A Vaccine to Prevent Cancer: the Moral Imperative to Improve HPV Vaccination Rates

Transcription

1 A Vaccine to Prevent Cancer: the Moral Imperative to Improve HPV Vaccination Rates Lois M Ramondetta MD Professor Gynecologic Oncology Department of Gynecologic Oncology and Reproductive Medicine Chief Gynecologic Oncology LBJ Hospital UT MD Anderson Cancer Center & Harris Health System

2 Disclaimer & Disclosures No conflicts of interest. Policies and standards of the Texas Medical Association, the Accreditation Council for Continuing Medical Education, and the American Medical Association require that speakers and planners for continuing medical education activities disclose any relevant financial relationships they may have with any entity producing, marketing, reselling, or distributing health care goods or services consumed by, or used on, patients whose products, devices or services may be discussed in the content of the CME activity. The planners and speakers have no relevant relationships to disclose. I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation.

3 Agenda 1. HPV Cancers 2. HPV Vaccine Rates 3. HPV Vaccine Updates 4. The Moral Imperative

4 Pt 1 46 (36) Pt 2 33 (22) Pt 3 45 (35) Pt 4 36 (26) Pt 5 43(33) Pt 6 42 (32) Pt 7 61 (51) Pt 8 48 (38) Pt 9 31 (21) Pt (42) Pt 11 61(51) Pt 12 38(28) Pt (44) Pt (31) My Service

5 Pt 1 46 (36) Pt 2 33 (22) Pt 3 45 (35) Pt 4 36 (26) Pt 5 43(33) Pt 6 42 (32) Pt 7 61 (51) Pt 8 48 (38) Pt 9 31 (21) Pt (42) Pt 11 61(51) Pt 12 38(28) Pt (44) Pt (31 My Service

6 Cancers Caused by HPV Vulvar Vaginal Cervical Penile Anal Oropharyngeal (throat and back of tongue)

7 HPV Associated Cancers United States, From 2008 to 2012 HPV associated cancers climbed to nearly 39,000 11,700 cases of cervical cancer 12,600 oropharyngeal cancers in males 5,000 anal cancers 30,700 (79%) can be attributed to HPV, 28,500 of these are attributable to HPV types preventable with the 9 valent HPV vaccine Viens LJ et al. Human Papillomavirus Associated Cancers United States, MMWR Morb Mortal Wkly Rep 2016;65:

8 HPV Infection & Disease: Understanding the Burden Almost ALL will be infected with at least 1type HPV at some point Most will never know they ve been infected Can occur with any intimate sexual contact Intercourse is not necessary for infection Estimated 79 million Americans currently infected 14 million new infections/year in the US HPV infection most common in teens 20s Jemal A et al. J Natl Cancer Inst 2013;105:

9 HPV Types Differ in their Disease Associations ~40 Types Mucosal sites of infection Cutaneous sites of infection ~ 80 Types High risk (oncogenic) HPV 16, 18 most common Low risk (non-oncogenic) HPV 6, 11 most common Cervical Cancer Anogenital Cancers Oropharyngeal Cancer Cancer Precursors Low Grade Cervical Disease Genital Warts Laryngeal Papillomas Low Grade Cervical Disease Common Hand and Foot Warts

10 Persistent infection and Integration in basal keratinocytes Viral genome (8 genes as circular double stranded DNA) incorporated into host cell genome. HPV genome disrupted at E2 gene so no more E2 protein E2 down regulate two genes: E6 and E7. Without functional E2, E6 and E7 expression is uncontrolled E6 and E7 are oncogenes/oncoproteins. E6 causes degradation of tumor suppressor protein 53. E7 interferes with retinoblastoma protein and the host cell cycle. E6 and E7 cause "immortalization of these dysfunctional cells

11 HPV Types HPV types 16 and 18 cause 70% of all cervical, anal, and genital cancers in women, and 70% of anal cancers in men. HPV types 6 and 11 cause 90% of all genital warts in men and women. Seventy percent of cancers of the oropharynx may be linked to HPV.

