1. Screening for H. Pylori – finding out if it prevents stomach cancer
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Screening for H. Pylori – finding out if it prevents stomach cancer
Nicholas Wald
Wolfson Institute of Preventive Medicine
London
Adult Medical Screening Conference
29 November 2002
Version 2 – created (27/11/02) for Adult Medical Screening Conference
29 November 2002
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© N. Wald

2. Five leading causes of cancer death worldwide
Million/year*
Lung
1.10
Stomach
0.65
Liver
0.55
Colon/rectum
0.49
Breast
0.37
* In 2000
Parkin et al 2001 Int J Cancer
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3. Stomach cancer in five different countries
Age-adjusted death rates per 100,000
Male
Female
From Cancer mortality statistics in 33 countries 1953 – 1992, Tominaga, Kuroishi & Aoki (Eds), IUCC, 1998
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4. Prevalence of H. Pylori infection
Colombia
95%
India
80%
Peru
Mexico
75%
Japan
70%* UK
40%*
France
Italy
* At about age 55
Marshall 1994 , Hazel 1994
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5. Prevalence of H. Pylori infection
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6. Epidemiology of H. Pylori infection
Infection acquired in early childhood
It is associated with
Number of siblings
Birth order: last born is most likely to be infected
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7. H. Pylori
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H. Pylori infection and number of siblings, and other children, at home (up to age 12)
Total children at home
Odds of being H. Pylori positive
1.00 1
1.01 2
1.09 3
1.38 4
2.03 5
2.50 6
3.89 7
8.42
results from the BUPA study
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8. Prevalence of H. Pylori infection according to age
Prevalence of infected persons
<20
15%
20 – 49
35%
50 – 69
50%
70+
65%
JMS, 1999
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9. Does this mean that the incidence of infection increases materially with age?NO
The age relation is a “cohort effect” – the infection occurs in childhood and the chance of children being infected has decreased over the last century.
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10. First prospective study of H. Pylori infection and stomach cancer:
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First prospective study of H. Pylori infection and stomach cancer:
BUPA study and Caerphilly study
Risk of stomach cancer was about three times higher in H. Pylori positive men than in negative men (OR 2.77, 95 CI 1.04 – 7.97)
Forman et al, BMJ, 1991
Not sure what is relationship of “BUPA study and Caerphilly study” to rest of title. Is the colon right?
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11. Nested case-control design
H. Pylori
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Nested case-control design
Advantages of a prospective study
Economy of a retrospective study
Collected blood and stored serum samples on about 25,000 men
Receive notification of cancer and deaths from ONS
Retrieve stored serum samples on stomach cancer cases and matched controls
Should it be “case-control”? What was sig of bracketing on N’s original? Tenses don’t agree.
The results were clear with only 29 cases!
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12. All showed a higher risk in H. Pylori infected people
12 prospective studies
All showed a higher risk in H. Pylori infected people
Helicobacter and Cancer Collaboration Group
Gut, 2001
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13. Lower oesophageal/cardia cancer
H. Pylori
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Lower oesophageal/cardia cancer
A non-significant case-control study (Chow et al, 1998) found a lower risk of this cancer in infected people (OR 0.7, 95% CI 0.4 – 1.1) suggesting that infection may be protective.
Results from a subsequent meta-analysis showed no effect (OR 1.0, 95% CI 0.7 – 1.3).
Is title correct incl capitalisation?
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14. Association between H. Pylori infection and non-cardia stomach cancer is greater if people are surveyed many years before the cancer occurs.
Tested for infection
Relative risk if infected
 10 years before cancer develops
5.9
 10 years before cancer develops
2.4
Helicobacter and Cancer Collaboration Group Gut, 2001
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15. The bacterium, over many years, destroys its own habitat.
Why?
Because the H. Pylori infection tends to be lost with the atrophic gastritis that the organism causes.
The bacterium, over many years, destroys its own habitat.
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16. H. Pylori and stomach cancer
H. Pylori infection causes about 60% of the 7000 deaths a year from stomach cancer in the UK
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17. H. Pylori and peptic ulcer
H. Pylori infection causes >70% of gastric ulcers and >90% of duodenal ulcers
About 4,500 people per year in the UK die from the complications of such ulcers (haemorrhage or perforation)
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18. H. Pylori
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Two randomised endoscopy studies on H. Pylori positive subjects in China
Triple therapy
Placebo
Changle
Yantai
819
294
809
292 7 5* 11 9* 12 20
Subjects
Gastric cancers
after 5-7 years
Fujian – province, Yantai – medium city, Changle – Small city
* Includes dysplasia
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19. Helicobacter pylori screening study
A randomised prevention trial
HPSS
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20. HPSS
Does H. pylori screening and the treatment of those with positive results prevent stomach cancer and, if so, to what extent?
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21. Cancer Research Campaign (now part of Cancer Research UK)
HPSS
A unique example of UK medical research conducted as a university – private sector collaboration
Funding:
Cancer Research Campaign (now part of Cancer Research UK)
BUPA Foundation
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22. There is sufficient evidence that it is
HPSS
The trial is not intended to show whether H. Pylori infection is a cause of stomach cancer
There is sufficient evidence that it is
The trial is intended to see if eradication of H. Pylori infection in middle-age can reverse the risk, or is it too late?
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23. Randomised by week of attendance at BUPA
HPSS
Recruitment
Men aged 35 – 69
Women aged 45 – 69
Randomised by week of attendance at BUPA
UK Residents, registered with an NHS GP
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24. HPSS 45 40 85 7,000 (25%) HP Positive 28,000 Screened 21,000
H. Pylori
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HPSS 85 40 45
Expected gastric cancers with no treatment
21,000
HP Negative
7,000 (25%)
HP Positive
28,000
Screened
56,000
People
28,000
controls
© N. Wald

25. HPSS 62 85 45 22 40 85 7,000 (25%) HP Positive 22 HP positive 45 HP
H. Pylori
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HPSS
Expected gastric cancers with treatment
7,000 (25%)
HP Positive 62 85 45 22
22 HP
positive
45 HP
40 HP
negative
P =
0.005
P =
0.06
28,000
Screened
21,000
HP Negative 40
56,000
People 85
test sera
at end
of study
28,000
controls
© N. Wald

26. Nested randomised trial
Application of the nested case-control concept to a randomised trial
Saves cost
Increases statistical power
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27. Statistical power of HPSS
Assuming 50% reduction in gastric cancer among H. pylori positive individuals, the study has 80% power of detecting a difference at p<0.05 level of statistical significance.
Recruitment is expected to take 5 years with a follow-up period of 15 years through ONS records.
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28. The treatment is: Lansoprazole 30mg Metronidazole 400mg
H. Pylori
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The treatment is:
Lansoprazole 30mg
Metronidazole 400mg
Clarithromycin 250mg
Twice daily for 7 days
Hmm. Not sure if we can get it undistorted – it’s a bit close-range. Maybe worth another try.
Also, we need to open the pack and photograph the contents too – but not till we are sure we are finished with it unopened!
Provided free of
charge to HPSS by Wyeth
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© N. Wald

29. Intervention is simple and acceptable
H. Pylori
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Conclusions
First and only example of a randomised trial of primary prevention of a cancer through screening
One of only a few randomised trials of primary cancer prevention by any means
Intervention is simple and acceptable
Potential impact worldwide could be great
This is really the last slide
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