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HPV Vaccination Rate/Recommendation Update & HPV Cancer Incidence: What you

can do!Texas Immunization Conference

Addison Texas

Lois Ramondetta MD

Professor Gynecologic Oncology

MD Anderson Cancer Center Houston Texas

Objectives

• Discuss HPV vaccine recommendations (updated ACIP recommendations) age 9-26 (RW) and coverage rates in US and throughout Texas (RW)

• Shared decision making –age 27-45 (LR)

• Review incidence of HPV cancers and the epidemiology of and treatment for the most common HPV cancers (cervix, oropharynx, and anal cancers)-(LR)

• Discuss the importance of partnering (RW)

• DSHS partnerships and tools (RW)

• ACS partnerships/Texas ACS HPV/Action Guides (RW)

• Oncologists and Survivors partnerships (LR)

.

Total (by site)

44,000

Oropharynx Cervix

Anus Vulva

Penis Vagina3

39%

31%

18%

8%

2%2%

TOTAL (HPV)34,800

80%

14%

6%

MALES14,100

11%

53%

20%

13%

3%

FEMALES20,700

~60,000 for 2019

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Average annual number and rate of human papillomavirus (HPV)–associated cancers a and annual numberof cancers attributable to HPV, by HPV type, cancer type, and sex — United States,* 2012–2016

Cancer type Reported HPV-associated cancers† Estimated no.§ (%) of cancers attributable to HPV types¶

Total no.** Rate†† 9vHPV-targeted Other HPV HPV-negativeCervix 12,015 7.2 9,700 (81) 1,200 (10) 1,100 (9)Vagina 862 0.4 600 (73) 0 (2) 300 (25)Vulva 4,009 2.1 2,500 (63) 300 (6) 1,200 (31)Penis 1,303 0.8 700 (57) 100 (6) 500 (37)Anus 6,810 1.8 6,000 (88) 200 (3) 600 (9)Female 4,539 2.3 4,100 (90) 100 (2) 300 (8)Male 2,270 1.3 1,900 (83) 100 (6) 300 (11)Oropharynx 19,000 4.9 12,600 (66) 900 (5) 5,500 (29)Female 3,460 1.7 2,100 (60) 100 (3) 1,300 (37)Male 15,540 8.5 10,500 (68) 800 (5) 4,200 (28)Total 43,999 12.2 32,100 (73) 2,700 (6) 9,200 (21)Female 24,886 13.7 19,000 (76) 1,700 (7) 4,200 (17)Male 19,113 10.6 13,100 (69) 1,000 (5) 5,000 (26)

Abbreviations: 9vHPV = 9-valent HPV vaccine; ICD-O-3 = International Classification of Diseases for Oncology, Third Edition.

Estimated annual number of HPV–attributable cancers, by cancer type, HPV type, and state — United States,¶

2012–2016

State

Estimated no.**

All cancers Oropharynx (male and female) Cervix

9vHPV-targeted

Other HPV

HPV-negative

9vHPV-targeted

Other HPV

HPV-negative

9vHPV-targeted

Other HPV

HPV-negative

Texas 2,310 200 620 830 50 360 890 110 100

MMWR Morb Mortal Wkly Rep. 2019 Aug 23;68(33):724-728MMWR Morb Mortal Wkly Rep. 2019 Aug 23;68(33):718-723.

92% of Cancers Caused by HPV Could be Prevented

• The number of cancers attributable to HPV types targeted by the vaccine ranged by state from 40 in Wyoming to 3,270 in California.

• Oropharyngeal cancer was the most common cancer attributable to the vaccine types in all states, except in Texas where cervical cancer was most common.

• In Alaska, the District of Columbia, New Mexico, and New York, the estimates of oropharyngeal and cervical cancers attributable to the types in the currently available HPV vaccine were the same.

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Benefits of Australia’s national qHPV vaccination program

(1) Declining HPV prevalence in young women, sufficient to provide herd protection to unvaccinated women

(2) Declining high-grade cervical lesions in the youngest women

(3) Genital warts approaching elimination in young people

(4) Declining JOPP

(5) Oral HPV infections 88% lower in vaccinated individuals

(6) Trend in decreasing Cervical Cancer RatesNovakovic D et al. Laryngoscope 2016Chesson HW et al. Vaccine 2012; NovakovicD et al. J Infect Dis2017DroletM et al. Lancet Infect Dis2015; 15:565–80TabriziSN et al. Lancet Infect Dis 2014; 14:958–66Brotherton JM et al. Lancet2011; 377:2085–92

Korostil IA et al. Sex Transm Dis 2013; 40:833–5.Chaturvedi AK et al. J Clin Oncol. 2018;36(3):262-7Luostarinen et al, IJC, 2017

Numbers and incidence rates (/100,000 woman‐years) of HPV associated cancers in 9,529 14‐ to 17‐year‐old female HPV16/18 or HPV6/11/16/18 vaccine recipients vs 17,838 non‐HPV vaccinated, 14‐ to 19‐year‐old women

HPV vaccinated women Non‐HPV vaccinated women

Malignancy Person years n Rate (95% CI) Person years n Rate (95% CI)

Cervix cancer 65,656 0 – 124,245 8 6.4 (3.2, 13)

Vulva cancer 65,656 0 – 124,245 1 0.8 (0.1, 5.7)

Oropharyngeal cancer

65,656 0 – 124,245 1 0.8 (0.1, 5.7)

Other HPV cancersaa

Vaginal carcinoma, anal carcinoma.

