Presented in Multiple Meetings in the UK and Abroad

1. Cervical Screening
Ayman Ewies
Consultant Gynaecologist
The Ipswich Hospital
24th April 2009

2. Background: Natural History

3. 3
Natural History of Cervical Carcinoma
 Cervical cancer is the 2nd commonest female cancer
worldwide (breast cancer is the commonest).
 It accounts for 12% of cancers in women worldwide.
o Worldwide 470,000 new cases and 233,000 deaths per year.
o 80% in developing countries.
o Only 5% of all cancer resources spent in 3rd world.
o Highest incidences in Madras (India) and Coli (Columbia)
– 48-52/100,000 women per year.
– 60-80% diagnosed with stage III/VI disease.
 Women with cervical cancer die at a younger age than
those with any other non-childhood cancer.

4. 4
Natural History of Cervical Carcinoma
 It is, potentially , the most preventable major form of cancer, given the
long natural history of pre-cancer stage.
 Countries that introduced organized cervical screening programmes
have seen significant falls in the incidence and mortality associated
with cervical cancer.
 In the UK, the cumulative risk for cervical cancer is 1.4% up to age 80
years.
 2,800 cases per annum UK.
 1,100 deaths per annum UK.
 Bimodal age distribution peaks at 30-35 / 80+
21 women die each week
on average in the UK

5. Natural History of Cervical Carcinoma
Time
6
27
Deathsper100,000
Mortality in developing countries
Mortality in developed countries
Effect of health education, regular check-ups &
availability of appropriate management services
Introduction of screening
Effect of screening

6. 6
Risk Factors For Cervical Cancer
1. HPV infection: RR 116
2. Early onset of sexual activity before age of 16:
- Intercourse within one year of menarche  RR 16
3. Multiple sexual partners (self or of the partner):
- ≥ 6 life time partners  RR 5
4. Low socio-economic status (irrespective of other factors): RR 3
5. Black race compared to white: RR 2

7. 7
Risk Factors For Cervical Cancer
6. Heavy long-term tobacco smoking: RR 2
7. Use of COC:
 Using COC ≥5 years + HPV positivity  RR 3
 Death from cervical cancer among current and recent users (within
10 years)  RR 10
8. Immuno-compromise (e.g. organ transplant, lupus disease & HIV
infection)  RR 5

8. Sexual
activity
Normal
mucosa
CIN
Persistent
HPV
infection with
high risk
types
Invasive
cervical
cancer
“Seed, soil and nutrient” model for cervical carcinogenesis
Aetiology of Cervical Cancer
Co-factors:
Smoking
OC use
Other STD’s
Immunosuppression
Transient HPV
infection

9. 9
Cervical Screening in The UK
 The NHS cervical screening programme is recognised
as world leading.1
 Cervical cancer incidence fell by 42% between 1988 and
1997 (England and Wales). This fall is believed to be
directly related to the cervical screening programme2
which was introduced in 1988.
1. http://cancerscreening.org.uk/cervical/publications/cervical-annual-review-2004.pdf Accessed 12/10/05
2. NHS. Cervical Screening pocket guide. 2004.

10. 10
Cervical Screening in The UK
 Computerised call / recall since 1988 reduced deaths from cervical
cancer by 60% despite increased incidence CIN 2/3.
 Success of UK screening attributed to coverage of >80% of eligible
population.
 Almost 5000 deaths per year prevented by cervical screening in UK.
 England - incidence cervical cancer fallen from 15.4/ 100,000 to 9.6/
100,000
• Increased fall of mortality from 1-2% to 7% per year.
• Now decreased to 5% per year.
 England - screening of almost 4 million women per year
• Cost £150 million @ £37.5 per woman screened.

12. 12
Cervical cancer incidence rates per 100,000
women, England and Wales, 1971-98

13. 13
Cervical cancer mortality, England and Wales,
1971-2000

14. Screening Programmes

15. 15
Screening programmes
 1949 first organised regional cervical screening programme.
– British Columbia
 1960’s further programmes.
– Scandinavia, USA, Scotland
Variation of current programmes:
– USA – screening at onset sexual activity.
– Holland – 5 yearly from 30 years.

16. 16
Screening programmes - UK
 England and N. Ireland: 3 yearly 25-49  5 yearly 50-65.
 Wales: 3 yearly 20-65.
 Scotland: 3 yearly 20-60.

17. 17
Screening programmes - UK
Outcome of cervical cytology %
90.55 negative
1.74 inadequate
3.95 borderline dyskaryosis
2.37 mild dyskaryosis
0.67 moderate dyskaryosis
0.59 severe dyskaryosis
0.04 ?invasion
0.08 abnormal glandular cells
Source - CSP Wales Jan – Jun 2006

18. 18
Screening programmes
Developing Countries
 4.6 billion people living in developing countries  Only 5% of women
offered screening.
 900m adults illiterate and >1 billion live on <$1 US/ day.
 3rd world screening fails because
– Lack of organisation/ monitoring.
– Lack of motivation of staff having other disease priorities.
– Lack of professional awareness in public health.
– Poor coverage.
– Poor patient compliance/ understanding.
– Poor availability/ affordability/ sustainability.

19. 19
Screening programmes
Developing Countries
 VIA and VILI are easy to teach but have limited reliability
 may be useful in resource poor countries.
 VIA: Sensitivity 79%, specificity 83%, PPV 12%, NPV
99%
– for detecting CIN 2/3
– >100,000 women from 25 studies.
 Performance VILI appears comparable.
 VILI could follow VIA for borderline cases.
 No magnification.

20. 20
Screening programmes
Developing Countries
 See and treat patients offered cryotherapy for abnormal
results.
 VIA/ VILI less useful in postmenopausal women.
 Screening result:
– 1 visit @ 35 yrs  reduces lifetime risk cancer by 25-
36%.
– 2 visits @ 35-40 yrs  reduces risk by further 40%.
(Goldie et al, 2005)

21. Human Papilloma Virus (HPV)

22. 22
HPV Infection
 HPV DNA is present in virtually all cervical tumours.
 It has been proposed as the first ever identified “necessary
cause” of a human cancer.
103 HPV genotypes known
35 infect the genital tract
20 carcinogenic
16 & 18 found in75% of cervical cancer cases

23. 23
HPV Infection
HPV infection can be:
1- Sub-clinical (flat warts)
 Changes similar to CIN 1 that become apparent only with the
application of acetic acid.
 Satellite lesions may present outside the TZ.
2- Clinical (exophytic warts = condylomas)
 Visible on naked eye inspection.
 The viral type is usually non-oncogenic ( 6 or 11 in 90% of cases).
 Histological confirmation is important since they may mimic invasive
lesions.

24. 24
HPV Infection
Exophytic warts

25. 25
HPV Infection
 Reported incidence in developed countries varies between 10-30% in
the adolescent age group (16-24 years).
The incidence drops to 5% above age of 30 years.
An estimated 80% of sexually active women will be exposed to the virus
by age 50.
60-80%
Clear spontaneously
(within 1-2 years)
20-40%
CIN
(within 2-4 years)

26. 26
HPV Infection
Women >30 years with high risk HPV positive and normal
smear  the risk of developing CIN 3 is 116 times higher
than women with an HPV negative and normal smear.
The progression rate of CIN in women with high risk HPV
positive is 5% per year.

27. 27
HPV Vaccination
 In September 2008 national HPV vaccination programme
introduced using Cervarix (GSK), prophylactic vaccine
against HPV 16/18.
 Vaccination will target 12/13 year old girls.
 Catch-up programme over next 3 years:
– 18 years old girls vaccinated during 2008/9.
– 16/17 years old girls during 2009/10.
– 14/15 year old girls during 2010/11.

28. 28
HPV Vaccination
 Case for HPV vaccination based on evidence from RCT
showing virus like particle (VLP) vaccine effectively
prevented HPV 16/18 specific high grade CIN.
 Evidence of cross protection against HPV 31/45 in the
longer term.
 Cervarix does not protect against genital warts.
 Cervarix will reduce incidence HPV 16 related VaIN/ VIN.

29. 29
HPV Vaccination
 Since >60% CIN2/3 cases are HPV 16/18 related 
incidence is expected to ↓ over next 15 years.
 However, cervical screening will still be needed for
unvaccinated women and to prevent non HPV 16/18 related
cancer in vaccinated women.
 Further modelling studies/ trials to design changes to
screening programme are required.
• ? increasing screening intervals

30. 30
HPV Vaccination
 The vaccine should be administered as 3 IM injections at months 0, 2
and 6.
 Each dose is 0.5ml.
 Presented in a pre-filled syringe with safety device.
 The vaccination schedule permits flexibility if necessary.
 Generally well-tolerated:
-The commonly reported adverse events were injection site
reactions and mild fever.