#PreteenVaxScene Webinar #1: HPV Vaccine Recommendation Update

#PreteenVaxScene Webinar #1: HPV Vaccine Recommendation Update


Jill: Hello, everyone. This is Jill Roark from the
Centers for Disease Control and Prevention, and I’m glad
that you are all able to join us today. I do want to go ahead
and get started. We have a lot of
great information. We’re going to be having
two presenters today. We’re going to have Dr. Lauri
Markowitz, who is the lead for the HPV work group here
at CDC and also the CDC lead for the ACIP’s HPV
vaccination workgroup. And Lauri’s going to go
over the changes in the recommendation after
the most recent ACIP meeting. Next, we’re going to have Tim–
I’m sorry, Tom Shimabukuro, who is in our
immunization safety office and he will be giving
us an update on HPV-9 vaccine safety. So I’m going to go next to
our webinar logistics and just remind everyone, all of
your lines are muted. And because of that, we’re
going to have to do our Q&A session a little bit
differently than we have in the past. We are recording this webinar–
um, and everyone is notified that–is recording. The presentation will also
be available online later, and that’s why we’re
recording this today. And we will send that
out once it’s available. Also, as I said before,
since everyone is in
a listen-only mode, you’re going to need to
type your question into the question panel on
“go to webinar,” in that side panel. And then when it’s time for
questions we’ll read the selected question out loud
for our presenters to answer. And Ian Brennan, who is on
the adolescent immunization communications team
will be moderating the questions for us. We are going to hold all
questions until the end after both presenters
have presented. And now I’m going to go
ahead and turn it over to Dr. Markowitz. Dr. Markowitz: OK. Good morning. It’s Lauri Markowitz. And today as was just
mentioned, I will be giving an update on HPV vaccination
recommendations in the United States. OK, it looks like I don’t have
control to advance, so please advance the slide. OK, this is an
outline of my talk. I will be giving an overview
of HPV vaccines available in the U.S., HPV-associated
cancers due to
different HPV types, I’ll review data from
the 9-valent HPV vaccine trials, and then
summarize the updated recommendations of ACIP. Next slide. All available prophylactic
HPV vaccines are virus-like particle vaccines, and these
vaccines are made from the L1 major capsid protein of the
virus which is expressed through
recombinant technology. And the L1 proteins self-
assemble into virus-like particles which
are noninfectious. Until recently, there were two
available HPV vaccines–the bivalent vaccine, also called
Cervarix, which is directed against HPV 16 and 18, and the
quadrivalent vaccine called Gardasil, directed against
types 6 and 11 as well as 16 and 18. The HPV 16 and 18 are
oncogenic HPV types, which cause cancers, and HPV
6 and 11 cause genital warts. As I mentioned, both of
these vaccines are similar in that they’re both
VLP vaccines. And in addition to the
differences between the vaccines to the different
HPV types, the vaccines also differ in their adjuvants. The recently licensed 9-valent
vaccine, also called Gardasil 9, is directed against
the same 4 types as in the quadrivalent vaccine 6,
11, 16, 18, and 5 additional cancer-causing types shown
in red on this slide. The quadrivalent and the
9-valent vaccine are produced by the same manufacturer and
they have the same adjuvant. As I just presented, all HPV
vaccine types target oncogenic or high-risk types
HPV 16 and 18. These two types are
responsible for most cervical cancers and the majority of
other HPV-associated cancers. This graph shows the
percentage of cervical cancers attributed to the high-risk
types worldwide, and you can see that HPV 16 and 18 account
for 60% and 10% respectively of cervical cancers
that were HPV-positive. The other high risk types
each accounted for a small percentage of
cervical cancers. And while there’s some
variation by geographic location, 16 and 18 account
for the vast majority of HPV-positive cervical
cancers worldwide. In addition to cervical
cancer, HPV causes cancers at other sites. And this slide shows data from
the U.S. with the estimated number of cancer cases at
anatomical sites where H– where they have been
attributed to HPV. For males on the left and for
females on the right–and the purple portion of the bars
show the cancer cases at these sites that are
attributable to HPV. And you can see that most
but not all of the cancers at these sites are
attributable to HPV, and this does vary somewhat
by the cancer. The most common HPV-associated
cancer for females is cervical cancer. And the most common HPV-
associated cancer for males is cancer of the oropharynx. Now, these data are from a
study conducted to examine the specific HPV types in
cervical as well as other HPV-associated cancers in the
U.S. The first column are the cancers associated with HPV,
and the second column are the percent of cancers at these
sites in which HPV has been detected. The third column shows the
percent attributable to HPV 16 and 18,
and the last column, the percent attributable
to the 5 additional types in the 9-valent vaccine. You can see that the majority
of cancers at all sites are attributable to HPV 16 and 18
ranging from 48% to 80%. The percent attributable
to the 5 additional types in the 9-valent vaccine
is lower, ranging from 4% for oropharyngeal cancers
in males to 18% of vaginal cancers. Using data that I just showed
from the previous study, this slide shows the estimated
number of cancers at these anatomic sites attributable
to HPV 16 and to the 5 additional types in the U.S.
