On Day 3 of
the Annual
Clinical and Scientific meeting, ACOG 2016 the
question at this year’s John and Marney Mathers Lecture was Is
HPV testing ready to replace Pap testing as the first-line test for cervical
cancer screening for women 25 and older?
Warner K.
Huh, MD, professor and division director of gynecologic oncology, senior
scientist in the University of Alabama-Birmingham (UAB) Comprehensive Cancer
Center, and Margaret Cameron Spain endowed chair in Obstetrics and Gynecology
at the UAB School of Medicine are positive about it while George F. Sawaya, MD,
professor of Obstetrics, Gynecology and Reproductive Sciences and Epidemiology
& Biostatistics at the University of California, San Francisco, argued for
a more cautious approach during the morning session debate on May 16, 2016.
Dr. Huh
believes that HPV testing has the most sensitivity and negative predictive
value out of all the screening technologies. A negative result gives a long
time assurance about absence of cervical malignancy. In support of his argument
he cited the Canadian cervical cancer screening trial (CCCaST) of 10,171
women ages 30-69 randomized to HPV testing or pap test. The results
showed that verification-bias adjusted sensitivity of Pap cytology was 55.4%
while that of HPV testing was 94.7%. Pap test also suffers from variation in
collection, storage and lab performance.
He also said
“Keep in mind that cytology has never been subject to a randomized control
trial, and if you actually submitted the test to the FDA today, what’s
interesting is that it would probably be resoundingly rejected by the FDA
because of its low sensitivity.”
An aggregate
of 4 studies published in the Lancet in 2011 found that when all the women who
had a normal Pap test were analyzed there was rate of 7.5 instances of cancer
per 100,000 women in a year while the same rate for HPV negative patients was
3.8 cervical cancers per 100,000. Women who were both HPV-negative and had a
normal Pap test had 3.2 cervical cancers per 100,000.
Dr. Huh
opined that when actually calculated it is 60% risk reduction in cervical
cancer over the years. HPV screening further missed less cases when it comes to
diagnosis of adenocarcinomas.
The Other
Debater Dr. Sawaya said that major groups and association continues to
discourage HPV testing in women younger than 30 independent of the COBAS HPV
strategy of following up a positive test with HPV 16/18 type-specific testing
followed by colposcopy, cytology or future follow-up.
He is also
of the opinion that HPV testing will lead to more surveillance, uncertainty and
confusion specially in the younger and the older age groups. A screening test
must simplify life by maximizing benefits and avoiding life style disruptions,
unnecessary surveillance, treatment and interventions.
He also
talked about the ATHENA Trial, a US-based, 3 years’ multicenter study,
comparing COBAS HPV vs. cytology (ASC-US+). According to him both techniques
are at par when diagnosing CIN 2+ citing that in the ATHENA trial a
cohort of 1000 women, 25+ and older after the first round of screening, the HPV
screening group found CIN2+ in eight women, while cytology found CIN 2+ in six.
The cytology
group after the screening has had 10 percent abnormal cytology, 7 percent
colposcopy and 5 percent in surveillance while those following COBAS algorithm
had 21 percent HPV positive, 10 percent colposcopy and 19 percent in
surveillance. The increased percentage of patients in surveillance does
have increased psychological issues.
He suggests
screening with cytology alone every three years, with HPV triage for ASC-US.
He further
added “The loveliness of this strategy is that after a single screening round,
they go to colposcopy or go back to routine screening. There’s not this middle
ground of coming back in a year. There’s not this uncertainty.”
But, ACOG
does updated its guidelines on December 22, 2015 and the practice bulletin is
cited here “The Practice Bulletin provides interim guidance on the
use of the FDA-approved HPV test for primary cervical cancer screening, which
it states can be considered as an alternative to current cytology-based cancer
screening methods (the Pap test) in women 25 years and older. Women younger
than 25 years should continue to be screened with cytology alone. Additional
guidance is included that addresses a number of important clinical issues not
specified in the FDA product labeling for the test, including when to rescreen
after a negative test result, how to manage positive test results, and when to
stop screening in women with negative screening histories.”
In addition, The
Society of Gynecologic Oncology (SGO), the American Society for Colposcopy and
Cervical Pathology (ASCCP), with input from representatives of five other US
national medical organizations (ACOG, ACS, ASCP, ASC, CAP) issued an Interim Guidance Report after the U.S. Food and Drug Administration (FDA) approved
the cobas® HPV Test as a primary, or first, test performed for
cervical cancer screening. This new guidance is in addition to the
existing 2012 guidelines and specifically addresses the implementation of HPV
testing in primary screening.
The
guidance recommends:
- Primary
HPV testing can be considered for women starting at age 25.
- Women
with a negative primary HPV test result should not be retested again for at
least three years. This is the same screening interval recommended under
current guidelines for a normal cytology test result.
- An
HPV test positive for HPV 16 or 18, two types associated with a higher risk of
future disease, should be followed with colposcopy.
- A
test that is positive for HPV types other than 16 or 18 should be followed with
cytology testing.
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