65,656 0 – 124,245 0 –

All HPV associated invasive cancers

65,656 0 – 124,245 10 8.0 (4.3, 15)

Breast cancer 65,656 2 3.0 (0.8, 12) 124,245 10 8.0 (4.3, 15)

Thyroid cancer 65,656 1 1.5 (0.2, 11) 124,245 9 7.2 (3.8, 14)

Melanoma 65,656 3 4.6 (1.5, 14) 124,245 13 10.5 (6.1, 18)

Non‐melanoma skin cancer

65,656 2 3.0 (0.8, 12) 124,245 3 2.4 (0.8, 7.5)

Cervical Cancer Incidence Women aged 15-24 2001–2014

Any Histology SCC & non SCC

Guo F et al Am J Prev Med 2018;55(2):197–204

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ACIP Discussions: Should HPV vax be recommended for 27-45?• No right answer

• Options for ACIP when deciding on recommendations• We don’t recommend the intervention

• We recommend the intervention

• We recommend shared clinical decision making

• All decided -No full support

• Thus decision between Reject or Shared Decision Making

What to do?????

• For clinical decision making

• Some might benefit

• Guidance can be given

• MDs face the requests anyway

• Insurance will cover

• Allows flexibility

• For Do Not Recommend

• Few people benefit

• Might detract from adolescent program

• Better use of resources

• Global vaccine shortage

• SCDM hard to do

Shared Clinical Decision-Making: for HPVVaccine

HPV Vaccination

Communicate that a choice exists,

ask patient to share in decision

Discuss the benefits and harms of

vaccinating or not vaccinating

Take into account what matters

most to patient

Decide together on best option

Arrange for the action & follow-up

Plan to monitor decision or revisit

the decision

The Policy Note states no need to discuss HPV vaccine with everyone in this age group.

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“Shared Decision Making” Points to Consider

• Consider vaccinating• New partners

• Planning new partners

• Immunocompromized

• Multiple partners +/-

• Consider not vaccinating• Monogamous forever

• No or one partner

• Patient does not feel at risk

• Patient doesn’t want vaccine

DON’T FORGET THAT PROVIDER RECOMMENDATION IS IMPORTANT!

≥ 90%

80% - 89%

70% - 79%

60% - 69%HI

A

K

DC

Percentage* of parents who reported receiving a provider recommendation for HPV vaccine, NIS-Teen 2018

National estimate:77.5%

Massachusetts: 90.7%

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Vaccination coverage higher among those reportinga recommendation

Received

recommendation?

78%

22%

Yes

No

75%

25%

Vaccinated

Not vaccinated

47%

53%

Vaccinated

Not vaccinated

Survivors and Oncologist Working together

• Kara Million Video

• Constance Hill Video

Knowledge matters and empowers: HPV vaccine advocacy among HPV-related cancer survivorsZeena Shelal1 • Dalnim Cho2 • Diana L. Urbauer3 • Qian Lu2 • Bridgette Y. Ma4 • Anna M. Rohrer5 • Shiney Kurian1 •Erich M. Sturgis6 • Lois M. Ramondetta 1

Received: 18 April 2019 / Accepted: 8 August 2019

Purpose: To describe knowledge about human papillomavirus (HPV), HPV-related care behavior, and advocacy intent among HPV-related cancer survivors.Methods A cross-sectional online survey was offered to HPV-related cancer survivors who were eithervolunteers at a cancer center or patients of survivorship clinics.Results N=200. Only 33.2% of respondents reported knowing their cancer was HPV-related and 56.8% reported HPV vaccine is safe. Participants who knew that their cancer was caused by HPV were more likely to have vaccinated their children (p < .001). Also, participants who knew that the vaccine is safe were more willing to recommend the vaccine (p < .001), to be a peer mentor for others with HPV-related cancers (43.2% vs. 14.0%, p < .001), and to act as an advocate for increasing vaccination rates (44.1% vs. 24.4%, p = 0.01). Survivors who were aware of the vaccine’s effectiveness in decreasing precancerous lesions were more likely to recommend vaccine (45.7% vs. 12.0%, p = .002).Conclusions Raising survivor awareness of the link between HPV and cancer and HPV vaccine safety may increase their willingness to serve as powerful opinion leaders and peer mentors to promote HPV vaccination. Providers may take the simple step of informing patients that their cancer is HPV-related and HPV vaccine is safe to increase the number of informed and empowered survivors.

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How Effective is this???

• The answer is we don’t know….

Call to Action for Oncologists▪ Missed opportunities

– Talk to your patients with HPV cancers about HPV and the Vaccine

– Familiarize yourself with facts about the vaccine

– Be prepared to address parents’ questions about the HPVvaccine

– Talk to your patients about getting the HPV vaccine for their children

– Talk to patients age 27-45 about +/- of getting vaccinated

▪ Cancer Organizations

– Support the ACS HPV Roundtable

– Partner with organizations focused on rural health

– Start where you live….your institution

https://www.cdc.gov/pcd/issues/2018/17_0320.htm

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A New Age Requires New Strategies:Lines between face-to-face and online/virtual interaction will continue to blur.

• Disseminate and communicate new scientific evidence

• National awareness days are opportunities

• Find new resources/strategies to personalize scientific data and give opinions directed at parents and the lay public • Persuasive messages are straightforward and strong!