using data from 2006 to 2010. Again, as noted in the
previous slide, the majority of all cancers that are
attributable to HPV are attributable to 16 and 18. The blue bars show the cancers
that are attributable to the 5 additional types in the
9-valent vaccine, and you can see here that for females,
the largest number of cases to the 5 additional types
are for cervical cancers. So, in summary, just to
review what I went over, in the United States there’s
approximately 33,000 HPV-associated cancers
per year. About 64% of these are
attributable to 16 and 18. 16 and 18 account for about
66% of cervical cancers, and for the other cancers
the percent ranges from 48% to 80%. About 10% of HPV-associated
cancers are attributable to the 5 additional types in
the 9-valent vaccine, 15% of cervical cancers, and for
the other cancers the range is 4% to 18%. Due to the differences in the
HPV types attributable to the cancers at different sites,
there are differences by sex. The 5 additional types account
for about 14% percent of HPV-associated cancers
in females. Only 4% of HPV associated
cancers in males. And for cervical precancer
lesions that are detected through cervical cancer
screening, about 50% are attributable to HPV 16 and
18 and about 25% to the 5 additional types in
the 9-valent vaccine. Now I’d like to move on and
talk about data from the 9-valent HPV vaccine
clinical trials. The 9-valent vaccine
was licensed by FDA in December 2014. The trials conducted for
licensure included a pivotal efficacy trial, immunogenicity
and immunobridging trials, and concomitant use trials. The 9-valent efficacy trial
included over 14,000 women age 16 to 26 years, and they were
randomized to receive either the 9-valent vaccine or
the quadrivalent vaccine. There was no unvaccinated
group for comparison in this study. The objectives were to
demonstrate efficacy for HPV 31, 33, 45, 52, and 58-related
endpoints and to demonstrate non-inferior immunogenicity
for the HPV types 6, 11, 16, and 18. Since both vaccines target the
4 types in the quadrivalent vaccine, it was not possible
to evaluate efficacy against those 4 types. The 9-valent HPV vaccine
efficacy trial showed high efficacy against the
5 additional types,
the 9-valent vaccine, in the per protocol
population. You can see here there
was high efficacy against a combined endpoint of high-
grade cervical, vag–vulvar and vaginal lesions due to the
5 additional types, 96.7%. There were a variety of other
endpoints evaluated, and I am showing here the efficacy
against 6-month persistent infection, which was 96%. As noted on this slide,
there were few high-grade outcomes due to HPV 6, 11, 16,
and 18 types that–against which both vaccines protect. There was only one case in
the 9-valent group and 3 in the quadrivalent group. And because of this,
efficacy was inferred from immunogenicity. Antibody titers were
evaluated for these types, and the non-inferior
immunogenicity was demonstrated for all 4 types. There was over 99% zero
conversion and geometric mean titers were non-inferior
between the two groups– non-inferior in the quadrivalent
group compared to–in the 9-valent group compared to
the quadrivalent group. This slide shows results from
the 9-valent vaccine adult- adolescent immunobridging
study. This is one of the studies
that allowed licensure in the younger age group. And this study compared the
geometric mean titers in 9- to 15-year-olds shown here in
green to females 16 to 26. This was the age group that
was in the efficacy trial, and that’s shown in
purple on this slide. Not only was non-inferior
criterion met for all 9 HPV vaccine types, but the
geometric mean titers were higher in the
younger age group. This is a similar finding
to what was seen for the quadrivalent and the
bivalent vaccines previously, that the antibody response
to vaccination is higher in the younger adolescents. This slide summarizes some of
the data I just presented as well as some other
data from the trials. Efficacy–there was about
97% protection against the 5 additional types in the
9-valent vaccine and similar protection against the 4 types
shared by both the quadrivalent and the
9-valent vaccine. There was non-inferior
immunogenicity for HPV 6, 11, 16, 18 compared with
the quadrivalent vaccine and for all 9 types in
adolescent females and males compared to adult females,
and in adult males compared to adult females. The concomitant use studies
show that there was no impact on immunogenicity or safety
when the 9-valent vaccine was administered with
Menactra or Adacel. As always, safety is evaluated
and reviewed in the pre-licensure trials. The trials included over
15,000 9-valent vaccine recipients, and 9-valent
vaccine was generally well tolerated. And the safety profile
was similar to the quadrivalent vaccine. There were more injection site
reactions with the 9-valent vaccine, specifically
swelling and erythema. And these–these reactions
increased with the number of doses administered–again
as was seen in the quadrivalent trials. And then in the concomitant
use studies there was no difference in the safety
profile when co-administered with other vaccines
that were evaluated. Now I’ll discuss the
updated ACIP recommendations. This slide shows
ACIP’s previously published recommendations. Since 2011, the
recommendations have been for routine vaccination of
boys and girls at age 11 or 12, and the vaccination series
can be started at age 9 years. Vaccination is also
recommended through age 26 for females and through
21 for males not previously vaccinated. Vaccination is recommended
for immunocompromised persons, including persons with HIV
infection, and for men who have sex with men
through age 26. A 3-dose schedule is
