OKAY, WE'RE BACK IN SESSION
AND WILL ASK DR. BOCCHINI TO GET
US STARTED ON THE HUMAN
PAPILLOMAVIRUS VACCINE SESSION.
THANK YOU, GOOD MORNING.
WE'RE NOW GOING TO BEGIN A VERY
IMPORTANT HPV VACCINE SESSION,
AND WE'LL DESCRIBE THAT FOR YOU
IN THE NEXT COUPLE OF SLIDES.
TODAY WE'RE GOING TO HAVE
PRESENTATION BY MERCK FOR A
REVIEW ON THE INVESTIGATIONAL
9-VALENT HPV VACCINE, WHICH
CONTAINS THE QUADRIVALENT
VACCINE AND HAVE FIVE ADDITIONAL
SEROTYPES TO THE PRODUCT.
IN ADDITION, WE'RE GOING TO
REVIEW AND APPROVE THE UPDATED
HPV VACCINE ACIP STATEMENT, EACH
OF THE COMMITTEE MEMBERS HAS
REVIEWED THE MOST RECENT DRAFT
AND WE THANK MANY OF YOU FOR THE
COMMENTS THAT YOU'VE GIVEN US TO
IMPROVE THE DRAFT.
THIS STATEMENT THAT INCLUDES
RECOMMENDATIONS FOR THE HPV 16
AND 18 BIVALENT VACCINE AND THE
QUADRIVALENT VACCINE AND
CONSOLIDATES THE INFORMATION
AVAILABLE FOR MALES AND FEMALES.
JUST A REVIEW, IN OCTOBER, WE
PROVIDED AN UPDATE ON HPV
VACCINATION COVERAGE IN THE
UNITED STATES, AND WE HEARD FROM
MERCK ON THE NINE-VALENT HPV
DEVELOPMENT PROGRAMS, SO YOU
HEARD ABOUT THE STUDIES INVOLVED
IN THE DEVELOPMENT OF THIS
VACCINE.
YOU ALSO SAW AND CONTRIBUTED TO
A DISCUSSION ON AN OVERDRAFT,
OVERVIEW, OF WHAT WAS THEN THE
CURRENT DRAFT OF THE UPDATED
ACIP STATEMENT.
SINCE THAT TIME, THE WORK GROUP
HAS HAD A NUMBER OF CONFERENCE
CALLS AND WE'VE REVIEWED DATA
FROM THE 9-VALENT CLINICAL
TRIALS AND HPV PIPE ATTRIBUTION
AND HPV ASSOCIATED DISEASES AND
HAVE NOW INITIATED DISCUSSIONS
FOR GRAVE CONSIDERATION FOR
POSSIBLE LICENSURE OF THE
9-VALENT HPV VACCINE.
DERATION OF THE ROPOSED TIME
9-VALENT HPV VACCINE.
TODAY, I'LL FLUSH THIS OUT A
LITTLE BIT FURTHER, WE'RE GOING
TO TALK ABOUT ATTRIBUTION OF
TYPES HPV ASSOCIATED DISEASE AND
YOU'LL HEAR THE FIRST
PRESENTATION OF CLINICAL TRIAL
DATA.
IN JUNE YOU'LL HEAR ADDITIONAL
INFORMATION ABOUT CLINICAL TRIAL
RESULTS AND A HEALTH ECONOMICS
PRESENTATION.
WE ANTICIPATE IN OCTOBER TO HAVE
THE GRADE EVALUATION COMPLETED
WITH RECOMMENDATION OPTIONS AND
DISCUSSION FOR ACIP, AND
FEEDBACK TO MAKE THE FINAL
RECOMMENDATIONS, WHICH WE EXPECT
TO HAVE IN FEBRUARY OF 2015 AND
PENDING THE DECISION BY FDA FOR
LICENSURE, A VOTE, AND THEN A
VSC VOTE, AS WELL.
SO TODAY, THE FIRST TWO TALKS
ARE ON TYPE ATTRIBUTION, HPV
TYPE ATTRIBUTION IN CERVICAL
PRECANCERS BY SUSAN HARIRI FROM
THE CDC, AND THAT WILL BE
FOLLOWED BY HPV TYPE ATTRIBUTION
AND HPV ASSOCIATED CANCERS BY
DR. MONA SARAIYA, WHO'S ALSO
FROM THE CDC.
OUR PLAN, AND I'LL TALK MORE
ABOUT TYPE ATTRIBUTION IN A
SECOND, BUT FOLLOWING THESE TWO
TALKS TO OPEN THIS FOR
QUESTIONS, FOR THOSE TWO
PRESENTATIONS, WE'LL FOLLOW THAT
WITH A PRESENTATION BY
DRDR. A
DRDR. ALAIN
LUXEMBOURG FROM MERCK ON THE
CLINICAL TRIAL DATA, THEN
DR. LAURI MARKOWITZ WILL PROVIDE
A SUMMARY AND THE NEXT STEPS
RELATED TO THE 9-VALENT HPV
VACCINE PROGRAM, AND THEN SHE
WILL REVIEW WITH US THE UPDATED
STATEMENT AND GET ADDITIONAL
FEEDBACK FROM THE ACIP AND THEN
FOLLOW THAT BY AN ACCEPTANCE OF
THAT.
SO, JUST TO TALK BRIEFLY ABOUT
BURDEN OF DISEASE, CLEARLY, AS
WE ADVANCE VACCINE DEVELOPMENT,
IT BECOMES VERY IMPORTANT TO
UNDERSTAND THE ROLE THAT VARIOUS
SEROTYPES PLAY IN THE
DEVELOPMENT OF THE CANCERS,
PRECANCERS ASSOCIATED WITH
DIFFERENT SEROTYPES OF HPV.
IN ADDITION, IT'S ALSO IMPORTANT
FOR US TO ESTABLISH GUIDES FOR
FUTURE EVALUATION OF THE IMPACT
OF THESE VACCINES.
SO, THE INTERNATIONAL AGENCY FOR
RESEARCH ON CANCER HAS DEFINED
SOME CANCERS AS HAVING A STRONG
EVIDENCE OF CAUSAL IDEOLOGY, SO
FOR HPV-ASSOCIATED CANCERS, THEY
INCLUDE CERVICAL, VAGINAL,
LOBAR, PENIL, ANAL CANCERS AND
THE PRESENCE OF HPV IN THESE
CANCERS IS CONSIDERED TO BE
INDICATION OF CAUSALITY.
HOWEVER, THE DETERMINATION OF
THE TYPE OF HPV THAT'S INVOLVED
IN A PARTICULAR DISEASE REALLY
DEPENDS ON A NUMBER OF FACTORS,
WHICH INCLUDE THE QUALITY OF THE
SPECIMEN THAT'S BEING EVALUATED,
THE ASSET USED TO DETECT HPV,
THE ALGORITHM TO ASSIGN
ATTRIBUTABLE TYPE WHEN MULTIPLE
TYPES ARE DISCOVERED IN THE SAME
PREPARATION, AND THEY CAN VARY
BASED ON A POPULATION SAMPLE.
AND THAT'S WHY IT'S IMPORTANT TO
HAVE THESE TWO PRESENTATIONS,
WHICH WILL GIVE US SOME
UNDERSTANDING OF WHERE WE ARE
AND THE PROGRAMS THAT ARE
AVAILABLE FOR US TO GET A BETTER
PICTURE OF THE RELATIVE ROLES OF
THE VARIOUS SEROTYPES AND
PRECANCER AND CANCER LESIONS.
I WANT TO THANK THE WORK GROUP,
THE MEMBERS OF THIS WORK GROUP
HAVE BEEN VERY ACTIVE AND
INVOLVED IN OUR CONVERSATIONS ON
THE PHONE AND IN OTHER EFFORTS,
PARTICULARLY WANT TO THANK LAURI
MARKOWITZ FOR HER ORGANIZATIONAL
SKILLS AND ABILITY TO KEEP THIS
COMMITTEE ON TASK ANDIR
CONTRIBUTIONS, AS WELL.
SO WITH THAT, I'D LIKE TO TURN
THIS OVER TO DR. HARIRI, WHO
WILL PROVIDE THE FIRST
PRESENTATION.
THANK YOU.
I FORGOT TO MENTION ONE THING,
THE ACIP MEMBERS HAVE A FULL
COPY OF DR. LUXEMBOURG'S
PRESENTATION, HOWEVER, WHAT WE
FOUND IS THAT FOR THE PUBLIC AND
THOSE AROUND OUTSIDE THE TABLE,
THE ONLY HALF OF THE TALK HAS
BEEN COPIED.
YOU'RE MISSING EVERY OTHER PAGE.
AND SO WE APOLOGIZE FOR THAT,
AND SO THE PLAN IS TO MAKE SURE
THAT YOU'RE ALL AWARE THAT THESE
SLIDES WILL BE PUBLISHED ON THE
WEB WHEN THE SLIDES BECOME
AVAILABLE, SO THANK YOU.
GOOD MORNING.
TODAY I'M GOING TO BE PRESENTING
DATA ON HPV TYPETHE U.S.
I'M GOING TO START WITH BRIEFLY
REVIEWING THE NATURAL HISTORY OF
CERVICAL HPV INFECTION AND
ASSOCIATED OUTCOMES.
AND THEN I'LL REVIEW SOME
PUBLISHED DATA ON THE
DISTRIBUTION OF HPV TYPES IN
HIGH GRADE CERVICAL LESIONS IN
WOMEN FROM THE DIFFERENT AREAS
OF THE WORLD, AND I'LL ALSO
REVIEW METHODS USED FOR
ATTRIBUTION AND THE REASON FOR
THEM.
THEN FINALLY, I'M GOING TO
PRESENT DATA FROM THE U.S. ON
HPV TYPE ATTRIBUTION TO
NONINVASIVE HIGH GRADE CERVICAL
LESIONS.
AS YOU KNOW, INFECTION WITH
GENITAL HPV IS RESPONSIBLE FOR A
SPECTRUM OF CERVICAL
ABNORMALITIES.
THE MAJORITY OF THESE
ABNORMALITIES ARE BENIGN AND
DON'T PROGRESS THE DISEASE.
IN FACT, ABOUT 90% OF INFECTIONS
BECOME UNDETECTABLE WITHIN TWO
YEARS WITHOUT CAUSING ANY
SYMPTOMS.
HOWEVER, INFECTION WITH HIGH
RISK HPV TYPES CAN PERSIST AND
THAT COULD LEAD TO MILD CERVICAL
ABNORMALITIES THAT TEND TO
REGRESS WITHOUT TREATMENT OR
HIGH GRADE LESIONS THAT ARE MORE
LIKELY TO PROGRESS INVASIVE
CERVICAL CANCER IF THEY ARE NOT
TREATED.
AND ROUTINE CERVICAL CANCER
SCREENING WITH THE PAP AND MORE
RECENTLY WITH HPV BASED TESTS IS
USED TO DETECT PRECANCEROUS
LESIONS AS A STRATEGY.
THE FOCUS OF THIS PRESENTATION
IS ON NONINVASIVE HIGH GRADE
CERVICAL LESIONS, SPECIFICALLY
ON GRADE TWO AND THREE AND SITE
TWO, WHICH I WILL BE
COLLECTIVELY REFERRING TO AS
BINT PLUS.
THEY ARE THE MOST LIKELY TO
PERSIST OF ALL HPV TYPES.
ABOUT 30% OF CIN TWO-PLUS
LESIONS ARE ESTIMATED TO
PROGRESS TO CERVICAL CANCER.
HPV 16 IS THE MOST COMMON TYPE
IN CIM LESIONS, WHERE AS HPV 18
IS THE MOST COMMON TYPE IN AIS
LESIONS.
SIN-TWO PLUS WERE USED IN THE
TRIALS AND ALSO USED AS
INTERMEDIATE END POINTS TO
MONITOR POST LICENSURE IMPACT IN
SOME COUNTRIES THAT HAVE
ESTABLISHED SCREENING PROGRAMS.
SO THIS GRAPH WAS ADAPTED FROM A
META ANALYSIS OF INTERNATIONAL
STUDIES THAT WERE CONDUCTED TO
DETERMINE HPV TYPE DISTRIBUTION
IN NONINVASIVE HIGH GRADE
CERVICAL LESIONS IN WOMEN AROUND
THE WORLD, AND THE HIGH RISK HPV
TYPES HERE ARE COMBINED INTO TWO
GROUPS.
THE BLUE BARS REPRESENT HPV
TYPES 16 AND 18 AND THE RED BARS
INCLUDE HPV TYPES 31, 33, 45,
52, AND 58, WHICH ARE THE FIVE
ADDITIONAL TYPES IN THE
CANDIDATE 9-VALENT VACCINE.
SO YOU CAN SEE FROM THE BLUE
BARS THAT THERE'S VARIATIONS
GLOBALLY IN THE PROPORTION OF
HPV 16 AND 18 DETECTED IN HIGH
GRADE CERVICAL LESIONS FROM 66,
OVER 60% IN WOMEN IN NORTH
AMERICA, EUROPE, AND SOUTH AND
CENTRAL AMERICA TO LESS THAN 50%
IN WOMEN IN EAST ASIA AND
AFRICA.
THERE IS LESS VARIABILITY IN THE
FIVE ADDITIONAL TYPES, WITH
ABOUT 40% DETECTED IN WOMEN
ACROSS ALL REGIONS, EXCEPT FOR
IN EAST ASIA, WHERE IT WAS
DETECTED IN 60% OF LESIONS.
