david forman section of cancer information€¦ · de martel c, ferlay j, vignat j, franceschi s,...

Infection and cancer: a significant part of the global cancer burden

David Forman

Section of Cancer Information

Cancer & Infection Session

Global burden of cancers attributable to infections in 2008

Goals •  Estimate the number of incident cancers attributable to

infection worldwide: –  Geographic distribution. –  Relation to total cancer burden –  Assess global cancer impact of most important

infectious agents •  Help set regional priorities for cancer control •  Update previous estimates for 1990 and 2002

Monograph 100. A review of human carcinogens Part B: Biological agents (February 2009)

http://monographs.iarc.fr/ENG/Monographs/vol100B/


•  GLOBOCAN 2008 (globocan.iarc.fr) estimates of cancer incidence, mortality and prevalence in the year 2008 –  184 countries –  27 cancer sites

•  We extended estimates to include sub-sites associated with infection.

•  Incidence estimates were aggregated into eight geographic regions.


•  12.7 million cancer cases (Globocan 2008) •  2.0 million (16%) attributable to infection

– 22.9% in less developed countries – 7.4% in more developed countries

•  10-fold variation between regions – 32.7% in Sub-Saharan Africa – 3.3% in Australia and New Zealand

Fraction of new cancer cases attributable to infection: Population attributable fraction (PAF) by world regions

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Number of new cancer cases occurring in 2008 attributable to infectious agents by anatomic site


Cancer site Global incidence estimate

Number attributable to infection

Population Attributable Fraction (%)

Gastric (non-cardia) 870,000 650,000 74.7 Liver 750,000 580,000 76.9 Cervix uteri 530,000 530,000 100 Nasopharynx 84,000 72,000 85.5 Kaposi’s sarcoma 43,000 43,000 100 All other 893,000 168,000

Total 2 million

de Martel et al. (Lancet Oncol, 2012)

Numbers are rounded to two significant digits

Number of new cancer cases attributable to infection in 2008 by development status

Number of new cancer cases attributable to infection in 2008 by development status

Less developed regions

More developed regions Th

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Relative percentage of new cancer cases attributable to infection by sex, age group, and development status

Human papillomavirus

•  HPV is a necessary cause of cervical cancer •  Prevalent in other anogenital cancers:

–  Penis: 50% –  Anus: 88% –  Vulva: 43% –  Vagina: 70%

•  Found in a sub-set of oropharyngeal cancers (oropharynx, including tonsils and base of tongue) –  Prevalence from 56% (N America) to 13% (Outside

Europe, N America, Australia & New Zealand, Japan)

Cancers attributable to HPV

Worldwide, cervical cancer dominates the HPV-associated cancers

In N America, where cervical cancer is controlled by screening, HPV-associated cancers at other sites are equally important.

Hepatitis viruses

•  Both HBV and HCV are strong risk factors for liver cancer (R ~ 20)

•  HCV is also associated with non-Hodgkin lymphoma (PAF=8%)

•  Strong geographical variation in prevalence of both HBV and HCV in liver cancer cases.

Prevalence of HBV in cases of hepatocellular carcinoma

0 86.1

Prevalence of HCV in cases of hepatocellular carcinoma

0 78.7

Helicobacter pylori

•  H. pylori is a risk factor for gastric cancer, but risk is restricted to non-cardia location.

•  H. pylori is also associated with non-Hodgkin lymphoma of gastric location (MALT and DLBC), PAF=74%

•  Once acquired (usually in childhood), infection tends to be lifelong

•  Treatment is c. 90% effective with a combination of antibiotics and acid lowering drugs

•  Screen and treat is a policy that may be an effective means of preventing gastric cancer – not yet adequately evaluated

Comparison of other estimates of proportion of cancers attributable to infection

•  World (2002) – 17.8% (Parkin 2006) vs 16.1%

•  China – 25.9% (Xiang et al 2011) vs 26.1%

•  South Korea – 21.2% (Shin et al 2011) vs 22.5% (E Asia)