recommended, and previously the vaccines that were
licensed and recommended were bivalent or quadrivalent
vaccine for females and quadrivalent
vaccine for males. Before I review the updated
recommendations, I want to mention the licensed age
groups for the 3 available vaccines in the U.S. The
bivalent vaccine is licensed for females 9 to 25 years. The quadrivalent vaccine is
licensed for females and males 9 to 26 years. And the 9-valent vaccine is
licensed for females 9 to 26 years and males
9 to 15 years. At the time of the first
application to FDA, the 9-valent vaccine trials in
males 16 to 26 years had not been completed. Immunogenicity data for 16- to
26-year-olds are now available and were reviewed by ACIP last
year, and these data have been submitted to FDA. When ACIP deliberated
on 9-valent vaccine, the committee recommended
use of 9-valent vaccine in the currently recommended
age groups, including for males. The 16- to 26-year-old
recommendation for males then is currently an off-
label recommendation. So, these are the updated
recommendations. Again, the first three
bullets are exactly the same. The routine recommendation
is for vaccination at age 11 or 12 years. Vaccinations are recommended
through age 26 for females and through age 21 for males
not previously vaccinated. And vaccinations recommended
for men who have sex with men and immunocompromised men,
including those with HIV infection, through age 26. Vaccination of females is
recommended with bivalent or quadrivalent vaccine or
the 9-valent vaccine, and vaccination of males
is recommended with the quadrivalent vaccine or
the 9-valent vaccine. The updated recommendations
include some wording on the differences between the
vaccine including the fact that the bivalent,
the quadrivalent, and 9-valent all protect against 16 and 18,
types that cause about 66% of cervical cancers and
the majority of other HPV-attributable cancers
in the United States. The 9-valent vaccine targets
5 additional cancer-causing types which account for about
15% of cervical cancers, and 9-valent–4–quadrivalent
and 9-valent vaccine also protect against 6 and 11,
types that cause genital warts. For administration, there
are minor wording changes but the recommendation is
similar to what it was before. Sorry. Um… interchangeability first. Um…the wording here for
interchangeability states that if vaccination providers
do not know or do not have available the HPV
vaccine product previously administered, or are in
settings transitioning to 9-valent vaccine for
protection against HPV 16 and 18,
any vaccine product may be used to continue or complete
the series for females, and quadrivalent or 9-valent
vaccine may be used to continue or complete
the series for males. Now for administration. For administration, there
are minor wording changes, but the recommendation is
similar to what it was in our previous recommendations. The vaccines are each
administered in a 3-dose schedule and the second does
is administered at least one to two months after the first
dose, and the third dose at least 6 months
after the first dose. And if the vaccine schedule is
interrupted, the vaccination series does not need
to be restarted. There are no changes in the
recommendation regarding vaccination during pregnancy. Vaccine is not recommended
for pregnant women. And if a woman is found to be
pregnant after initiating the series, the remainder of the
doses should be delayed until after completion of pregnancy,
but no intervention is needed and no pregnancy testing is
needed before vaccination. A new pregnancy registry has
been established for 9-valent vaccine, and of note,
the vaccine pregnancy registries have been closed
for the quadrivalent vaccine and the bivalent vaccine
with concurrence from FDA. One question that has been
raised is about 9-valent vaccine for persons who
have completed HPV vaccination series. Of note,
the manufacturer did not seek indication for 9-valent
vaccination for persons who previously completed an
HPV vaccination series. However, a study of 9-valent
vaccine in prior quadrivalent vaccinees was conducted
mainly to evaluate safety. Due to time limitations,
there was an abbreviated ACIP meeting in February. This was not discussed and
will be presented to ACIP at a subsequent meeting. So in summary, the 9-valent
HPV vaccine was licensed by FDA in December 2014 and
was recommended by ACIP in February 2015. It is one of three vaccines
that can be used for routine vaccination of females and
one of two for males. It targets 5 additional
high-risk types. Overall, 14% of HPV-associated
cancers in females and 4% in males are attributable
to these types and 15% of cervical cancers. There are a variety of next
steps, but I want to mention that the 9-valent vaccine
has been available from the manufacturer starting
in February 2015. CDC has awarded a contract
for the 9-valent vaccine, and of course efforts are
needed to continue to increase HPV vaccination coverage
in the U.S. I want to end with this slide which I think
is– it shows a graph that is similar to–to many of you. It shows the national
estimated vaccination coverage among adolescents 13 to 17 in
the U.S. In the red line is coverage with at least one
dose of HPV vaccine, showing increases initially but then
leveling off in recent years, reaching 57% in 2013. 3-dose coverage shown in
orange, with 38% in 2013. And in blue are the 1-
and 3-dose male coverage estimates. The increase in coverage in
males started after vaccine was licensed in males in 2009
and further increased after the routine recommendation
for males in 2011. In 2013, at least 1- and
3-dose coverage was 35% and 14% in males. And further efforts are
ongoing to increase HPV vaccine coverage in the U.S.
