Vaccination in Cancer Prevention: Cervical Cancer is Largely Preventable,

But is Increasing Globally

Douglas R. LowyDeputy Director, National Cancer Institute

National Institutes of Health

National Academy of MedicineOctober 15, 2018

The views expressed are my own and do not necessarily reflect those of NCI/NIH

Disclosures• National Institutes of Health (NIH) has patents on

papillomavirus L1 virus-like particle (VLP) vaccine technology. I am an inventor.

• NIH has licensed L1 VLP technology to Merck and GlaxoSmithKline, the two companies with commercial versions of the vaccine.

• Licensees of other NIH technologies of which I am an inventor: GlaxoSmithKline, Sanofi, Shanta Biotech, CytosBiotech, Aura Biosciences, Etna Biotech, Acambis, PanVax

Figure 1

Gastroenterology 2016 151, 472-480.e1DOI: (10.1053/j.gastro.2016.05.048)

Hepatitis B Virus vaccination can reduce liver cancer risk, but high impact takes many years

From Chang et al, Gastroenterology 2016

• Universal HPV vaccination at birth begun in Taiwan in 1986• Very long interval between infection and development of cancer

PresenterPresentation NotesComparison of the incidence rates for HCC and incidence rate ratios (95% CI) by age for birth cohorts born before vs after the start of the universal HBV vaccination program. There is a significant reduction in the incidence of HCC in vaccinated birth cohorts in all age groups between 6 and 26 years old.

The paradox of cervical cancer: a largely preventable cancer that globally is still common

• A cancer that disproportionally affects women from poor countries & poor women

• Current high quality cervical cancer screening and HPV vaccination need to become more cost-effective for their widespread dissemination to less developed regions of the world

Cervical cancer mortality rates will continue to increase in less developed regions of the world

Projections developed from Globocan 2012

CRPV

100,000

200,000

300,000

400,000

230,000

0

2015 2012

Less developedregions

251,000

363,000

More developed regions

36,000 37,000 41,000

2030 Less developed regions: Where ~90% of worldwide cervical cancer deaths occur; where cervical cancer accounts for ~10% of female cancer deaths; where cervical cancer represents ~90% of HPV-associated cancer

Global control of cervical cancer and other HPV-associated cancers should soon be feasible

• Research for vaccination and screening is likely to lead to changes in standard of care with increased cost-effectiveness in the near future

• Once that point has been reached, resources are needed to widely implement the interventions; there may be sufficient global commitment to marshal these resources

Precancer = Cervical Intraepithelial Neoplasia Grade 3Lehtinen Lancet Oncol 2011; Munoz JNCI 2010; Huh Lancet 2017

First successful vaccines against a local sexually transmitted infection2016: 9-valent vaccine approved for 2 doses for 9-14 year olds

High efficacy of HPV L1 VLP vaccines against new cervical precancer and genital warts by vaccine-targeted types in randomized trials

End Point Sex Age Vaccine Targeted HPV Types Efficacy(95% CI)

Precancer Female 15-26 Quadrivalent / GardasilHPV 6, 11, 16, 18 100%

(85.5-100)

GenitalWarts Female 15-26

Quadrivalent / Gardasil HPV 6, 11, 16, 18

96.4% (91.4-98.4)

Precancer Female 15-25 Bivalent / Cervarix HPV 16, 18100%

(90.5-100)

Precancer Female 16-26 Nonavalent / Gardasil-9HPV 6, 11, 16, 18, 31, 33, 45, 52, 58

97.1%(83.5-99.9)

In women with no genital HPV infection detected in at the start of each trial

PresenterPresentation NotesThe important point here is that the vaccines have very high efficacy if the analysis is restricted to protection disease caused from new infection by vaccine-targeted types. The vaccines have limited prophylactic activity against other HPV types and don’t induce lesion regression. The mostly likely explanation for the the somewhat lower efficacy in men is that it is easier miss pre-existing infections of the maie genitalia.

Herd Immunity: Decreased incidence of genital warts in heterosexual Australian men following female HPV vaccine implementation in 2007

Ali et al, BMJ 2013

>30 years21-30 years

Trends in U.S. Vaccination Rates: Ages 13-17 YearsMMWR Vol. 67, #33, August 24, 2018

From Aimee Kreimer et al, unpublished data

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

35.0%

40.0%

45.0%

3 doses 2 doses 0/6 1 dose UCG

N = 956 N = 62 N = 112 N = 1,107

HPV 16/18 HPV 31/33/45 Other HPV

The Costa Rica Vaccine Trial: Prevalent HPV infection 11 years after bivalent HPV vaccination: One dose is not inferior to three doses (post-hoc analysis)

0 dose

2 3 4 5 6 7 8 9 10 1110

100

1000

10000

HPV

16 A

ntib

ody

Geom

etric

Mea

ns (E

U/m

L)

3 doses

2 doses (0/6)

1 dose

natural Immunity

100% of HPV-vaccinated women remained HPV16 seropositive 11 years after HPV vaccination

Stable HPV seropositivity for 11 years

From Aimee Kreimer et al, unpublished data

Summary and Conclusions• Basic research led to identification of HPV as the cause of

several cancers and to development of the HPV vaccines– The vaccines can confer high protection and herd immunity

• Increased vaccine uptake in US is needed to achieve personal protection for more individuals and greater herd immunity

• Control of cervical cancer and other HPV-associated cancers as worldwide public health problems may soon be feasible

Slide Number 1DisclosuresSlide Number 3The paradox of cervical cancer: a largely preventable cancer that globally is still commonSlide Number 5Global control of cervical cancer and other HPV-associated cancers should soon be feasible Slide Number 7Slide Number 8Slide Number 9Slide Number 10Slide Number 11Summary and Conclusions