Presentation on theme: "HPV-RELATED CANCER Understanding the Burden of HPV Disease and the Importance of the HPV Vaccine Recommendation Lois Ramondetta, MD Professor Gynecologic."— Presentation transcript:
HPV-RELATED CANCER Understanding the Burden of HPV Disease and the Importance of the HPV Vaccine Recommendation Lois Ramondetta, MD Professor Gynecologic Oncology MD Anderson Cancer Center Chief Gynecologic Oncology at LBJ Hospital
Objectives Review the epidemiology of HPV. Compare the impact of HPV infection on cancer in females and males. Examine prevention mechanisms for HPV. Analyze societal resistance to HPV vaccine Formulate community education plans that support HPV prevention.
HPV Infection Almost ALL will be infected with at least one type of HPV at some point Most will never know they’ve been infected 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:
HPV Types Differ in Their Disease Associations Mucosal sites of infection Mucosal sites of infection Cutaneous sites of infection Cutaneous sites of infection ~ 80 Types “Common” Hand and Foot Warts “Common” Hand and Foot Warts ~40 Types Genital Warts Laryngeal Papillomas Low Grade Cervical Disease Genital Warts Laryngeal Papillomas Low Grade Cervical Disease Low risk (non-oncogenic) HPV 6, 11 High risk (oncogenic) HPV 16, 18 Cervical Cancer Anogenital Cancers Oropharyngeal Cancer Cancer Precursors Low Grade Cervical Disease Cervical Cancer Anogenital Cancers Oropharyngeal Cancer Cancer Precursors Low Grade Cervical Disease
Cervical Cancer Screening Pap (Papanicolaou) Test A test which collects cells from the surface of the cervix and looks for abnormal cells Precancer can be detected and treated before cervical cancer develops HPV testing added as part of screening, resulting in improved sensitivity while safely allowing for extension of screening intervals
New Cervical Cancer Screening Guidelines: ACS, USPSTF, ACOG ACS 2012 USPSTF 2012 ACOG 2012 Age to startAge 21 years Women ages years Pap every 3 years Pap every 3 years Women ages years Cotesting every 5 years (preferred) or Every 3 years with Pap alone Cotesting every 5 years or Every 3 years with Pap alone Cotesting every 5 years (preferred) or Every 3 years with Pap alone Screening among fully vaccinated Same as for non- vaccinated Not reviewedSame as for non- vaccinated *All guidelines recommend that women who have been adequately screened can discontinue Pap at age 65. ACS: American Cancer Society USPSTF: US Preventive Services Task Force ACOG: American College of Obstetricians and Gynecologists
Section 1: HPV is common and easily transmitted
HPV Infection/Exposure Can occur with any intimate sexual contact Intercourse is not necessary for infection Nearly 50% of high school students have already engaged in sexual (vaginal-penile) intercourse 1/3 of 9th graders & 2/3 of 12th graders have engaged in sexual intercourse 24% of high school seniors have had sexual intercourse with four or more partners Jemal A et al. J Natl Cancer Inst 2013;105:
Cervical Cancer Cervical cancer - most common HPV-associated cancer 500,000 cases & 275,000 deaths world-wide in 2008 11,000+ cases & 4,000 deaths in 2011 in the U.S. 37% cervical cancers occur between the ages of 13% (or nearly 1 in 8) between 24% (or nearly 1 in 4) between CDC. HPV–associated cancers—US, 2004–2008. MMWR 2012;61(15):258–261. Cervical Cancer Counts by Age. US Cancer Statistics data from 2010, CDC.gov.
