Everything you and your patients should know about HPV ...
Everything you and your patients should know about HPV vaccination Rebecca B. Perkins MD, MSc Assistant Professor of Obstetrics and Gynecology Boston University School of Medicine/ Boston Medical Center September 16th 2014 Presenter Disclosure Information Rebecca B. Perkins MD MSc Consultant No relevant conflicts of interest to declare or
relevant conflict Grant Research/Support No relevant conflicts of interest to declare or relevant conflict Speakers Bureau No relevant conflicts of interest to declare or relevant conflict Major Stockholder
No relevant conflicts of interest to declare or relevant conflict Other Financial or Material Interest No relevant conflicts of interest to declare or relevant conflict Off Label Use of Vaccines Will be discussed, but in accordance with
current ACIP recommendations Adult Immunization Conference 2014 Questions for you (1) 1. Do you routinely see pre-teens and young adolescents (ages 10-14) in your clinical practice? a. Yes b. No c. Sometimes Questions for you (2) 2. Do you routinely see middle/late adolescents and
young adults (15-26) in your clinical practice? a. Yes b. No c. Sometimes Objectives Overview of HPV-related disease HPV vaccine and recommendations Vaccine safety, impact, and vaccination rates Discuss common barriers in vaccine discussions with parents and evidence-based ways to overcome them What is the morbidity from HPV?
3 million Americans seek medical care for HPV each year 33,000 develop HPV-related cancers HPV currently causes more illness and death than all other vaccine-preventable diseases combined (except influenza) Why do we vaccinate? To prevent HPV-associated cancer Current screening is NOT enough Pap history in women diagnosed with cervical cancer Pap smear within % women
3 years of cancer diagnosed with diagnosis cervical cancer None 53% Normal 28% Abnormal with f/u 9%
Abnormal, no f/u 4% Sung et al, Cancer 2000; 88: 2283-9 Average Number of New HPV-Associated Cancers by Sex, in the United States, 2005-2009 Women(N=20,413) Men(N=12,002) Vagina 4%
Oropharynx Vulva 15% 11% Anus 15% Cervix 55% Jemal A et al. J Natl Cancer Inst 2013;105:175-201
Anus 14% Penis 8% Oropharynx 78% Risk factors for HPV+ and HPVoropharyngeal cancers differ: HPV+: sexual behavior, tobacco HPV-: tobacco, alcohol
Survival from HPV+ and HPVoropharyngeal cancers differs: HPV+: 69% reduction in risk of death (after adjustment for age, when dxed, etc.) Markowitz, ACIP, Oct 2011 HPV-Associated Oropharyngeal Cancers HPV+ cancers increased from 16.3% (1984) to 71.7% (2004) HPV+ cancers
increased by 225%, while HPV- cancers declined 50% Chaturvedi, 2011, J Clin Oncol- data from SEER Why do we want to protect boys from HPV? Oropharyngeal cancers more common in men No screening test for oropharyngeal cancers If trends continue, the annual number of HPV-positive oropharyngeal
cancers is expected to surpass the annual number of cervical cancers by the year 2020 Without vaccination, annual burden of genital HPV in U.S. females: 3 million cases, $7 billion 10,846 new cases of cervical cancer 4,000 deaths 330,000 new cases of HSIL (CIN2/3) 1 million new cases of genital warts 1.4 million new cases of LSIL (CIN1)
American Cancer Society. 2008;. Schiffman Arch Pathol Lab Med. 2003; Koshiol Sex Transm Dis. 2004; Insinga, Pharmacoeconomics, 2005 HPV infection causes preterm delivery 330,000 women undergo cone/ LEEP procedures every year LEEP/HPV infection associated with obstetric morbidity Preterm delivery Preterm rupture of membranes Low birth weight Long term developmental outcomes, neonatal intensive care costs
HPV vaccination can prevent preterm deliveries! Recommendations, Safety, Impact, & Coverage Rates HPV VACCINE HPV Prophylactic Vaccines Recombinant L1 capsid proteins that form virus like particles (VLP) Non-infectious and nononcogenic Produce higher levels of neutralizing antibody than natural infection
HPV VLP ACIP HPV Vaccine Recommendations Population Recommendation Females Routine vaccination with either HPV4 or HPV2 Routine catch-up vaccination either HPV4 or HPV2*
Routine vaccination with HPV4 Catch-up vaccination HPV4 Permissive recommendation HPV4 Catch-up vaccination HPV4 11-12 (as young as 9) 13-26 Males