12 Average Number of New HPV-associated Cancers Women Overall, and by Sex, in the United States, Women Vulva 13% Vagina 3% Men Penis 8% Anus 15% Cervix 59% 10% Anus 15% Oropharynx 77%

13 Correlation between HPV and cervical cancer is higher than that between smoking and lung cancer

14 HPV Associated Cervical Cancer Incidence Rates by State, United States,

15 Head and Neck Cancer Nose/Paranasal Sinuses Nasopharynx Oral Cavity (mouth) Oropharynx Soft palate or uvula Tonsil Base of tongue or lingual tonsil posterior or lateral oropharyngeal wall Hypopharynx Larynx (voicebox)

16 Cervix Oropharynx

17 Oropharyngeal Cancer HPV(+) HPV(-)

18 Epidemic of HPV Cancers in U.S. Men APC: +5% +5% +3% Penis < 1/100,000 ~0%

19 Newly Diagnosed-Untreated Cases Presenting to MD Anderson Each Year Oropharynx Cervix Anus Vulva Penis Vagina Number of Cases

20 Anal Cancer 8,080 new cases annually (2,920 men and 5,160 women) 1,080 deaths annually (440 men and 640 women)

21 Increased risk of anal cancer Women with a history of high grade cervical, vulvar, vaginal dysplasia or cancer HIV positive men and women Men who have sex with men Individuals with a history of anal warts Iatrogenic immunosuppression (eg,transplant recipients, long term oral corticosteroids)

22 Penile Cancer Risk Factors Age: 50 to 70 years old, 1/3 under 50 Tobacco use HPV Lack of circumcision Phimosis: AIDS

23 Annual Deaths From HPV-Related Cancers, Whooping cough Meningitis Anal cancer Oropharyngeal cancer Cervical cancer Deaths in US Deaths in Texas 357

24 Vaccination Recommendations HPV vaccination is recommended for both females and males ages years: HPV vaccine series should be completed before the 13 th birthday Recommend the same way as other teen vaccinations (Tdap and menningococcal) on the same day

25 Boys Need the HPV Vaccine Too Girls & Boys can start HPV vaccination at age 9 Preteens should finish HPV vaccine series by age 13 Plus girls years old who haven t started or finished HPV vaccine series Plus boys years old who haven t started or finished HPV vaccine series. Also can be given to men 22-26

26 HPV Prophylactic Vaccines Recombinant L1 capsid proteins that form virus like particles (VLP) Non infectious and non oncogenic Produce higher levels of neutralizing antibody than natural infection HPV Virus Like Particle

27 HPV Vaccines Currently Licensed in U.S. Bivalent 2vHPV (Cervarix) Quadrivalent 4vHPV (Gardasil) 9 Valent 9vHPV (Gardasil 9) Manufacturer GlaxoSmithKline Merck Merck HPV Types Included Contraindications Dose Schedule 16, 18 6, 11, 16, 18 Hypersensitivity to latex* 3 dose series: 0, 1, 6 months Hypersensitivity to yeast 3 dose series: 0, 2, 6 months 6, 11, 16, 18, 31, 33, 45, 52, 58 Hypersensitivity to yeast 3 dose series: 0, 2, 6 months * only contained in pre filled syringes, not single dose vials

28 Vaccinating age Many believe it can wait Why to vaccinate now! Where did come from? Clinical trial inclusion (looking at result of screening) Exposure (before exposure) Duration of protection (don t know and needed to work into screening) Adolescent platform Programmatic reasons Immune response (don t know clinical relevance of this is) Effectiveness (showing data that it worked required correlation with testing)

29 Monitoring Impact of HPV Vaccine Programs: HPV associated Outcomes 29

30 It works! HPV Prevalence Rates % Age HPV 6,11,16, % Age HPV 6,11,16,18 Within 6 years of the vaccine s use Decrease in prevalence of the most dangerous HPV strains 64% in girls yrs and 34% in ages yrs

31 Impact of HPV vaccination in Australia Proportion of Australian born females and males diagnosed as having genital warts at first visit, by age group, Females Males Ali, et al., Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data. British Med J 2013;346:f