•  UK – 3.1% (Parkin 2011) vs 7.0% (Europe) or –  vs 4.0% (N America)


Conclusions •  Wide geographic variation in the fraction of cancers

attributable to infection. •  Almost a quarter of all cancers in less developed

countries have an infectious cause. •  Importance of HPV, H. pylori, HBV, and HCV as main

cancer-related infectious agents. •  Available strategies for prevention

–  vaccination against HBV and HPV –  use of safe injection practices and avoidance of

parenteral treatment for HCV –  antibiotics for control of H. pylori (requires evaluation)


Infection and Cancer Epidemiology Group •  Catherine de Martel •  Martyn Plummer •  Jerome Vignat •  Silvia Franceschi

Section of Cancer Information

•  Jacques Ferlay •  Freddie Bray •  David Forman

De Martel C, Ferlay J, Vignat J, Franceschi S, Bray F , Forman D, and Plummer M. Global burden of cancers attributable to infections in 2008: A review and synthetic analysis. Lancet Oncology,13:607-15, 2012

GAVI’s mission

Strategic goals 2011–2015

!  Accelerate the uptake and use of underused and new vaccines

!  Contribute to strengthening the capacity of integrated health systems to deliver immunisation

!  Increase the predictability of global financing and improve the sustainability of national financing for immunisation

!  Shape vaccine markets

To save children’s lives and protect people’s health by increasing access to immunisation in poor countries

The power of partnership: the GAVI Alliance Board

What countries have achieved with GAVI support

!  Immunised 326 million children

!  Prevented over 5.5 million future deaths

!  Accelerated vaccine introductions in over 70 countries

!  Strengthened health systems to deliver immunisation

!  Helped shape the market for vaccines

Source: These estimates and projections are produced by the WHO Department of Immunization, Vaccines and Biologicals, based on the most up-to-date data and models available as of 30 September 2011. *Includes deaths averted by GAVI-supported vitamin A supplementation programmes.

Future deaths averted

Accelerating Hepatitis B vaccine introduction in low-income countries

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Source: WHO, Vaccine introduction database

Driving equity in vaccine access

Source: WHO, Vaccine introduction database.

Hepatitis B

Routine use of vaccines in high- and low-income countries

GAVI support 2000-2011

Source: GAVI Alliance 2012

Increased competition reduces vaccine price

Price decline of pentavalent vaccine and number of manufacturers

Source: UNICEF Supply Division, 2012

Pentavalent vaccine - 5 in one shot - diptheria tetanus pertussis hep B and hib

Source: GAVI Alliance data as of 13 April 2012

Approved for pentavalent vaccine support 2000 – April 2012

China hepatitis B vaccine success story

!  US$ 76 million project equally funded by GAVI and the Government of China

!  Aim: accelerate integration of hep B vaccine into EPI and ensure injection safety

!  Focus: W. China and poor areas in Central China

!  Results: 2001-2009 in project counties !  Hep B 3 coverage - 40% to 95% increase

!  Hep B at birth coverage - 50% to 88% increase

!  90% use of autodisable syringes

!  Carrier rate in children under 5 dropped 10% to 1%

!  Catalytic: Government fully funding Hep B vaccines

�rop in chronic carrier rate between 1979 - 2006

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India: Pentavalent vaccine introductions 2011–2012

Introduced 2011

Introductions 2012

Courtesy: WHO and UNICEF, India

11

Thank you

UNICEF/2006/Josh Estey

Source: UNICEF Supply Division, 2010

Hepatitis B price decline

HPV vaccine: a critical component in a comprehensive cervical cancer

prevention program

UICC World Cancer Congress Montreal, August 27-30, 2012

Vivien Tsu

Background on cervical cancer •  Estimated to increase from

529,828 cases in 2008 to 776,032 in 2030*

•  Failure of cytology screening to have impact in low- or middle-income countries

•  New prevention opportunity in form of vaccines against primary causal agent—human papillomavirus (HPV)

Incidence highest in low and middle income countries

*Globocan, 2008

Two vaccines available

•  Both highly effective against HPV types 16 and 18—responsible for ~70% of cervical cancer*