SO THE OBJECTIVE OF THIS
ANALYSIS WAS TO EVALUATE HIGH
GRADE HPV TYPE ATTRIBUTIONS TO
CERVICAL TYPE TWO AMONG U.S.
WOMEN AGE 21 TO 39 WHO WERE
DIAGNOSED FROM 2008 THROUGH
2011.
AND WE ALSO WANTED TO EXAMINE
WHETHER HPV TYPE ATTRIBUTION
DIFFERED BY RACE AND ETHNICITY.
SO THESE DATA COME FROM THE HPV
IMPACT PROJECT, WHICH IS A
POPULATION BASED SURVEILLANCE
SYSTEM THAT WAS ESTABLISHED IN
2008 TO MONITOR HPV VACCINE
IMPACT ON HIGH GRADE CERVICAL
LESIONS AND HPV TYPES ASSOCIATED
WITH THEM.
THIS IS A CDC COLLABORATION WITH
FIVE EMERGING INFECTIONS SITES
AND IT INCLUDES SIMILAR SIZES
WITH ABOUT 300,000 WOMEN IN EACH
CATCHMENT, IN CALIFORNIA,
CONNECTICUT, NEW YORK, OREGON,
AND TENNESSEE.
AND EACH SITE ARE RATED AND
ASKED TO REPORT CONFIRMED IN 18
AND OLDER.
LABS ARE ALSO ASKED TO SUBMIT
ARCHIVE DIAGNOSTIC TISSUE FROM
WOMEN DIAGNOSED BEFORE THE AGE
OF 40 FOR HPV TYPING.
DEPENDING ON THE NUMBER OF WOMEN
WHO REPORTED AND RESOURCES
AVAILABLE, THE SITES REQUEST ALL
OR A RANDOM SAMPLE OF SPECIMENS
FROM WOMEN FROM EACH REPORTING
LAB, AND LABS ARE ASKED TO
SELECT TISSUE THAT'S MOST
REPRESENTATIVE OF THE DIAGNOSTIC
LESION AND TO CUT AND PROCESS
THE TISSUE ACCORDING TO STANDARD
PROTOCOL FOR SPECIMENS.
THEN THE PROCESS SPECIMENS ARE
SENT TO CDC AND HERE THEY ARE
REVIEWED AGAIN BY A PATHOLOGIST
TO ENSURE THE TISSUE IS ADEQUATE
FOR TYPING, AND IF IT IS, THEN
DNA IS EXTRACTED AND TESTED FOR
37 INDIVIDUAL HPV TYPES USING AN
ARRAY GENE TYPING.
AND FOR SPECIMENS NEGATIVE, THEY
ARE RETESTED USING A SECOND
GENOTYPING AND THAT REPRESENTS
THE 10% OF SPECIMENS OVERALL.
SO BETWEEN 2008 AND 2011, WE HAD
ADEQUATE TYPING RESULTS FOR OVER
5,000 SPECIMENS AND ALMOST ALL
OF THEM, 97%, WERE POSITIVE FOR
HPV AND ONLY A SINGLE TYPE WAS
DETECTED IN 79% OF THE
SPECIMENS.
HPV 16 AND 18 WAS DETECTED IN A
LITTLE OVER HALF OR 53% OF ALL
SPECIMENS, AND HPV 31, 33, 35,
52 AND 58 WERE DETECTED IN 31%
OF THE SPECIMENS OVERALL.
SO THESE ARE TYPING RESULTS
BROKEN OUT BY SEVERITY OF
LESION, WHICH IS THE LOWEST
GRADE, OR THE HIGHEST GRADE
LESION.
IT'S COMBINED BECAUSE OF SMALL
NUMBERS, BECAUSE IT REPRESENTS
LESS THAN 2% OF ALL THE REPORTED
CASES.
AND THERE'S ALSO ABOUT 900
SPECIMENS IN WHICH SPECIFIC
GRADE WAS NOT DISCRIMINATED AND
ARE NOT INCLUDED HERE IN THIS
TABLE, BUT DO REPRESENT THE TWO
GRADES, AND SOME THINGS TO NOTE
HERE IS THAT CIM TWO ACCOUNTS
FOR A LARGER FRACTION OF ALL
DIAGNOSES AND THAT 16 AND 18
TYPES ARE MORE COMMON IN CIN 3
COMPARED TO CIN 2, 63% VERSUS
40%, WHEREAS THE OTHER FIVE
ADDITIONAL TYPES IN THE
CANDIDATE VACCINE ARE MORE
COMMON IN CIN 2 THAN CIN 3 AND
AIS.
THIS GRAPH SHOWS THE P PREVALEN
OF INDIVIDUAL HPV TYPES BY HIS
LOGIC GREAT GRADE AND JUST TO
ORIENT YOU, THE BLUE BAR
INDICATE CIN 2, RED BARS ARE NOT
DISCRIMINATED AND ARE LABELED AS
FLASH THREE AND THE GREEN BARS
ARE CIN 3 OR AIS.
THE HPV TYPES ARE GROUPED ALONG
THE X AXIS, SO THE FIRST GROUP,
HPV 16 AND 18 AND WHAT'S NOTABLE
HERE IS THAT 16 IS DETECTED BY
FAR THE MOST DETECTED TYPE IN
ALL OF THE LESIONS, ALTHOUGH IT
DOES INCREASE FROM 35% IN CIN 2
LESIONS TO 60% IN CIN 3 AND AIS.
AND HPV 18 IS RELATIVELY
UNCOMMON AND ACCOUNTS FOR ABOUT
5% TO 6% OF LESIONS.
THEN THE NEXT SET OF TYPES ARE
THOSE IN THE CANDIDATE 9-VALENT
VACCINE AND HERE, HPV TYPE 31 IS
THE MOST COMMON, FOLLOWED BY HPV
TYPES 52 AND 58, WHICH ARE BOTH
MORE COMMON IN CIN 2 THAN CIN 3
AND 33 AND 35 WERE DETECTED IN
LESS THAN 5% OF SPECIMENS ACROSS
ALL HISTOLOGIC GRADES.
THE LAST SET ARE OTHER HIGH RISK
TYPES NOT INCLUDED IN ANY
VACCINE.
AND HERE YOU CAN SEE THAT TYPES
31 AND 55 ARE THE MOST COMMON.
AND THAT THE OTHER TYPES OCCUR
IN 5% OR LESS OF SPECIMENS
ACROSS ALL HISTOLOGIC GRADES.
SO FOR THE PURPOSE OF HPV TYPE
ATTRIBUTION FOR CERVICAL
LESIONS, USUALLY WHEN ONLY A
SINGLE HPV TYPE IS DETECTED IN A
LESION, THAT TYPE IS CONSIDERED
TO BE CAUSED ASSOCIATED WITH THE
LESION.
HOWEVER, MORE THAN ONE HPV TYPE
IS DETECTED IN ABOUT 20% OF CINC
PLUS LESIONS AND THE ROLE OF
EACH TYPE IN THE COINFECTED
LESIONS IS LESS CLEAR, SO
DIFFERENT METHODS ARE USED TO
ATTRIBUTE INDIVIDUAL HPV TYPE OR
GROUP OF TYPES TO CERVICAL
LESIONS AND THESE METHODS ARE
USED TO EVALUATE THE POTENTIAL
IMPACT OF HPV VACCINE.
SO IN THIS ANALYSIS, WE APPLIED
THE TWO MOST COMMON METHODS THAT
ARE USED FOR HPV TYPE
ATTRIBUTION.
THE FIRST IS HIERARCHICAL, WHICH
BASICALLY ASSIGNED ATTRIBUTION
TO THE MOST OCOGENIC TYPE IN A
LESION.
SO TO GIVE AN EXAMPLE, IF YOU
HAVE A CIN 3 SPECIMEN WITH HPV
16 AND 31 DETECTED IN THE
LESION, THE WHOLE SPECIMEN WOULD
BE ATTRIBUTED TO HPV 16.
SO THIS TEND TO OVERESTIMATES
BECAUSE THEY ARE THE MOST
OCOGENIC TYPES OF ALL THE HIGH
RISK TYPES.
THE SECOND METHOD IS THE
PROPORTIONAL ATTRIBUTION METHOD
AND WEIGHTS ARE ASSIGNED TO
FREQUENCY IN SINGLE INFECTIONS
IN EACH DISEASE GRADE, SO TO USE
THE SAME EXAMPLE, WE WOULD
CALCULATE THE PROPORTION OF EACH
TYPE THAT OCCUR AS A SINGLE
INFECTION IN THAT HISTOLOGIC
GRADE.
SO HERE IT WOULD BE 61% OF HPV
16 AND 9% FOR HPV 31, AND THEN
THAT IS DIVIDED BY THE SUM OF
THE TOTAL ATTRIBUTION OF ALL THE
TYPES IN THE LESIONS.
AND WE FOUND THAT THERE WAS A
LESS THAN 2% DIFFERENCE BETWEEN
THE TWO METHODS THAT WE APPLIED,
SO THE RESULTS I'M GOING TO BE
PRESENTING ARE BASED ON THE
PROPORTIONAL ATTRIBUTION METHOD.
OKAY.
SO HERE IS THE PROPORTIONAL TYPE
ATTRIBUTION BY HISTOLOGIC GRADE.
THE BLUE BARS, AGAIN, ARE CIN 2,
CIN 3, AND AIS.
THE LIGHTER PORTION OF EACH BAR
REPRESENTS LESIONS WITH SINGLE
TYPE INFECTION AND THE DARK PART
AT THE TOP IS MULTIPLE
INFECTIONS.
AND AS YOU CAN SEE, 38% OF CIN 2
LESIONS WERE ATTRIBUTABLE TO HPV
16 AND 18 TYPES AND THE PERCENT
ATTRIBUTION OF 16 AND 18
INCREASED WITH THE VARIETY OF
LESION UP TO 64% IN CIN 3 AND
AIS.
28% OF CIN 2 AND SLIGHTLY LESS
OF HIGHER GRADES WERE
ATTRIBUTABLE TO THE FIVE
ADDITIONAL TYPES IN THE
CANDIDATE VACCINE AND THE OTHER
HIGH RISK TYPE ATTRIBUTION
RANGED FROM 21% IN CIN 2 TO LESS
THAN 10% IN CIN 3 AND AIS.
SO THIS GRAPH SHOWS YOU THE
PROPORTIONAL HPV TYPE
ATTRIBUTION BY AGE GROUP, AND
HERE THE BARS REPRESENT THE
GROUPS OF HPV TYPES.
THE BLUE BARS ARE 16 AND 18, THE
RED BARS ARE THE FIVE ADDITIONAL
TYPES, AND THE GREEN BARS ARE
THE OTHER HIGH RISK TYPES.
AND AS YOU CAN SEE, HPV TYPE 16
AND 18 ARE ATTRIBUTABLE TO THE
HIGHEST PROPORTION OF LESIONS
ACROSS ALL AGE GROUPS, HOWEVER,
THERE IS A DECLINE IN THE
PROPORTION OF HPV 16 AND 18 IN
THE OLDEST AGE GROUP, AND IN
THAT GROUP, WE SEE AN INCREASE
IN THE FIVE ADDITIONAL TYPES.
AS FAR AS THE OTHER HIGH RISK
ATTRIBUTIONS, IT'S FAIRLY
SIMILAR ACROSS ALL AGE
CATEGORIES.
THIS GRAPH IS SIMILAR TO THE
PREVIOUS ONE, EXCEPT THAT THIS
IS PROPORTIONAL TYPE ATTRIBUTION
DONE BY RACE AND ETHNICITY.
AGAIN, I WANT TO POINT YOUR --
BRING YOUR ATTENTION TO THE FACT
THAT HPV 16 AND 18 ARE
ATTRIBUTABLE TO THE HIGHEST
PROPORTION OF LESIONS ACROSS ALL
RACIAL AND ETHNIC GROUPS,
HOWEVER, HPV 16 AND 18
ATTRIBUTION IS HIGHER AMONG
NONHISPANIC WHITES, COMPARED TO
THE OTHER RACE AND ETHNIC
GROUPS.
CONVERSELY, THE FIVE ADDITIONAL
TYPES ARE MORE COMMON IN RACIAL
AND ETHNIC MINORITIES COMPARED
TO NONHISPANIC WHITES.
AND THE OTHER HIGH RISK TYPES
ARE SIGNIFICANTLY HIGHER IN
NONHISPANIC BLACKS COMPARED TO
THE OTHER RACIAL AND ETHNIC
GROUPS.
SO THE PREVIOUS SLIDES SHOWED
YOU ATTRIBUTION BY GROUPS OF
TYPES, AND HERE YOU CAN SEE
BROKEN UP BY INDIVIDUAL TYPES,
AGAIN, BY RACE AND ETHNICITY,
AGAIN, I WANT TO POINT OUT THAT
HPV 16 IS THE PREDOMINANT TYPE
ACROSS ALL RACIAL AND ETHNIC
GROUPS.
IT IS HIGHER IN NONHISPANIC
WHITES COMPARED TO THE
NONHISPANIC BLACKS.
