CERVICAL SCREENING UPDATE

Louise Cadman

Research Nurse Consultant and Nurse Colposcopist

Centre for Cancer Prevention

Wolfson Institute of Preventive Medicine

E-LfH Learning Portal – (e-SRH) Sexual and Reproductive Healthcare – Cervical Screening

Learning objectives:State the objectives of the cervical screening programme Identify the principles of screening programmes Explain the way screening programmes operate in the UK Identify the causes and prevalence of cervical screening abnormalities Manage cervical screening results correctly Explain colposcopy to a patient

Cervical cancer – the size of the problem

Worldwide cervical cancer incidence 2012

• fourth most common cancer worldwide for females

• seventh most common cancer overall

• >527,000 new cases diagnosed

• 266,000 deaths

• 85% in the developing world

The 20 most common cancers in women, 2011Number of New Cases, UK

12th most common cancer amongst females in the UK

2851 cases/year 972 deaths/year 67% survived ≥ five years

(2005-2009)

Age-specific incidence rates and number of cases diagnosed by five year age group, England 2009

6 in 10 of all new cases of cervical cancer are diagnosed in women under 50 years

European Age-Standardised Cervical Cancer Incidence & Mortality Rates per 100,000 Female Population, UK

Prepared by Cancer Research UKOriginal data sources:Office for National Statistics. Cancer Statistics: Registrations Series MB1. http://www.ons.gov.uk/ons/search/index.html?newquery=series+mb1Welsh Cancer Intelligence and Surveillance Unit. http://www.wcisu.wales.nhs.ukInformation Services Division Scotland. Cancer Information Programme. www.isdscotland.org/cancer

1975-2011 European age-standardised incidence rates of cervical cancer per 100,000 population, by

age, females, Great Britain

Number of cases by morphology, England 1988-2009

0

500

1000

1500

2000

2500

3000

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

Year of Diagnosis

Squamous

Adenocarcinoma

Unclassified EpithelialAdenosquamous

Neuroendocrine

Other Epithelial

Other

Cervical screening as secondary prevention of cervical cancer

Cervical screening → ↓morbidity ↓ mortality

! Limitations:does not prevent:

oncogenic HPV infection precursor lesions (high grade Cervical Intraepithelial Neoplasia (CIN))

less efficient for early stages of adenocarcinomascreening programmes not achievable in many countriesmay not detect lesions which progress quickly in timeonly effective if women attend regularly, when invited

NHS Cervical Screening Programme Coverage

Source: KC53, Health and Social Care Information Centre.

Five year coverage of the target age group (25-64), Primary Care Organisation, England, 31st March 2013

Cervical screening coverage by London Primary Care Organisation, 2012-13

(% less than 5 years since last adequate test)

NHS Cervical Screening Programme, 2003-2013: coverage-less than 5 years (%)

Five year coverage of the target age group (25-64) England at 31st March, 2003 to 2013

© Data prior to 2005, re-used with the permission of the Department of Health.Source: KC53, Health and Social Care Information Centre.

Anatomy of the cervix

The Uterine Cervix Uterus ÷

Upper body Cervix

Cervix Cylindrical ~ 3cm length ~ 2.5cm diameter 1/3 protrudes into the

vaginal vault Os – the hole Ectocervical = outside the

external os Endocervical = inside

cervical canal

Stratified squamous epithelium

Columnar epithelium

Squamo-columnar junction (SCJ)

Cervical Epithelium

Squamous epithelium Usually on ectocervix Cells are multilayered Usually appears as smooth,

shiny, pale pink Columnar epithelium

Mostly endocervical Single layer column shaped cells Delicate and usually appears red

(ectopy when on ectocervix) Squamo-columnar junction

(SCJ)

Transformation zone

HPV Infection in the Cervix

Normal Epithelium

HPV Infection CIN I CIN II CIN IIICancer

DecadesYearsMonths

HPV infects cell integrates its DNA into the host cell DNA

Persistence cell damage (pre-cancer)

Eventually cancer

Dyskaryosis – identified by cytology

CIN 1

CIN 3

CIN 2

Screening intervals and sample taking

Screening Intervals in England

25 years - first invitation from GP lists

invitation should not be before age 24.5 years

25–49 years - three yearly

50–64 years - five yearly

65+ years - only screen those not screened since age 50 or with recent abnormal tests

Summary percentage preventable by 3- and 5-yearly screening

Annual 3 yearly 5 yearly

20–39 years

76% 61% 30% (39%)

40–54 years88% 84% 73%

55–69 years87% 87% 83%

* The percentage in parentheses is obtained by replacing RRs greater than one with 1.0 when averaging

Benefit of cervical screening at different ages: evidence from the UK audit of screening historiesP Sasieni, J Adams and J Cuzick

British Journal of Cancer (2003) 89, 88–93.

Samples examined by source of sample, 2012-13

31

Prior to the examination

Some women may wish to agree a non-verbal

sign

Some women prefer it if you ‘just get on with it’

Avoid the word relax!

