HPV vaccine update:

Nonavalent HPV vaccine

Assoc Prof Julia Brotherton

Medical Director, Public Health Physician

National HPV Vaccination Program Register

Medical Director, Registries and Research, VCS

Honorary Principal Fellow

School of Population and Global Health

University of Melbourne

Dr TedrosAdhanomGhebreyesus Director-General WHO calls for an end to cervical cancer, May 2018

3

Nations or territories with HPV vaccine on routine immunization schedule (year of introduction)

American Samoa (2008) Cyprus (2016) Liechtenstein (2013) Samoa (2009)

Andorra (2014) Czech Republic (2012) Lithuania (2016) San Marino (2008)

Anguilla (2016) Denmark (2008) Luxembourg (2008) Seychelles (2014)

Antigua & Barbuda (2013) Dominican Republic (2017) Macedonia FYR (2009) Singapore (2010)

Argentina (2011) Ecuador (2014) Malaysia (2010) Slovenia (2009)

Aruba (2014) Federated States of Micronesia § (2010) Malta (2012) South Africa * (2014)

Australia (2007) Fiji † (2008-09, stopped 2010; 2013) Marshall Islands § (2009) South Korea (2016)

Austria (2008) Finland (2013) Mauritius (2016) Spain (2007)

Bahamas (June 2015) France †† (2006) Mexico † (Subnational 2008-2011; 2012) Sri Lanka (2017)

Barbados (2014) French Polynesia ‡ (2008) Monaco (2006) St. Eustatius (2014)

Belgium (2007, 2010 school prog) Germany (2007) Monserrat (2017) St. Maarten (2013)

Belize (2016) Greece (2008) Netherlands †† (2010) St. Vincent and the Grenadines (2017)

Bermuda (2011) Guam § (2008) New Caledonia (2011) Suriname (2013)

Bhutan * (2010) Guatemala (2018) New Zealand (2009) Sweden (2011)

Bolivia * (2017) Guyana *† (Subnational 2012-13; 2017) Northern Mariana Islands § (2008) Switzerland (2008)

Bonaire (Sep 2015) Honduras (2016) Norway (2009) Tanzania * (2018)

Botswana * (2015) Hungary (2014) Palau (2008) Thailand * (2017)

Brazil * (Mar 2014) Iceland (2011) Panama † (2008) Trinidad & Tobago (2013, stopped 2013;

2015)

British Virgin Islands (2008) India † (Subnational 2016) Paraguay (2013) Turkmenistan (2016)

Brunei (2012) Ireland (2010) Peru * (2011, stopped 2012; 2014) Uganda *† (2015)

Canada (2007) Israel (2010) Philippines † (2015 phased intro 24 provinces) United Arab Emirates (2013)

Cayman Islands (2012) Italy (2008) Portugal (2008) United Kingdom (2008)

Chile (Sep 2014) Jamaica (2017) Puerto Rico (2008) United States (2006)

Colombia † (2012) Japan (2011) Romania (2009-10, stopped 2011) U.S. Virgin Islands (2012)

Cook Islands (2011) Latvia (2010) Russia † (Subnational 2009) Uruguay (2013)

Croatia (2016) Lesotho * (2012, stopped 2015) Rwanda (2011) Vanuatu * (2013, stopped 2013; 2015)

Curaçao (2013) Libya (2014) Saba (2013) Zimbabwe * (2018)

As of 17 August 2018BOLD signifies WHO Member State (n = 90, of which 88 are currently vaccinating and 2 have stopped)

*National/territorial introduction has followed pilot. † National/territorial introduction in phases, either based on geography, target population, or

both. § Introduction as a part of the United States Vaccine for Children Program; may or may not report separately to WHO on Joint Reporting

Form as an official WHO Member State. †† Includes all overseas departments of France and overseas territories of the Netherlands

108 countries and

territories (90 are

WHO Member States)

have HPV vaccine on

national schedule

4

As of 17 August 2018

18 countries and 3 territories

have gender-neutral HPV

vaccination schedules

*province or region specific

Nations or territories with gender-neutral HPV vaccination

schedules (year of introduction)

American Samoa (2011) Grenada (2018)