HPV 45, 52, AND 58 WERE
SIGNIFICANTLY DIFFERENT BY RACE
AND ETHNICITY AMONG THOSE THAT
ARE IN THE CANDIDATE 9-VALENT
VACCINE, AND THEN THE LAST TWO
TYPES ON THIS GRAPH ARE THOSE
THAT OCCURRED IN AT LEAST 5% OF
LESIONS IN AT LEAST ONE OF THE
RACIAL AND ETHNIC GROUPS, AND
YOU CAN SEE THAT HPV 35 HERE IS
SIGNIFICANTLY HIGHER IN
NONHISPANIC BLACKS COMPARED TO
THE OTHER TWO GROUPS.
SO, IN SUMMARY, THESE DATA FROM
A LARGE POPULATION BASED SAMPLE
OF WOMEN IN THE U.S. SHOWED THAT
50% OF LESIONS ARE ATTRIBUTABLE
TO HPV 16 AND 18, AND THE
ATTRIBUTION RANGES FROM 40% IN
CIN 2 LESIONS TO OVER 60% IN CIN
3 AND AIS.
ANOTHER 25% OF CIN 2 PLUS
LESIONS ARE ATTRIBUTABLE TO HPV
31, 33, 35, 52, AND 58, WHICH
ARE INCLUDED IN THE CANDIDATE
NINE VALENT VACCINE.
WE FOUND THAT THERE WAS A HIGHER
PROPORTION OF LESIONS DUE TO HPV
16 AND 18 IN WOMEN WHO WERE
UNDER THE AGE OF 35, AND THIS IS
CONSISTENT WITH EVIDENCE THAT
INDICATES HPV 16 AND 18 ARE
STRONGER CARCINOGENS AND MORE
LIKELY TO PROGRESS FASTER TO
DISEASE.
WE ALSO FOUND THAT THE HIGHEST
PROPORTION OF CIN 2 LESIONS WERE
ATTRIBUTABLE TO HPV 16 AND 18,
IRRESPECTIVE OF RACIAL AND
ETHNIC CATEGORY, HOWEVER, THERE
WAS A HIGHER PROPORTION OF
LESIONS ATTRIBUTABLE TO 16 AND
18 IN NONHISPANIC WHITE WOMEN
COMPARED TO OTHER RACIAL AND
ETHNIC GROUPS.
AND THE REASONS FOR THESE
DIFFERENCES ARE NOT CLEAR AND
PROBABLY MULTIFACTORIAL, BUT MAY
BE DUE TO DIFFERENCES IN THE
UNDERLYING PREVALENCE OF HPV
INFECTION AND THE DIFFERENT SUB
POPULATION OR TO DIFFERENCES IN
SCREENING AND TREATMENT.
THANK YOU.
THANK YOU MUCH.
WE'RE GOING TO HOLD A COMMENT
AND QUESTION UNTIL AFTER THE
NEXT PRESENTATION BY
DR. SARAIYA.
>> GOOD MORNING.
THE OTHER WAY?
GOOD MORNING.
BEFORE I START TALKING ABOUT
ATTRIBUTION, I WANTED TO REVIEW
THESE DATA FROM THE ANNUAL
REPORT TO THE NATION PUBLISHED
LAST YEAR SHOWING THE INCIDENCE
RATE OF CERVICAL, VAGINAL
CANCERS.
THE ORANGE BAR REPRESENTS ALL
RACE ETHNICITY AND THE TEAL BAR,
HISPANIC AND THE PURPLE BAR
BLACK AND SO ON, AND I WANTED TO
SHOW THE BLACK WOMEN AND
HISPANIC WOMEN HAVE THE HIGHEST
RATE OF CERVICAL CANCER AND
BLACK WOMEN ALSO HAVE THE
HIGHEST RATE OF VAGINAL CANCER.
THE RATE OF ORAL AND ANAL
CANCERS BY RACE ARE SEEN HERE,
AND HERE WHAT I WANT TO POINT
OUT IS BLACK MALES AND FEMALES,
AS NOTED BY THE PURPLE BAR, HAVE
THE SECOND HIGHEST RATE OF ORAL
CANCER AND FOR ANAL CANCER,
BLACK MALES HAVE THE HIGHEST
RATE.
THESE ARE INTERNATIONAL DATA
ARCHIVED CERVICAL CANCER
SPECIMENS, INVASIVE CERVICAL
CANCER SPECIMENS COLLECTED ALL
AROUND THE WORLD AND TYPED BY
ONE LAB AND THE ADDITIONAL TYPES
AND THE CANDIDATE 9-VALENT HPV
VACCINE, AND THE TITLE IS CALLED
"RELATIVE CONTRIBUTION," BECAUS
HPV-POSITIVE CANCERS AND WHEN
THE DENOMINATOR DATA IS AMONG
ALL CANCERS, THE TERMINOLOGY
USED IS ATTRIBUTION.
IMPORTANT ISSUES TO HIGHLIGHT
HERE ARE THE MAJORITY OF
CANCERS, WHETHER THEY ARE IN
IA, OR EUROPE, HAVE
16, 18, USUALLY IN THE RANGE OF
AROUND 70% AND AN ADDITION
TO 20% HAVE CONTRIBUTION BY THE
OTHER FIVE TYPES.
THE OTHER THING I WANTED TO
POINT OUT HERE WAS THAT THERE
HAVE ASES THAT
HAVE BEEN ANALYZED IN NORTH
AMERICA, AROUND 160, FROM THIS
COMPARATIVE STUDY AND THAT'S WHY
WE UNDERTOOK THE CDC STUDY I
WILL DESCRIBE LATER.
THE SAME GROUP THAT DID THIS
PARTICULAR STUDY HAS ALSO
CONDUCTED RELATIVE CONTRIBUTIONS
FOR OTHER CANCERS, BUT MOST OF
THOSE DATA ARE NOT AVAILABLE.
THIS SLIDE SUMMARIZES LITERATURE
FROM U.S. STUDIES PRIOR TO 2006
THAT HAVE EXAMINED TISSUES FROM
THESE PARTICULAR CANCERS AND
ATTRIBUTED THEM TO HPV.
SO THE FIRST COLUMN SUMMARIZES
THE ATTRIBUTION TO ANY HPV AND
THE SECOND COLUMN SUMMARIZES
ATTRIBUTION TO 16 AND 18, SO FOR
CERVICAL, FOR EXAMPLE, USING 96%
WAS ATTRIBUTABLE TO HPV AND
AMONG ALL CERVICAL CANCERS, 76%
WERE ATTRIBUTABLE TO 16, 18, AND
FOR VAGINAL, 64% FOR ANY HPV AND
56% TO 16, 18.
THE OBJECTIVE OF THIS PARTICULAR
ANALYSIS WERE TO ESTABLISH
SYSTEMIC POPULATION BASED
APPROACH TO MONITORING THE HPV
TYPES AND CERVICAL, AS WELL AS
OTHER HPV ASSOCIATED CANCERS AND
TO DETERMINE THE ATTRIBUTION OF
16, 18, AND ADDITIONAL TYPES IN
THE CANDIDATE 9-VALENT VACCINE
AND SEE IF THERE WERE
DIFFERENCES BY RACE ETHNICITY.
SO THE STUDY, BASICALLY, WE USED
CANCER CASES THAT WERE
IDENTIFIED THROUGH CANCER
REGISTRIES MOST OF WHICH
COLLECTED FROM 2004 TO '05,
RIGHT BEFORE THE VACCINE WAS
LICENSED TO HELP US GET A BASE
LINE.
THE REGISTRIES HAVE INFORMATION
ABOUT THE CANCER DIAGNOSIS, BUT
IN ORDER TO GET THE ACTUAL
TISSUE SPECIMEN FOR THE CANCER
REGISTRIES, WENT TO PATHOLOGY
LABS AND THREE HAD EXISTING
REPOSITORY.
MOST OF THE CANCERS THAT WERE
COLLECTED WERE INVASIVE CANCERS,
BUT WE DID HAVE A FEW CANCERS
LIKE CERVICAL INSITU, BECAUSE OF
REGISTRIES HAD THE LEGAL
AUTHORITY TO COLLECT THESE DATA.
THE HPV GENOTYPING WAS DONE BY
THE CDCSUSAN
HARI
HARIRI.
THE ADDITIONAL FIVE TYPES AND
THE VALENT VACCINE, ANY OTHER
HPV TYPES AND HPV NEGATIVES, AND
THE DENOMINATOR INCLUDED ALL
CANCERS.
THIS FIGURE IS A SCHEMATIC OF
THE TISSUE SAMPLE REQUEST AND
SUBMISSION PROCESS, SO ON THE
LEFT-HAND SIDE, THE FOUR CANCER
REGISTRY, LOUISIANA, CALIFORNIA,
KENTUCKY, GENERATED ELIGIBLE
CANCER CASES, SAMPLE THEM, THEN
REQUESTED THE LOCAL HOSPITAL
PREPARE SEND TO H THE TISSUE
THE CDC HPV LAB.
ON THE -- ON THE RIGHT-HAND SIDE
WHAT YOU SEE IS HAWAII, IOWA,
AND LOS ANGELES COUNTY.
WHAT THEY DID WAS THEY ALREADY
HAD EXISTING TISSUE
REPOSITORIES, SO THEY PREPARED
THE SAMPLE AND THE TISSUE IN
HOUSE AND SENT THEM DIRECTLY TO
THE CDC HPV LAB.
AND IN THE PATH LAB, THE TISSUE
SPECIMENS WERE PREPARED
ACCORDING TO A COMMON STANDARD
PROTOCOL AND THE COMPLETE
RESULTS WERE LINKED WITH THE
DEMOGRAPHIC DATA COLLECTED BY
EACH OF THE CANCER REGISTRIES,
AND SO WE HAD 3,017 TISSUE
SPECIMENS THAT MADE IT TO THE
CDC HPV LAB AND DUE TO EITHER
SPECIMEN INADEQUACY OR OTHER
ISSUES, WE HAD A FINAL SAMPLE OF
2,670 CANCERS.
THIS SLIDE SHOWS THAT PERCENT
HPV DETECTION BY CANCER SITE, SO
IN THE STUDY, YOU ALSO SEE THE
NUMBER OF CANCER CASES FOR EACH
OF THE SITES.
91% HAD HPV OF CERVICAL CANCERS
HAD HPV DNA DETECTED.
99% OF CERVICAL CANCER, 69% OF
BULVAR CANCERS HAD HPV DETECTED,
75% FOR VAGINAL CANCERS, 91% FOR
ANAL, 61% FOR PENILE.
THIS SHOWS THE TOP FIVE CANCER
TYPES AND THE SLIDE MIGHT BE
DIFFICULT TO SEE IN TERMS OF THE
SPECIFIC TYPES, BUT THE BIG,
BROAD PICTURE IS HPV 16 IS THE
MOST COMMON TYPE IN ALL OF THESE
CANCERS.
AND I WILL GO OVER THESE CANCERS
IN A LITTLE BIT MORE DETAIL.
HERE WE HAVE ATTRIBUTION BY THE
FOUR HPV GROUPS, BLUE BEING 16,
18, AND YELLOW THE ADDITIONAL
FIVE TYPES AND THE CANDIDATE
VACCINE, GREEN BEING OTHER HPV
TYPES, AND GRAY, HPV NEGATIVE.
SO FOR CERVICAL CANCER, YOU SEE
66% OF THE CANCERS HAD 16, 18,
ATTRIBUTED TO 16, 18, ADDITIONAL
15% ATTRIBUTED TO THE CANDIDATE
OF THE FIVE TYPES IN THE
CANDIDATE VACCINE, 10% FOR OTHER
TYPES, AND 9% WERE NEGATIVE.
SO ANAL CANCER HAS THE HIGHEST
PROPORTION OF 16, 18 DETECTED
AND FOR THE ADDITIONAL FIVE
TYPES AND THE CANDIDATE VACCINE,
THE CANCERS WITH THE HIGHEST
ATTRIBUTION WERE CERVICAL
CANCERS, VAGINAL, AND VULVAR
CANCERS.
SO WE CONDUCTED LOTS OF ANALYSES
AND THE GENERAL FINDINGS, WHICH
WE'LL GO INTO MORE DETAIL, WERE
BY AGE, THERE WAS DEFINITELY A
HIGHER PROPORTION OF CANCERS IN
YOUNGER AGE ATTRIBUTABLE BY RACE
ETHNICITY, THERE WAS NO
SIGNIFICANCE EXCEPT THE CERVICAL
CANCERS AND ORAL CANCERS AND BY
GENDER, NO DIFFERENCE EXCEPT FOR
ORAL CANCER.
THIS SLIDE LOOKS AT THE
ATTRIBUTION BY RACE ETHNICITY
FOR INVASIVE CERVICAL CANCER ON
TOP AND INSITU CERVICAL CANCER
ON BOTTOM.
AND THERE ARE DIFFERENCES IN
TERMS OF A LOWER PROPORTION
OF -- LOWER PROPORTION OF 16,
18.
LOWER PROPORTION OF 16, 18, FOR
BLACK -- AMONG BLACK,
NONHISPANIC POPULATION, AS WELL
AS LOWER PROPORTION AMONG
HISPANIC POPULATION.
SO THIS PATTERN IS SIMILAR TO
WHAT WAS SEEN BY HARIRI, BUT WE
HAVE TO KEEP IN MIND FOR INSITU
CERVICAL CANCERS, WE HAD A LOWER
NUMBER OF SAMPLES.