for both females and males. There are a variety of
resources I want to remind everyone about. Of course, the ACIP website
includes slides, minutes, and recommendations. And there are a variety
of resources for providers and patients at CDC websites
listed on this slide. Thank you. Dr.Shimabukuro:
Hi, good morning. Uh, I’m Tom Shimabukuro. I’m the Deputy Director of
the Immunization Safety Office at CDC. And today I’m going to
present an update of Human Papillomavirus vaccine safety
monitoring and evaluation. Next slide. Next slide, please. In this presentation, I’ll
provide an update of HPV postlicensure vaccine safety
monitoring and publications, which are predominately
studies of quadrivalent HPV vaccine. I’ll describe ongoing HPV
vaccine safety-related activities currently
being conducted at CDC. And then I’ll outline plans
for vaccine safety monitoring for the recently licensed
9-valent HPV vaccine. Next slide. This slide summarizes CDC’s
vaccine safety monitoring infrastructure and shows the
3 main components. The Vaccine Adverse Event
Reporting System, which is our national spontaneous reporting
system that detects potential vaccine safety problems,
the Vaccine Safety Datalink, which is a consortium of
large-link databases used for active surveillance and
research, and the Clinical Immunization Safety Assessment
Project, a consortium of vaccine safety experts that
consults on complex vaccine safety cases and conducts
vaccine safety research. There have been a number of
publications addressing the safety of HPV vaccine that
we wanted to highlight. With regards to general
safety, the postlicensure safety profile of quadrivalent
HPV vaccine was first described in JAMA in 2009, when
results from the first two and a half years of VAERS
safety surveillance were published. Close monitoring of U.S.
VAERS reports found that the proportion of reporting
for veno–a venous thrombus– thromboembolism or VTE
and syncope, or fainting, was higher than expected. No other safety
signals were identified. Updated VAERS reviews have
also been published as part of the 2013 and 2014 MMWR
reports on HPV coverage among adolescent girls and
postlicensure safety monitoring in the
United States. In both reports, it was found
that reporting to VAERS was consistent with prelicensure
data and no new safety concerns had been identified. Another study that was
conducted was through CDC’s Vaccine Safety Datalink
in which near real-time monitoring was performed
looking at 8 pre-specified conditions as listed
on this slide. No statistically significant
associations were found, however there was some
nonsignificant elevated risk for venous thromboembolism
in females 9 to 17 years. Lastly, as part of the
manufacturers’ quadrivalent HPV vaccine postmarketing
commitment with FDA, a general safety assessment was
conducted that included approximately 190,000 females
who received quadrivalent HPV vaccine in two large
U.S. health plans. Using a self-controlled risk
interval design the study found that quadrivalent
HPV vaccine was associated with syncope on the same
day of vaccination and skin infections in the two
weeks after vaccination. A review of skin infection
diagnoses suggested that some of these cases may have
been local injection site reactions, although the
medical records contain insufficient detail to
exclude acute infections. Next slide. Because of the suggestions
and concerns of increased risk of specific health conditions,
we wanted to highlight recent publications on VTE
autoimmune conditions and neurologic diseases. On this slide I describe
postlicensure safety work that has been conducted
surrounding VTE. Addressing the VTE findings
from both the previously described VAERS and VSD
studies, there have been two large population-based studies
that have been published using national registry data from
Denmark and Sweden in which both studies found no
association between VTE and HPV-4–and
quadrivalent HPV vaccine. In addition, while not
published, the Vaccine Safety Datalink has recently
completed a study evaluating the risk of VTE in vaccinated
persons aged 9 to 26 years which found no increased risk
of VTE following quadrivalent HPV vaccine. Concerns have been identified
with both autoimmune and neurologic disease
following quadrivalent HPV vaccine. There have been 4 large
epidemiologic studies in which no evidence for causal
associations have been observed. These studies were conducted
in the United States, Scandinavia, and France. And I’ll pause briefly to
let you digest some of the material
on–material on this slide. Next slide, please. Finally, we wanted to also
remind you that the–of the Institute of Medicine’s report