32 Reduction in HPV 16/18 associated high grade cervical lesions (US ) Prevalence of HPV 16/18 in CIN2+ lesions decreased 53.6% to 28.4% among women >= 1 dose (P=<.001) Unvaccinated (57.1% vs 52.5%; P=.08) Unknown vaccination status (55.0% vs 50.5%; P=.71). Prevention effectiveness for CIN2+ dependent on timing 21% (95% CI: 1 37) if initiated vaccination months 49% (95% CI: 28 64) ) if initiated vaccination months 72% (95% CI: 45 86) if initiated vaccination >48 months prior to the screening test that led to CIN2+ diagnosis. Vaccine Mar 24;33(13):

33 Impact of Bivalent HPV Vaccine on Oral HPV Infection Of 7,466 women yrs randomized to receive HPV vaccine or hepatitis A vaccine 5,840 oral specimens at final 4 year study visit Oral prevalence of mucosal HPV was low (1.7%) 15 HPV 16/18 infections in hepatitis A group vs 1 in HPV vaccine group estimated vaccine efficacy of 93.3% Herrero R, et al. Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV vaccination in a randomized clinical trial in Costa Rica. PLOS ONE 2013;8:e

34 VIVIANE Study In women older than 25 years, the HPV 16/18 vaccine continues to protect against infections, cytological abnormalities, and lesions associated with HPV 16/18 and CIN1+ irrespective of HPV type, and infection with non vaccine types HPV 31 and HPV 45 over 7 years of follow up. Lancet Dec 20;384(9961):

35 Pap Smear Guidelines

36 Healthy People 2020 goal is 80% Combined boys/girls HPV vaccination rate =56% for one shot Females 63% one dose 42% three doses Males 50% one dose 28% three doses

37 HPV Vaccine Communications During the Healthcare Encounter HPV vaccine is often presented as optional whereas other adolescent vaccines are recommended Some expressed mixed or negative opinions about the new vaccine and concerns over safety/efficacy When parents expressed reluctance, providers were hesitant to engage in discussion Ineffective communication skills Some providers shared parents views that teen was not at risk for HPV and could delay vaccination until older Don t recommend (many reasons) Lack knowledge about HPV or vaccine Miss opportunities (few visits for adolescents) Goff S et al. Vaccine 2011;10: Hughes C et al. BMC Pediatrics 2011;11:74

38 Why are rates so low? Providers A clear recommendation from YOU-the provider- Is the main reason parents decide to vaccinate

39 Some Basic Information

40 Do I need to restart the HPV vaccine Never! series? ACIP recommends that all three shots of the HPV vaccine series be given over six months; 2 nd shot one to two months after the first 3 rd dose should be 6 months after the 1 st If longer - do not need to restart the series Even if months or years just complete the series

41 Vaccine Questions Already been exposed to virus? Do not withhold HPV vaccine from people who are already sexually active. Can still get protection from HPV types that have not been acquired

42 HPV vaccines should not be given to: Patients with allergies to any vaccine component. HPV 9 & 4 vaccine not recommended if allergies to yeast or a reaction to it before. HPV 2 vaccine (prefilled syringes) not recommended if life-threatening latex allergy. Patients with moderate or severe acute illnesses. wait until the illness improves before getting vaccinated.

43 Safety? 90 Million Doses in the US 200 Million Doses World Wide

44 HPV Vaccine Safety Monitoring: VAERS No new safety concerns have been identified in post licensure vaccine safety surveillance among male or female recipients of HPV4 vaccine 7.9% serious side effects=headache, N/V, fatigue, dizziness, syncope, generalized weakness Syncope a frequently reported adverse event following immunization among adolescents 15 minute observation period is encouraged 44

45 Ethics/Liability Providers: As a provider, it is your duty to inform patients of the HPV vaccine as cancer prevention the same way as recommending mammography and colonoscopy.

