Catching up on HPV-related cancers: diagnostic advances and treatment controversies
Together We Can Prevent HPV-Related Cancers...Together We Can Prevent HPV-Related Cancers Kristin...
Transcript of Together We Can Prevent HPV-Related Cancers...Together We Can Prevent HPV-Related Cancers Kristin...
Together We Can PreventHPV-Related Cancers
Kristin Oliver, MD, MHS, FAAPAssistant Professor, Pediatrics & Environmental Medicine and Public HealthIcahn School of Medicine at Mount SinaiConsultant, New York City Department of Health and Mental Hygiene
The learner should be able to:1. Discuss latest trends in HPV disease prevalence and
prevention.
2. Employ evidence-based techniques for increasing HPVvaccination rates in your own practice.
3. Apply useful & compelling communication strategiesandpractical tips to inform parents about HPV.
Every year in the United States over 30,000 people are diagnosed with a cancer caused by HPV.
That’s 1 case every 20 minutes.
Average Number of New Cancers Probably Caused by HPV, by Sex, United States, 2008-2012
Data Source: MMWR2016;65(26):661-666.
Women (n = 19,200)
Oropharynx n=2,000 10%
Cervix n=10,700 56%
Vagina n=600 3%
Vulva Anus n=2,400 n=3,000 13% 16%
Men (n = 11,600)
Anus n=1,600 14%
Oropharynx n=9,100 78%
Penisn=7006%
Rectumn=200 2%
Disparities in Cervical Cancer Incidence and Death Rates
State Variation in Rates of Cervical Cancer
Data Source:www.cdc.gov/cancer/cervical/statistics/state.htm
Cervical Cancer Incidence Rates by State, 2013
Implications of Pre-Cancerous Lesions
Ongoing medical follow-up isrecommended
Cervical conization and LEEP (loop electrosurgical excisionprocedure) are associated with adverse obstetric morbidity
Subsequent pregnancies are at riskof: Perinatalmortality Pretermdelivery Low birthweight
Financial costs ofcare
HPV Vaccination Eliminates HPV Infection and the Downstream Consequences
Data Source: Schiffman M et al., 2013
Cervical Pre-cancer 330,000
Cervical Cancer12,000
Oropharyngeal Cancers
Data Source: M. Moore. Adopted from Chaturvedi A., 2010
More neworopharyngeal cancersthan cervical cancers
HPVnegativeSmoking and alcohol-
related Decreased50%
HPVpositive Increased by225%
Photo Credit (left): www.inhealth.com/category_s/60.htmPhoto Credit (right): https://nn.wikipedia.org/wiki/S%C3%A5r_hals
Anatomy of the Oropharynx
Photo Credit: Dr. Michael Moore, UC Davis
Oropharyngeal Cancers
Side Effects of Non-surgical Therapy
Data Source: Irune, et al, 2014; Kocak-Uzel, et al, 2014; Nutting, et al, 2011; McBride, et al, 2014Photo Credit: http://www.jpalliativecare.com/viewimage.asp?img=IndianJPalliatCare_2010_16_2_74_68408_f3.jpg
State-based Disparities in HPV-Associated Oropharyngeal Cancer
Data Source: Adapted from www.cdc.gov/cancer/hpv/statistics/state/oropharyngeal.htm
Data Not Available 4.53 to 7.02 7.03 to 8.19 8.20 to 9.73 Data Not Available .80 to 1.52 1.53 to 1.82 1.83 to 2.33
0.14 0.04
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Meningococcal Disease(all serogroups)
Meningoccal Disease Serogroup B
Pertussis Oropharyngeal SCC (HPV associated)
Cervical cancer (HPV associated)
Incidence of Diseases Covered in Adolescent Vaccine Series
Meningococcal Data Source: 2014 CDCABCs Pertussis Data Source: 2015 CDCABCsCervical & Oropharyngeal Data Source: 2008-2012 SEER
Deaths from Diseases Covered in Adolescent Vaccine Series
70 67.5
4210
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Meningococcal Disease(all serogroups)
Meningoccal Disease SerogroupB Pertussis Cervical cancer (HPV associated)
Meningococcal Data Source: 2014 CDCABCs Pertussis Data Source: 2015 CDCABCsCervical Data Source: 2016 American Cancer Society
Est
imat
ed a
nnua
ldea
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908070605040302010
0
%
HPV Related Cancer Type
HPV 31/33/45/52/58
HPV 16/18
Percentage of HPV types found in common HPV related cancers, US Data
9-valent vaccine is estimated to prevent:85% of cervical, 70% of oropharyngeal,80% of anal, and 60% of penile cancers
2017 Immunization Schedule
Age at 1st dose of HPVvaccine
Before 15th Bday: 2doses On or after 15th Bday: 3dosesImmunocompromised: 3 doses
What Forms of “Immunocompromise” Necessitate a 3-dose HPV Vaccine Series?