11-12 (as young as 9) 13-21 22-26 MSM & HIV+ Males 22-26 * Irrespective of history of abnormal Pap, HPV, genital warts MMWR, May 28 2010; 59(20):626-629 , 630-632 MMWR , December 23 2011; 60(50);1705-1708
Parents and adolescents want to know IS IT SAFE? DOES IT WORK? WILL IT CHANGE MY CHILDS BEHAVIOR? HPV Vaccine Safety Most common adverse events reported were
considered mild For serious adverse events reported, no unusual pattern or clustering that would suggest that the events were caused by the HPV vaccine These findings are similar to the safety reviews of MCV4 and Tdap vaccines 57 million doses of HPV vaccine distributed in US since 2006 100 million doses worldwide (Europe, Australia) HPV vaccine long-term safety data Kaiser-Permanente: 190,000 females who received 1
dose of HPV vaccine August 2006 and March 2008 No increase in emergency room visits, hospitalizations, or any of 200 categories of illnesses Karolinska Institute: Register based cohort study, Denmark and Sweden, October 2006 to December 2010. 997,585 girls aged 10-17, among whom 296,826 received a total of 696,420 qHPV vaccine doses
No increase in auto-immune disease, thromboembolic disease, neurologic disease Arnheim-Dahlstrm, BMJ, Oct 2013 Klein NP, Archives of Pediatrics and Adolescent Medicine Oct 2012 Serious and nonserious reports of adverse events after administration of HPV4 vaccine in females, by year Vaccine Adverse Event Reporting System, United States, June 2006March 2013 HPV Vaccine Impact: US 33% of teens are fully vaccinated
56% decline in HPV 6/11/16/18 in girls age 14-19 20% decrease in all CIN2/3 among 21-24 year olds Substantial decrease in genital warts among female military under age 26 between 2007 to 2010 Garland et al, Prev Med 2011; Ali et al, BMJ 2013; Markowitz JID 2013; Niccolai, Cancer Epidemiol Biomarkers Prev 2013; Nsouli-Maktabi MSMR 2013 Genital warts in Australia 2004-11 70% vaccination rate Women Men
51% decline 73% decline 93% decline Ali H et al. BMJ 2013;346:bmj.f2032 2013 by British Medical Journal Publishing Group 82% decline 46% effectiveness against high-grade
cervical lesions Efficacy exceeds trial data Crowe E et al. BMJ 2014;348:bmj.g1458 2013 by British Medical Journal Publishing Group Extrapolating the prior pyramid with projections of vaccine efficacy based on Australian data Cervical cancer 46% reduction in CIN2/3 requiring LEEP* 85% reduction in genital warts 35% reduction in CIN1 Having sex gives you HPV,
but getting an HPV vaccine does not make you have sex! HPV Transmission 80% of people will be infected with HPV Most common route is sexual intercourse genital-genital, anal-genital, oral-genital, manual- genital Nearly 50% of high school students have already engaged in sexual (vaginal-penile) intercourse 1/3 of 9th graders and 2/3 of 12th graders have engaged
in sexual intercourse 24% of high school seniors have had sexual intercourse with 4 or more partners Jemal A et al. J Natl Cancer Inst 2013;105:175-201 HPV is found in virgins Study examined the frequency of vaginal HPV and the association with non-coital sexual behavior in longitudinally followed cohort of adolescent women without prior vaginal intercourse HPV was detected in 46% of women prior to first vaginal sex
70% of these women reported non-coital behaviors that may in part explain genital transmission Shew, J Infect Dis. 2012 Infection From Time of First Rapid acquisition of HPV in following sexual debut Sexual Intercourse Study of 18-23 year-old males (n=240) Study of female college students (N=603)
Cumulative Incidence of HPV Infection 1 0.8 0.6 0.4 0.2
0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 Months Since First Intercourse From Winer RL, Lee S-K, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157:218226. Reprinted with the permission of Oxford University Press. Partridge, JID 2007
HPV may never go away Infection remains dormant for decades, then reactivates later in life as immune system declines Risk of HPV infection among women 50+ was associated with total lifetime partners but not new partners. Conclusion: Reactivation risk may increase around age 50 years and contribute to a larger fraction of HPV detection at older ages, compared with new acquisition. 85% of incident infections occurred during periods of abstinence of monogamy, and were associated with lifetime number of sexual partners