46 Cost should not be an issue VFC, ASN, ACA AAP has created numerous resources to help practices understand their costs to immunize and to lower costs 124/Supplement_5/S573

47 Healthcare Effectiveness Data and Information Set National Committee for Quality Assurance (NCQA) released new technical specifications for the 2017 edition of health care s most widely used performance improvement tool, the Healthcare Effectiveness Data and Information Set (HEDIS1) 90% of health care plans participate

48 HEDIS: What gets measured, gets done Previously assessed receipt of adolescent vaccines using 2 separate measures. Assessed proportion of females who had received three doses of the HPV vaccine by age 13. Assessed all adolescents receipt of the meningococcal and Tdap vaccines by age 13 Now combined in single measure that reports receipt of recommended vaccines (mening, Tdap, HPV) for female and males Low HPV rates will pull you down

49 Practical Implications for Continuing Education Clinicians should strongly recommend that all of their patients be vaccinated against HPV at age years Bundled with Tdap and MCV4 Completion of series by 13 for greatest effectiveness. Clinicians and their staff should be ready to answer FAQs accurately and succinctly. The CDC has scripts, tips, time savers, and other free resources

50 Communication Skills Building and Q&A

51 What to Avoid Patronizing Information dump Don t give information they did not ask for Don t correct them harshly Don t focus on HPV as an STI (focus on cancer) Don t focus on mandatory vs. recommended Don t use close ended questions Ex: Do you want to do this? Don t close off opportunity for future discussion Find something to affirm ( I think you are doing a great job. )

52 Provide a strong bundled HPV vaccine recommendation: Jack is due for three vaccines today. These will help protect him from meningitis, HPV cancers, and pertussis. We ll give those shots at the end of the visit. Do you have any questions?

53 Provide a strong recommendation for Adults: "I noticed you have not received the HPV vaccine (or finished/completed). I recommend the you start/continue that series today.

54 Provide a strong recommendation for Adults: It can protect you from infection by the HPV virus. HPV infections can lead to cervical, vulvar, and vaginal cancer in women and penile cancer in men and oropharyngeal and anal cancer in both men and women.

55 Some Parents Just Need Reassurance Some parents may be interested in vaccinating, yet still have questions. They need additional reassurance from YOU, the clinician they trust with their child s health care Our team is so dedicated to cancer prevention that I m sure the doctor will want to talk with you further about your concerns. Ask parents about their main concern (be sure you are addressing their real concern) I think I hear that you are concerned about. Reinforce that this is just about preventing cancer in their child, plain and simple.

56 Hesitance vs. Resistance Hesitance vs Low Vaccine Confidence? More often people are hesitant, not resistant Make providing facts more collaborative Examples: Would you be willing to take a look at this fact sheet? I have found it helpful for people who have questions about the HPV vaccine. Would you be willing to let me share some of what I have learned?

57 Last Try with Those Resistant I understand your view and ultimately this is your decision. I would like to give you a fact sheet in case you have any further questions Affirmation with a twist Affirmation of their concerns I understand your decision to delay despite the risks

58 Why does my child need this vaccine? The HPV vaccine is very important because it prevents cancer. I know we d both like to protect Maureen from cancer and I d feel better if she got her first dose of the HPV vaccine series today.

59 The HPV vaccine will be a green light for sex.

60 The HPV vaccine will be a green light for sex. Studies have shown that getting the HPV vaccine doesn t make kids more likely have sex, or to have sex at a younger age.

61 My son/daughter will wait for marriage/won t be exposed.

62 My daughter will wait for marriage/won t be exposed HPV is so common that almost everyone will be infected at some time. When your daughter marries, she could catch HPV from her husband. He might have been infected before he ever met her.

63 Why Now? Let s wait until the child is older.

64 Why Now? Let s wait until the child is older. HPV vaccination provides the best protection when given at age 11 or 12, which is why I recommend starting the HPV vaccine series today.

65 Would you give it to your child?

66 Would you give it to your child? Yes, I gave it to my child (or grandchild, etc) because I think preventing cancer is very important.

67 Before leaving the exam room, remind parents when to come back. To work, Robert needs the full HPV vaccine series, so... When you check out, please make sure to make an appointment for about 6 weeks and 6 months for the next two shots. Put that appointment on your calendar before you leave the office today!

