November 2005

Guy HayhurstConsultant in Public Health, Eastern Cheshire PCT

OVERVIEW OF THE CERVICAL SCREENING PROGRAMME

The aim of the NHS Cervical Screening Programme is to reduce the number of women who develop invasive cervical cancer, and the number of women who

die from the disease

Screening for Cervical Cancer – Evolution of National Policy

• 1966 Population screening introduced. Five yearly tests for women aged 35 and over

• 1973 Screening extended to women under 35 who have been pregnant on 3 or more occasions

• 1984 Commence screening when woman first attends for contraceptive advice. Also early in every pregnancy. Screen at five year intervals. Cease at age 64 after 2 negative tests

• 1988 Implement computerised call and recall systems, inviting women aged 20 to 64. Recall at least every five years

• 1993 Three to five yearly screening from 20 to 64• 1997 Quality Assurance arrangements at regional level• 2003 Three yearly screening from 25 to 49, five yearly from 50

to 64. Five-year timescale for implementing LBC

Criteria for Screening Programmes

• The Condition – should be an important health problem, and the natural history should be known

• The Test – simple, safe and acceptable screening test, known distribution and cut-off point for test values, with an agreed policy on further diagnostic investigation

• The Treatment – should be effective, leading to better outcomes, there should be evidence-based policies on who should be offered treatment

• The Screening Programme – should be shown to

be effective in reducing mortality or morbidity

The Three Most Common Cancers in MenEngland and Wales 1971-2001

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40

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71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01

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Prostate Lung Colorectal

Cancers in England 2001 Prostate 26,027 (23.1%) Lung 18,545 (16.5% Colorectal 14.836 (13.2%)

The Three Most Common Cancers in WomenEngland and Wales 1971-2001

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20

40

60

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71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01

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Breast Colorectal Lung

Cancers in England 2001 Breast 34,347 (30.6%) Colorectal 12,693 (11.3% Lung 11,940 (10.6%)

Risk Factors for Cervical CancerRisk is closely related to any sexual behaviour that

increases transmission of the causal HPV infectionHigh-risk women can be defined as those who are

persistent carriers of a high-risk HPV type

Factors that increase risk include:• sexually active at an early age (of either partner)• many sexual partners (of either partner)

Among women persistently exposed to HPV infection, some additional exposures further increase risk of progression:

• cigarette smoking • long-term oral contraceptive use (five or more years)• parity above five full term pregnancies

Causality criteria for the association between HPV DNA and cervical cancer

1. Exposure must precede disease

2. Reduction in disease following reduction in exposure

3. Strong (& consistent) association in different populations

4. Risk of disease is related to level of exposure

Cohort studies of HPV infected women followed up to CIN2/3

Early vaccination trials of women followed up to CIN show high type-specific protection

International case-control studies

Studies on sexual behaviour and number of sexual partners

Estimates of HPV type-specific relative risk from nine case-control studies

From: The Aetiology of Cervical Cancer. NHSCSP Publication No 22. September 2005

Current vaccine availability

Global Incidence of Cancer of the CervixFrom: IARC Handbook of Cancer Prevention. Cervix Cancer Screening. 2005

Age-standardised Incidence of Invasive Cervical CancerEngland and Wales, 1971-2001

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2

4

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14

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18

71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01

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0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Co

vera

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Incidence Coverage

National call and recall introduced

From: Update to Cancer Trends in England and Wales 1950-1999. National Statistics 2005

Age-specific Incidence of Invasive Cervical Cancer England and Wales, 1971 and 2001

0

5

10

15

20

25

30

35

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45

15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

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1971 2001

Previously screened cohorts

From: Update to Cancer Trends in England and Wales 1950-1999. National Statistics 2005

From: Cancer Trends in England and Wales 1950-1999. National

Statistics 2001

Women

0 20 40 60 80 100

Melanoma of skin

Hodgkin's disease

Breast

Uterus

Cervix

Non-Hodgkin's lymphoma

Rectum

Bladder

Colon

Kidney

Leukaemia

Ovary

Myeloma

Brain

Stomach

Oesophagus

Lung

Pancreas

Relative survival (%)