Gravitt, JID 2013; Rostich Cancer Res 2012 Receiving HPV Vaccine Does Not Increase Promiscuity National Survey of Family Growth n=1243 15-24 yo females HPV vaccination NOT associated with: Being sexually active Number of sexual partners HPV vaccination was associated with: More consistent condom use among 15-19 year olds (AOR=3.0, always wearing condom)
Kaiser Permanente Center for Health Research n=1398 11-12 yo girls in 2006, 30% of whom were vaccinated, followed thru 2010 No difference in markers of sexual activity including pregnancies, counseling on contraceptives, and testing for or diagnoses of sexually transmitted diseases Liddon NC, Am J Prev Med 2012;42:44 Bednarczyk RA, Pediatrics 2012;130:798 Understanding missed opportunities
WHY ARENT WE VACCINATING MORE? Questions for you (3) 3. What proportion of high school students have had one dose of the meningitis vaccine? a. 25% b. 50% c. 75% Questions for you (4) 4. What proportion of female high school students have had at least one dose of HPV vaccine? a. 25%
b. 50% c. 75% US behind other nations in uptake of 3 doses HPV vaccine 90 80 70 60 50 40 30 20 10
0 Australia UK Canada Netherlands Brotherton, Lancet 2011; Cuzick BJC 2010; Ogilvie et al., 2010; Marc et al., 2010, NIS-Teen 2011 USA
National Estimated Vaccination Coverage Levels among Adolescents 13-17 Years, National Immunization Survey-Teen, 2006-2013 Tdap: tetanus, diphtheria, acellular pertussis vaccine. MCV4: meningococcal conjugate vaccine HPV: human papillomavirus vaccine Actual and Achievable Vaccination Coverage if Missed Opportunities Were Eliminated: Adolescents 13-17 Years, NIS-Teen 2013 Missed opportunity: Encounter when some, but not all ACIP-recommended vaccines are given. Sotkley, MMWR 2014.
Strength of HPV Vaccine Recommendation for Female Patients, Pediatricians and Family Physicians (N=609) Allison et al. https://cdc.confex.com/cdc/nic2011/webprogram/Paper25181.html Delay more common than refusal Providers introduce HPV vaccination at 11 but do not recommend it strongly Id honestly say its rare that I spend more than 20 seconds on it at 11 So few 11 year olds are physically mature to be sexually active that its, I find its almost sort of an awkward conversation.
Parents do not understand the reason to vaccinate at early I thought that it didnt really make any difference as long as they had the three vaccines before their 20s. Perkins et al, Pediatrics, 2014 Uptake of 3 doses HPV vaccine by age 100 90 80 70 60 50
40 30 20 10 0 NIS-Teen 2012 13 14 15
16 17 Prevalence of sexual activity by age 82% 67% 35% 18 to 24 Markowitz MMWR 2007; Holl Henry J Kaiser Found 2003;
Mosher Adv Data 2006 The younger the better, but better late than never Vaccine 50% more effective when vaccination occurs age 15-17 compared with over age 18 46% vs. 35% reduction in HSIL 35% vs. 0% reduction in LSIL No protection if evidence of infection prior to vaccination (i.e. abnormal pap) Mahmud et al, J Clin Onc, Jan 2014
HPV vaccine effectiveness for cervical abnormalities in Australia Gertig DM, BMC Med 2013 HPV vaccination for ages 18-26 <20% of eligible females vaccinated National Longitudinal Study of Adolescent Health (n=3276) 9% of women positive for HPV 6,11,16 or 18 0% of women positive for all 4 types Provider recommendation most
influential factor in this age group Price Cancer 2011; Dempsey Vaccine 2008 and 2011; Rosenthal, Vaccine, 2010 Top 5 reasons for not vaccinating boys and girls, NISTeen 2013 * Not mutually exclusive. ** Did not know much about HPV or HPV vaccine. Framing makes a difference BAD Provider: Meghan and Mark are due for some shots today: Tdap and the meningococcal vaccine. There is also the HPV vaccine - Vaccine perceived as different, optional, unimportant
GOOD Provider: Meghan and Mark are due for some shots today: HPV, meningococcal vaccine, and Tdap. Presumption of vaccine uptake Vaccination percieved as normative, important CATCH UP Provider: I see that Meghan and Mark havent gotten their HPV vaccines yet. We should definitely start that today! - Presumption of vaccine uptake, conveys message of importance Opel et al 2014 Each adolescent visit may be your last chance to vaccinate!