Argentina Israel

Australia (2013) Italy *

Austria (2006) Liechtenstein (2016)

Barbados New Zealand (2017)

Brazil Northern Mariana Islands (2011)

Canada (2013*) Norway

Croatia (2016) Panama

Czech Republic (2016) Switzerland (2015)

Germany United States (2011)

Guam (2011)

National HPV Vaccination Program• 4vHPV vaccine 3 dose course prevents

infection and disease (CIN, cervical, anogenital cancers and genital warts) due to HPV types 16/18/6/11

• 2007-2009: catch up females aged 12-26

• 2009-present: routine school based vax girls (1st

yr high school – usual age 12-13)

• 2013-2014: catch up program males at school age 12-15 (+ some GP delivery)

• 2015: routine school based vax boys and girls (1st yr high school – usual age 12-13)

• July 2017: routine catch up extended to age 19

• 2018: Two dose course of 9vHPV vaccine

HPV vaccine coverage is rising over time

• Dose 1/2/3 coverage by age 15 years in 2015

– 86/83/78% females

– 78/75/67% males

• By age 15 in 2016 higher

– 87/84/79% females

– 81/79/73% males

National human papillomavirus (HPV)

vaccination coverage for girls at age 15, by dose

number and year, Australia, 2007–2015

Source: Brotherton et al, Med J Aust 2017www.hpvregister.org.au/research/coverage-data

Meta-analysis of outputs from 16 transmission dynamic models suggestselimination of HPV types 6/11/16/18 at 80%+ coverage when both females and males are vaccinated

Brisson et al. Lancet Public Health 2016

Relative reduction of HPV prevalence among women and men after girls-only vaccination….

…and after vaccination of boys in addition to girls

1 2 3 4 5

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A n y H P V t y p eH ig h -r is k H P V

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3 1 , 3 3 , 4 5 ,

5 2 , 5 8

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A n y h ig h -r isk

H P V t y p e s

HPV INFECTIONS AMONG 18-24 YEAR OLD WOMEN ATTENDING CERVICAL SCREENING, BY STUDY PERIOD

92% relative reduction

Unvaccinated 100% 12.5% 10.5%

Partially vaccinated 0% 36.3% 24.5%

Fully vaccinated 0% 51.2% 65.5%

Machalek DA, Garland SM, Brotherton JM et al. JID 2018Slide courtesy of Dorothy Machalek

Reduction in high grade histology- Australia

Catch up HPV vaccination

program

<20s 70.4% p<0.0001

20-24 yrs46.7% p<0.0001

25-29 yrs10.1% p=0.17

30-34 yrs9.1% p=0.32

Source: Cervical Screening in Australia 2018 (AIHW)

Nine valent HPV vaccine

Schiller & Muller. Next generation prophylactic human papillomavirus vaccines. Lancet Oncol. 2015 May;16(5):e217 - e225

The Australian Cervical Cancer Typing Study

Brotherton/Tabrizi et al. Int J Cancer 2017

Nine valent HPV vaccine

96-97% Joura et al NEJM 2015

Slightly more injection site events90.7 vs 84.9% (Joura et al NEJM 2015)

2 dose 9vHPV – what you need to know• Must be aged 14 years or under at time of FIRST dose

– 2nd dose can be given at any age as long as the first dose was under 15 years.

• 2 dose recommended interval is 6-12 months between doses– 12 month interval provides higher antibody level – balance against likely increasing loss to follow up

and risk of sexual activity using a wider routine interval.

– There is NO maximum interval - you can always complete a HPV vaccine course regardless of how long it is since the first dose – they never need to be restarted.