• Massey PM Prev Chronic Dis 2018;15:170320

Educate Patients! No Missed Opportunities

HPV related Oropharyngeal & Uncommon Cancer

Screening Trial Of meN

HOUSTON Study

Recruiting 5,000 men 50-64 years of age

• Questionnaire

• Blood sample

• Saliva sample

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Questions?

Lois Ramondetta, MD

Professor, Department of Gynecologic Oncology and Reproductive MedicineThe University of Texas MD Anderson Cancer Center

lramonde@mdanderson.org

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10/18/2019

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Update on HPV in Texas

Texas Immunization Conference, Oct 23-25, 2019Rachel Wiseman, MPH

Department of State Health Services Immunization Unit

ACIP RecommendationsSection Subtitle

2019 Texas Immunization Conference

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• All females 9-26 years

• All males 9-21 years

• Males 22-26 yrs high risk onlyPrevious

• All males and females 9-26 yrs

• Clinical Decision: 27-45 years

• Recommended at 11-12 yearsCurrent

ACIP Recommendations

Age

9-14

• 2 doses

• 6 months apart

Age

15-45

• 3 doses

• 0,1-2 months, and 6 months

Immunocompromised

• 3 doses

• 0,1-2 months, and 6 months

Current ACIP Recommendations

HPV Coverage RatesSection Subtitle

2019 Texas Immunization Conference

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Vaccination Coverage Estimates for 13-17 Year Old Children in Texas and U.S., 2017-2018

VaccineU.S. National

Average 2018Texas 2017 Texas 2018

≥1 dose of Tdap 88.9% 83.2% 83.4%

≥1 dose MenACWY 86.6% 85.1% 86.7%

≥1 dose HPV 68.1% 57.8% 59.9%

HPV Up-To-Date (UTD) 51.1% 39.7% 43.5%

≥1 HPV, females 69.9% 60.4% 64.6%

HPV UTD, females 53.7% 43.5% 47.8%

≥1 dose HPV, males 66.3% 55.2% 55.5%

HPV UTD, males 48.7% 36.0% 39.4%

≥2 doses MMR 91.9% 84.7% 83.1%

≥2 dose VAR 89.6% 82.9% 82.0%

Comparison of ≥1 Dose HPV and HPV UTD Coverage in US, Texas, and Select Jurisdictions, 2018

68.1%

51.1%

59.9%

43.5%

70.1%

50.9%

66.3%

49.4%

62.8%

45.9%

65.4%

48.0%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

≥1 HPV HPV UTD

Co

vera

ge E

stim

ate

US Texas City of Houston

Hidalgo County Tarrant County Bexar County

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Comparison of ≥1 Dose HPV Coverage by Gender in US, Texas, and Select Jurisdictions, 2018

69.9%66.3%64.6%

55.5%

77.1%

63.6%

69.4%

63.5%63.8%61.7%

71.1%

59.7%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

≥1 HPV, females ≥1 HPV, males

Co

vera

ge E

stim

ate

US Texas City of Houston

Hidalgo County Tarrant County Bexar County

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Comparison of HPV UTD Coverage by Gender in US, Texas, and Select Jurisdictions, 2018

53.7%48.7%47.8%

39.4%

54.2%

47.8%49.7% 49.2%45.5% 46.4%

52.5%

43.6%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

HPV UTD, females HPV UTD, males

Co

vera

ge E

stim

ate

US Texas City of Houston

Hidalgo County Tarrant County Bexar County

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Comparison of ≥1 Dose HPV Coverage by Gender, US and Texas, 2013-2018

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2013 2014 2015 2016 2017 2018

≥1 HPV Female, Texas ≥1 HPV Male, Texas

≥1 HPV Female, US ≥1 HPV Male, US 11

Comparison of ≥1 Dose HPV Coverage by Gender, City of Houston and Texas, 2013-2018

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2013 2014 2015 2016 2017 2018

≥1 HPV, Texas females ≥1 HPV, Texas males

≥1 HPV, City of Houston females ≥1 HPV, City of Houston males12

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Comparison of ≥1 Dose HPV Coverage by Gender, Bexar and Texas, 2013-2018

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2013 2014 2015 2016 2017 2018

≥1 dose HPV, Texas females ≥1 dose HPV, Texas males

≥1 HPV, Bexar county females ≥1 HPV, Bexar county males

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HPV Activities and CollaborationsSection Subtitle

2019 Texas Immunization Conference

• Replacing AFIX for TVFC providers

• Launched Oct 1, 2019 in Texas

• 600 providers will have IQIP visits 10/1/19-6/30/20

• Reviewing TVFC provider coverage rates from ImmTrac2

• Providing information on using ImmTrac2

• Targeting improvement in the provider’s immunization process workflow

• Setting coverage rate targets for 1 year follow up

Immunization Quality Improvement Project: IQIP

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TVFC Adolescent Vaccine Report aka HPV:Tdap Ratio Letter

10/23/19 17

• Northeast Texas Public Health District (NETHealth) • Patient/provider reminders at local health systems

• Mobile vaccination clinics in rural counties

• HPV education/outreach with local schools/universities

• American Cancer Society• Target FQHCs to increase HPV vaccination

• Adoption of provider/client reminders

• Adoption of standing orders

• Provider assessment and feedback

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DSHS Texas Comprehensive Cancer Control Program Partnerships

• ASTHO HPV ECHO• ACS, TPS, TMA, DSHS, MD Anderson

• Learning from other states’ HPV activities

• Cancer Alliance of Texas• Wide variety of partners across the state

• HPV presentations and shared resources

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Other Collaborations, Activities, Resources, and Opportunities

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Steve's Story from Iowa Public Health (YouTube)

• Texas Medical Association• Published "Physician Role in Increasing Vaccination for HPV“

• HPV-specific CME development and dissemination

• Texas School Nurse Organization• HPV-focused session at last annual meeting (including

presenters from the HPV Coalition!)