Needs 3 doses irrespective of age:Primary or secondary conditions thatmight reduce cell-mediated or humoral immunity
Examples:o B lymphocyte Ab deficiencieso T lymphocyte complete or partial defectso HIV infectionso Malignant neoplasmo Transplantationo Autoimmune diseaseo Immunosuppressive therapy
Can use 2-dose series for those initiatingbefore 15th birthday:
Asthma Asplenia Diabetes mellitus Sickle celldisease Chronic granulomatous disease Chronic disease of liver, lung, kidneys Heart disease CNS barrier defects (eg, cochlearimplant) Complement deficiency, persistent
complement component deficiency
Slide courtesy of Dr. SeanO’Leary
Data Source: Luxembourg presented at February 2016ACIP
2 –Dose Immunogenicity Trial
Does Immunity Last?
Follow-up through month 60
RESULTS:Antibody kinetics• Similar in 2 groups• Steady• > Natural infection
2 doses (0, 6 mos) (ages 9-14 y)3 doses (0, 1, 6 mos) (ages 15-25y) Natural infection
Data Source: Adopted from Romanowski, 2016
Evidence of lasting immunity
For 2-or 3-dose series? No evidence of waning protection after a 3-doseseries So far, antibody persistence after a 2-dose seriesappears
similar to 3-dose series
How long? Data available through ~10 years for 2vHPV and4vHPV Longer follow-up, through 14 years, ongoing insome
studies
9vHPV Vaccine Safety
7 pre-licensure studies including 15,000males and females
Generally well-tolerated Adverse event profile similar to that of 4vHPVacross
age, gender, race, and ethnicity More injection-site reactions expected amongthose
who receive 9vHPV
HPV Vaccine Long-Term Safety DataNo increased risk of:
2011- Allergic reactions, anaphylaxis, GBS, stroke, bloodclots, appendicitis, or seizures (than unvaccinated or who received other vaccines)
2013 –Blood clots or AEs related to the immune & CNS (almost1 million girls)
2014 – Venous thromboembolism or blood clots (>1 million women)
2012 & 2014 – Autoimmune disorders (2studies) 2015 – Multiple sclerosis or other demyelinating diseases 2016- Over 60conditions 2012 - Vaccine may be associated with skin infections where the
shot is given during the two weeks after vaccination and fainting on the day the shot is received
Vaccine Efficacy from Clinical Trials
Vaccine DiseaseEfficacy, Females
Efficacy, Males
HPV4
High-grade abnormalities in cervix 100% N/A
High-grade abnormalities in vagina 100% N/A
High-grade abnormalities in vulva 100% N/A
High-grade abnormalities in anus N/A 75%*
Genital Warts 99% 89%
HPV2 High-grade abnormalities in cervix 93% N/A
* Only among men-who-have-sex-with-men
Efficacy vs Effectiveness
Efficacy - reduction in disease underexperimental conditionsClinical trials
Effectiveness – reduction in disease in “realworld” settingObservational/ecological studiesLinked studies
Source: ACS. Saslow2016
HPV Vaccine Effectiveness from NHANES 2003-2014
Age Group 4v HPV Prevalence Prevaccine Era (2003-2006)
4v HPV PrevalenceVaccine Era (2011-2014)
14-19 y 11.5% 3.3%
20-24 y 18.5% 7.2%
25-29 y 11.8% 8.8%
Source: Oliver SE. J Infec Dis. 2017
HPV Vaccine Effectiveness
Graph Source: Gertig DM, 2013