HPV-Associated Cervical Cancer Rates by State, United States - Rates are per 100,000 and age-adjusted to the 2000 U.S. Standard Population (19 age groups – Census P ) standard. - Data from population-based cancer registries participating in the CDC’s supported National Program of Cancer Registries or NCI’s -supported Surveillance, Epidemiology, and End Results Program, includes all states meeting USCS publication criteria for all years 2006–2010 and covers approximately 94.8% of the U.S. population.National Program of Cancer Registries - Results†Source:
Oropharyngeal and Anal Cancer Oropharynx is principal site of head & neck cancers HPV-related in 60-80% of cases HPV type 16 accounts for more than 90% of HPV positive cases In the US, 10,000-12,000 new cases yearly A.K. Chaturvedi JCO 2011 Anal Cancer In US, greater than 7,000 new cases yearly More than 80% are HPV related
HPV-Associated Cervical Cancer Rates by Race and Ethnicity, United States, 2004–2008 Jemal A et al. J Natl Cancer Inst 2013;105:
Oropharynx Average Number of New HPV-Associated Cancers by Sex, in United States, n=3039 n=2317 n=3084 n=11279 n=9312 n=1687 n=1003 Jemal A et al. J Natl Cancer Inst 2013;105: n=694
Annual Report to the Nation on the Status of Cancer: HPV associated cancers From 2000 to 2009, oral cancer rates increased 4.9% for Native American men 3.9% for white men 1.7% for white women 1% for Asian men Anal cancer rates doubled from 1975 to 2009 Vulvar cancer rates rose for white and African- American women Penile cancer rates increased among Asian men
HPV-Associated Oropharyngeal Cancers Prevalence increased from 16.3% ( ) to 71.7% ( ) Population-level incidence of HPV-positive cancers increased by 225% while HPV-negative cancers declined by 50% 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 Chaturvedi, 2011, J Clin Oncol- data from SEER
Numbers of Cancers and Genital Warts Attributed to HPV Infections, U.S. CDC. Human papillomavirus (HPV)-associated cancers. Atlanta, GA: US Department of Health and Human Services, CDC; Available at
Complications related to current methods of cervical cancer prevention Infertility due to treatment of cervical cancer by hysterectomy Cervical conization and loop electrosurgical excision procedure (LEEP) procedures associated with adverse obstetric morbidity Subsequent pregnancies are at risk of Perinatal mortality Severe and extreme preterm delivery (<32/34 or <28/30 weeks) Severe and extreme low birth weight (< 2000g or 1500g) These outcomes have a considerable impact—not only on the mothers and infants concerned—but also on the cost of neonatal intensive care
Section 2: High HPV vaccination rates have measurable population-level effects
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 VLP
HPV Vaccine Quadrivalent/HPV4 (Gardasil) Name Bivalent/HPV2 (Cervarix) Merck Manufacturer GlaxoSmithKline 6, 11, 16, 18 Types 16, 18 Females: Anal, cervical, vaginal and vulvar precancer and cancer; Genital warts Males: Anal precancer and cancer; Genital warts Indications Females: Cervical precancer and cancer Males: Not approved for use in males Pregnancy Hypersensitivity to yeast Contraindications Pregnancy Hypersensitivity to latex (latex only contained in pre-filled syringes, not single-dose vials) 3 dose series: 0, 2, 6 months Schedule (IM) 3 dose series: 0, 1, 6 months
Quadrivalent HPV vaccine (Gardasil) Recommendation for Males Age for prevention of anal cancer and gential warts Age who haven’t started or completed series Age may get vaccine Teen -26 who identify as gay or bisexual and haven’t started or completed series
Nonavalent human papillomavirus vaccine HPV-types 6/11/16/18/31/33/45/52/58 Coming soon near you!
HPV Vaccine Safety Most common adverse events reported-considered mild For serious adverse events, no unusual pattern or clustering that suggest events caused by HPV vaccine Similar to safety reviews of MCV4 and Tdap vaccines 57 million doses of HPV vaccine in US since 2006
HPV Vaccine Safety Monitoring: VAERS & IOM No new safety concerns identified among male or female recipients of HPV4 vaccine Among the 7.9% of reports coded as “serious”, most frequently cited are headache, nausea, vomiting, fatigue, dizziness, syncope, generalized weakness Inadequate evidence found for causal relationships between HPV vaccination and 12 other specific health events studied Syncope frequently reported among adolescents Adherence to a 15-minute observation period after vaccination is encouraged 24 Institute of Medicine. Adverse Effects of Vaccines: Evidence and Causality. Washington DC. The National Academies Press, 2012.