BUT WE HAVE A PRETTY GOOD SAMPLE
SIZE HERE, WHAT YOU SEE IS HPV
NEGATIVE PROPORTION WAS LOWER
AMONG BLACKS AND HISPANICS THAN
WHITES, BUT MORE IMPORTANTLY,
THERE WERE NO DIFFERENCES IN THE
PROPORTIONS OF 16 AND 18.
67%, 68%, AND 64%, OF THE
DIFFERENT RACIAL ETHNIC GROUPS.
MANY OF YOU MIGHT ASK HOW CAN
CERVICAL CANCERS BE NEGATIVE?
WE HAVE THIS PREVIOUS STUDY
THAT'S FOUND 99.7% TO BE HPV
POSITIVE, BUT WE HAVE TO KEEP IN
MIND THAT THE STUDY WAS BASED ON
MULTIPLE HPVS THAT WERE DONE AND
CANCERS THAT MATCHED SELECT
CRITERIA AND WHAT WE'RE DOING IS
A POPULATION BASED SURVEILLANCE
STUDY.
THERE MAY BE MISCALCULATION OF
THE ANATOMIC SITE IN THAT THE
LOWER SEGMENT UTERINE CANCERS
CANNOT BE DISTINGUISHED FROM THE
UPPERS, THERE MAY BE FALSE
NEGATIVES IN THERE IS HPV, BUT
WE CAN'T DETECT IT OR THE
SPECIMEN AND TISSUE IS NOT WELL
PRESERVED, THEN THERE ARE
ACTUALLY TRUE HPV NEGATIVE HPV
NEGATIVE CERVICAL CANCERS ALBEIT
THE RARE HISTOLOGY 1% TO 2% AT
THE MOST.
THIS SLIDE LOOKS AT ANAL
CANCERS.
HERE ON THE LEFT-HAND SIDE WHAT
YOU SEE THERE'S NOT MANY
DIFFERENCES BY RACE ETHNICITY
FOR 16/18 ATTRIBUTION ABOUT 80%
IS ATTRIBUTED.
BY AGAINER ON THE RIGHT-HAND
SIDE THERE ARE NO DIFFERENCES,
79% COMPARED TO 80% AMONG
FEMALES.
ALTHOUGH IT APPEARS THAT FEMALES
MAY HAVE A HIGHER PERCENTAGE OF
THE ADDITIONAL FIVE TIMES THAN
THE CANDIDATE VACCINE THIS
DIFFERENCE WAS NOT SIGNIFICANT.
THIS IS OROPHARYNGEAL CANCER, AN
HPV ATTRIBUTION.
ON THE LEFT-HAND SIDE WHAT WE
SEE IS THE RACE FOR 16/18 WHAT
WE SEE IS THAT THERE'S A HIGHER
PERCENTAGE OF NEGATIVE CANCERS
FOR BLACKS.
50% COMPARED TO 25% TO 27% FOR
WISE AND HISPANICS AND A LOWER
PROPORTION OF 16/18 CANCERS
OVERALL AMONG BLOCKS EVEN WHEN
THE CANCER ARE LIMITED TO HPV
POSITIVE CANCERS.
BY AGAINER HIGHER PROPORTION OF
HPV NEGATIVE CANCERS AMONG
FEMALE AND LOWER PROPORTION OF
HPV 16/18 CANCERS AS WELL.
SO IF WE USE THE DATA FROM THIS
PARTICULAR STUDY AND REVISED OUR
ESTIMATED PERCENTAGES, WE CAN
DEFINITELY SAY WITH MORE
AUTHORITY THAN POPULATION BASED
THAT OUR ATTRIBUTION RATE FOR
POSITIVITY WOULD BE SLIGHTLY
REVISED FOR CERVICAL WE SEE 91%
WITH HPV ATTRIBUTES.
61% THE CERVICAL CANCER 58% AND
15% FOR THE ADDITIONAL.
ON THE SAME NOTE LIKE FOR
EXAMPLE FOR OROPHARYNGEAL, FOR
MALES 72% WOULD BE HPV
ATTRIBUTABLE AND 63% FOR 16/18
AND 4% OF THE NINE TIMES
VACCINE.
62% OF INVASIVE CANCERS ARE
ATTRIBUTABLE TO 16/18.
THIS RANGES FROM PENILE AND ANAL
CANCERS AND WHEN YOU LOOK AT IT
BY GENDER 62% OF IF HE MALES
ATTRIBUTABLE TO 16/18 COMPARED
TO MALES.
THIS TRANSLAYS TO 25,000 CASES
ANNUALLY.
11% OF THE INVASIVE CANCERS ARE
ATTRIBUTABLE TO THE ADDITIONAL
FIVE TIMES.
THIS RANGES BASED ON THE CANCER
TYPE 6% FOR OROPHARYNGEAL AND
18% FOR VAGINAL.
DIFFERENCE BY AGAIN GENDER.
FOR RACIAL ETHNIC DIFFERENCES
THE ATTRIBUTION IT WAS
ATTRIBUTABLE TO HPV POSITIVE OR
HPV 16/18 AMONG BLACKS.
THIS DATA WILL BE USEFUL IN
ESTIMATING THE CANDIDATE VACCINE
ON CANCERS AS WELL AS COST
EFFECTIVE ANALYSIS.
I WOULD LIKE TO ACKNOWLEDGE THE
CO-AUTHORS FOR THIS PARTICULAR
STUDY AS WELL AS THIS
PRESENTATION.
>> THANK YOU.
I THINK WE'RE OPEN FOR
QUESTIONS.
VERY HELPFUL PRESENTATION.
SUSAN I THINK YOU KNOW I'M A BIG
FAN OF THE IMPACT STUDIES BUT I
WONDER IF I UNDERSTAND CORRECTLY
THE CASES THAT YOU ARE LOOKING
AT HERE, THEY SPAN A TIME RANGE
OF BEFORE AND AFTER WHEN THE
VACCINE WAS BEING USED AND GIVEN
WHAT WE KNOW ABOUT COVERAGE
WHICH WAS GIVEN LOW, I'M
WONDERING WHETHER WE MIGHT BE
UNDERESTIMATING THE AMOUNT WE
CAN ATTRIBUTE TO AND 18 IF
WE'RE INCLUDING IN THE STUDIES
SOME OF THE CASES OCCURR
BASICALLY AFTER THE VACCINE IS
ALREADY BEING UTILIZED OR IF YOU
THINK THAT'S AN ISSUE OR NOT.
SURE, THAT'S QUITE POSSIBLE
FOR THAT.
THANK YOU FOR THAT COMMENT.
AS YOU KNOW, WITHIN HPV PROJECT
ONE OF THE THINGS THAT WE TRY TO
DO IS COLLECT HPV VACCINATION
HISTORY ON ALL THE CASES AND WE
CAN'T, SOMETIMES CAN'T FIND HPV
VACCINATION HISTORY ON EVERYBODY
BUT WE DO HAVE VACCINATION
HISTORY ON ABOUT 50% OF THE
CASES, AND AMONG THOSE THAT WE
HAD VACCINATION HISTORY FOR
THERE WAS A PRETTY SIZABLE
PROPORTION IN THE 18 TO
20-YEAR-OLD FEMALES.
AND I DID NOT PRESENT THAT DATA
HERE.
I ACTUALLY EXCLUDED THOSE.
THERE WERE A FEW IN THE 21 TO
29-YEAR-OLD GROUP BUT WHEN WE
EXCLUDED THOSE FROM THE ANALYSIS
IT DIDN'T SIGNIFICANTLY CHANGE
THE RESULTS.
SO, IT'S POSSIBLE THAT THERE IS
SOME IMPACT, BUT BECAUSE WE
DON'T HAVE, YOU KNOW,
VACCINATION HISTORY ON 50% OF
THE CASES, IT'S REALLY HARD TO
KEEP THAT APART.
THANK YOU VERY MUCH FOR THIS
PRESENTATION.
I WONDER IF YOU COULD REMIND US
ABOUT COST PROTECTION AGAINST
NON16/18 FROM THE VACCINES WHICH
TYPES MIGHT THERE BE PROTECTION
AGAINST AND DO THE VACCINES
DIFFER IN THEIR ABILITY TO DO
THAT?
>> SO, THERE HAS BEEN SOME CROSS
PROTECTION SHOWN FOR BOTH
VACCINES, MOSTLY IN TYPE 31, 33
AND 45, AND I THINK THE CROSS
PROTECTION HAS BEEN A LITTLE BIT
STRONGER FOR THE VACCINE
ALTHOUGH IT'S DIFFICULT TO
COMPARE THE TWO VACCINES
HEAD-TO-HEAD.
SO, YES, THERE'S SOME CROSS
PROTECTION THAT'S BEEN
DEMONSTRATED, THE DURATION OF
PROTECTION IS UNKNOWN.
BUT, YEAH.
THERE DOES SEEM TO BE SOME CROSS
PROTECTION.
>> CAROL HAYES WITH AMA.
DR. HARIRI I HAD A QUESTION
RELATED TO YOUR SLIGHT 17 AND
11.
YOU MAY NOT BE ABLE TO ANSWER
THE QUESTION WHEN I LOOK AT THE
DATA IT APPEARED TO ME THERE
WERE TWO STRAINS OF HPV THAT
SEEM TO BE HIGHER THAN THE ONES
USED IN THE NEW 9-VALENT VACCINE
AND I'M CONFUSED BY THAT.
THE ONES OVER ON THE RIGHT YOU
CAN SEE THAT 51 AND 35 ARE
HIGHER THAN 33 AND 45.
SO WHY WERE 35 AND 51 NOT
INCLUDED IN THE VACCINE AND WHY
WAS 33 AND 45?
I'M NOT SURE THAT I CAN
REALLY ANSWER THAT QUESTION.
ONE THING THAT I WANT TO POINT
OUT, THOUGH, IS THAT THIS
PREVALENCE IS VERY LOW COMPARED
TO TYPE 16 ACROSS THE BOARD FOR
ALL OF THE TYPES AND YOU'RE
RIGHT THAT 35 AND 51 ARE MORE
COMMON BUT THAT'S MOSTLY IN THE
CIN2 LESIONS WHICH ARE KIND OF A
LOWER HISTOLOGIC RATE AND ARE
PROBABLY NOT THE TRUE
PRE-CANCERS.
THE PREVALENCE IS SIGNIFICANTLY
LOWER IN THE CIN3 AND AIS
LESIONS.
BUT AS FAR AS, YOU KNOW, THE
DECISION TO -- WHICH TYPES TO
INCLUDE IN THE VACCINE I CAN'T
REALLY SPEAK TO THAT.
AND JUST TO -- THESE ARE
PRE-CANCERS AND MOST OF THE
DECISIONS ARE BASED ON TYPE OF
CANCE ARE
LESS LIKELY TO PRODUCE CANCERS
THAN 16 AND 18?
[ INAUDIBLE ]
THEY ARE IN THE CURRENT
VACCINE.
THERE'S A LITTLE BIT OF A
DIFFERENCE BETWEEN THE U.S. DATA
SHOWN HERE AND THE GLOBAL RATE.
>> THANK YOU.
DR. BENNETT.
>> THANK YOU.
THANK YOU FOR THIS GREAT
PRESENTATION.
IT'S TERRIFIC.
I'M INTERESTED IN THE RACIAL
DIFFERENCES.
COULD YOU REMIND US WHAT WAS
SHOWN IN THE CARRIAGE DATA WHICH
FROM THE NA SURVEY WHAT THE
RACIAL DIFFERENCES IN THOSE AT
THAT TIME AS WELL?
SO, WE CAN ACTUALLY MONITOR
HPV PREVALENCE USING THE
NATIONAL HEALTH AND NUTRITION
EXAMINATION SURVEY WHICH IS THE
NATIONAL SURVEY OF THE
NON-INSTITUTIONALIZED U.S.
POPULATION.
WE LOOKED AT HPV TYPE PREVALENCE
OVER TIME AND, YES, IT'S TRUE
THAT THERE ARE RACIAL
DIFFERENCES, BUT MOSTLY THE
DIFFERENCES ARE THAT THERE'S A
HIGHER PREVALENCE OF TYPES, OF
ALL TYPES IN NON-HISPANIC BLACKS
COMPARED TO NON-HISPANIC WHITES.
AND WE'RE SORT OF -- WE'RE IN
THE PROCESS LOOKING AT THE DATA
MORE CLOSELY BUT THERE DOESN'T
SEEM TO BE A DIFFERENTIAL
INCREASE OR DECREASE IN THE
PREVALENCE OF THE TYPES OF 16
AND 18.
SO IT'S JUST HIGHER FOR ALL THE
TYPES.
WE'RE LOOKING AT THAT DATA NOW.
>> SO, YOU HAVE ANY THOUGHTS
ABOUT WHY WE WOULD FIND THAT
PATTERN IN THE EARLY LESIONS AND
IT SOUNDS LIKE NOT IN THE
EITHER --
DIFFERENCES IN 16 AND 18?
>> YEAH.
AS I SAID 16 AND 18 ARE MORE
OF MORE ONCOGENIC POTENTIAL THAN
THE OTHER TYPES.
AS YOU SAW IN DR. SARAIYA'S
PRESENTATION WE DON'T SOME ANY
DIFFERENCE IN RACE WHEN WE LOOK
AT CANCERS AND LESIONS.