Percent reduction in cervical dysplasia 5 years after vaccination, by age in 2007
Perc
ent d
yspl
asia
redu
ctio
n
Age at introduction of vaccination
HPV Vaccine Effectiveness from NHANES 2003-2014
Unvaccinated (2011-2014) Vaccinated (2011-2014)
4v HPVPrevalence
12.2% 2%
Source: Oliver SE. J Infec Dis. 2017
This corresponds to a vaccine effectiveness of 83%
HPV Vaccine Effectiveness
Source: Kjaer. CID2018
One or More Doses HPV Vaccine Among Females and Males 13-17 Years of Age, US
Source: CDC NIS Teen 2016. MMWR Aug 25,2017
One or More Doses HPV Vaccine Among Females and Males 13-17 Years of Age, US
Source: CDC NIS Teen 2016. MMWR Aug 25,2017
HPV Vaccine Coverage Among Femalesand Males 13-17 Years of Age, NYC
60%
70%
80%
90%
Perc
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cove
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50%
40%
30%
20%
10%
0%Q1-2009 Q3-2009 Q1-2010 Q3-2010 Q1-2011 Q3-2011 Q1-2012 Q3-2012 Q1-2013 Q3-2013 Q1-2014 Q3-2014 Q1-2015 Q3-2015 Q1-2016 Q3-2016 Q1-2017
Quarter-YearData Source: NYC DOHMH Citywide Immunization Registry (numerators) and NYC DOHMH Epiquery and 2010 US Census (population estimates). 1ACIP has recommended routine HPV vaccination for females ages 9-26 since 2006 and for males ages 11-21 since 2011.2 Series can be completed with 2 or 3 doses depending on series initiation at <15 years of age and interval between dose 1 and dose 2 is >5 months
Female - 1dose Female - seriescomplete
Male - 1dose Male - seriescomplete 75%
52%
59%
70%
Disparities in HPV Vaccine Coverage, NYC, Series Complete
Females18% - 45%46% - 57%58% - 68%69% - 89%
Source: NYC DOHMH New York Citywide Immunization Registry Denominator: Vintage 2016 Population Estimates for 2015
Review Date: March 31, 2017Creation Date: May 3, 2017
Unpopulated areas
NYC Overall: 63.0%
Disparities in HPV Vaccine Coverage, NYC, Series Complete
Males
14% - 38%39% - 50%51% - 63%64% - 82%Unpopulated areas
NYC Overall: 56.1%
Source: NYC DOHMH New York Citywide Immunization Registry Denominator: Vintage 2016 Population Estimates for 2015
Review Date: March 31, 2017Creation Date: May 3, 2017
Missed Opportunities for HPV Vaccine Administration, NYC
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Month and Year
Tdap, MCV4, and first HPV doses administered to 11 year-olds each month from January 2005 – April 2017. Overall Tdap and MCV4 dosesare shown. HPV vaccine doses are reported separatelyfor males and females.Reference: Sull M, et al. Pediatrics,2014;134(6):e1576-1583
Tdap
MCV
HPV1-Females
HPV1- Males
How Should We Introduce the Vaccine?
How Should We Introduce the Vaccine?
Opel et al: ‘Presumptive recommendation’“We have some shots to do today”Observational study
Brewer et al: ‘Announcements’“Your child is due for 3 vaccines today…”RCT
Putting Presumptive into Practice: Same Day, Same Way
“Your child needs 3 vaccines today- Tdap, HPV and meningococcal”
“Today, your child should have 3 vaccines. They’re designed to protect him from meningitis, cancers caused by HPV and tetanus, diphtheria, and pertussis.”
