Cervical Cancer Screening Every 3 Years for Most Women

May 19, 2011 — A single test for the human papillomavirus (HPV) was
found to be superior in predicting cervical cancer or high-grade
cervical intraepithelial neoplasia than a single Pap test, according to a
new study.
The results, which were highlighted at a press briefing held in
advance of the annual meeting of the American Society of Clinical
Oncology (ASCO), confirmed that for women with a negative HPV test and
normal cytology, a 3-year follow-up appears to be safe and appropriate.
Women who tested negative for HPV had a 5-year cancer risk that was
similar to those who tested negative for HPV and had normal cytology
(3.8 vs 3.2 per 100,000 women per year; P = .8). This was half
the cancer risk of women who had a negative result on Pap testing only
(3.8 vs 7.5 per 100,000 women per year; P = .3).
Concurrent HPV testing and cervical cytology (cotesting) is an
approved and promising alternative to cytology alone in women 30 years
and older. Screening guidelines from organizations such as the American
College of Obstetricians and Gynecologists and the American Cancer
Society have endorsed the use of cotesting in this age group as a safe
alternative to Pap testing alone.
Safety Data Lacking

However, the authors note that broad acceptance of cotesting has been
hindered by a lack of evidence supporting its performance in routine
clinical practice, especially related to the safety of 3-year screening
intervals for women who test negative for HPV and have normal cytology
results.
"Data are lacking on the safety of these guidelines in routine
clinical practice," said lead author Hormuzd Katki, PhD, from the
division of cancer epidemiology and genetics at the National Cancer
Institute (NCI). "In particular, we need to know the actual cancer rates
with cotesting, especially for women who test negative for HPV and have
a normal Pap test."
Dr. Katki noted that his group at the NCI has been collaborating with
Kaiser Permanente in Northern California, which began a cotesting
program in 2003. In their study, Dr. Katki and colleagues obtained data
on 331,818 women 30 years and older who enrolled in Kaiser's cotesting
program from 2003 to 2005, and who were followed through 2009.
The women were categorized by their HPV and Pap test results at
enrollment, explained Dr. Katki. "Then we estimated 5-year cumulative
rates of cervical precancer and cancer."
5-Year Risk for Cancer/Precancer by Test Results

Test Results	5-Year Risk (%)	Excess Risk (%)
HPV positive	7.6	7.4
HPV negative	0.2
Pap positive	4.7	4.3
Pap negative	0.4
HPV positive/Pap positive	12.0
HPV positive/Pap negative	6.0
HPV negative/Pap positive	0.9
HPV negative/Pap negative	0.2

Pap Test Not Obsolete

HPV testing identified more women who were at high risk for cervical
cancer than Pap testing. "Women who tested HPV positive at enrollment
had higher 5-year risks of developing cervical cancer or precancer than
women with an abnormal Pap test at enrollment," said Dr. Katki, "and
vice versa. Women who tested HPV negative had a lower risk of developing
cancer or precancer" than those who had normal cytology results.
This shows that the HPV test is better able to separate those who are
at high risk for cancer from those who are at low risk, he noted.
But Dr. Katki emphasized that the Pap test is not useless. Pap tests
remain useful for triaging women with positive HPV tests, and can
identify women with immediate disease.
Dr. Katki concluded that this study shows that a negative HPV test
provides 5 years of an extremely low risk for cancer; the risk was not
appreciably lowered by a negative Pap test. The data suggest that all
women who test negative for HPV can safely extend their screening
interval to at least 3 years.
"The data presented us with a strong hypothesis that will need to be
tested in practice: Instead of doing cotesting, we could do HPV
testing," and ask those with negative results to extend their screening
interval to at least 3 years, Dr. Katki explained.
"Pap testing would then be reserved only for those in the
HPV-positive population," he said. "In the Kaiser population, this would
have reduced the number of Pap tests by 95% and could potentially
retain all of the safety of cotesting."
Real-World Data

Comoderator George W. Sledge Jr, MD, president of ASCO, noted that he
found this to be a "wonderful population-based study from a large
real-world experience."
"It also tells us not just where we're going with cervical cancer,
but perhaps with cancer screening in general," said Dr. Sledge, who is
Ballve-Lantero Professor of Oncology and professor of pathology and
laboratory medicine at the Indiana University School of Medicine,
Indianapolis. "It is a switch from our classic approach of using
now-ancient techniques of cytopathology to more molecular-based
techniques that allow us to actually look at the specific cause of
cancer in patients with cervical carcinoma."
Dr. Sledge noted that he "suspects that we'll see this again and
again as we look at screening going forward for other diseases."
"This is going to be increasingly important — not just to medical
oncologists, but also to all those who take care of these women," he
said.
The study received no outside funding. Dr.
Katki has disclosed no relevant financial relationships. His coauthor
Mark Schiffman, MD, MPH, from the NCI, reports receiving research
funding from BD Biosciences, Roche, and Qiagen.

Annual Meeting of the American Society of Clinical Oncology. Abstract 1508. To be presented June 6, 2011.