YOU KNOW, LIKE I SAY, IT'S
REALLY -- WE'RE NOT REALLY SURE
WHAT ATTRIBUTES THE DIFFERENCE,
RACIAL DIFFERENCES TO BUT IT
COULD HAVE SOMETHING TO DO WITH
THE PREVALENCE COMBINED WITH THE
DIFFERENTIAL ONCOGENIC
DIFFERENCES OF THE TYPE BUT
THAT'S SOMETHING THAT NEEDS BE
FURTHER INVESTIGATED.
>> ANY OTHER COMMENT OR
QUESTIONS?
ALL RIGHT.
THANK YOU.
I GUESS WE MOVE ALONG TO THE
PRESENTATION FROM DR.
LUXEMBOURG.
GOOD MORNING, EVERYONE. IN O
OF LAST YEAR.
AND THIS TIME WE ARE GOING TO
SHOW YOU SOME OF THE KEY DATA
FROM THE PROGRAM.
JUST A FEW ABBREVIATIONS FOR
EVERYONE TO BE ON THE SAME PAGA
HERE.
SO WE TALK ABOUT 2 HPV VACCINE
ONE IS 9-VALENT VACCINE WHICH IS
THE INVESTIGATIONAL VACCINE AND
9 VH HPV AND LICENSED VACCINE IS
QHPV.
GENITAL LESIONS THAT WE TALK
ABOUT HAVE ALSO BEEN MENTIONED.
CIN, CERVICAL.
VIN, VUL SAR INTRAEPITHE LYNCH
AL.
VEIN VAGINAL INTRAEPITHELIAL.
GRADE 2/3 HIGH GRADE LESION,
PRE-CANCER.
A FEW SLIDES.
EXISTING VACCINE COVERS 70%
OF CANCERS WORLDWIDE.
NEXT MOST FREQUENT TYPES WITH
POTENTIAL TO REACH 90%
PREVENTION.
SO TO ANSWER THE QUESTION THAT
WAS ASKED PREVIOUSLY, FIVE NEW
TYPES WAS THE FREQUENCY IN
CANCER, NOT IN PRE-CANCER AND
DYSPLASIA AND CANCER WORLDWIDE.
THE FIVE TYPES THAT ONCOGENIC
REPRESENT TYPE TO 6% TOTAL
CANCER WORLDWIDE.
LOOKING NOW AT PRE-CANCERS,
AGAIN WORLDWIDE, THERE IS ALSO A
POTENTIAL FOR ADDITIONAL
COVERAGE WITH THE NEW TYPES.
AND ESPECIALLY THE PRE-CANCERS
THERE'S A POTENTIAL TO INCREASE
PROTECTION FROM 50% WITH THE
VACCINE TO 80%.
WHICH EXCEEDS THE BEST CERVICAL
CANCER SCREENING PROGRAMS.
IT'S AN EXCITING POSSIBILITY.
AS YOU CAN SEE CONTRIBUTION IN
CANCER IS SLIGHTLY LOWER THAN IN
PRE-CANCER, AND MOST LIKELY DUE
TO A FASTER PROGRESSION OF
CANCER WITH TYPE 16 AND 18 AS
WAS DISCUSSED BEFORE.
SO, YOU KNOW, THE POTENTIAL, YOU
KNOW, IN THE PREVIOUS SLIDE, THE
POTENTIAL IS NOT ONLY PREVENTION
OF CANCER WORLDWIDE BUT ALSO
POTENTIAL OF PREVENTION OF
PRE-CANCER LESION WHICH MEANS IN
COUNTRIES WHICH CERVICAL CANCER
SCREENING PROGRAM, LOWER NEED
FOR INVASIVE PROCEDURES BECAUSE
THESE PRE-CANCER CELLS ARE
TREATED BY SURGERY.
LOWER COST, LOWER HEALTH CARE,
BETTER QUALITY OF LIFE, LOWER
RISK.
THEY ARE A WIDE RANGE OF BENEFIT
THAT COULD BE INCUBATED.
ON THIS SLIDE YOU SEE THE
VACCINE, IT'S AN LPV VACCINE.
IT LOOKS LIKE A VIRUS.
OUTSIDE IT LOOKS LIKE A VIRUS,
IT IS SEEN AS A VIRUS.
IT CONTAINS TYPES 6 AND 11 WHICH
ACCOUNT FOR 60% OF THE GENITAL
WARTS AND BENIGN LESIONS.
16 AND 18 RESPONSIBLE FOR MOST
CERVICAL CANCERS.
THE INTERVENTION IS THE SAME.
THE AMOUNT HAS BEEN INCREASED TO
KEEP IT TO 20 RATIO THE SAME AND
AMOUNT OF ANTIGEN FOR THE
ORIGINAL TYPES HAS ALSO BEEN
INCREASED TO PRESERVE IT.
THE GOAL IS TO TRANSFER FROM
FOUR TO NINE VALENT.
IT WAS DESIGNED TO ASSESS THAT.
THE GOAL IS TO SHOW FOUR
ORIGINAL TYPES, THE TWO VACCINES
ARE THE SAME.
WE WANT TO TRANSITION FULLY.
WE WANT THE VACCINE TO DO THE
SAME AS THE ORIGINAL VACCINE.
IN ADDITION FOR THE NEW
ADDITIONAL TYPES WE WOULD LIKE
TO DEMONSTRATE THAT THE NEW
VACCINE PROVIDES SUBSTANTIAL
BENEFIT, WHICH MEANS IT'S HIGHLY
PRODUCTIVE AGAINST INFECTION DUE
TO ADDITIONAL TYPES.
THIS IS THE TARGET POPULATION.
HOWEVER WE CANNOT ASSESS BECAUSE
THEY ARE NOT EXPOSED TO HPV MOST
OF THEM AND SO SIMILAR TO WHAT
WAS DONE IN THE VALENT PROGRAM,
THE FINDINGS IN YOUNG WOMEN
EXPOSED TO HPV WILL BE EXTENDED
BASED ON ETHNICITY.
THE PROGRAM IS DESIGNED TO
DEMONSTRATE THAT.
FINALLY OBVIOUSLY WE WANT TO
DEMONSTRATE THE SAFETY
TOLERABILITY IS ACCEPTABLE.
IT WOULD SHINE OUR MINDS THAT.
THIS IS DONE WITH SIX STUDIES
WHICH ARE INCLUDED IN THE
INITIAL FINDING.
ON THIS SLIDE YOU HAVE THE THREE
STUDIES THAT SUPPORT THE KEY
INDICATION, WE HOPE.
AND THE STUDY RESULTS WILL BE
PRESENTED TODAY.
ONE IS THE PROGRAM IN YOUNG
WOMEN.
STUDIES COMPLETED AND THE
EXTENSION IS ON GOING TO ASSESS
LONG TERM EFFECTIVENESS.
AS I MENTIONED WE CONDUCTED
IMMUNOBRIDGING STUDY.ED STUDY I
EXTENSION IS ON GOING FOR TEN
YEARS OR SO TO ASSESS LONG TERM
EFFECTIVENESS.
PROTOCOL NINE IS TO ASSESS
WHETHER THERE'S A VALENT IN THE
SAME ETHNICITY.
NEXT SLIDE IS GOING TO SHOW
STUDIES, THE THREE MOST STUDIES
WE INCLUDED IN THE INITIAL
FINDINGS AND WILL BE PRESENTING
THAT AT THE NEXT HPV MEETING.
SEEN TWO VACCINES THAT ARE
COMMONLY USED AND WITH 9-VALENT.
FIVE ADDRESSES THE VACCINE AND
VACCINE COMMONLY USED IN
AMERICAS.
AND SEVEN REPRESENTS REPEVAX
COMMONLY USED IN THE EUROPEAN
UNION.
AND FINALLY THERE'S ONE STUDY
THAT YOU NEED, WHICH IS TO
ASSESS THE VACCINES, THE
9-VALENT VACCINE HPV RECIPIENTS.
AMONG THEM EVEN A SMALL FRACTION
IS INTERESTED IN VACCINATION
WITH 9-VALENT, WE FEEL OBLIGED
TO PROVIDE DATA AND YOU CAN MAKE
THE CHOICE.
WE LOOK FOR AN INDICATION IN
THAT CASE BUT FEEL IT'S
IMPORTANT TO DISCUSS.
AND FINALLY YOU COULD ASK THE
YOUNG MEN BECAUSE THE INITIAL
FIND CIGARETTE IN BOYS 9 TO 15
YEARS OF AGE.
GIRLS AND YOUNG 920 YEARS OF
AGE.
THE YOUNG MEN'S STUDIES IS
ONGOING, STARTED LATER BUT WE'LL
HAVE THE RESULTS LATER THIS
YEAR.
THESE ARE NOT THE ONLY STUDIES
ONGOING FOR THE 9-VALENT
PROGRAM.
FOR SAKE OF TIME WE CANNOT
PRESENT EVERYTHING BUT I WOULD
LIKE TO MENTION ALSO ONE STUDY
THAT MAY BE OF INTEREST OF THIS
GROUP, WE HAVE RECENTLY STARTED
AN EVALUATION OF THOSE MEN FOR
THE 9-VALENT VACCINE.
WHY THE 9-VALENT VACCINE BECAUSE
THE FOCUS IS ON THE 9 VA LENT
AND NOT ON THE 4-VALENT.
WE EXPECT FULL TRANSITION VERY
RAPIDLY IN THE U.S. AND SO THE
FOCUS OF THE DOSE IS ON
9-VALENT.
WE HAVE INITIAL STUDIES TO
ADDRESS THE QUESTION OF
FEASABILITY.
TODAY WE'LL TALK ABOUT STUDY
RESULTS DATA AND THE DATA WILL
FOCUS ON YOUNG WOMEN AND SAFETY.
FROM PROTOCOL ONE.
THEN WE TURN TO -- PROTOCOL 2
AND 9, TWO EMERGING STUDIES.
PROTOCOL ONE IS A VERY LARGE
STUDY.
IT'S ENROLLED MORE THAN 14,000
YOUNG WOMEN.
IT WAS A BLIND STUDY.
WE DIDN'T CHOOSE PLACEBO FOR
ETHICAL REASONS.
IT'S WILDLY RECOMMENDED, WIDELY
AVAILABLE AND WE CAN'T HAVE
PEOPLE WITH PRE-CANCER IN OUR
STUDIES.
SO KEEP IN MIND THE STUDY WAS
CONDUCTED IN 2007, CONDUCTED ONE
YEAR AFTER THE DRUG WAS
LICENSED.
AND AT THAT TIME FOCUS WAS
REALLY TO BRIDGE TO THE
9-VALENT.
THE KEY POINT, WOMEN WITH
GENITAL, BEGGYNOCOLGY EXAMINATI
AND PAP TEST EVERY SIX MONTHS.
THERE'S A TRIAGE TO ASSESS.
ETHNICITIES WERE ASSESSED FOR
ALL HPV TYPES AND ALSO ASSESSED
THROUGH STAND OUT METHODS.
SO ONCE AGAIN VERY LARGE EFFORT,
VERY LARGE TRIAL.
IT'S BEEN GOING ON FOR ALMOST
SIX YEARS NOW.
AND SUBJECTS HAVE HAD FOLLOW UP
UP TO FOUR YEARS
POST-VACCINATION.
A SCREENING EVERY SIX MONTHS TO
MAKE SURE WE DON'T MISS ANY
LESIONS SO WE HAVE A VERY HIGH
QUALITY DATA PACKAGE HERE.
NEXT SLIDE IS SHOWING THE
PRIMARY OBJECTIVE.
ONCE AGAIN WE DON'T HAVE A
PLACEBO CONTROL.
A CONTROL IS EXISTS FOR THE
VALENT VACCINE WHICH WE KNOW IS
HIGH LLY EFFICACIOUS.
AND IF IT'S SUCCESSFUL WE EXPECT
VERY FEW 9-VALENT FROM THE
ORIGINAL TYPES WHICH MEANS
HEAD-TO-HEAD COMPARISON BASED ON
EFFICACY AND PARTS IS NOT
FEASIBLE.
WE'LL HAVE TOO FEW END POINTS TO
MAKE A COMPARISON.
BASED ON THAT THE DEMONSTRATION
OF EFFICACY, PRIMARY
DEMONSTRATION ON ETHNICITY
ORIGIN.
THE GOAL TO BRIDGE THE EFFICACY
FINDINGS WITH THE VACCINE TO THE
9-VALENT VACCINE.
FOR THE ADDITIONAL TYPES WE
EXPECT A DIFFERENCE BETWEEN THE
TWO VACCINES IN TERMS OF THE END
POINTS.
AS MENTIONED THERE'S SOME CROSS
PROTECTION BUT IT IS STILL, YOU
KNOW, INSUFFICIENT TO COVER ALL
THE TYPES AND SO WE SHOULD USE
THE VALENT TO VACCINATED TYPES.
IF KNIGANYTHIN ANYTHING, IT MEA
UNDERVACCINATION.
SO HERE WE HAVE TWO TYPES.
THE POPULATION THAT I USED FOR
THE PRIMARY, WE WANT TO ANALYZE
THE VACCINE IN WOMEN THAT ARE
NOT INFECTED.
FOLLOW THEM DURING THE STUDY FOR
INFECTION AND INCIDENT OF
INFECTION.
SO SIMILAR -- DEFINITION VERY
SIMILAR TO THE ONE USED
PREVIOUSLY IN VALENT PROGRAM.