NYC Advertising Campaign
Effectiveness Evaluation of Citywide HPV Campaigns, 2014
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2013, females
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HPV TV ads aired- 11% increase among 11 year-old girls compared to 2013- 17% increase among 11 year-old boys compared to 2013
Reminder/Recall Strategies Can Increase HPV Vaccination Rates
Graph Sources: Left) Kharbanda. E et al., 2011; Right) Suh CA et al., 2012
Text Messages1
Letters &Telephone calls2
HPV
CIR for Coverage Reports
CIR for Recall: Customizable
CIR for Recall: Lists Letters
CIR Text Message Recall
Impact of Text Message Recall
Patients included in text message recall jobs
n=70,890
3,414 (11%) vaccinatedwithin 28 days
2,345 (6%) vaccinatedwithin 28 days
TEXTED n=31,388(44%)
NOT TEXTED n=39,502(56%)
171 text message recall jobs completed by 62 facilities,
8/27/15 – 12/31/15
Standing OrdersSingle physician order for all patients for
recommended vaccinesStipulate that all patients meeting certain criteria
should be vaccinated – age, underlying medicalcondition
Components1. Nurse/MA tracks immunization history2. Nurse/MA identifies eligible patients3. Nurse/MA educates patients –alert provider if
patient still has questions or wants to talk with theprovider
4. Nurse administers vaccines
Benefits of Standing Orders
Shown to be effective in both adults and children For children, use of standing orders is associated witha
median increase in vaccination coverage of 28% Most effective evidence-basedmethod
Overcome administrative barriers and save time
‘Presumptive’ recommendation in action
Source:www.thecommunityguide.org/vaccines/RRstandingorders.html
The Denver Health Story
Large vertically integratedcommunity health system Cares for about 1/3 ofall
children in Denver 8 community healthcenters,
16 school-based healthcenters
For many years, had ‘typical’immunization process, withsimilar rates to nationalaverage
Photo Credit: https://commons.wikimedia.org/wiki/File:The_Childrens_Hospital_of_Denver_Front.JPG
Adolescent Vaccine Rates with Standing Orders
Graph Source: Farmar, Anna-Lisa M., et al., 2016
Why Vaccinate at Ages 11-12?
Antib
ody
resp
onse
Data Source: Dobson, Simon RM, et al., 2013
1) Better immune response
Graph Source: Rand CM et al., 2007; reprinted with author’s permission
Males
Why Vaccinate at Ages 11-12?
Females
2) More chances to vaccinateEarly adolescents have 3 times more preventive care visits than late adolescents
Why Vaccinate at Ages 11-12?
Data Source: Finer, Lawrence B., and Jesse M. Philbin, 2013
30
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Male
3) Lack of exposureU.S. Teen Sexual Activity
Percent of adolescents who have had sex
Why Vaccinate at Ages 11-12?
4) Long duration of immunity
No evidence of waning protection up to 10years after 3-dose schedule
Antibody kinetics with 2-dose schedules aresimilar, suggesting there will be similarprotection
Why Vaccinate at Ages 11-12?
Graph Source: Gertig DM, 2013
Percent reduction in cervical dysplasia 5 years after vaccination, by age at vaccination
Perc
ent d
yspl
asia
redu
ctio
n
Age at introduction of vaccination
5) Prevents twice as much pre-cancer
Why Vaccinate at Ages 11-12?
What I say to patients:
“The HPV vaccine works better and prevents more cancers at younger ages.
If Ella gets the vaccine today she will only need 2 doses, but if we wait until she’s older she may need 3 doses.”
Why Vaccinate at Ages 11-12?
Why NOT Vaccinate at Ages 9 - 10?
You can’t vaccinate too early….. Only too late
HPV VACCINATION RESOURCES
Provider FAQs
Tear-off Pad* (for parents)
Key Strategies Card
HPV Provider Toolkit
https://www1.nyc.gov/site/doh/providers/resources/public-health-action-kits-hpv.page
Double-sided English/Spanish. Also available in Chinese,Arabic, Bengali, Urdu, Haitian-Creole, Korean, French,Russian
• NYC DOHMH• CIR
• http://www1.nyc.gov/assets/doh/downloads/pdf/cir/cir-recall-guide.pdf
• CDC• https://www.cdc.gov/hpv/hcp/index.html
• AAP• Info for parents (www.healthychildren.org)• Info for clinicians (https://www.aap.org/en-
us/advocacy-and-policy/aap-health-initiatives/immunizations/HPV-Champion-Toolkit/Pages/HPV-Champion-Toolkit.aspx)
• CHOP Vaccine Education Center• http://www.chop.edu/centers-programs/vaccine-
education-center
For More Information
Contact info
New York City Department of Health and Mental Hygiene
Bureau of Immunization [email protected]
(347)396-2400