Age group

Number of

Cervix patients Relative (95% CI) Relative (95% CI)

All adults 9,971 82.2 (81.4 - 83.0) 63.1 (61.9 - 64.2)

15-39 3,240 95 (94 - 96) 86 (84 - 87)40-49 2,071 90 (89 - 91) 74 (72 - 76)50-59 1,421 84 (82 - 86) 62 (59 - 65)60-69 1,117 77 (74 - 79) 50 (46 - 53)70-79 1,292 63 (60 - 66) 33 (29 - 36)80-99 830 52 (48 - 55) 31 (26 - 36)

Patients diagnosed 1998-2001

One-year survival (%) Five-year survival (%)

From: Cancer Survival, England, 1998-2003. National Statistics

Five-year age-standardised survival (%), Women 1998-2001, England

Five-year survival by year of diagnosis

1996-1999 61.3%

1998-2001 63.1%

Influences on Risk in the under 25’sFactors that increase risk include:• HPV infection• sexually active at an early age• many sexual partners • smoking

Factors that reduce risk include:• regular condom use

• between 2001-2003, the Manchester ARTISTIC trial found a 33% prevalence of HPV infection in women aged 20-29, with a clearance rate of 59% within 1 year (1)

• following HPV infection, around a quarter of young women will develop transient cytological abnormalities (2)

• most low-grade changes will regress spontaneously within 36 months (3)

• there is some evidence that high-grade intraepithelial lesions will also regress in young women (4)

(1) Kitchener H C, et al. 21st Int. Papillomavirus Conf; Feb 2004; Abstract 268

(2) Moscicki A B, et al. JAMA. June 2001; 285; 2995-3002

(3) Moscicki A B; et al. Lancet. Nov 2004; 364; 1678-1683

(4) Szarewski A, Sasieni P. Lancet. Nov 2004; 364; 1642-1644

Prevalence of high-risk HPV by age group, and age-specific cervical cancer incidence

From: The Aetiology of Cervical Cancer. NHSCSP Publication No 22. September 2005

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64

Borderline Mild Moderate Severe

Results of GP and community smears screened in Cheshire & Merseyside Laboratories in 2003/04

197 severe and 362 moderate dyskaryosis at ages 20-24

236 severe and 252 moderate dyskaryosis at ages 25-29

2887 abnormal tests in total

0%

2%

4%

6%

8%

10%

12%

14%

15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

From: National Statistics 2001

In 2001 there were 2,418 new cases of invasive cervical cancer (40 under 25), and 1,046 women died from the disease (6 under 25)

Frequency distribution of new cases of invasive cervical cancer diagnosed in England in 2001

Following computerisation of call and recall, new cases have fallen among women in older age groups where there has been high screening uptake. But - screening coverage has fallen in women aged 25 to 49

Death rates in women aged 20-24 have not been affected by computerised call and recall

Harm versus Benefit in the under 25’s

Harm may arise from:

• abnormal smears are common, with little prognostic value

• women are labelled at-risk (minor changes lead to follow-up)

• the damage to the cervix that may result from treatment

The Benefits are unclear:

• the UK case-control study (5) looked at screening histories of 1,305 women (all ages) and 2,532 age-matched controls

• 26 out of the 34 women with invasive cancer aged 20-24 had a previous negative smear, which suggests that cytology is not very sensitive for these tumours(5) Benefit of cervical screening at different ages. Sasieni P, Adams J, Cuzick J. British Journal of Cancer. July 2003; 89; 88-93

Coverage by Age, England 1995 to 2004

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72

74

76

78

80

82

84

86

88

1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

% w

om

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ith

ad

equ

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test

in

th

e la

st f

ive

year

s

25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64

Age 60-64

Age 30-34

Age 25-29

Age 55-59

From: Cervical Screening Programme, England: 2003-04. Department of Health

0.1

0.2

0.5

1

2

0 1 2 3 4 5 6 0 1 2 3 4 5 6 0 1 2 3 4 5 6

age 20-39 age 40-54 age 55-69

Rel

ativ

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sk

Years since last negative smear

Following a negative cervical smear, the magnitude and duration of protection against cervical cancer increases with age

The Benefits of Cervical ScreeningBenefit of cervical screening at different ages. P Sasieni, J Adams, J Cuzick. Br. J Cancer.