• Shared resources on educating parents

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Other Collaborations, Activities, Resources, and Opportunities

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NationalHPVRoundtable

hpvroundtable.org

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• Clinic & Health System Action Guides• Physicians, Physician

Assistants, and Nurse Practitioners

• Nurses and Medical Assistants

• Dentists and Hygienists• Other Administrative Staff

Teams• Small Private Practices• Large Health Systems

Example Resources

• Affiliate of the National HPV Roundtable

• Over 40 organizations represented

• 4 workgroups:• Provider Education• Data and Technology• Systems Improvement• Awareness

Texas HPV Coalition

http://texashpvcoalition.org

• Published HPV Team-Based Learning Module in MedEdPORTAL• Outreach to Texas medical schools to include HPV Team-Based

Learning modules in curriculum

• Created a Texas HPV Vaccine Champion Award

• Assessment and recommendations underway to improve HPV data quality

• Dental healthcare provider education

• Engagement with Health System Quality Improvement staff

Texas HPV Coalition Projects

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Thank you!

Update on HPV in TexasRachel.Wiseman@DSHS.Texas.gov

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What’s KnownProvider recommendations are critical for HPV vaccine uptake, but need improvement.• 1 out of 3 parents have not received a provider recommendation.1

• Many providers report recommending HPV vaccine infrequently, late, or not at all.2

• Providers less often recommend HPV vaccine for preteens, males, and some racial/ethnic minorities.2

Evidence-based interventions are available to improve clinical communication. We know that training providers to use presumptive recommendations for HPV vaccination increases uptake.3,4

What’s NewNow that we know how to introduce HPV vaccination to parents, the next step is to understand how providers can support parents who have questions and concerns. Emerging evidence suggests that:

• Emphasizing cancer prevention and addressing knowledge gaps are effective communication strategies, while emphasizing urgency with these parents may be counterproductive.5

• Leveraging technology, such as educational videos viewed during the clinical visit, is a promising approach to increasing HPV vaccine uptake.6

• Persistence is important. Adolescents are more likely to get HPV vaccine when providers address parental hesitancy with clear support for HPV vaccination.7 Bringing up the topic across multiple visits may also be needed.8

Presumptive recommendations initiate vaccination conversations with an assumption that parents will vaccinate. For example, “Now that your son is 11, he is due for three vaccinations today to help protect from meningitis, HPV cancers, and whooping cough.”

HPV Vaccination Communication in Clinical Settings

HPV Best Practices Conference Evidence Summary 2019

What’s NextIn the coming years, we can expect to learn more about approaches for addressing parental HPV vaccine hesitancy and strategies for implementing evidence-based communication trainings. For example:

• What is the added benefit of pairing presumptive announcements with motivational interviewing for HPV vaccine hesitant parents?

• How can we better engage healthcare teams, including nurses, to support HPV vaccination?

• What is the potential for using technology-assisted or train-the-trainer models to implement communication training?

Additional areas for future investigation include addressing the needs of providers who may be hesitant about HPV vaccine and building providers’ confidence in responding to parental concerns.

1 Lu PJ, Yankey D, Fredua B, O’Halloran AC, Williams C, Markowitz LE, Elam-Evans LD. Association of provider recommendation and human papillomavirus vaccination initiation among male adolescents Aged 13-17 Years—United States. The Journal of Pediatrics. 2019 Mar 1;206:33-41.

2 Gilkey MB, McRee AL. Provider communication about HPV vaccination: a systematic review. Human Vaccines & Immunotherapeutics. 2016 Jun 2;12(6):1454-68.3 Brewer NT, Hall ME, Malo TL, Gilkey MB, Quinn B, Lathren C. Announcements versus conversations to improve HPV vaccination coverage: a randomized trial. Pediatrics. 2017

Jan;139(1): e20161764.4 Dempsey AF, Pyrznawoski J, Lockhart S, Barnard J, Campagna EJ, Garrett K, Fisher A, Dickinson LM, O’leary ST. Effect of a health care professional communication training

intervention on adolescent human papillomavirus vaccination: a cluster randomized clinical trial. JAMA Pediatrics. 2018 May 1;172(5):e180016-.5 Shah PD, Calo WA, Gilkey MB, Boynton MH, Dailey SA, Todd KG, Robichaud MO, Margolis MA, Brewer NT. Questions and concerns about HPV vaccine: a communication

experiment. Pediatrics. 2019 Feb 1;143(2):e20181872.6 Dixon BE, Zimet GD, Xiao S, Tu W, Lindsay B, Church A, Downs SM. An educational intervention to improve HPV vaccination: a cluster randomized trial. Pediatrics. 2019 Jan

1;143(1):e20181457.7 Shay LA, Baldwin AS, Betts AC, Marks EG, Higashi RT, Street RL, Persaud D, Tiro JA. Parent-provider communication of HPV vaccine hesitancy. Pediatrics. 2018 Jun

1;141(6):e20172312.8 Kornides ML, McRee AL, Gilkey MB. Parents who decline HPV vaccination: who later accepts and why? Academic Pediatrics. 2018 Mar 1;18(2):S37-43.