published in 2011 titled “Adverse Affects of Vaccines:
Evidence of Causality.” This report was a review
of published literature and the committee concluded
that syncope can be associated with any injected vaccine,
including HPV vaccines. And the report also concluded
that anaphylaxis can be causally related to HPV
vaccines, but HPV is only one of many vaccines for which
a causal relationship to anaphylaxis–anaphylaxis
exists. We want to provide an update
on HPV vaccine safety-related activities currently being
conducted within CDC’s Immunization Safety Office. Within VAERS, there is ongoing
monitoring of U.S. reports of both types of HPV vaccines,
clinical reviews of deaths and other pre-specified
adverse event outcomes as needed, and data mining is
conducted to identify signals within the data by
our FDA colleagues. CISA’s conducting an
intervention clinical trial to assess the effectiveness
of drinking water before vaccination to prevent
symptoms associated with syncope. The following studies are
currently being conducted within the Vaccine
Safety Datalink. Addressing HPV vaccine
safety in populations. There is a safety study
among males currently being conducted as well as an
inadvertent HPV vaccination study among pregnant women. These are women who
inadvertently received HPV vaccine during pregnancy. And just to remind you,
the vaccine does not recommend it –neither vaccines are
recommended during pregnancy. The Vaccine Safety Datalink
is also addressing safety concerns that have been
identified from case reports and/or media. And these include evaluating
the risk of autoimmune disease following quadrivalent HPV
vaccine, premature ovarian insufficiency following
quadrivalent HPV vaccine, and mortality following
quadrivalent HPV vaccine and other adolescent vaccines. So moving on to the recently
licensed 9-valent HPV vaccine. The 9-valent HPV vaccine was
licensed in December 2014, as Dr. Markowitz indicated
in her presentation. Now, in this slide–it’s a
brief summary of the safety profile as described in
FDA’s regulatory action documentation. Among 6 pre-licensure studies,
9-valent HPV vaccine was found to be generally
well-tolerated. The adverse-event profile
was similar to that of the quadrivalent vaccine. However, there was more
injection-site swelling and erythema in the 9-valent
HPV vaccine group. Among those inadvertent
pregnancies during the preclinical studies,
the proportion of adverse outcomes observed were
consistent with those observed in the general population. A sub-analysis was conducted
of the identified pregnancies within 30 days that resulted
in a spontaneous abortion. These were more frequent
than those who received quadrivalent HPV vaccine. However, these spontaneous–
the spontaneous abortions observed were within what
is expected for early loss of pregnancy. At CDC,
the following safety work will be conducted for
9-valent HPV vaccine. In VAERS, reports will be
monitored along with clinical reviews, and FDA data mining
will also be conducted
to identify safety signals. In the Vaccine Safety
Datalink, a rapid cycle analysis will be conducted. And because the label
indicates a possible increase of spontaneous abortion
following 9-valent HPV-9–HPV vaccine compared to 4-valent
HPV vaccine, the VST plans on conducting an
evaluation of this issue. 9-valent HPV vaccine
postmarketing commitments to be conducted by Merck
include the following– Completion of two 10-year
study extensions evaluating long-term safety,
immunogenicity, and effectiveness. One study will be conducted
among males and females 9 to 15 years of age and the
other will be conducted among females 16 to 26
years of age. There will be an observational
study to further characterize the safety profile
in 10,000 persons. And a pregnancy registry
will be established to prospectively collect data
from spontaneous reports of inadvertent vaccination. The pharmacovigilance plan
for FDA’s Sentinel Initiative– Initiative includes
a general safety study and a pregnancy outcome study. So in conclusion, quadrivalent
HPV vaccine has a good safety profile as demonstrated by
VAERS and Vaccine Safety Datalink safety monitoring
data and published in preliminary data
from many sources. Safety monitoring and
evaluation will continue for all HPV vaccines. Thank you. This concludes
my presentation. Jill: Great. Thank you very much to
both of our speakers. And now we’re going to
go ahead and open it up for questions. And Ian is on. And, Ian, if you would
go ahead and ask the first question. Ian: The first question
we have is, so–oh. Jill: Ian, I’m sorry. I just realized we were
supposed to go to our
polling questions. I apologize.