HPV Vaccine Safety The 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
HPV Vaccine Safety Data Sources Post-licensure safety data (VAERS) 1 Post-licensure observational comparative studies (VSD) 2 Ongoing monitoring by CDC and FDA Post-licensure commitments from manufacturers Vaccine in pregnancy registries Long term follow-up in Nordic countries Official reviews WHO’s Global Advisory Committee on Vaccine Safety 3 Institute of Medicine’s report on adverse effects and vaccines, Vaccine Adverse Events Reporting System, 2 Vaccine Safety Datalink,
HPV Vaccine Impact: HPV Prevalence Studies NHANES Study National Health and Nutrition Examination Survey (NHANES) data used to compare HPV prevalence before the start of the HPV vaccination program with prevalence from the first four years after vaccine introduction In year olds, vaccine-type HPV prevalence decreased 56 percent, from 11.5 percent in to 5.1 percent in Other age groups did not show a statistically significant difference over time The research showed that vaccine effectiveness for prevention of infection was an estimated 82 percent Cummings T, Zimet GD, Brown D, et al. Reduction of HPV infections through vaccination among at-risk urban adolescents. Vaccine. 2012; 30:
HPV Vaccine Impact: HPV Prevalence Studies, continued Clinic-Based Studies Significant decrease from 24.0% to 5.3% in HPV vaccine type prevalence in at-risk sexually active females years of age attending 3 urban primary care clinics from , compared to a similar group of women who attended the same 3 clinics in 2010 Significant declines in vaccine type HPV prevalence in both vaccinated and unvaccinated women aged years who attended primary care clinics from compared to those from the pre-vaccine period ( ) Kahn JA, Brown DR, Ding L, et al. Vaccine-Type Human Papillomavirus and Evidence of Herd Protection After Vaccine Introduction. Pediatrics. 2012; 130:
HPV Vaccine Impact: Genital Warts Studies Ecologic analysis used health claims data to examine trends in anogenital warts from among a large group of private health insurance enrollees The study found significant declines after 2007 in females aged year (38% decrease from 2.9/1000 PY in 2006 to 1.8/1000 PY in 2010) Smaller declines were observed among those years but not in those over 30 years A similar study evaluated genital wart trends in males and females attending public family planning clinics and found Significant decrease of 35% (.94% to.61%) in females under 21 years of age and a 19% decrease in males less than 21 years No decreases were reported in the older males or females
HPV Vaccine Impact: High HPV Vaccine Coverage in Australia 80% of school-age girls in Australia are fully vaccinated High-grade cervical lesions have declined in women less than 18 years of age For vaccine-eligible females, the proportion of genital warts cases declined dramatically by 93% Genital warts have declined by 82% among males of the same age, indicating herd immunity Garland et al, Prev Med 2011 Ali et al, BMJ 2013
HPV Vaccine Impact: High HPV Vaccine Coverage in Australia 80% of school-age girls in Australia-fully vaccinated High-grade lesions declined in women less than 18 years of age Proportion of genital warts declined by 93% For vaccine eligible females Genital warts declined by 82% among males of the same age, indicating herd immunity In the US, prevalence of vaccine types declined by more than half (33% of teens fully vaccinated) Garland et al, Prev Med 2011 Ali et al, BMJ 2013
ESTIMATED 3-DOSE COVERAGE Markowitz L et al, JID, 2013 Markowitz L et al, Vaccine, 2012 Ali H et al, BMJ, 2013
The Perfect Storm Vaccine issues sensationalized by popular media Different reasons for why some don’t get the first shot and why some don’t finish all 3 shots Parents think sexuality instead of cancer prevention Many clinicians aren’t giving strong recommendations Parents have questions that are seen as hesitation by doctors Systems interventions depend on clinician commitment Phased girls then boys recommendations initially confusing
National Estimated Vaccination Coverage Levels among Adolescents Years, National Immunization Survey-Teen, CDC. National and State Vaccination Coverage Among Adolescents Aged 13–17 Years — United States, 2012 MMWR 2013; 62(34);
Coverage of 1 or More Doses of HPV Vaccine, Female Adolescents Age Years, st Shot 51% of eligible girls 24% of eligible boys All Three 30% girls and 7% boys.