68 What ELSE Can You DO to prevent death? Increase your knowledge Learn communication skills Engage your entire clinic Identify a champion SOP Multilevel interventions AFIX ACS Steps Audit and Feedback

69 Multilevel Interventions Better patient reminder systems Streamline provider workflows Increase flexibility for patients Standardize provider language Engage providers to use data Improve EHR usability Support interoperability between EHR and iis Support interstate data exchange

70 Evidence Based Approaches to increase HPV rates Enhancing access Increasing community demands Provider based interventions html

71 Review of 34 Peer Review Studies Majority work to increase community demand Patient reminders work! Multi component interventions are effective Strategies with inconsistent findings School located vaccination Provider reminders used alone Vaccination required for attendance (exemption) Programs to reduce out of pocket costs Overall increase in rates small Human Vaccines and Immunotherap 2016, 12:6,

72 ACS HPV Roundtable rhealthcareprofessionals/nationalhpvvaccinati onroundtable/ ResourcesandEducation/SitePages/Home.aspx

73 TOOLS Steps for Increasing HPV Vaccination in Practice: An Action Guide for Clinicians

74 ACS Action Guide Launched June 2015 Tool kit Road map Portal to resources Texted and improved by 30 FQHC pilots Goal to saving lives through cancer prevention Provide overview on steps to start and QI

75 AFIX AFIX as a system/intervention Delivery system to reach providers A&F evidence based Increases coverage for early childhood vaccines Evolved over time Creative solutions needed to QI challenges Communication the problem of low coverage Incentivizing and maintaining participation Setting and measuring goals for improvement

76 Internal Competition Clinic #1 Clinic #2 Clinic #3

77 MD Anderson Cancer Center HPV Cancer Moonshot Program

78 MD Anderson Cancer Center HPV Moon Shot: Organization Flagship #1 Prevention & Screening Flagship #2 Discovery Policy & Education (Lois M. Ramondetta) Screening (Kathleen M. Schmeler) Genomics (Curtis R. Pickering) Target Discovery (Faye M. Johnson) Cancer Prevention & Control Platform: Health Policy Government Relations Professional Education Public Education Platforms/Engines: Cancer Genomics Lab Institute for Applied Cancer Sciences Flagship #3 Immunotherapy & Novel Trials Rare Tumors (Cathy Eng) GYN (Michael M. Frumovitz) Head & Neck (William N. William) Platforms/Engines: Center for Co-Clinical Trials Immunotherapy

79 Flagship 1 Goals Increase HPV vaccination rates for adolescents ages in Texas to 80 percent by 2020; Improve access to cervical cancer screening in underserved populations in the United States and globally; Develop new screening paradigms for noncervical HPV-related malignancies

80 Released January 27, 2016

81 Impact Selected Examples of Media Coverage This is really a sentinel event to have all the centers get together and say we re really not doing the best for our kids, said Dr. Ramondetta, who is also co director of MD Anderson s HPV related Moon Shot initiative. We feel this is an effective, safe and long lasting vaccine that we re not taking advantage of. January 28, 2016 NBC News Channel HPV Consensus Statement Broadcast on over 30 local NBC newscasts nationwide

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83 Educate Providers & Improve Systems Information Transfer Demonstration Project Education staff Education providers A&F Pre/post test Check list progress Plaque provider recognition

84 Packet Patients/Parents: Magnets (write-on) Posters in clinic (CDC and TMA) Patient information Providers: Tips and Time Savers HPV Fact Sheet Clinic/System baseline rates

85 Survivors Linda Ryan: Why my kids get the HPV vaccine: A cervical cancer survivor s story

86 Environmental Change Mass reach social marketing campaign

87 MD Anderson HPV Vaccination Clinic

88 Questions? Lois Ramondetta, MD Professor, Department of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Chief, Division of Gynecologic Oncology Lyndon Baines Johnson General Hospital Harris Health System Co Lead MD Anderson HPV Cancer Moonshot

89 Evidence Based HPV Disease Prevention HPV VACCINE