Numbers Game
Researchers explore whether fewer than
3 doses of HPV vaccine are effective
V
accinating adolescents for human papillomavirus (HPV),
the most common sexually transmitted virus in the United
States, continues to present challenges both nationally and
globally, and now researchers are questioning whether all 3
doses of the vaccine are necessary.
New evidence indicates that 1 or 2 doses of the vaccine may
be as effective as 3; however, those same researchers do not want
parents or adolescents to think that they need only 2 doses. “The
vaccines have not been approved in the United States for fewer
than 3 doses, and the last thing we need is to have a pause in
our attempts to get coverage with all 3,” says Cosette Wheeler,
PhD, regents’ professor in the departments of pathology and
gynecology at the University of New Mexico Health Sciences
Center in Albuquerque. “We don’t have the data we need to
make a change in the recommendations.”
Dr. Wheeler, who has spent more than 20 years researching
the molecular epidemiology of HPV in cervical precancer and
cancer and was involved with early research on HPV vaccines,
Cancer
CANCER
January 1, 2016
JANUARY 1, 2016
was one of the co-authors of a study recently published in
Lancet Oncology.1 The study involved a combined analysis
of 2 independent studies of the bivalent HPV-16/18 AS04adjuvanted vaccine (Cervarix) and showed that 3 doses, 2 doses,
and 1 dose of the vaccine protected equally against infection
with the HPV types included in the vaccine 4 years after
vaccination.
The results were pooled from the National Cancer Institute–
sponsored Costa Rica Vaccine Trial and the GlaxoSmithKline
Biologicals–sponsored Papilloma Trial Against Cancer in Young
Adults (PATRICIA). In both trials, participants were randomly
assigned to receive 3 doses of the HPV-16/18 vaccine or a
control vaccine. Investigators decided to conduct the pooled
analysis after they had seen results from the Costa Rican trial
showing that although approximately 20% of the participants
received fewer than 3 doses, most often because of pregnancy,
the efficacy was the same, regardless of the number of doses
received. They decided to pool the data with results from the
PATRICIA trial to confirm their findings and also to address
other research questions.
The pooled findings included 611 participants who received
2 doses and 292 who received just 1 dose of the vaccine.
Another key finding was that participants who received 2 doses
of the vaccine 6 months apart showed evidence of partial crossprotection against other HPV types not included in the vaccine;
however, women who received 1 dose or 2 doses just 1 month
apart showed no evidence of cross-protection. (Current US
guidelines state that the vaccines should be given in 3 doses over
a 6-month period.)
“These results are very helpful,” says Electra Paskett,
PhD, professor of cancer research in the Division of Cancer
Prevention and Control at Ohio State University. “They give
more ammunition for researchers to study the efficacy of 3
versus 2 versus 1 dose and the amount of time that should occur
between doses.”
Elise Kohn, MD, head of gynecologic cancer therapeutics
at the National Cancer Institute, says, “The authors are to
be congratulated for getting the per case data and examining
the depth of the question to provide detailed and provocative
findings to further support the potential value of this vaccine in
less than 3 doses.”
Other Vaccines
This study focused only on Cervarix, which is the 2-valent
HPV vaccine manufactured by GlaxoSmithKline. It specifically
targets the HPV-16 and HPV-18 strains, which cause 75% of
cervical cancers. The trial did not look at the efficacy of different
numbers of doses of the 2 other vaccines currently approved by
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1
© TATIANA SHEPELEVA; JES2U.PHOTO / SHUTTERSTOCK.COM
Oncology Issues in Focus | BY CARRIE PRINTZ
the Food and Drug Administration (FDA) for use in the United
States: Gardasil, approved in 2006, which prevents infection by
4 strains of HPV (6, 11, 16, and 18) and Gardasil 9, approved
in 2014, which protects against the 4 strains in the previous
version of Gardasil as well as strains 31, 33, 45, 52, and 58.
Both are produced by Merck.
Although Cervarix was approved by the FDA in 2009, it
was approved to be administered only to females aged 10 to 25
years. Meanwhile, Gardasil was approved by the FDA for use
in males and females aged 9 to 26 years. For those reasons and
probably because it was approved earlier, Gardasil is currently
the main HPV vaccine used in the United States, Dr. Wheeler
says.