Sorry, everyone. So before we ask questions,
just for the slides that we’ve just gone through, if–we’re
going to go ahead and do our first polling question,
which is–How helpful was the information presented
during the webinar? And we should have a–the
poll should be popping up now. Um… Go ahead
and answer that. So please select from
extremely helpful to not helpful at all. Hopefully it was helpful. OK, and we’ll give folks
a couple more minutes to answer this. OK, let’s go to the second
question to help us get feedback about this– the usefulness of our webinar. All right, our second question
is–have we moved to our second question now? All right. Great. So we’ve got our answers. Poll results–extremely likely
to use the information posted. Great. Wonderful. All right, so, now we will
go to our questions that have been coming in from the
presenters–I mean, from the, um, participants. So, presenters, we’ll let you
know which question this is– who this is for. OK, Ian, you can go ahead. Ian: Ok, so this
question is for Lauri. Can you offer an opinion or
guidance with reference to healthcare professionals
recommending the 9-valent vaccine for males and females
in the recommended age groups who were previously vaccinated
with the bivalent or quadrivalent vaccine? Dr. Markowitz: Well, this is
a very common question we’ve been getting. But as I mentioned, the ACIP
has not deliberated on this issue yet. So we do not have any
official guidance. We have,
um, done some review of the data, and we have
done some modeling to show, you know, what the cost
effectiveness of re-vaccination would be. But I do want to stress that
the vast majority of all HPV-associated disease for
both males and females, but particularly for males,
is due to 16 and 18, the types that are covered in the
quadrivalent vaccine. But we do anticipate that ACIP
will be reviewing these data in the coming ACIP meetings. Ian: OK. So second question we have is,
if they started on the 4-valent vaccine
can they finish with the 9-valent vaccine? Dr. Markowitz: Yeah, and I did
have a slide which reviewed this, that the recommendations
do state that the 9-valent vaccine can be used to
complete a series that was started with the
quadrivalent vaccine. That is in the policy note
which was published at the end of March. Ian: So we have another
question with regard to the recommendation for
males ages 16 and older. They’re wondering if
it’s recommended for this age group. Dr. Markowitz: Yeah,
as I mentioned also–so, when the– when the studies
were– the prelicensure studies that were done
and initially submitted with the application to
FDA only included the immunobridging studies
in males 9 to 15. The studies in females
included a variety of studies including the efficacy study
that was done in females 16 to 26. So, FDA licensed the
vaccine for females 9 to 26 but for males 9 to 15. The studies in males 16 to
26 have now been completed. Those data have been reviewed
by ACIP and have now been submitted to FDA. When ACIP deliberated on
the recommendations for the 9-valent vaccine,
they did recommend it through the age groups that are
currently recommended for vaccination. So the recommendation is
currently an off-label recommendation for males 16
to 26, but as I mentioned, those data aren’t–have
been submitted to FDA. So at the present time
they’re off-label, but the recommendation by ACIP
is through the currently recommended ages for males,
which is routine at 11 to 12 and through age 21 for those
not previously vaccinated and through age 26 for
men who have sex with men and immunocompromised men. Ian: OK, this
question is for Tom. They’re asking, when will the
Gardasil mini sentinel data regarding VTE be published? Dr. Shimabukuro: I don’t
have an answer to that. I would have to check with our
–with our colleagues at FDA and get back to you on that. Ian: OK, this person has
a question for Lauri. Overall, what percent of HPV
disease would the 9-valent vaccine cover, for male–for
females versus males? Dr. Markowitz: So, I don’t know
if we want to go back to one of my slides that
can review this. But I can just review it. But it is on slide–it is
on one of the slides. But basically, based on
studies in the U.S.– Hmm. I don’t know. My slide numbers I think
are different than yours. But it says
summary attribution of 16, 18. But basically it–for females,
about 14% of all HPV-associated cancers are due
to the 5 additional types, but for males, it’s only 4%. And the reason why it’s
so different is because the cancers of
the different sites are attributable to different
proportion of the types. So again–yes, thank you
for bringing that slide up. So you can see here on the
bullet, we see 10% of cancers overall attributable to the
5 additional types. 15% of cervical cancers
are attributable to the 5 additional types, but there
are differences by sex. So 14% of the HPV-associated
cancers in females and only 4% of the HPV-associated cancers
in males are attributable to these additional 5 types. Ian: OK, this–um, this
question is with regard to the VFC program. And they’re wondering, will
the HPV-9 vaccine replace all HPV-4 vaccines? Dr. Markowitz: Well, the–
currently there is a contract for the 9-valent vaccine. I think this is a question
more in terms of the company’s plans, perhaps. But right now both the
quadri –quadrivalent and the 9-valent vaccines
are available from the manufacturer. There will–we anticipate