HPV Vaccination Legislation Across U.S. Mandatory for school attendance Require schools to provide information to parents/guardians; allow pharmacists to provide vaccination, etc. No 2014 legislation WA OR CA NV IDID IL TX CO KS IA NB MT WY UT ND SD AZ NM MN OK AK HI LA AR MO WI IN MI MSAL FL MD PA OH WV KY TN NC GA SC NY NJ VT NHNH ME VA DE RI CT MA Only Virginia and D.C. have enacted mandatory HPV vaccination for school attendance Source: NCSL
HPV Vaccination Legislation Across U.S. Passed Failed WA OR CA NV IDID IL TX KS IA NB MT WY UT ND SD AZ NM MN OK AK HI LA AR MO WI IN MI MSAL FL MD PA OH WV KY TN NC GA SC NY NJ VT NHNH ME VA DE RI CT MA Only Virginia and D.C. have enacted mandatory HPV vaccination for school attendance Source: NCSL CO
Vaccination Estimates among Adolescent Girls Years by Race/Ethnicity, NIS-Teen 2011 ** ** statistically significant (p<0.05) 2011 NIS-Teen available at
HPV Vaccination Uptake among Adolescent Boys Available data represents vaccination activities prior to implementation of routine recommendation approved in October, 2011 8.3% of boys years of age have initiated the series So far vaccine uptake (coverage) follows the same pattern as observed for girls Higher coverage among boys living below the poverty level Higher coverage among Black and Hispanic boys Based on only one year of data 2011 NIS-Teen available at
Among girls unvaccinated for HPV, 78% had a missed opportunity Actual and Achievable Vaccination Coverage if Missed Opportunities were Eliminated: Adolescents Years, NIS-Teen 2011 Missed opportunity: encounter when some but not all ACIP-recommended vaccines are given HPV-1: receipt of at least one dose of HPV 2011 NIS-Teen available at
Avoid Missed Opportunities HPV vaccine can safely be given at the same time as the other recommended adolescent vaccines Provide HPV vaccine during routine sports, or camp physicals Review immunization record even at acute care visits Encourage parents to keep accurate vaccination records and to review the immunization schedule Systems interventions depend on clinician commitment- determine what would work best for YOUR practice
Why We Need to Do Better in HPV Vaccination of 12 year olds For each year we stay at 30% coverage instead of achieving 80%, 4,400 future cervical cancer cases and 1400 cervical cancer deaths will occur. Currently 26 million girls <13 yo in the US; If none of these girls are vaccinated then: 168,400 will develop cervical cancer and 54,100 will die from it Vaccinating 30% would prevent 45,500 of these cases and 14,600 deaths Vaccinating 80% would prevent 98,800 cases and 31,700 deaths
Is she really too young? Take 1 (a conversation you may be familiar with) Doctor: Meghan is due for some shots today: Tdap, meningococcal conjugate vaccine, and HPV. Parent: Why does she need an HPV vaccine? She’s only 11! Doctor: We want to make sure she gets the shots before she becomes sexually active. Parent: Well I can assure you Meghan is not like other girls- she’s a long way off from that! Doctor: We can certainly wait if that would make you feel more comfortable.
Rationale for vaccinating early: Protection prior to exposure to HPV Markowitz MMWR 2007; Holl Henry J Kaiser Found 2003; Mosher Adv Data % 18 to 24
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
A Strong Recommendation at 11 Doctor: Meghan is due for some shots today: Tdap, meningococcal conjugate vaccine, and HPV. Parent: Why does she need an HPV vaccine? She’s only 11! Doctor: HPV vaccine will help protect Meghan from cancer caused by HPV infection. And I want to make sure Meghan receives all 3 doses and develops protection long before she becomes sexually active. Parent: But it just seems so young… Doctor: We’re vaccinating today so your child will have the best protection possible well before the start of any kind of sexual activity. HPV vaccine is also given when kids are 11 or 12 years old because it produces a better immune response at that age. That’s why it is so important to start the shots now and finish them in the next 6 months. This vaccine can’t wait.