2003

Changes in Frequency of Screening

Guidance on Liquid-based Cytology

• July 2000 Health Technology Assessment Review LBC likely to be beneficial, but a pilot study is required

• Jan 2002 Scottish Pilot Study Training of lab staff and smear takers is feasible; also reductions in lab workload and inadequate rates, and an increase in detection of high grade lesions

• Dec 2002 English Pilot Study Initial report on effects and costs of introducing LBC describes a clear reduction in the rate of inadequate smear tests

• Oct 2003 NICE Guidance on use of LBC for Cervical Screening LBC is an improvement over Pap smears; it reduces the need for repeat smears, improves detection of high grade lesions, increases productivity in laboratories

• Dec 2003 Department of Health “Advice to the Service”

It is recommended that liquid-based cytology (LBC) is used as the primary means of processing samples in the cervical screening programme in England and Wales.

There is currently insufficient evidence to recommend one LBC product over another. The NHS Cervical Screening Programme and Cervical Screening Wales may wish to consider evaluating further the different products as the method is introduced.

Ceasing Women from Screening

Ceasing a woman from the NHS Cervical Screening Programme means she will receive no further invitations and her name will be removed permanently from future prior notification lists

There are two main reasons for ceasing a woman. These are 1) age - women aged 60 or over with three consecutive negative tests; and 2) no cervix

The following should not automatically be ceased:

• women with physical disabilities

• women with learning disabilities

• for “clinical” or “medical”

reasons alone

• terminally ill women

• circumcised women

• women who have never

had sex with a man

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20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64

Ceased (no cervix) Ceased (other reasons) Ceased (age)

Women ceased from Cervical Screening in North, Central and South Liverpool PCTs in 2003/04

From: Cervical Screening Programme, England: 2003-04. Department of Health

England N.West Liverpool

No cervix8.2% 8.4% 6.0% (8,708)

Age reasons 1.4% 1.4% 1.0% (1,298)

Other reasons 1.0% 1.4% 1.6% (2,177)

79134

262

220

26

700429

321

6

Cervical Screening – Past and Future

1973

Population Screening Introduced

Computerised Call and Recall

Liquid Based Cytology

2004 2005

Age/Interval Changes

Quality Assurance

Routine HPV Vaccination

GP Contract

Computer Assisted Reading

HPV DNA Testing

Molecular Markers of Progression

Extended to Under 35’s

1997

1988

1988

1966

0%

2%

4%

6%

8%

10%

12%

14%

15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

From: National Statistics 2001

In 2001 there were 2,418 new cases of invasive cervical cancer (40 under 25), and 1,046 women died from the disease (6 under 25)

Frequency distribution of new cases of invasive cervical cancer diagnosed in England in 2001

Following computerisation of call and recall, new cases have fallen among women in older age groups where there has been high screening uptake. But screening coverage has fallen in women aged 25 to 49

Death rates in women aged 20-24 have not been affected by computerised call and recall

Cervical Cancer Indices by Health Authority

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160

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5-ye

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%

Incidence SRR (new cases 1998-00)

Mortality SMR (deaths 2001-03)

5-Year Survival % (patients diagnosed 1995-97)

From: Clinical and Health Outcomes Knowledge Base 2005

Greater Manchester SHA 136.7, 129.0, 63.8%

Cumbria and Lancashire SHA 109.7, 105.3, 62.2%

Cheshire and Merseyside SHA 108.3, 130.4, 58.2%