there will be eventually only the 9-valent vaccine
available, but the transition will not be immediate as it
was maybe for the transition from Prevnar-7 to
Prevnar-13. I think it probably–it’s
anticipated it would take about a year or slightly
longer for that trish–uh, transition to take place. I–I can’t comment on vaccine
availability through VFC. I don’t know if there’s anyone
else on the call that can comment on that. Jill: Shannon, if people
need to know about vaccine availability through VFC,
who can they contact? Shannon: Hi, yes. They should contact their
state immunization program and talk to them about the
availability of the 9-valent vaccine through
the VFC program. It is–um…you know, we do
have a contract for that, so it is available through the
VFC program, but they’ll need to talk with their state
immunization program to find out when they’re available to
start ordering it and how much is available. Ian: OK. This is a question–I’m not
sure if we answered this exact question earlier, but they’re
asking if–started on HPV-4 then switched to HPV-9,
will they need to have three doses of 9-valent? Dr. Markowitz: Right now
there is no recommendation for 9-valent vaccination for
individuals who have completed a HPV vaccination series. So we have no recommendation
for that. So if someone has started,
they can complete the series with the 9-valent vaccine. There are no data right now
on whether or not that will provide protection against
the additional 5 types. But we do not have a
recommendation right now for additional vaccination
with the 9-valent vaccine if you’ve already completed
a vaccination series with any vaccine. Ian: Great. So this question–there’s
a question with regard to vaccine safety. This person is wondering
if there was any evidence of increased episodes of
syncope in the 9-valent HPV vaccine study group. Dr. Shimabukuro: This is Tom. Oh–Lauri, go ahead. I’m actually not familiar if
there was any in the clinical trials for 9-valent. Dr. Markowitz: There were–
there have been very few syncopal cases in the trials. Part of the reason for that is
that they–you, know, during trials they make sure
people are sitting down or laying down. But they–there have been very
few cases and there were no differences in the trial,
to my knowledge. Dr. Shimabukuro: So I’ll just
add that the IOM concluded that syncope is causally
related to receipt of any vaccine, any
injectable vaccine. It’s also related to any type
of medical procedure that involves a needle stick,
like a blood draw or donating blood. So, um–it’s–and it’s been–
it’s been observed following vaccines, particularly
in adolescence. But there are recommendations
about waiting periods, and it’s important to observe
those waiting periods to prevent any complications
from a syncopal episode. Ian: OK. OK, this–um, this person
is wondering if the interval of vaccination for the
quadrivalent vaccine is the same as the interval
for vaccination of the 9-valent vaccine. Dr. Markowitz: Yes, the
trials that were done for the quadrivalent were 0,
2, and 6 months, and those were the same intervals that
were used for the 9-valent vaccine trial –0, 2,
and 6 months. Ian: We have another question
about if vaccinations should be given to males ages–if
vaccination can be given to males ages 22 to 26 regardless
of sexual orientation? Dr. Markowitz: Yes, the–we–
the vaccine is licensed through–the quadrivalent
vaccine, let me see, was licensed in males
through age 26 and the same recommendation is currently
for the 9-valent vaccine, that it’s recommended
through age 21. It can be given through age
26, but it’s specifically recommended for men who have
sex with men through age 26 and immunocompromised men. Ian: OK. Um…I’m not sure if someone
on the panel will be able to speak to this question,
but they’re wondering if there’s a cost comparison
between the quadrivalent and 9-valent HPV vaccine. Dr. Markowitz: Yes, you mean
the private sector cost or the public sector cost or a
cost effectiveness analysis? Ian: They don’t specify. Maybe if you could
just provide some cost- effectiveness data
that you found? Dr. Markowitz: Yeah, I mean,
as is required, we do cost- effectiveness analyses at the
time ACIP deliberates on any new vaccine. And there was some cost-
effectiveness modeling done for this. And three different models
have been–have looked at this question in terms of the cost
effectiveness of the 9-valent vaccine compared to the
quadrivalent vaccine and that analysis was done because I
think, as most people know, the vast majority of vaccine
being used in this country is quadrivalent vaccine. And all those models show that
under the base case as well as in sensitivity analyses,
looking at a different variety of assumptions, that the
9-valent vaccine–assuming it didn’t cost any more than
about $13 more than the quadrivalent vaccine–that the
9-valent vaccine would be cost savings compared to the
quadrivalent vaccine in a program of both male
and female vaccination. So I hope that
answers the question. Ian: Great.
That’s awesome. Jill: Before we go to the next
question, actually, can we have someone answer about
the cost of 9-valent vaccine. I think we have the
public sector cost, don’t we, Shannon? Shannon: Yeah, so, um…in
the –on the public sector, the 9-valent vaccine costs
about $134 per dose. In the private sector,
it’s around $163 per dose, but that may vary in
the private sector. Jill: Great.
