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

6.5

4.5

7.4

0

1

2

3

4

5

6

7

8

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

0

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4000

4500

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

ths

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

ent

cove

rage

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

0

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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

0

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2013, females

2013, males

2014, females

2014, males

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

20

10

0

40

80

70

60

50

10 11 12 13 14 15 16 17 18 19 20

Female

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 nycimmunize@health.nyc.gov

(347)396-2400