SUBJECTIVE TO BE NEGATIVE FOR
HPV AND DURING THE VACCINATION
PERIOD.
AND RECEIVE THREE VACCINATIONS.
WE ALSO HAVE PROTOCOL DEFINITION
AS WELL.
SUBJECT RECEIVED THREE DOSE,
COMPLIANCE WITH THE STUDY WAS
VERY GOOD AND THERE WAS NO
DIFFERENCE BETWEEN THE TWO
VACCINE CALLS AND 90% CONTINUED
IN THE EFFICACY EVALUATION
PHASE.
WE'RE LOOKING HERE AT, YOU
REMEMBER WE'RE LOOKING AT
ORIGINAL TYPES FIRST AND LOOKING
AT ETHNICITY.
WE'RE LOOKING AT SEVEN ANTIBODY
WHICH IS CONCOMITANT.
AND USED FOR ALL FOUR TYPES.
WITH GENDER RATIOS CLOSE TO ONE,
AND, YOU KNOW, THESE DEMONSTRATE
PRIMARY EFFICACIES.
EVERY INDIVIDUAL VANED WITH THE
REGIMENT AFTER THREE DOSES.
LET'S EXAMINE THE DATA FOR THE
ADDITIONAL TYPES.
THAT'S PRIMARY OBJECTIVE.
YOU ARE LOOKING AT THREE
EFFICACY POINTS.
LOOKING AT DISEASE OR INFECTION
CAUSED BY ANY OF THE FIVE NEW
TYPES.
ON THE FIRST OUR PRIMARY POINT
HIGH GRADE CERVICAL AND VAGINAL
DISEASE DUE TO ANY OF THE NEW
TYPES AND THEN WE HAVE CERVICAL
OF ANY GR
IN THE HIGH 90s.
WE NOW HAVE TWO VACCINES THAT
ARE BASED ON THE SAME
TECHNOLOGY, AND TWO DIFFERENT
CLINICAL TRIALS TO BE SHOWED
HIGHLY EFFICACIOUS.
WE HAVE TWO VACCINE FROM THE
SAME FAMILY OR FAMILY OF
VACCINE, FAMILY OF PRODUCT.
NEXT SLIDE.
HERE WE'RE LOOKING AT CERVICAL
AND VAGINAL DISEASE TAKEN
SEPARATELY.
FOR HIGH GRADE CERVICAL, ALL
GRADE CERVICAL DISEASE, HIGH
GRADE VAGINAL DISEASE, IT WAS
VERY HIGH AS WELL.
AND I WOULD LIKE TO MENTION THAT
WE HAVE ONE CASE OF HIGH GRADE
CERVICAL DISEASE.
IN THIS CASE IT'S CO-INFECTED
WITH A KNOWN VACCINE TYPE, TYPE
56.
AND IT MOST LIKELY TYPE 56 IS A
CAUSAL OF, CAUSAL VIRUS BECAUSE
THE SUBJECT WAS INFECTED FROM
DAY ONE AND THROUGH THE FIRST
TWO YEARS WHEREAS 58 WAS FOUND
ONLY, ONLY AT THE TIMES THE
EFFICACY WAS DONE.
IT WAS MOST LIKELY A TRANSIENT
INFECTION.
SLIDE.
NEXT SLIDE SHOWS PROCEDURES THAT
ARE RELATED, SEE ADDITIONAL
TYPES.
YOU CAN SEE HERE THAT DIFFERENT
THERAPI
THERAPIES.
IT IS DECREASED IN VERY
SUBSTANTIAL AS WELL WHICH TELLS
YOU THAT NOT ONLY THE VACCINE
HAS A POTENTIAL PUT TO PRESENT
PROCEDURES.
NOW VACCINE RELATED EXPERIENCES
ARE SUMMARIZED HERE.
AND HERE COMPARISON BETWEEN THE
TWO VACCINES.
IT LOOKS THE SAME WITH VERY FEW
VACCINE-RELATED ADVERSE
EXPERIENCE.
NO VACCINE RELATED DEATHS.
VERY FEW DISCONTINUATION.
REALLY THE ONLY DIFFERENCE THAT
CATCHES THE EYE SO TO SPEAK IS
AT INJECTION SITE WHERE THERE'S
A HIGHER FREQUENCY FOR INJECTION
SITE SO WE'LL LOOK AT THE DATA
IN MORE DETAIL.
I WOULD LIKE TO SAY IT'S NOT A
SURPRISE WE HAVE KNOWLEDGE OF
THAT AND MORE.
LET'S LOOK AT THE INJECTION SITE
DATA.
HERE WE'RE NOT SEEING SWELLING
WHICH IS BY FAR THE MOST COMMON
AND WE CAN SEE THAT THERE IS A
DIFFERENCE FOR ALL THREE.
IN PARENTHESIS IT'S STATISTICAL
DIFFERENCE.
FROM THE CLINICAL STANDPOINT
MOST INJECTION SITES WERE OF
LOWER INTENSITY WITH BOTH
VACCINES SO WE ANTICIPATE THAT
THE CLINICAL SIGNIFICANCE OF IT
WILL BE MINIMAL.
LOOKING NOW AT SYSTEMIC
VACCINE-RELATED EVENTS, HERE WE
HAVE ALL SYSTEMIC
VACCINE-RELATED WITH MORE THAN
2%.
I WANT TO REMIND YOU WE'RE
LOOKING AT A STUDY OF 14,000
SUBJECTS.
ALL EVENTS ARE EVERY DAY LIFE
EVENTS,ú COMMONLY USED IN MANY
VACCINE STUDIES AND THERE'S
REALLYLY NO SUBSTANTIAL DIFFEREE
BETWEEN THE TWO VACCINES.
WE HAVE OBSERVED -- WE HAVE
OBSERVED FOUR VACCINE RELATED
EVENTS, TWO IN THE 9-VALENT
GROUP AND TWO IN THE 4-VALENT
GROUP.
THESE IN TERMS HAVE ALREADY BEEN
SEEN PREVIOUSLY IN THE 4-VALENT
GROUP, IN THE 4-VALENT CLINICAL
PROGRAM AND ALL EVENTS WERE
PROMPTLY RESOLVED.
IN CONCLUSION FOR PROTOCOL ONE,
IN TERMS OF EFFICACY WE
DEMONSTRATED NON-INFERIOR IMMUNE
RESPONSE.
DEMONSTRATED 97% REDUCTION IN
DISEASE.
THE VACCINE THAT APPEAR WELL
TOLERATED IN MORE THAN 7,000
YOUNG WOMEN AND ADVERSE
EXPERIENCES PROFILE WAS
GENERALLY COMPARABLE BETWEEN THE
TWO VACCINES.
WE NOTED HIGHER FREQUENCY OF
INJECTION SITE ADVERSE EVENT
WITH 9-VALENT VACCINE BUT MOST
WERE OF MILD OR MODERATE
INTENSITY.
LET'S GO TO PROTOCOL TWO NOW.
LET'S SWITCH GEARS AND WE HAVE
FOUR GOALS AND ONE IMPORTANT
GOAL IS TO ASSESS.
PROTOCOL TWO IS INTERNATIONAL
STUDY TO DEMONSTRATE
NON-INFERIOR IMMUNIMMUNOGENICIT.
WE WANT TO DEMONSTRATE THE SAME.
SAFETY HERE, STUDY INCLUDES BOYS
AND GIRLS.
AND AS WELL AS YOUNG WOMEN.
THEY RECEIVED A VACCINE THREE
DOSE REGIMEN AND ACCESSED DAY
ONE TO MONTH 12.
IN TERMS OF ANTIBODY, YOU SEE
HERE THE GMT IN GIRLS VERSUS
YOUNG WOMEN.
GIRLS ARE IN PINK AND YOUNG
WOMEN ARE IN RED.
AND IT'S CLEAR THAT WE MET
NON-INFERIORITY IS HIGH IRIN
SOME GIRLS COMPARED TO YOUNG
WOMEN.
IT'S DIFFERENT FROM WHAT HAS
BEEN SEEN IN THE 4-VALENT
PROGRAM.
THE GMT RATIO IS AROUND TWO.
ONCE AGAIN, ANOTHER SIMILARITY.
SIMILAR SAFETY, SIMILAR
EFFICACY.
LET'S GO NOW TO BOYS, NEXT
SLIDE.
AND THE BOYS ALSO -- I'M SORRY.
BEFORE WE GO TO BOYS LET'S LOOK
AT RATES.
THIS SLIDE SHOWS GO FROM NINE
TYPES AFTER THE REGIMEN BOTH IN
GIRLS AND YOUNG WOMEN.
NOW WE'LL TALK ABOUT THE BOYS.
AND AS YOU CAN ANTICIPATE, THE
BOYS ARE IN BLUE SO WE HAVE BOYS
IN BLUE AND YOUNG WOMEN IN RED
HERE, AND LIKE THE COMPARISON
BETWEEN THE GIRLS AND THE YOUNG
WOMEN, BOYS HAVE A HIGHER
IMMUNOGENOCITY.
WE HAVE CLEARLY SUPERIOR
IMMUNOGENOCITC AS WELL.
RATES WERE VERY GOOD THROUGH ALL
SUBJECTS IN ALL NINE TYPES.
SAFETY, THIS IS A SAFETY
SCENARIO OF VACCINE ADVERSE
EVENTS.
ONE TO 15 FOLLOWING VACCINATION
AND IT'S APPARENT THAT THE
SAFETY PROFILE IS SIMILAR
BETWEEN THE THREE DEMOGRAPHIC
GROUPS.
SAFETY MIGHT EVEN LOOK SLIGHTLY
MORE FAVORABLE WITH THE BOYS,
WHICH IS SIMILAR TO WHAT HAS
BEEN SEEN FOR THE 4-VALENT
VACCINE FOR THE VALENT PROGRAM.
IN CONCLUSION WE'VE DEMONSTRATED
NON-INFERIOR IMMUNOGENICITY
WHICH SUPPORTS THE FINDINGS IN
YOUNG WOMEN TO THE OTHER SAMPLE
POPULATION.
AND VACCINE WAS GENERALLY WELL
TOLERATED AT ALL AGE AND
GENDERS.
LET'S FINISH NOW WITH PROTOCOL
NINE.
PROTOCOL NINE WAS AN
IMMUNOBRIDGING STUDY.
IT ASKED A DIFFERENT QUESTION.
HOW ABOUT IMMUNOGENICITY.
LET'S LOOK AT THE NEXT SLIDE.
A SMALLER STUDY, DOUBLE BLINDED.
AND WE LOOKED AT SEVEN.
COMPLIANCE WAS VERY GOOD.
MOST SUBJECTS COMPLETED THE
STUDY, RECEIVED THE THREE DOSE
REGIMEN AND NON-INFERIORITY WAS
DEMONSTRATED.
HERE WE'RE LOOKING AT THE TWO
TYPES 16 AND 18 AND IT'S
COMPARABLE BETWEEN TWO VACCINES.
IT MIRRORS IN THE YOUNG WOMEN
AND THE TWO VACCINES HAS THE
SAME PROFILE.
NEXT PROFILE SHOWS 16 AND 11 AND
SIMILAR OBSERVATION, WE HAVE
ETHNICITY.
MOST SUBJECTS HAD 100% SUBJECTS
AFTER THREE DOSE REGIMEN IN BOTH
VACCINE GROUPS WHICH SHOWED THE
VACCINE WAS HIGHLY IMMUNOGEN.
IN CONCLUSION WE DEMONSTRATED
COMPARABLE IMMUNIMMUNOGEN VACCI
YOUNG GIRLS IN THE POPULATION.
IT WAS BETWEEN 9-VALENT AND
4-VALENT.
FOR SAKE OF TIME I DIDN'T SHOW
THE DATA.
MOST INJECTION SITES WERE
MODERATE INTENSITY.
IN CONCLUSION, WE BELIEVE WE
HAVE SUCCESSFUL CLINICAL
PROGRAM.
WE'VE MET ALL EFFICACY AND
IMMUNOAGAIN -- IMMUNOGENOCITY.
AND ALSO IN ADULTS.
VACCINE WAS GENERAL WELL
TOLERATED.
THESE THREE STUDIES TAKEN
TOGETHER INCLUDE MORE THAN
10,000 SUBJECTS AND THE PROFILE
WAS GENERALLY SIMILAR.
THERE ARE MORE DATA TO PRESENT
AND, YOU KNOW, WE'LL KEEP THAT
FOR THE NEXT TIME.
WE MENTIONED ASSESSMENT.
IN STUDYING YOUNG MEN HOPEFULLY
IT'S GOING TO BE AVAILABLE
BEFORE THE END OF THE YEAR AND
WE WOULD LIKE TO SHOW THAT ALSO
TO THIS GROUP.
PRESENTLY, THE 9-VALENT VACCINE
IS STILL UNDER INVESTIGATION
EVEN THOUGH THE STUDY HAS
COMPLETED.
THE PRODUCT IS UNDER NO FDA
REVIEW.
AND IT'S UNDER STANDARD REGULAR
REVIEW AND HAS RECENTLY BEEN
ACCEPTED AND VALIDATED AND WE
EXPECT REGULATORY ACTION WITHIN
THE NEXT FEW MONTHS.
THANK YOU VERY MUCH.
THANK YOU.