30% of adolescents never present for preventive care 1 in 15 adolescent visits is for preventive care. Preventive visits decline after age 13 Late adolescent males had the fewest preventive visits - 6% of all visits Late adolescent females had the most visits, but only 3% were for preventive care.
Early adolescents (11-14 years old) had 3 times more preventive visits than late adolescents. Rand et al. Arch Pediatr Adolesc Med Addressing all concerns in 45 seconds Provider: Meghan and Mark are due for their HPV vaccine. Parent: Why do they need an HPV vaccine? Provider: The HPV vaccine will help protect them from cancer caused by HPV infection. We know that HPV infection is dangerous 33,000 people in the US get cancer from HPV every year. And we know that the HPV vaccine is safe over 100 million doses have been given and there havent been any serious side effects. Parent: I dont think they need that yet
Provider: Vaccines only work if theyre given before exposure we never wait until a child is at risk to give any recommended vaccines. HPV vaccine is also given as early as possible because it produces a better immune response in younger adolescents. Thats why it is so important to start the shots now and finish all 3 of them in the next 6 months. Parents weigh risks and benefits Parents who declined vaccine and those who accepted had similar concerns Both had concerns related to safety and sexuality but accepters weighed cancer prevention more heavily Most parents also believed their daughters would at some point be at risk for STIs
Perkins et al, Clin Peds 2013; Perkins et al J of Peds 2010; Perkins et al J Healthcare Poor Underserved 2013 Providers overestimate parents concerns From what I understand the vaccine is safe, efficacious and Id be a fool and also have amnesia to believe that high schoolers do not engage in unwise sexual practices at times. Father of a 12 year-old 55-90% of parents and adolescents will follow provider recommendations Many adolescents seeking contraception will be unvaccinated family planners are very important vaccinators
Perkins et al, published abstract JAH, Brewer 2007, Prev Med Discuss HPV vaccination when you screen moms for cervical cancer One doctor says: In your experience with your health right now, you may be screened for cervical cancer by means of a pap smear because cervical cancer can obviously be something that can be life-threatening but if caught soon, it can be taken care of, and this is how your health is impacted by this virus right now. Well, children now have the option of getting the HPV vaccine which is actually very effective at reducing the risk for contracting that same virus.
HPV is common and dangerous 3 million Americans seek medical treatment for HPV-related disease every year 11,000 women every year get cervical cancer 30% of them were screened on time 21,000 men and women every year get HPVrelated cancers for which there are no screening tests We can do better HPV vaccination IS high quality care
75% reduction in cervical pre-cancer BEFORE AGE 14 35% reduction after age 14 85% reduction in genital warts 100 million doses have been given worldwide with no evidence of serious side effects A strong recommendation is critical Conclusions Vaccinating all your patients with HPV vaccines will save lives and improve health
For more information, including free resources for providers and patients: cdc.gov/vaccines/teens
rule 602 requires actual "knowledge" for most types of evidence. knowledge means physical perceptions only! but: in a practical justice system, we need some room for opinions. chap. 9 -- opinion evidence. 2018
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