The HPV Vaccination Roundtable convenes, communicates with, and catalyzes member organizations to increase HPV vaccination rates and prevent HPV cancers.

Learn more at hpvroundtable.org.

What’s KnownHealthcare systems own and manage networks of hospitals and clinics, and thus, can influence the provision of care for large numbers of patients. In pediatrics and family medicine, healthcare systems increasingly dominate the market, making them important partners in efforts to increase HPV vaccine uptake. To date, research suggests that systems-level interventions can improve HPV vaccination, with effects typically being modest in size and dependent on implementation.

• Reminder/recall interventions use text, email, phone, or mail to let parents know their child is due for HPV vaccination.1-10 Almost all evaluations find that reminder/recall interventions yield small to medium increases in HPV vaccination rates for at least some doses or populations.1-10 However, these interventions can be expensive to implement.11

• Provider prompts, such as EHR alerts, remind providers to recommend HPV vaccination during a patient visit.6, 9, 12, 13 Provider prompts have shown small increases in HPV vaccination rates, with “elaborated prompts” that suggest language to recommend HPV vaccine demonstrating greater increases than simple prompts without recommended language.6

• Assessment and feedback interventions give providers data on their immunization rates to help them improve their performance.12, 14, 15 Such interventions typically demonstrate small increases in HPV vaccination rates,12, 15 but sometimes only among younger adolescents.14

• Multi-level interventions may be especially effective,9, 12, 14-17 particularly when they combine clinical system interventions with provider communication training.13, 18

HPV Vaccination: Improving Clinical Systems to Increase HPV Vaccine Uptake

HPV Best Practices Conference Evidence Summary 2019

What’s NewRecent studies have focused on increasing the reach and impact of systems interventions:• Interventions that target both providers and systems can create improvements

in vaccination rates that are sustainable beyond the active intervention phase.

• Engaging clinical champions within systems is a promising approach for maximizing providers’ participation.19

What’s NextIn the coming years, ongoing studies will tell us more about how to deliver systems-level interventions effectively, including:• How can interventions tested at the clinic level be successfully disseminated in large integrated

delivery systems?

• How can we best motivate and support systems with low vaccination rates and in rural settings to undertake multi-level interventions?

• How can existing programs, like the CDC’s Immunization Quality Improvement for Providers (IQIP, formerly known as AFIX), support systems’ efforts to improve HPV vaccination rates?

1 Kharbanda EO, Stockwell MS, Fox HW, Andres R, Lara M, Rickert VI. Text message reminders to promote human papillomavirus vaccination. Vaccine. 2011;29(14):2537-41.

2 Matheson EC, Derouin A, Gagliano M, Thompson JA, Blood-Siegfried J. Increasing HPV vaccination series completion rates via text message reminders. Journal of Pediatric Health Care. 2014;28(4):e35-e9.

3 Patel A, Stern L, Unger Z, Debevec E, Roston A, Hanover R, et al. Staying on track: A cluster randomized controlled trial of automated reminders aimed at increasing human papillomavirus vaccine completion. Vaccine. 2014;32(21):2428-33.

4 Rand CM, Vincelli P, Goldstein NP, Blumkin A, Szilagyi PG. Effects of phone and text message reminders on completion of the human papillomavirus vaccine series. J Adolesc Health. 2017;60(1):113-9.

5 Szilagyi PG, Albertin C, Humiston SG, Rand CM, Schaffer S, Brill H, et al. A randomized trial of the effect of centralized reminder/recall on immunizations and preventive care visits for adolescents. Academic Pediatrics. 2013;13(3):204-13.

6 Zimet G, Dixon BE, Xiao S, Tu W, Kulkarni A, Dugan T, et al. Simple and elaborated clinician reminder prompts for human papillomavirus vaccination: a randomized clinical trial. Academic Pediatrics. 2018;18(2, Supplement):S66-S71.

7 Chao C, Preciado M, Slezak J, Xu L. A randomized intervention of reminder letter for human papillomavirus vaccine series completion. J Adolesc Health. 2015;56(1):85-90.

8 Szilagyi PG, Humiston SG, Gallivan S, Albertin C, Sandler M, Blumkin A. Effectiveness of a citywide patient immunization navigator program on improving adolescent immunizations and preventive care visit rates. Archives of pediatrics & adolescent medicine. 2011;165(6):547-53.

9 Fiks AG, Grundmeier RW, Mayne S, Song L, Feemster K, Karavite D, et al. Effectiveness of decision support for families, clinicians, or both on HPV vaccine receipt. Pediatrics. 2013;131(6):1114-24.

10 Tiro JA, Sanders JM, Pruitt SL, Stevens CF, Skinner CS, Bishop WP, et al. Promoting HPV vaccination in safety-net clinics: a randomized trial. Pediatrics. 2015;136(5):850-9.

11 AvSmulian EA, Mitchell KR, Stokley S. Interventions to increase HPV vaccination coverage: A systematic review. Hum Vaccin Immunother. 2016;12(6):1566-88.

12 Perkins RB, Zisblatt L, Legler A, Trucks E, Hanchate A, Gorin SS. Effectiveness of a provider-focused intervention to improve HPV vaccination rates in boys and girls. Vaccine. 2015;33(9):1223-9.