Questions Should Be Encouraged, Not Interpreted as Refusal Doctor: Olivia needs her Tdap and meningococcal vaccines today. We could also give her the HPV vaccine. Parent: Do you think she needs all of those today? Can’t we just skip the HPV one? I’m not sure she really needs that anyway. Doctor: Sure, we can wait until her next visit to give her that one.
Parents who do not intend to vaccinate daughter in next 12 months, NIS-Teen * Not mutually exclusive. ** Did not know much about HPV or HPV vaccine.
Receipt of HPV Vaccine Does Not Increase Sexual Activity or Decrease Age of Sexual Debut Kaiser Permanente Center for Health Research 1,398 girls who were 11 or 12 in 2006, 30% of whom were vaccinated, followed through 2010 No difference in markers of sexual activity, including pregnancies counseling on contraceptives testing for, or diagnoses of STDs Risk perceptions after HPV vaccination were not associated with riskier sexual behaviors Bednarczyk et al Pediatrics Oct 2012 Mayhew A Mayhew A et al Pediatrics. Mar 2014Pediatrics.
How to respond to Mom Doctor: Olivia needs the HPV, Tdap and meningococcal vaccines today. Parent: Do you think she needs all of those today? Can’t we just skip the HPV one? I’m not sure she really needs that anyway. Doctor: HPV vaccination is very important to help prevent cancer caused by HPV infection. I want to help protect Olivia from cancer and I know you want that too. That’s why I’m recommending that Olivia receive the first dose of HPV vaccine today. Parent: I didn’t realize that. Doctor: She’ll need to come back in for the next 2 doses of the HPV vaccine for full protection. Please make your appointments at the front desk for the 2 nd and 3 rd doses of the HPV vaccine.
What about boys? Take 1 Doctor: Henry is due for 3 vaccinations today: Tdap, MCV4 and HPV vaccine. Parent: Why does he need HPV vaccine- isn’t that just for girls? Doctor: It could help protect his partners in the future. Parent: That seems like the girl’s responsibility. Henry is a nice boy—if nothing will happen to him, then why bother? Doctor: It’s completely up to you.
Recommendation for Males Quadrivalent HPV vaccine (Gardasil) recommended for boys at age 11 or 12 years for prevention of anal cancer and gential warts Also for boys 13 through 21 who haven’t started or completed series Young men, 22 through 26 years of age, may get the vaccine Teen boys through age 26 who identify as gay or bisexual and haven’t started or completed series should be vaccinated
Clincian Knowledge of Recommendation for Males Qualitative research with clinicians demonstrated less knowledge about indications and benefits for males When responses were provided, most mentioned protecting their partners; some mentioned prevention of genital warts Few clinicians stated that HPV could cause anal, penile or oropharyngeal cancers in men
Get it for your son, take 2 Doctor: Henry is due for 3 vaccinations today: Tdap, MCV4 and HPV vaccines. Parent: Why does he need HPV vaccine- isn’t it just for girls? Doctor: Boys should also get HPV vaccine when they are 11 or 12 years old. HPV causes cancers in men too. Over 7000 men each year develop a cancer of the mouth, tongue or throat that is caused by HPV, and this number is rising. HPV also causes cancer of the penis and anus. Parent: Wow, I had no idea. Yes, lets him that one too! Doctor: Henry will need to come back for the second and third shots- make an appointment today for those visits.