•  Both very safe—no deaths, rare serious adverse events (for women with other risk factors)

*One also protects against non-oncogenic types, HPV 6 and 11

•  Both registered in >120 countries

•  Both pre-qualified by WHO (i.e. safe and effective for UN purchase)

•  Recommended by WHO for girls aged 9-13

National and pilot introductions

43 countries – national 20 countries – pilot or demo

PATH HPV Vaccine Demonstration Projects

Vietnam (provinces)

Thanh Hoa

Peru (regions)

India (states)

Uganda (districts)

• Ibanda

• Nakasongola

•  Schools

•  Community health centers

•  Outreach programs

All countries

Vietnam, Peru, India (out-of-school girls)

Uganda

Over 66,000 girls eligible

Vaccine delivery strategies

Overall, coverage was high – both initial acceptance and completion

•  Little difference in coverage between strategies: greater variance in terms of cost per vaccinated child

•  Strong community mobilization efforts; careful training of health workers

India (Yr1) Peru (Yr1) Uganda (Yr2)

Vietnam (Yr2)

At least 1 dose 82% 84% 96% 97% All 3 doses 79% 82% 89% 96% Completion 1 → 3 97% 98% 93% 99%

Coverage survey data, school-based delivery

Communication materials developed •  Manuals

•  Leaflets

•  Posters

•  Fact book

•  Radio spots

•  Banners

Lessons learned: Factors for success

1.  Secure visible government endorsement / participation.

2.  Provide training for health workers, teachers, and others involved in program.

3.  Engage communities through sensitization and mobilization, with strategic use of media.

4.  Use pulsed schedules to facilitate community awareness and ease health worker burden.

5.  Build educational messages on positive attitudes towards vaccines, prevention of cancer.

6.  Have crisis communication plan in place.

7.  Tailor delivery strategy. Schools can reach majority of eligible girls, with mop-up for those not in school (or absent on vaccination day).

Practical Experience Series from PATH

•  Lessons learned and resources for decision-making and vaccination program planning.

–  Planning

–  Formative research

–  Vaccine implementation

–  Evaluation

–  Screening

www.rho.org/HPV-practical-experience.htm

Vaccine financing

•  Low income countries

–  GAVI approved, 2011

–  Contingent on final price negotiated (<$5/dose) and country ability to deliver successfully

•  Middle income

–  Price drop (~$15-30/dose)

–  PAHO Revolving Fund (~$13/dose)

$0

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2006 07 08 09 2010

Price per Dose

GAVI opportunity

•  57 countries eligible for GAVI assistance

•  2 HPV vaccine pathways approved –  National introduction

–  Demonstration project

•  Demonstration project has 3 objectives 1.  Learn by doing, on small scale first

2.  Explore opportunities for integrating with other adolescent interventions

3.  Strengthen or develop comprehensive national cervical cancer control strategy

Many resources now available

•  Online library at

www.rho.org

•  Action planner

WHO tools for cervical cancer prevention and control

http://www.who.int/nuvi/hpv/resources/en/index.html http://www.who.int/reproductivehealth/topics/cancers/index.html

Why a comprehensive prevention approach?

•  Vaccine not 100% effective – still need screening

•  Issue of generational equity – many women already infected, won’t benefit from vaccine

•  In long run, vaccine will ease burden on screening as there are fewer positives needing treatment

•  Synergies in raising awareness about cervical cancer prevention – both screening and vaccine >> demand

•  Engages broader range of stakeholders

•  Allows countries to start from where they are and build accordingly

Conclusions •  Immunization is trusted, familiar, and less

likely than other services to have inequities in coverage.

•  Many synergies for combining screening and HPV vaccination, although timetables for introduction and scale-up may differ.

•  Options for affordable screening and HPV vaccine now exist.

•  In the long term, a comprehensive approach offers the biggest payoff.

Thank you

Vivien Tsu, PhD MPH Director, HPV Vaccines Project [email protected] www.path.org/cervicalcancer

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