• Absolute minimum spacing (not recommended) is 5 months. – If<5 months apart require a third dose (at least three months after the second dose and at least five

months since dose 1)

• Revaccination if previously immunised with 4vHPV or 2vHPV not recommended– Majority of vaccine effectiveness delivered by protection against 16/18

– Produces lower antibody responses to 31/33/45/52/58 than in naïve subjects but clinical significance unknown

– Likely increased incidence of local reactogenicity

– Burger et al (Cli Inf Dis. 2017) estimated that of HPV infections that ever cause cervical cancer 50% already acquired by age 20 and 75% by age 30

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Cervix Vulva Vagina Anal Oropharynx Penis Anus Oropharynx

HPV-31/33/45/52/58

HPV-16/18

4- and 9-valent HPV vaccinePotential for cancer prevention

&: 1) Saraiya, JNCI 2015

Women Men

HPV-t

ype s

pecif

icposi

tivit

y

15

Slide courtesy of Marc Brisson

0

2,000

4,000

6,000

8,000

10,000

12,000

Cervix Vulva Vagina Anal Oropharynx Penis Anus Oropharynx

31/33/45/52/58

16/18

Ref: 1) Jemal JNCI 2013; 2) Saraiya, JNCI 2015

Num

ber

of

case

s per

year

WomenMen

16

4- and 9-valent HPV vaccine Potential for cancer prevention in the US

Slide courtesy of Marc Brisson

Immunocompromised need 3 doses: who?• Immunocompromised individuals with select major medical conditions require three

doses

– Primary or secondary immunodeficiencies (B lymphocyte antibody and T lymphocyte complete or partial deficiencies)

– HIV infection

– malignancy

– organ transplantation

– significant immunosuppressive therapy

(but does not include asplenia or hyposplenia)

The recommendation for a three-dose schedule does NOT apply to children aged ≤14 years with asplenia, asthma, chronic granulomatous disease, chronic heart/liver/lung/renal disease, CNS anatomic barrier defects (e.g., cochlear implant), complement deficiency, diabetes, or sickle cell disease, in the absence of any of the above conditions.

Ref: Clinical fact sheet for GPs, Dept of Health

Global experience with 9vHPV

• At mid 2017, 9vHPV approved in 60 countries

• As of the 4th quarter 2017, 34.5 million doses distributed since 2015

• US using since 2015. Passive and active safety monitoring (VAERs, CISA, VSD, FDA sentinel)

– ACIP meeting Oct 2017 – update of ongoing analyses “no safety concerns”

– Detailed data presented Feb 2018

https://www.cdc.gov/vaccines/acip/meetings/meetings-info.htmlGee J et al. Human Vaccines & Immunotherapeutics, 2016:12:6, 1406-1417

VAERS summary , ACIP 2018

Source: Presentation by Jorge Aranahttps://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2018-02/HPV-02-Arana-508.pdf

VAERS summary , ACIP 2018

Source: Presentation by Jorge Aranahttps://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2018-02/HPV-02-Arana-508.pdf

AusVaxSafety surveillance data

Source: http://www.ncirs.edu.au/vaccine-safety/current-data/

Australian analysisSimms et al, Lancet Public Health 2016

See also Simms et al, Int J Cancer 2016 for estimation of screens per lifetime needed with 9vHPV vaccine

Is cervical cancer elimination possible?

WHERE WE HOPE TO GET TO…SOON

• A global one dose HPV vaccine strategy in childhood for both sexes, with once or twice in a lifetime HPV based screening for all women

Transition of HPV Register to Australian Immunisation Register

• As of 10 September 2018, all vaccines delivered by school based programs can be recorded on AIR, including HPV.

• All existing HPV records transferred to AIR. Historical HPV vaccinations are now available on consumers’ Immunisation Statements in the AIR.

• From 1 November 2018, the HPV Register will no longer accept HPV vaccination records. Vaccination providers will need to notify HPV doses to the AIR.

• Registered vaccination providers can access and print their patients’ immunisation records using the AIR site. Medical practitioners, nurse practitioners and midwives with a Medicare provider number are automatically recognised as vaccination providers on the AIR.

• The quickest way to submit a HPV dose to the AIR is by using your practice management software or the AIR site. Manual forms can take up to two weeks to reach the AIR.

• Vaccinations will be recorded on the AIR using the individual’s details registered with Medicare. Encourage parents/vaccinees to update their personal information with Medicare.

www.hpvregister.org.au

jbrother@vcs.org.au

• VCSR is funded by the Victorian Government and operated by VCS

• NHVPR is owned and funded by the Australian Government Department of Health and operated by VCS Foundation

VCS acknowledges the support of the Victorian Government

Thank you

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