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
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.
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)
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.
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.