13 Rand CM, Schaffer SJ, Dhepyasuwan N, Blumkin A, Albertin C, Serwint JR, et al. Provider communication, prompts, and feedback to improve HPV vaccination rates in resident clinics. Pediatrics. 2018;141(4):e20170498.

14 Gilkey MB, Dayton AM, Moss JL, Sparks AC, Grimshaw AH, Bowling JM, et al. Increasing provision of adolescent vaccines in primary care: a randomized controlled trial. Pediatrics. 2014;134(2):e346.

15 Moss JL, Reiter PL, Dayton A, Brewer NT. Increasing adolescent immunization by webinar: A brief provider intervention at federally qualified health centers. Vaccine. 2012;30(33):4960-3.

16 Dempsey AF, Pyrznawoski J, Lockhart S, Barnard J, Campagna EJ, Garrett K, et al. Effect of a health care professional communication training intervention on adolescent human papillomavirus vaccination: a cluster randomized clinical trial. JAMA Pediatr. 2018;172(5):e180016-e.

17 Paskett ED, Krok-Schoen JL, Pennell ML, Tatum CM, Reiter PL, Peng J, et al. Results of a multilevel intervention trial to increase human papillomavirus (HPV) vaccine uptake among adolescent girls. Cancer Epidemiol Biomarkers Prev. 2016;25(4):593-602.

18 Rand CM, Tyrrell H, Wallace-Brodeur R, Goldstein NPN, Darden PM, Humiston SG, et al. A learning collaborative model to improve human papillomavirus vaccination rates in primary care. Academic Pediatrics. 2018;18(2S):S46-S52.

19 Gilkey MB, Parks MJ, Margolis MA, McRee AL, Terk JV. Implementing evidence-based strategies to improve HPV vaccine delivery. Pediatrics. 2019;144(1).

The HPV Vaccination Roundtable convenes, communicates with, and catalyzes member organizations to increase HPV vaccination rates and prevent HPV cancers.

Learn more at hpvroundtable.org.

What’s KnownHigh-quality studies have shown that HPV vaccination prevents precancers and genital warts and is safe. Clinical trials established the efficacy and safety evidence of HPV vaccination, leading to recommendation for routine provision of HPV vaccine to adolescents ages 11-12,1-4 recommendation of 9-valent HPV vaccine,5 and a reduced dosing schedule for younger adolescents.6 Post-licensure safety studies with millions of patients across at least 6 countries continue to document no increased risk of autoimmune or neurologic conditions following HPV vaccination.7,8

What’s NewLong-term observational studies continue to confirm the effectiveness and safety of HPV vaccine.

HPV vaccine effectiveness• Vaccine-type HPV infections have decreased by 78% for US women ages 20-24 and 38% for ages 25-29.11

These declines also occurred in unvaccinated women, offering evidence of community protection (i.e., herd immunity) from HPV vaccination.

• Trials show long-term prevention of HPV pre-cancers and cancers, with only 1 breakthrough case (low-grade CIN1) over 12 years in a cohort of over 2,000 women,12 and 0 breakthrough cases of HPV-related cancers over 65,656 person-years of follow-up for 9,529 vaccinated females compared to 10 cases of HPV-related cancers among 124,245 person-years of follow-up for 17,838 non-vaccinated females.13

• The average annual decrease in high-grade cervical pre-cancers was 24% for women ages 18-20 and 10% for women ages 21-24 who received cervical screening in an active surveillance area in the US between 2008 and 2013.14

• Population-level cervical cancer incidence, estimated from the Surveillance, Epidemiology, and End Results (SEER) registry, decreased in young women by 29% (ages 15-24) and 13% (ages 25-34) between 2003-2006 (before the vaccine was available) and 2011-2014 (after US licensure).15

• Preliminary estimates from population-based observational studies16 and post-hoc analyses of clinical trial data17,18 indicate that a single dose of HPV vaccine may be effective for prevention of cervical cancer.

• Systematic reviews9,10 of HPV vaccine effectiveness have highlighted protection against HPV-related pre-cancers and cancers, with a recent meta-analysis10 estimating 83% reduction in HPV-16 and -18 infection in 13-19-year-olds and 66% reduction in 20-24-year-olds, with 51% reduction in CIN2+ among 15-19-year-olds and 31% reduction among 20-24-year-olds.

Epidemiologic Evidence of HPV Vaccine Effectiveness and Safety

HPV Best Practices Conference Evidence Summary 2019

HPV vaccine safety• A Cochrane Review of randomized trials and a general narrative review of 109 studies documented no

significant increases in adverse events following HPV vaccine receipt.9,19

• Multiple large studies in several countries have substantiated the lack of increased risk of autoimmune or neurologic conditions in adolescents20 and adult women21 following HPV vaccination.

• A large cohort study documented no increase in primary ovarian insufficiency (POI) after HPV vaccination nor other adolescent vaccinations.22

What’s NextIn the next 5-7 years, research studies will demonstrate more clearly the impact of HPV vaccination on cancer outcomes. Of particular interest is whether these studies will show decreases in oropharyngeal cancer, an important outcome given that no screening test exists for this HPV cancer. Studies will also document protection against HPV pre-cancers beyond 12 years, reduction of HPV infections and HPV pre-cancers among 27-45-year-olds following updated vaccine licensure, the long-term effectiveness of a two-dose HPV vaccine regimen, and the effectiveness of a 1-dose regimen. 1 Centers for Disease Control and Prevention. Fda Licensure of Quadrivalent Human Papillomavirus Vaccine (Hpv4, Gardasil) for Use in Males and Guidance from the Advisory Committee on Immunization Practices

(Acip). MMWR Morb Mortal Wkly Rep. 2010;59(20):630-632. 2 Centers for Disease Control and Prevention. Recommendations on the Use of Quadrivalent Human Papillomavirus Vaccine in Males--Advisory Committee on Immunization Practices (Acip), 2011. MMWR Morb Mortal

Wkly Rep. 2011;60(50):1705-1708. 3 Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER. Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (Acip). MMWR Recomm

Rep. 2007;56(Rr-2):1-24. 4 Markowitz LE, Dunne EF, Saraiya M, Chesson HW, Curtis CR, Gee J, Bocchini JA, Jr., Unger ER. Human Papillomavirus Vaccination: Recommendations of the Advisory Committee on Immunization Practices (Acip).

MMWR Recomm Rep. 2014;63(Rr-05):1-30. 5 Petrosky E, Bocchini JA, Jr., Hariri S, Chesson H, Curtis CR, Saraiya M, Unger ER, Markowitz LE. Use of 9-Valent Human Papillomavirus (Hpv) Vaccine: Updated Hpv Vaccination Recommendations of the Advisory

Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2015;64(11):300-304. PMC4584883.6 Meites E, Kempe A, Markowitz LE. Use of a 2-Dose Schedule for Human Papillomavirus Vaccination - Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep.

2016;65(49):1405-1408. 7 Gee J, Naleway A, Shui I, Baggs J, Yin R, Li R, Kulldorff M, Lewis E, Fireman B, Daley MF, Klein NP, Weintraub ES. Monitoring the Safety of Quadrivalent Human Papillomavirus Vaccine: Findings from the Vaccine Safety Datalink.

Vaccine. 2011;29(46):8279-8284. 8 Chao C, Klein NP, Velicer CM, Sy LS, Slezak JM, Takhar H, Ackerson B, Cheetham TC, Hansen J, Deosaransingh K, Emery M, Liaw KL, Jacobsen SJ. Surveillance of Autoimmune Conditions Following Routine Use of

Quadrivalent Human Papillomavirus Vaccine. J Intern Med. 2012;271(2):193-203. 9 Arbyn M, Xu L. Efficacy and Safety of Prophylactic Hpv Vaccines. A Cochrane Review of Randomized Trials. Expert Rev Vaccines. 2018;17(12):1085-1091. 10 Drolet M, Benard E, Perez N, Brisson M. Population-Level Impact and Herd Effects Following the Introduction of Human Papillomavirus Vaccination Programmes: Updated Systematic Review and Meta-Analysis.

Lancet. 2019. 11 Markowitz LE, Naleway AL, Lewis RM, Crane B, Querec TD, Weinmann S, Steinau M, Unger ER. Declines in Hpv Vaccine Type Prevalence in Women Screened for Cervical Cancer in the United States: Evidence of Direct

and Herd Effects of Vaccination. Vaccine. 2019. 12 Kjaer SK, Nygard M, Dillner J, Brooke Marshall J, Radley D, Li M, Munk C, Hansen BT, Sigurdardottir LG, Hortlund M, Tryggvadottir L, Joshi A, Das R, Saah AJ. A 12-Year Follow-up on the Long-Term Effectiveness of the

Quadrivalent Human Papillomavirus Vaccine in 4 Nordic Countries. Clin Infect Dis. 2018;66(3):339-345. 13 Luostarinen T, Apter D, Dillner J, Eriksson T, Harjula K, Natunen K, Paavonen J, Pukkala E, Lehtinen M. Vaccination Protects against Invasive Hpv-Associated Cancers. Int J Cancer. 2018;142(10):2186-2187. 14 Oakley F, Desouki MM, Pemmaraju M, Gargano JM, Markowitz LE, Steinau M, Unger ER, Zhu Y, Fadare O, Griffin MR. Trends in High-Grade Cervical Cancer Precursors in the Human Papillomavirus Vaccine Era. Am J Prev

Med. 2018;55(1):19-25. 15 Guo F, Cofie LE, Berenson AB. Cervical Cancer Incidence in Young U.S. Females after Human Papillomavirus Vaccine Introduction. Am J Prev Med. 2018;55(2):197-204. PMC6054889.16 Brotherton JM, Budd A, Rompotis C, Bartlett N, Malloy MJ, Andersen RL, Coulter KA, Couvee PW, Steel N, Ward GH, Saville M. Is One Dose of Human Papillomavirus Vaccine as Effective as Three?: A National Cohort

Analysis. Papillomavirus Res. 2019;8:100177. 17 Kreimer AR, Rodriguez AC, Hildesheim A, Herrero R, Porras C, Schiffman M, Gonzalez P, Solomon D, Jimenez S, Schiller JT, Lowy DR, Quint W, Sherman ME, Schussler J, Wacholder S. Proof-of-Principle Evaluation of the

Efficacy of Fewer Than Three Doses of a Bivalent Hpv16/18 Vaccine. J Natl Cancer Inst. 2011;103(19):1444-1451. PMC3186781.18 Sankaranarayanan R, Prabhu PR, Pawlita M, Gheit T, Bhatla N, Muwonge R, Nene BM, Esmy PO, Joshi S, Poli UR, Jivarajani P, Verma Y, Zomawia E, Siddiqi M, Shastri SS, Jayant K, Malvi SG, Lucas E, Michel A, Butt J,

Vijayamma JM, Sankaran S, Kannan TP, Varghese R, Divate U, Thomas S, Joshi G, Willhauck-Fleckenstein M, Waterboer T, Muller M, Sehr P, Hingmire S, Kriplani A, Mishra G, Pimple S, Jadhav R, Sauvaget C, Tommasino M, Pillai MR. Immunogenicity and Hpv Infection after One, Two, and Three Doses of Quadrivalent Hpv Vaccine in Girls in India: A Multicentre Prospective Cohort Study. Lancet Oncol. 2016;17(1):67-77. PMC5357737.

19 Phillips A, Patel C, Pillsbury A, Brotherton J, Macartney K. Safety of Human Papillomavirus Vaccines: An Updated Review. Drug Saf. 2018;41(4):329-346. 20 Arnheim-Dahlstrom L, Pasternak B, Svanstrom H, Sparen P, Hviid A. Autoimmune, Neurological, and Venous Thromboembolic Adverse Events after Immunisation of Adolescent Girls with Quadrivalent Human

Papillomavirus Vaccine in Denmark and Sweden: Cohort Study. Bmj. 2013;347:f5906. PMC3805482.21 Hviid A, Svanstrom H, Scheller NM, Gronlund O, Pasternak B, Arnheim-Dahlstrom L. Human Papillomavirus Vaccination of Adult Women and Risk of Autoimmune and Neurological Diseases. J Intern Med.

2018;283(2):154-165. 22 Naleway AL, Mittendorf KF, Irving SA, Henninger ML, Crane B, Smith N, Daley MF, Gee J. Primary Ovarian Insufficiency and Adolescent Vaccination. Pediatrics. 2018;142(3).

The HPV Vaccination Roundtable convenes, communicates with, and catalyzes member organizations to increase HPV vaccination rates and prevent HPV cancers.

Learn more at hpvroundtable.org.

What’s Known• Vaccination, screening and follow-up care can prevent almost

all cervical cancer, making it the first cancer that could be eliminated in the US.2

• In many geographic areas vaccines have eliminated diseases, including polio, as a public health problem.

• Several organizations in the US and around the world have issued statements calling for cervical cancer elimination as a public health problem.3

• The World Health Organization has set a draft cervical cancer elimination goal at 4 cases per 100,000 women per year.4 Some have proposed an elimination goal of 1 case per 100,000 for the US overall and for individual states.

What’s Possible• Vaccination could largely eliminate HPV infections that cause 90% of HPV cancers.2

• Australia could reach the cervical cancer elimination target of 4 cases per 100,000 by 2028 and the target of 1 case per 100,000 by 2066, according to mathematical modelling.5

• “Micro-elimination” may be possible for smaller units including states, health systems, and specific age cohorts.

• Several states have cervical cancer rates close to 4 per 100,000 as well as high cervical screening rates and high vaccination rates, e.g. Massachusetts, New Hampshire, North Dakota, and Vermont.

Elimination is defined as zero, or near zero, cases in a defined geographical area.

Elimination of HPV Cancers as a Public Health Problem, Starting with Cervical Cancers in the US

HPV Best Practices Conference Evidence Summary 2019

What Are the Challenges• The public health definition of elimination differs from the lay definition. The public may think that

elimination equals zero cases. A single message is needed that motivates everyone without getting too complicated.

• Messaging needs to respect survivors. It may be hurtful to say that cervical cancer has been eliminated even as new cases happen.

• Some rare types of cervical cancer are not caused by HPV, and screening is not 100% effective.

• Elimination efforts may divert resources to “prevent the last case” (e.g., divert resources away from preventing more common or deadly cancers).

• Once HPV vaccination rates get high enough, routine cervical cancer screening may no longer be recommended. Yet vaccination alone will only prevent 90% of cervical cancers, leaving the incidence of the remaining 10% unchanged.

• Cervical cancer elimination is not foreseeable for low- and middle-income countries where most cervical cancers occur, due to difficulties with broad implementation of effective screening and vaccination programs6 and temporary vaccine shortages.

• It will be much easier to largely eliminate cervical cancer than the other HPV cancers, for which no effective screening tests exist, and for which a larger proportion of cases are not caused by HPV.

1. Walter R. Dowdle, The Principles of Disease Elimination and Eradication, MMWR 48 (SU01);23-27, 1999. 2. Kane, M. and Giuliano, A.R.. Eliminating HPV-related diseases as a public health problem: Let’s start with cervical cancer. HPV World 2018;35:42-49. 3. http://hpvroundtable.org/get-involved/eliminate/4. https://www.who.int/docs/default-source/documents/cervical-cancer-elimination-draft-strategy.pdf?sfvrsn=380979d6_45. Hall, M.T. et al. The projected timeframe until cervical cancer elimination in Australia: a modeling study. Lancet Public Health 4:e19-e27, 2019.6. Simms, K.T. et al. Impact of scaled up human papillomavirus vaccination and cervical screening and the potential for global elimination of cervical cancer in 181 countries, 2020-

99: a modelling study. Lancet Oncol 20: 394-407, 2019.

The HPV Vaccination Roundtable convenes, communicates with, and catalyzes member organizations to increase HPV vaccination rates and prevent HPV cancers.

Learn more at hpvroundtable.org.