LET'S OPEN IT FOR QUESTIONS?
YES, DR. JENKINS.
>> IN TERMS OF ADVERSE EVENTS
FOR THE 4-VALENT VACCINE, THE
EFFICACY FOLLOWING THE
VACCINATION AND I DIDN'T SEE
THAT AS ANYTHING YOU MENTIONED.
WE MENTIONED THE EVENT.
SO IT WAS THE MOST FREQUENT.
THERE WAS NO EVENT OF 4 DURING
THE STUDY.
AND OBVIOUSLY WE'VE TAKEN ALSO
PRECAUTIONS SO SUBJECT TO
OBSERVE AND, YOU KNOW, THERE WAS
NO, THERE WAS NO EVENT LIKE
THAT.
THERE WAS ONE EVENT OF SYNCOPY
PRIOR TO BE OBSERVATION.
>> THANK YOU.
YOU MAY HAVE MENTIONED IT.
WHAT DOES THIS LOOK LIKE IN HPV
POSITIVE?
>> THE QUESTION HIV POSITIVE
WOMEN HAVE NOT BEEN STUDIED.
ALL THE STUDIES HAVE BEEN DONE
IS COMMON IN VACCINE STUDY IN
HEALTHY SUBJECTS.
THERE'S A STUDY IN HIV POSITIVE
CHILDREN, 7 TO 12 YEAEARS OF AG
FOR 4-VALENT VACCINE.
AND GIVEN THAT THE
IMMUNOGENOCITY PROFILES THE TWO
VACCINES ARE VERY SIMILAR WE
WOULD EXPECT THE SAME SAFETY AND
IMMUNOGENOCITY PROFILE ONE THAT
POPULATION AS WELL.
>> ALL RIGHT.
ANY DIFFERENCES IN SIDE
EFFECT BETWEEN THE FIRST, SECOND
AND THIRD DOSE?
THIRD DOSE OF THE PROFILE?
THERE ARE DIFFERENCES, AND IN
TERMS OF FREQUENCY OF INJECTION
SITES SWELLING AND INJECTION
SITE.
THE FREQUENCY INCREASE BY DOSE
AND IT'S SIMILAR TO WHAT'S BEEN
OBSERVED PREVIOUSLY WITH THE
4-VALENT VACCINE.
AS A FOLLOW UP TO THAT DO YOU
HAVE ANY DATA ON WOMEN WHO MAY
BE, MAY HAVE RECEIVED THREE
DOSES OF HPV-4 WITH REGARDS TO
INJECTION SITE REACTION IN THESE
WOMEN IF THEY RECEIVED THIS
HPV-9 VACCINE?
>> YOU KNOW, THEY MENTIONED AT
THE BEGINNING OF THE TALK WE
CONDUCTED ONE STUDY AND ONE OF
THE PRIMARY GOALS WAS TO LOOK AT
THREE.
AND WE HAVE FOUND THE SAFETY
PROFILE WAS ACCEPTABLE AND THAT
THERE WAS NO, YOU KNOW, MAJOR
INCREASE IN TERMS OF INJECTION
SITE.
>> THANK YOU.
THAT WAS REALLY VERY
COMPREHENSIVE AND CLEAR AND
REALLY ACROSS MULTIPLE STUDIES
AND POPULATIONS, YOU'RE SHOWING
THIS NON-VALENT VACCINE TO BE
COMPARABLE TO GARDASIL WHICH IS
GREAT NEWS.
THERE WAS A PRESS RELEASE TODAY
THAT REPORTED THAT GARDASIL
RECEIVED A POSITIVE OPINION FROM
EMA FOR A PSEUDO SCHEDULE.
I'M WONDERING YOUR CLINICAL
DEVELOPMENT PLAN FOR THE NO
NON-PSEUDO SCHEDULE.
WE'RE RECOGNIZING THE TOPIC
TO THE STUDY HAS BEEN INITIATED
FOR THE 9-VALENT AND WE WANT,
OBVIOUSLY, FIRST TO DEMONSTRATE
THE FEASIBILITY.
WE RECOGNIZE ALSO LONG TERM
FOLLOW UP IN TERMS OF LONG TERM
EFFECTIVENESS, IN TERMS OF THE
DURATION OF PROTECTION FROM TWO
DOSE VERSUS THREE DOSE IS A
CRITICAL QUESTION.
WE NEED TO TALK MORE ABOUT THE
PLANS AT THIS STAGE BUT WE HAVE
STUDIES STARTED.
AS A FOLLOW UP TO THAT, HOW
LONG HAS YOUR LONG TERM FOLLOW
UP OF THE VALENT TO THOSE
PROGRAMS HAVE BEEN AND,
THEREFORE, WHAT COULD BE
EXPECTED WITH THE 9-VALENT?
SO, JUST TO MAKE SURE I
UNDERSTAND THE QUESTION, WE HAVE
LONG TERM FOLLOW UP FOR THREE
DOSE REGIMEN FOR THE 4-VALENT,
THAT'S YOUR QUESTION, RIGHT?
>> I WAS REACTING TO THE COMMENT
THAT THE EMU JUST APPROVED TWO
DOSE.
FAVORABLE OPINION.
>> AT THIS TIME THERE IS NO
EVALUATION OF LONG TERM
EFFECTIVENESS FOR TWO DOSE
REGIMEN.
>> OKAY.
THANK YOU.
>> ANY ADDITIONAL QUESTIONS?
OKAY, SEEING NONE, DR.
MARKOWITZ.
I'LL GO A FEW THINGS ABOUT
FLANS AND GO KNOW THE UPDATED
ACIP STATEMENT WE WOULD LIKE
AFFIRMATION OF TODAY.
WE HEARD THE HIGH GRADE IS
CERVICAL LESIONS.
ABOUT 11% TO THE FIVE ADDITIONAL
TYPES AND LARGEST PERCENT OF HPV
CANCERS AATTRIBUTABLE TO 16/18
SOME DIFFERENCES FOR
OROPHARYNGEAL BUT NOT FOR THE
OTHER CANCERS.
WE HEARD THIS VERY CLEAR SUMMARY
OF SOME OF THE DATA FROM THE
NON-VALENT CLINICAL TRIALS.
AGAINST DISEASE RELATED TO THE
FIVE ADDITIONAL TYPES AND
IMMUNOBRIDGING STUDY.
THIS IS AN EXPAND VERSION OF THE
TIMELINE THAT DR. BOCCHINI
PRESENTED AND FOR CONSIDERATION
OF THE VACCINE BY ACIP.
SO TODAY WE HEARD THE TYPES ON
ATTRIBUTION.
WE HOPE TO HEAR ON
ADMINISTRATION AND THE DATA
ABOUT NON-VALENT VACCINE AND
WE'RE ALSO PLANNING TO HEAR
ECONOMIC DATA.
WE'RE HOPING THE DATA AT THAT
TIME WILD BE AVAILABLE THAT'S
CURRENTLY ON GOING IN MALES 16
TO 20 YEARS OF AGE.
DISCUSSION OF OPTIONS AND FOR
RECOMMENDATIONS AND THEN IF THE
VACCINE IS LICENSED THERE WOULD
BE A VOTE IN FEBRUARY.
THE CONSIDERATIONS ARE BEING
UNDERTAKEN BY THE WORK GROUP,
ONE OF COURSE IS FOR
RECOMMENDATION OF ROUTINE
VACCINATION AT AGE 11 OR 12.
WE'RE CONSIDERING THE
RECOMMENDATION FOR VACCINATION
OF OLDER FEMALES AND MALES WHO
WERE NOT VACCY NAETD AT THE
RECOMMENDED AGE AND WE'RE
DISCUSSING THE TIMING FOR
CONSIDERATION EVER MALES 16 TO
26 BECAUSE WE ANTICIPATE THAT
THE VACCINE WILL NOT BE LICENSED
IN THIS AGE GROUP AT TIMES OF
FIRES LICENSURE.
WE'RE CONSIDERING VACCINATION OF
PERSONS PARTIALLY OR FULLY V Y
VACCINATED.
OTHER HPV VACCINE WORK GROUP
ACTIVITIES.
WE'RE FOCUSING ON THE NON-VALENT
VACCINE.
WE HAVE ON GOING REVIEW OF
POST-LICENSURE SAFETY AND
COVERAGE DATA AND KEEPING
ABREAST ON THE DATA OF REDUCED
DOSE SCHEDULE ULS FOR HPV.
WE'LL REVIEW IT IN MORE DETAIL
IN THE FUTURE.
I WANT TO MENTION BRIEFLY,
SOMETHING ABOUT THE REDUCED DOSE
SCHEDULES BECAUSE THERE WAS A
QUESTION AT THE LAST MEETING,
THERE IS GLOBAL INTEREST IN
THESE SIMPLIFIED SCHEDULES.
IT WOULD REDUCE THE LOGISTICAL
CHALLENGES.
THERE'S DATA AVAILABLE.
THESE ARE PRIMARILY
IMMUNOGENOCITY STUDIES.
SOME JURISDICTIONS ARE USING TWO
DOSE SCHEDULES IN THEIR NATIONAL
PREVENTION IMMUNIZATION
PROGRAMS.
THEY GRANTED MARKETING FOR
CERVARIX FOR GIRS 20914 YEARS AS
A TWO-DOES.
THE 9-VALENT VACCINE IS
CURRENTLY IN TRIALS WHICH WE
JUST HEARD.
WE'LL BE KEEPING ABREAST OF
THESE DATA AND REPORT BACK TO
ACIP.
NOW I WOULD LIKE TO TOTALLY
CHANGE GEARS AND TALK ABOUT THE
UPDATED HPV VACCINE ACIP
STATEMENT.
WE TALKED ABOUT THIS AT THE LAST
ACIP MEETING AS WELL.
THIS REVIEWS EVOLUTION OF
VACCINE RECOMMENDATIONS IN THE
U.S.
THE FIRST RECOMMENDATION WAS IN
2006 FOR QUADRIVALENT VACCINES
IN FIANCE MEDALS.
THE TOP TWO BOXES ARE
RECOMMENDATIONS FOR FEMALES THE
BLUE BOXES IS FOR MALES.
THE MOST RECENT RECOMMENDATION
WAS MADE IN 2011 FOR ROUTINE
VACCINATION IN MALES.
BECAUSE OF THE EVOLVING
RECOMMENDATIONS AFTER WHAT WAS
PUBLISHED IN 2007 WE PUBLISHED
THREE POLICY NOTES.
2010 THERE WAS A RECOMMENDATION
FOR ROUTINE VACCINATION IN
FEMALES AND ALSO QUADRIVALENT
VACCINES IN MALES.
IN 2011 WAS RECOMMENDATION OF
ROUTINE VACCINATION OF MALES AND
THIS IS THE ONLY RECOMMENDATION
MADE USING GRADE BECAUSE GRADE
HAD BEEN ADOPTED BY ACIP JUST
BEFORE THAT POLICY NOTE.
SO THE OBJECTIVES OF THE UPDATED
HPV VACCINE STATEMENT ARE TO
CONSOLIDATE RECOMMENDATIONS FOR
FEMALES AND MALES, TO
CONSOLIDATE RECOMMENDATIONS FOR
THE VA LENTZ AND QUADRI VALENT
VACCINES AND THE WORDING THAT'S
DIFFERENT AND UPDATE BACKGROUND
INFORMATION AND DATA REGARDING
EFFICACY, SAFETY AND ET CETERA.
THIS OVERLAPS WITH OUR
CONSIDERATION OF THE 9-VALENT
VACCINE BUT WE FEEL THAT THE
UPDATED STATEMENT WILL
FACILITATE FUTURE PROGRAMS.
THE COMMITTEE HAS SEEN THIS
DOCUMENT BEFORE AND I'M GOING TO
JUST GO THROUGH VERY BRIEFLY
SOME PARTICULAR ISSUES.
THE SECTIONS THAT WE'VE INCLUDED
IN THIS STATEMENT ARE VERY
SIMILAR TO THE SECTION IN THE
2007 ORIGINAL DOCUMENT, THEY
INCLUDE BACKGROUND ON BIOLOGY,
NATURAL HISTORY.
WE INDIVIDUAL THE DATA ON
CANCERS THAT WAS PRESENTED TODAY
AND THE OTHER HPV RELATED
OUTCOMES BUT WE HAVE A SECTION
ON PREVENTION, TREATMENT AND
CERVICAL CANCER SCREENING WHICH
WAS UPDATED.
WE HAVE A SECTION CALLED HEALTH
CARE AND RESEARCH LABORATORY
WORKERS.
DATA ON VACCINES HAS BEEN
UPDATED WITH THE CLINICAL TRIAL
DATA FROM THE END OF STUDY DATA.
WE HAVE DATA IN HERE ON THE
CROSS PROTECTION.
WE TALK ABOUT THE POST-LICENSURE
SAFETY DATA WHICH WAS NOT
AVAILABLE AT THE TIME OF THEIR
ORIGINAL STATEMENT, OF COURSE IN
IN 2007.
WE HAVE SECTIONS ON ECONOMIC
BURDEN OF HPV DISEASE AND COST
EFFECTIVENESS.
WE HAVE A SECTION ON THE
VACCINATION PROGRAM IN THE U.S.
AGAIN THAT WAS NOT IN THE
ORIGINAL DOCUMENT IN 2007.