“We need more data on the vaccines we use in this country
to make these extrapolations,” Dr. Wheeler says. “When
we began these studies, we didn’t know how all the [vaccine
approval] decisions in the US would be made.”
The Cervarix vaccine is used in other countries, and a number
of other countries have already switched to administering 2
doses of the HPV vaccine because of evidence showing that the
number of antibody titers in patients appears the same when
2 doses are compared with 3 doses. However, that evidence
is not sufficient to change guidelines in the United States. A
randomized trial comparing different dose levels would be
needed for that, the researchers say.
At the same time, the Gardasil and Cervarix vaccines should
be compared with each other in terms of safety and effectiveness,
Dr. Wheeler says, because they are based on different adjuvants
that trigger different types of immune responses.
More data in that area are expected to become available
soon. GlaxoSmithKline is conducting a 3-year randomized
clinical trial to evaluate the immunogenicity and safety of
Cervarix administered according to a 2-dose schedule versus
Gardasil (4-valent vaccine) administered according to a 2-dose
schedule or the standard 3-dose schedule.
Is 1 Dose Enough?
“We all believe we can give 2 doses, but whether we can give
just 1 remains unknown,” Dr. Wheeler adds. The benefit of
using 1 dose would be increased uptake of the HPV vaccine
not just in the United States but worldwide, researchers note. In
the United States, for example, only 40% of female adolescents
(aged 13 to 17 years) are estimated to have received all 3 doses of
the HPV vaccine in 2014 according to the Centers for Disease
Control and Prevention (CDC). The goal of the CDC for herd
immunity is 80% coverage, Dr. Paskett says.
Most crucial, however, is HPV vaccination in the developing
world, where 80% to 85% of the annual cervical cancer deaths
occur. The vaccine is not widely available in those countries,
and few cervical cancer screening programs exist. A report by
the Kaiser Family Foundation notes that in 2013, Merck and
GlaxoSmithKline were awarded United Nations Children’s
Fund contracts to provide Gardasil and Cervarix vaccines to
people in developing countries at significantly reduced prices.
As a result, HPV vaccination is expected to be supported in 28
countries by the end of 2017.
With 1 dose [effectiveness], if we
could vaccinate every woman
under age 15 in the world, over
time you could eradicate cervical
cancer. —Cosette Wheeler, PhD
At the same time, if it is ultimately shown that only 1 dose of
the vaccine is needed, the evidence would significantly improve
vaccine coverage in developing countries by eliminating the
infrastructural, logistical, and cost challenges of providing more
than 1 dose in those countries, researchers say. “With 1 dose
[effectiveness], if we could vaccinate every woman under age 15
in the world, over time you could eradicate cervical cancer,” Dr.
Wheeler says. “There are not many examples of that. If it takes
3 doses, we probably can’t have that impact.”
Investigators note that a variety of other issues related to
HPV vaccines will have to be addressed with additional research.
They include assessing these vaccines at different dose levels in
boys as well as girls, monitoring the duration of protection
afforded by fewer doses, and learning the most effective intervals
between doses.
Reference
1. Kreimer AR, Struyf F, Del Rosario-Raymundo MR, et al. Efficacy of fewer
than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined
analysis of data from the Costa Rica Vaccine and PATRICIA trials. Lancet Oncol.
2015;16:775-786.
DOI: 10.1002/cncr.29815
Cancer Still Leading Cause of Death for US Hispanics
A
comprehensive report finds that cancer remains the leading
cause of death for US Hispanics even though it is the
second leading cause of death overall in the United States.1 At
the same time, however, cancer incidence rates are 20% lower
among Hispanics versus non-Hispanic whites, and cancer death
rates are 30% lower for Hispanics.
The report “Cancer Statistics for Hispanics/Latinos” is published
every 3 years by the American Cancer Society. The authors note that
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Hispanics are the largest racial/ethnic minority group in the nation
and represented 17.4% of the total population in 2014.
In 2015, 125,900 new cancer cases and 37,800 cancer
deaths are expected among Hispanics/Latinos nationwide. The
report includes some of the following projections:
• Lung cancer remains the leading cause of cancer death
for Hispanic men and accounts for about 1 in 6 cancer
deaths (17%).
Cancer
January 1, 2016