Thanks, Shannon. Ian: OK,
we have another question. A participant, their daughter
is supposed to get the third dose of the quadrivalent
vaccine and they’re wondering if they need to wait for the
9-valent vaccine to become available to get
that dose instead. Dr. Markowitz: Well,
our current recommendations is to be vaccinated with whatever
vaccine is available in the provider’s office. We don’t know when these–you
know, the 9-valent will be available in providers’
offices, so that is our current recommendation for–to
be vaccinated with whatever vaccine is currently
available. As I mentioned, the majority
of all HPV-associated disease in males and females is due to
HPV 16 and 18, which is–for which all vaccines
provide protection. Ian: And we have a follow-up
question to the question about cost. This person is wondering if
the $13 cost difference is per dose or for the
overall series. Dr. Markowitz: Yeah.
I’m sorry, yes. That was per dose. The modeling was based on a
per dose–in the base case it looked at the per dose cost
of $13 more for the 9-valent compared to the quadrivalent. It did use a range of,
um… of–of cost assumptions and it still remained cost
savings and certainly cost- effective if the price
increased beyond that, but that was the
base case used– additional $13 per dose. Those slides are on the ACIP
website but publication is not yet available. Jill: We still have time for a
couple more questions if folks still want to send
more of those in. Ian: OK. We have a question for further
clarification on the age– on the recommendation for
males age 22 to 26, wondering if 9-valent vaccine can be
given if not–if it’s not a man who has sex with
men or immunocompromised? Dr. Markowitz: Yeah, I mean,
it can be given in that age group. We do–that is the
current recommendation for the quadrivalent vaccine. As I mentioned, ACIP made
the same recommendation for the 9-valent vaccine. That it–it’s recommended
through age 21 but it can be given through age 26. Ian: One moment. I’m just
trying to scan through these questions. Um, this person is
wondering if we will see a revised Gardasil VIS,
and if so, when. Dr. Markowitz: Um, Shannon,
are you able to address that? I think there are revised
VIS that are being worked on for all the vaccines. That’s my understanding. Shannon: Yes, and I know that
they have developed a VIS for the 9-valent vaccine,
but I’m not exactly sure what day– when it will
become available. But I know that
has been developed. Jill: Um…this is Jill. And actually I was just
looking to see–I think it was supposed to be sometime
this week or next week. So it should be very shortly that that is up. And we will send out an
alert on the Preteen Vax News newsletter to let folks
know when that is available. Ian: We have a question. Somebody’s wondering if
ACIP will be evaluating data on a two-dose schedule
at a future ACIP meeting? Dr. Markowitz: Yes, ACIP has
reviewed data on two-dose schedules twice in the past
year or has had presentations on two-dose schedules. There are some data
available for the bivalent and quadrivalent. There’s currently a large
trial going on of the 9-valent vaccine, looking at
two-dose schedules. That is a trial looking
at both 0-6 and 0-12 month intervals between the
first and second doses. And we anticipate that those
data should be available at the end of this year or
early next year, and ACIP will be reviewing those data as
soon as they’re available. Ian: Um, let me see. Jill: Take a look for any
final questions right now. Ian: This person is wondering
that, uh…it says, “You noted that ACIP recommended either
the quadrivalent or HPV-9. They’re wondering why
not recommend only HPV-9. [Crosstalk] Jill: Go ahead, Lauri. I was just going to say,
that’s a question for you. Markowitz: Yeah. Eventually the–there will
be a complete transition to HPV-9. Um…I–and–and for–
particularly for males there is really little advantage to
the HPV-9 over the HPV–over the quadrivalent vaccine. But during this transition
period, the recommendation was for any vaccine, and ACIP
did not express a preference for one vaccine
over the other. Ian: I think that about covers
the questions we received. Jill: Excellent, great. Well, thank you, everyone,
so very much for participating and I would like to thank
both of our presenters, Lauri and Tom,
we really appreciate you coming on and providing
this information. This is the first in a series
of webinars that we will be having titled
“PreteenVaxScene” and we will be sending out notices of
those webinars the same way that you received the
one about this one. And we will also be posting
this webinar in the next couple of weeks with a link
to the YouTube site, CDC’s YouTube channel. CDC Streaming Heath will
be hosting the video. There’ll be a web–there
will be a web link from the CDC.gov/HPV site as well
as CDC.gov/vaccines/teens. And we will send it out
in the newsletter. And everyone that registered
for the webinar will also get a note about it
being posted as well. We thank you very much. And if you have any additional
questions, please do not hesitate to e-mail us at
[email protected] Thank you, everyone.

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