A SUMMARY OF OUR RATIONALE AND
THEN THE STANDARD SECTIONS UNDER
THE RECOMMENDATION.
THIS IS THE MAIN RECOMMENDATION.
IN HERE WE COMBINED THE WORDING
FROM THE FEMALE AND MALE
RECOMMENDATION.
WE INDIVIDUAL THIS WITH THE
COMMITTEE IN OCTOBER WE HAD A
SEPARATE STATEMENT FOR THE
FEMALE AND MALES AND WE RECEIVED
FEEDBACK THAT WE SHOULD COMBINE
THIS SO CURRENTLY IT READS ACIP
RECOMMENDS ROUTINE VACCINATION
AT AGE 11 OR 12 YEARS WITH HPV 4
OR 2 FOR FEMALES AND HPV 4 FOR
MALES.
IT CAN START AT AGE 9 YEARS.
WE TALK ABOUT THE DOSING
INTERVALS AND THEN VACCINATION
IS ALSO RECOMMENDED FOR FEMALES
AGE 13 TO 26 YEARS AND FOR MALES
AGE 13 TO 21 YEARS WHO HAVE NOT
BEEN PREVIOUSLY VACCINATED.
SO THIS IS THE COMBINED
STATEMENT FOR THE MAEMS AND THE
FEMALES.
THE OTHER SUB SECTIONS IN THE
RECOMMENDATION SECTION ARE THE
SPECIAL POPULATIONS.
AND THE PRECAUTIONS AND
CONTRAINDICATIONSES.
IN THE DOCUMENT THAT I
DISTRIBUTED TO THE ACIP NUMBERS
WE HAD LACTATING WOMEN IN THE
WRONG SECTION.
SECTION HERE IS SEXUAL ASSAULT
OR ABUSE.
WE DISCUSSED THIS WITH ACIP
SEVERAL TIMES.
THEN PRECAUTIONS AND
CONTRAINDICATIONS WE'VE HAD IN
PREVIOUS STATEMENTS.
FOR IMMUNO COMPROMISED PERSONS
THIS IS OUR RECOMMENDATION.
ROUTINE VACCINATION AT 11 OR 12
YEARS.
AND IT'S RECOMMENDED THROUGH AGE
26 YEARS IN COMPROMISED PERSONS
WHO HAVE NOT BEEN VACCINATED
PREVIOUSLY.
AND MEN WHO HAVE HAD SEX WITH
MEN HAS BEEN UNCHANGED.
HISTORY OF SEX ABUSE OR ASSAULT
WHILE HPV VACCINATION WILL NOT
PROMOTE VIRAL COR
PROTECT AGAINST DISEASE
PROGRESSION DUE TO TYPES ALREADY
ACQUIRED, VACCINATION WOULD
PROTECT AGAINST
VACCINE-PREVENTABLE TYPES NOT
YET ACQUIRED.
ACIP RECOMMENDS HPV VACCINATION
BEGINNING AT AGE 9 YEARS FOR
CHILDREN AND YOUTH WITH ANY
HISTORY OF SEXUAL ABUSE OR
ASSAULT WHO HAVE NOT INITIATED
SEX.
HERE WE SAY HPV-4 IS CONTRA
INDICATED IN PERSONS WITH
HISTORY OF HYPER SENSITIVITY TO
YEAST AND SYRINGES OF HPV 2 HAVE
LATEX IN THE RUBBER STOPPER AND
SHOULD NOT BE USED IN PERSONS
WITH ANAPHYLACTIC LATEX ALLERGY.
VACCINE IS NOT RECOMMENDED FOR
PREGNANT WOMEN.
THE REST OF THE WORDING THE SAME
WE HAD IN OUR PREVIOUS
STATEMENTS.
WE HAVE A NEW SECTION INCLUDED
ON MONITORING IMPACT OF
VACCINATION WHICH INCLUDES
LICENSURE IMPACT DATA AND AREA
OF ONGOING RESEARCH, ACTIVITIES
AND HERE AS WE MENTION AD
VARIETY OF ISSUES VERY BRIEFLY
INCLUDING INVESTIGATION OF
9-VALENT VACCINE AND REDUCED
DOSE SCHEDULES.
WE RECEIVED MULTIPLE VERY
HELPFUL COMMENTS FROM ACIP
MEMBERS AS WELL AS OTHER
REVIEWERS.
THESE WERE MULTIPLE SMALL EDITS,
REQUEST FOR CLARIFICATION.
REQUEST FOR MODIFICATION OF
WORDING OF SECTION ON HISTORY OF
SEXUAL ABUSE BUT NO CHANGE IN
THE RECOMMENDATION AND WE
RECEIVED REQUEST ON
POST-LICENSURE SAFETY
EVALUATION.
THIS IS A TABLE THAT'S IN THE
ACIP STATEMENT.
YOU'VE SEEN THIS.
I WANT TO POINT THIS OUT.
HERE WE HAVE LISTED THE
POST-LICENSURE SAFETY STUDIES
THAT HAVE BEEN DONE.
THIS IS AN UPDATE OF A TABLE
THAT WAS INCLUDED IN A MWR ON
HPV LAST SUMMER AND IT INCLUDES
THE DATA FROM THESE STUDIES.
WE ADDED ADDITIONAL TEXT TO THE
ACIP STATEMENT TO DESCRIBE
BRIEFLY EACH OF THESE STUDIES.
AND THESE ARE A FREMPBS THAT
TABLE FOR YOUR INFORMATION.
SO IN SUMMARY THE DRAFT
STATEMENT UPDATES BACKGROUND
INFORMATION AND CLINICAL TRIAL
DATA.
IT CONSOLIDATES AND CLARIFIES
RECOMMENDATIONS.
I WANT INCLUDES A VARIETY OF NEW
SECTIONS AND WE INCLUDED A
SUBSTANTIAL AMOUNT OF DATA.
THIS HAS TO GO THROUGH
CLEARANCE, EDITORIAL CLEARANCE.
I'M SURE THERE WILL BE A LOT OF
ADDITIONAL CHANGES AND WE HOPE
TO HAVE IT PUBLISHED IN THE
SPRING, HOWEVER.
WE DO KNOW THAT THERE'S A LOT OF
NEW DATA THAT'S GOING AVAILABLE
AND WE UNDERSTAND THAT
RECOMMENDATIONS WILL BE UPDATED
IN THE FUTURE AS MORE DATA
BECOME AVAILABLE.
SO I WANT TO THANK THE WRITING
TEAM AND THE WORK
AND THE LARGE NUMBER OF STAFF
THAT HAVE BEEN INVOLVED IN ALL
THESE EFFORTS.
I THINK WE'RE READY TO HAVE
QUESTIONS AND A VOTE.
THANK YOU, DR. MARKOWITZ FOR
A VERY THOROUGH REPORT.
I WANT TO REMIND THAT IT'S OUR
GOAL AT ACIP TO RENEW, REVISE OR
RETIRE STATEMENTS ABOUT EVERY
FIVE YEARS SO THIS IS VERY
TIMELY, WITH EVERYTHING THAT'S
GONE THROUGH THIS.
AND THE OTHER MENTION FOR THE
REST OF THE AUDIENCE HERE IS ALL
THE ACIP MEMBERS HAVE RECEIVED
THIS DOCUMENT AND HAVE REVIEWED
AND SUBMITTED COMMENTS ON IT
PREVIOUSLY.
BUT COMMENTS?
BOY WE'RE CHIMING IN.
THERE'S A MOTION TO ACCEPT THE
REVISED RECOMMENDATION.
YOU KNEW THAT, EXACTLY.
I'VE HAD A CHANCE TO REVIEW THE
DOCUMENT.
I'VE SEEN THE WORK THAT'S GONE
IN FROM EVERYONE.
SO THAT'S MY MOTION.
DO WE HAVE A SECOND?
I SEE SEVERAL BUT WE'LL GIVE
CREDIT TO DR. BENNETT.
>> I SECOND THE MOTION.
ADDITION COMMENT?
I THINK THIS IS THE WORK DONE BY
DR. MARKOWITZ AND THE REST OF
THE HPV TEAM.
THIS I THINK FOR ALL OF US WAS A
VERY READABLE -- ANY TIME WE
RECEIVE ANYTHING OF 50 PAGES TO
REVIEW IS DAUNTING BUT THIS READ
VERY QUICKLY AND WENT VERY
NICELY.
SO I GUESS WE CAN GO FOR A VOTE
AND WE'LL START TO THE RIGHT.
YES.
>> YES.
YES.
>> YES.
YES.
>> YES.
YES.
>> YES.
YES.
>> YES.
YES.
>> YES.
YES.
>> YES.
SO THE MOTION IS APPROVED
UNANIMOUSLY.
WE THANK, AGAIN, THE HPV WORK
GROUP FOR THIS.
BEFORE YOU STEP DOWN, LAURI, I'M
WONDERING IF THERE'S ANY COMMENT
OR QUESTION FOR THE WORK GROUP
REGARDING KIND OF THE NEXT
STEPS?
I'M JUST REFLECTING ON THE
DISCUSSION YESTERDAY ABOUT HOW
DIFFICULT IT IS TO CONSIDER
MAKING A CHANGE OR ESTABLISH A
VERY SUCCESSFUL VACCINE PROGRAM
TRYING TO REDUCE DOSES.
I'M CURIOUS AS TO WHAT TYPE OF
INFORMATION WE'RE GOING TO SEE
ON, YOU KNOW, POTENTIAL REVIEW
SCHEDULES IN THE NEXT COMING
MONTHS.
WE'VE BEEN WATCHING VERY
CLOSELY THESE DISCUSSIONS FOR
THE VACCINE BUT WE DON'T HAVE
ANYTHING TO BRING FORWARD TO
ACIP.
WE'RE KEEPING ABREAST AND WHAT'S
HAPPENING AND WE'RE AWARE
THERE'S A LOT OF INTEREST IN
THIS AREA.
I UNFORTUNATE WANTED TO MAKE
THAT POINT AND THAT'S WHY I
RAISED IT BECAUSE THERE'S A LOT
OF INFORMATION, THERE WILL BE
MORE INFORMATION COMING ONE.
WE'RE HAPPY TO PRESENT THOSE
DATA BUT WE'RE NOT REALLY READY
TO CRITIC AT THIS TIME ANY TYPE
OF A MOTION OR CONSIDERATION BY
ACIP.
>> THANKS FOR CONSOLIDATING
THESE RECOMMENDATIONS.
AS WE ALL KNOW, HAVING GUIDANCE
OUT THERE VERY USE FOWL PROVIDE
TOWERS STRONGLY RECOMMEND THIS
VACCINE AND I WANT TO TAKE THIS
OPPORTUNITY IN LYING OF WHAT YOU
JUST VOTED ON TO POINT OUT THE
YOU A DEAR COLLEAGUE LETTER
THAT'S NOW IN FRONT OF YOU ALONG
WITH A PRESS RELEASE TO MARKET
THE LETTER, ESSENTIALLY URGING
PROVIDERS TO NOT JUST GAVE
RECOMMENDATION FOR HPV
VACCINATION BUT THE
RECOMMENDATION ACTUALLY HAS TO
BE A VERY STRONG RECOMMENDATION.
THE TAG LINE FOR THIS DEAR
COLLEAGUE LETTER ESSENTIALLY IS
WHAT YOU SAY MATTERS BUT HOW YOU
SAY IT MATTERS EVEN MORE AND
IT'S BEEN A DELIGHT TO
COLLABORATE WITH THE AMERICAN
ACADEMY OF PEDIATRICS AND
AMERICAN ACADEMY OF FAMILY
PHYSICIANS, AND WITH THE CDC TO
CREATE THIS DEAR COLLEAGUE
LETTER THAT YOU NOW SEE IN FRONT
OF.
YOU THIS DEAR COLLEAGUE LETTER
WAS LAUNCHED TWO DAYS AFTER THE
CANCER PANEL AND WE'RE INDEED
FORTUNATE TO BE COLLABORATING
WITH THE PANEL TO MARKET THEIR
REPORT AND THIS LETTER HAS BEEN
VERY FAVORABLE RECEIVED IN THE
MEDIA.
I WANT TO DRAW YOUR ATTENTION TO
THAT.
IF THERE'S ANY QUESTIONS YOU CAN
DIRECT HOME TO ME.
THANK YOU VERY MUCH.
>> THANK YOU.
THIS IS JEAN SMITH MEDICAL
OFFICER WITH ACIP.
IN THE LAST TWO DAYS WE HEARD
MENTION OF TWO NERVES, THE 50
YEAR ANNIVERSARY OF ACIP, AND
THEN THE 20 YEAR ANNIVERSARY OF
THE IMPLEMENTATION OF THE AFC.
THIS IS THE TEN YEAR ANNIVERSARY
OF LAURI MARKOWITZ SERVING AS
THE WORK GROUP LEAD.
[ APPLAUSE ]
SHE HAS WORKED WITH SEVERAL ACIP
MEMBERS SERVING AS WORK GROUP
CHAIR AND I CAN PERSONALLY SAY
THAT I'M ASTONISHED AT HER
FORTITUDE AS PROBLEMS AND ISSUES
ARE THROWN UP AGAIN AND AGAIN
AND SHE ALWAYS MARCHES FORWARD
WITH ABSOLUTE CALM.
THANK YOU, LAURI.
[ APPLAUSE ]
>> THAT WAS A NICE WAY TO END
THE SESSION.