included 261 HIV-positive women who underwent 761 Pap
smears during the study; 209 (27%) of these smears were diagnosed as
The incidences of human papilloma virus (HPV, 35%), CIN I and
II (26%), and CIN III and carcinoma in situ (2.9%) were similar to
those observed in previous studies of ASCUS in HIV-untested
populations, Dr. Holcomb said. There were no cases of invasive
cancer, and there was no significant difference in the incidence or
severity of CIN in patients with severe immunosuppression.
The researchers concluded that a cytologic diagnosis of ASCUS in
HIV-positive women identifies a group at significant risk because a
majority of such patients will be diagnosed with HPV or CIN I or II.
In an interview, Dr. Holcomb said, I do recommend colposcopy
for HIV-positive women with ASCUS. A 6-month interval for colposcopy
and Pap is probably adequate.
In related work, Dr. Holcombs group evaluated the efficacy of
cervical conization in the treatment of CIN in HIV-positive women.
Although conization was not effective in eradicating CIN in
this population, it was successful in preventing progression to
cervical cancer, Dr. Holcomb told Oncology News International.
No cases of invasive cancer were found during the study period.
This study included 158 cone biopsies performed on 117 HIV-positive
patients. Eighty-seven of the biopsies had adequate follow-up
information to be included in the analysis. Patients were stratified
based on cone margin status and endocervical curettage (ECC) status,
and the rate of histologically proven recurrent CIN was calculated
for each group.
Dr. Holcomb reported that 54% of patients with negative margins
and ECC experienced recurrence, most within 36 months. There was no
significant difference in recurrence rates for patients with positive
margins, positive ECC, or positive margins and positive ECC, when
compared to patients with complete excision of dysplasia. Mean
CD4 count also did not affect risk of recurrence.
The degree of dysplasia was the most important predictor of
recurrence, and most patients had recurrence despite complete
excision of dysplasia. Although multiple procedures were
necessary in some patients, cone biopsy was effective in preventing
progression to invasive cancer in all cases, Dr. Holcomb reported.