How Can Clinicians Help? 1.Give a STRONG recommendation Ask yourself, how often do you get a chance to prevent cancer? 2.Start conversation early and focus on cancer prevention Vaccination given well before sexual experimentation begins Better antibody response in preteens 3.Offer a personal story Own children/Grandchildren/Close friends’ children HPV-related cancer case 4.Welcome questions from parents, especially about safety Remind parents that the HPV vaccine is safe and not associated with increased sexual activity
Take-home points 1. HPV causes around 32,500 cancers annually cervix (11,000), oropharynx (12,000), anus/rectum (5,000), vulva (3,000), penis/vagina (1500) 2. HPV vaccination most effective prior to exposure and can be transmitted prior to first coitus 3. Reminder of ACIP recommendation and AAP guidelines: Routine HPV vaccination recommended for males and females ages Catch-up ages (males); (females) Permissive use ages 9-10 (males and females); (males)
A Preventable Disease Lyndon Baines Johnson Hospital Uninsured/underinsured MDACC Outreach Program
Median age (range) 46.2 (25, 72) Race 1 African American Hispanic White Asian/Other 35 (25.2) 76 (54.7) 26 (18.7) 2 (1.4) Marital Status Married/partnered Single Divorced/Widowed/Other 56 (39.6) 55 (40.3) 28 (20.1) Education (missing, n=1) Grade 5 and below Grade 6 – 8 Grade 9 – 11 HS grad or GED Associate degree/some college or trade school College graduate 15 (10.9) 26 (18.8) 34 (24.6) 41 (29.7) 17 (12.3) 5 (3.6) Language English Spanish 99 (66.0) 40 (26.7) Smokers 65 (47.8) Number of children None 1-2 children 3-4 children 5+ children 8 (5.9) 48 (35.3) 46 (33.8) 34 (25.0) Stage at diagnosis IB1 and below IB2 IIA, IIB IIIA, IIIB IVA, IVB 31 (22.3) 25 (18.0) 39 (28.0) 29 (20.9) 15 (10.8) Study Population (n=139)
At diagnosis, 75.5% presented with vaginal bleeding 46% had pelvic and/or back pain 66.4% visited ER for symptoms prior to diagnosis 36.8% visited the ER on 2 or more occasions 67% stated they did not have a primary care physician 21% patients received transfusions for bleeding;
Item Pts with stage lB1 and below Pts with stage lB1 and higher p- value Had Harris County Gold Card prior to diagnosis 62.5%37.3%.01 Visited ER for symptoms13.8%81.4%<.001 Median # months between onset of symptoms and when patient sought care 6 (0, 18)6 (1, 60).20 Median # yrs (range) since last Pap test3 (.5, 20)6 (1, 26).23 Received tranfusion(s) for vaginal bleeding0%26%.003 Has a primary care physician66.7%23.3%<.001 % who answered YES when asked “When you were told you had cancer did you worry about spiritual issues?” 15.6%27%.19 % who answered YES when asked “When you were told you had cancer did you worry about guilty feelings?” 34.4%35.6%.90 Children live with patient33.3%42.2%.39 Patient cares for other family members13%30.8%.048
Why We Need to Do Better in HPV Vaccination of 12 year olds For each year we stay at 30% coverage instead of achieving 80%, 4,400 future cervical cancer cases and 1400 cervical cancer deaths will occur. Currently 26 million girls <13 yo in the US; If none of these girls are vaccinated then: 168,400 will develop cervical cancer and 54,100 will die from it Vaccinating 30% would prevent 45,500 of these cases and 14,600 deaths Vaccinating 80% would prevent 98,800 cases and 31,700 deaths Adapted from Chesson HW et al, Vaccine 2011;29:
MD Anderson Work Groups Comprehensive Cancer Control Cervical Work Group Summit 2012, 2013, 2014 College of American Pathologists (CAP): See Test, & Treat Prevention/Screening grant development HPV interest group Research Basic Science Collaborative
HPV Research Initiative Gynecologic Oncology (Cervix) Head and Neck Anal Cancer Penile cancer Retreat August 9th
Survivor Support 64 Stigma Poverty Uninsured Health Literacy
Questions? Lois Ramondetta, MD
For more information, including free resources for yourself and your patients, visit: cdc.gov/vaccines/teens questions or comments to CDC Vaccines for Preteens and Teens: