1. WHO : when is screening effective?
World health organisation, regional office for Europe
Assessing a screening procedure
1986
Wilson and Junge

2. principles for early detection:
the condition sought should be an important health problem
there should be an accepted treatment for patients with the recognised disease
facilities for diagnosis and treatment should be available
there should be a recognisable latent or early symptomatic stage
“the person being screened should have a reasonable chance of benefiting”

3. principles for early detection
there should be a suitable test or examination this test should be acceptable for the population
the natural history of the disease, including the development from latent to disease should understood
there should be an agreed policy on whom to treat as patients
the cost of case-finding (including diagnosis and treatment) should be economically balanced in relation to possible expenditure and medical care as a whole
case-finding should be a continuing process, and not a “once and for all” project

4. we want a test that is:
Valid and reliable
Specific and sensitive

5. National cancer plan
Fall of 20% in cancer deaths in under 75’s
Screening for cervix, breast, bowel.
No screening for prostate cancer at present

6. No screening for prostate cancer at present
Passes 1st requirement - Is 2nd biggest killer, mainly in over 50s – but fails all the others
Would use prostate specific antigen (PSA) - 2\3 men with raised PSA will not have cancer, whilst others with ca will not be identified
Treatment for ca prostate may be unnecessary
Treatment has side effects

8. Screening for bowel cancer
NHS bowel screening programme has been rolled out from
2006
is organised with regional hubs, each working with up to 20
local screening centres
each hub operates “call and recall” system, sends out FOBt
kits, analyses specs and post results
local centres provide nurse-led endoscopy clinics

9. Facts and figures - Cervical cancer
World wide 1\10 female cancers diagnosed is CaCx
Rate varies seven fold around the world
Highest rate is Zimbabwe, per 100,000 women yrs
Lowest rate in China, 2-3 per 100,000 women yrs
In UK is 9.3 per 100,000 women yrs,
Was about 15-16

10. Facts and figures
Cervical cancer is the 11th most common cause of cancer deaths in the UK
In 2000 there were 2,424 new registrants for invasive cancer, in there were 927 deaths, the first time that deaths had fallen below 1,000
there was a 42% fall in deaths from this cancer

11. Cervical cancer
Usually a primary
Squamous cell cancer \ carcinoma
Adenocarcinoma
Lymphoma
Symptoms include
abnormal vaginal bleeding
discomfort during sex
abnormal vaginal discharge.

13. Effectiveness of screening
In England screening prevents approximately 4,500 cancers pa
In UK screening prevents approx 3,900 deaths
Programme costs approx £150 million
Or £37.00 per woman screened
Or £33,000 per life saved

14. The epidemic that never was
Without screening, CaCx would have killed 1\65 U.K. women born since 1950
= 6,000 deaths a year
Are preventing 80% (5,000 of them)

16. Risk Factors Viruses and cancer HPV cervical cancer
Hepatitis B virus liver cancer
Epstein Barr Virus lymphoma and Hodgkins disease
HIV and cancer
??Mouse mammary tumour virus (MMTV)/breast cancer ??? from musculus domesticus
MMTV ? Transmitted from cancerous mothers to offspring via milk ( mice studies)

17. HPV subtypes
Are 100 different subtypes, are mostly harmless
Type 16 is greatest threat
Also types 18, 31, 33, 45
These are not associated with genital warts

18. Transcriptional units
E6 and E7 both oncoproteins that prevent tumour suppression
E6 is an oncoprotein that binds to and inactivates tumour suppressor gene p53 (“guardian of the genome”)
E7 binds to and inactivates retinoblastoma gene Rb, also p53 and p21
Transcription is 1st step of gene expression – DNA copied by RNA
Oncoprotein – coded by an oncogene( which is agene with potential to cause cancer) and the protein is involved in regulation of timourgenic cell growth

19. How common are “High risk” HPVs ?
1\5 of all year olds will test positive type16
Figure for over 50s is 1\20
World wide between million women
7% of all women in developed world and 15% in developing world
Problem is persistence of infection (eg over 6 months)
Needs to be present for 10 yrs for cellular changes to occur.

20. Other risk factors
Early (before 16yrs) sexual activity
High number (over 4) sexual partners
Cigarette smoking (including passive)
Immuno suppression and HIV
Early first pregnancy
Multiple pregnancies

21. Risk factors:
contraception
Barrier methods of contraception should be protective
Use of combined oral contraceptive seems to increase risk:
if taking COC for > 5yrs, rr1.1
if taking COC for 5-9yrs rr1.6yrs
if taking COC for > 10yrs rr2.2

22. Do we know in time?
60% of all cancers are diagnosed when changes confined to cervix
25% changes extended to vagina
10% changes in pelvic wall (symptoms)
5% changes extended beyond pelvis

23. BUT what do we do if we find it????
Should we screen for HPV?
Cancer research UK did a trial, offering 11,000 women screening for HPV and cytology
9% had HPV (900 women)
10% of them required treatment (90)
All those identified at cytology had HPV
97% of those requiring treatment would have been identified by HPV alone
76% would have been identified by cytology alone
So smears alone would have missed 8\11,000
HPV would have missed none
BUT what do we do if we find it????

24. Predications:
120,000 borderline\mild changes pa in UK
Of these, 10-20% will have CIN3
Expect 56% to be referred to colposcopy
This would give a rate of:
96% sensitivity
99.5% negative predictive value
Rebello G et al Human papillomavirus testing and the management of women with mildly abnormal smears: an observational study BMJ
2001;322:893-94

25. Could we prevent HPV?
Now offering immunisation against types 16 and 18, which together cause 70% of all cervical cancer
Will need to do it before they become sexually active
May also protect against anal and oral cancers

26. BUT
Current screening programmes identify cancers
“vaccine overload” and multiple immunisations
Immunising against STD is controversial
A backlash could affect other immunisation programmes
What about vertical transmission?
Both immunisations require multiple jabs
Long term results not available yet
More than 80% of all cervical cancer occurs in resource deprived countries
Offers no protection to those already colonised