Be realistic in the length of time it should take

Taking a sample

Following the examination

Explain that spotting

following the test is possible

and to be expected

If you cannot visualise the cervix, and nor can any

colleague you ask to assist, then the procedure should be abandoned and

referral made to a colposcopy clinic

From: Cervical screening - RCN guidance for good practice

Results and referral to colposcopy

Results of adequate tests for women aged 25-64, 2012-13

Total number of results: 3,283,438

• 99.8% of reports authorised within 0-2 weeks (0-14 days)• 0.2% of reports authorised within 3-4 weeks (15-28 days)

Cytology results by region and Primary Care Trust, 2012-13

Cytological referral for colposcopy or further assessment

Suggestion of invasive carcinoma (x1) Suggestion of glandular lesion (x1) Severe dyskaryosis (x1) Moderate dyskaryosis (x1) Mild/borderline and hr HPV +ve (x1) Persistent unsatisfactory smears (x3) 3 abnormal tests, any grade, in 10 year

period Treated for CIN, have not been returned to

routine recall and a subsequent test is reported as mild dyskaryosis or worse

URGENT - to be seen within 2 weeks

URGENT - to be seen within 4 weeks

ROUTINE - to be seen within 8 weeks

Cytology terminology and result codes

Previous terminology(BSCC 1986)

New Terminology  

Result code

Borderline changes Borderline changes in squamous cells (not HPV Tested) 8

Borderline changes in squamous cells (HPV tested) B

Borderline changes in endocervical cells (not HPV Tested) 9

Borderline changes in endocervical cells (HPV tested) E

Mild dyskaryosisBorderline changeswith koilocytosis

Low-grade dyskaryosis (not HPV Tested) 3

Low-grade dyskaryosis (HPV tested) M

Moderate dyskaroysis High-grade dyskaryosis (moderate) 7Severe dyskaroysis High-grade dyskaryosis (severe) 4Severe dyskaryosis?Invasive

High-grade dyskaryosis ?Invasive squamous carcinoma 5

?Glandular neoplasia ?Glandular Neoplasia endocervical type 6?Glandular Neoplasia (non-cervical) (not HPV Tested) 0

?Glandular Neoplasia (non-cervical) (HPV tested) G

Negative Negative (Not HPV tested) 2  Negative (HPV tested) NInadequate Inadequate 1

Clinically suspicious cervix Post-menopausal bleeding

Not using HRT

Symptoms → gynaecologist → colposcopy Post-coital bleeding

(particularly in women > 40 years of age) Intermenstrual bleeding Persistent vaginal discharge

Previous treatment for CIN Not returned to routine recall Test result > mild dyskaryosis

Referral for colposcopy or further assessment

URGENT - to be seen within 2 weeks

Direct referral for colposcopy

Colposcopy Programme and Management Guidelines (2010) state that:At least 90% of women with an abnormal test should be seen in a colposcopy clinic within 8

weeks of referral and that at least 90% of women with a test result of moderate or severe dyskaryosis should be seen within 4 weeks

Sample taken

Sample processed and cytology results

available

Sample taker receives results and made aware of direct referral

Direct referral from laboratory to colposcopy

Sample taken

Sample processed and cytology results

available

Sample taker receives results and refers to colposcopy

Referral from GP to colposcopy.

Patient sent appointment

Smear taker referral for colposcopy

COLPOSCOPY

Louise Cadman

Research Nurse Consultant and Nurse Colposcopist

Centre for Cancer Prevention

Wolfson Institute of Preventative Medicine

To determine extent of the lesion Visualise the entire squamocolumnar or the colposcopy is

‘unsatisfactory’. Identify the transformation zone (TZ).

Obtain directed biopsies from abnormal/-suspicious areas

To confirm nature of lesion and to rule out invasion

Aims of Colposcopy

Colposcopy

A specialist technique Gives a magnified image of the cervix Solutions applied which reveal changes in the epithelium

5% acetic acid Iodine

Colposcopic signs

VESSELS

COLOURMARGINS

IODINE

Normal Colposcopy

with acetic acid

with iodine

CIN I

with acetic acid

with iodine

2012-3 Procedure at colposcopy by reason for referral (N=3,320,389)

Treatment Methods

Large Loop Excision of the Transformation Zone - LLETZ

Large Loop Excision of the Transformation Zone - LLETZ

LLETZ

Local anaesthetic Cuts blocks up to 1.5 cm

deep Provides a specimen for

histology Good haemostasis Quick and simple Little thermal damage to

cervix or specimen

Cold coagulation

Heats superficial tissues to 100°C

Suitable for small lesions / low grade CIN

Rapid (20 seconds per field)

Cryocautery

Freezes using nitrous oxide

Treatment ablates affected area

Treats to a depth of 4 mm

LASER

Light

Amplification

Stimulated

Emission of

Radiation

Cold knife cone biopsy

Future developments

Prophylactic Vaccines

Gardasil(Sanofi Pasteur MSD)

Quadrivalent HPV types 6,11,16

and 18 Adjuvant –

aluminium salts

Cervarix(GSK)

Bivalent HPV types 16 and

18 Adjuvant – ASO4

UK vaccination programme introduced in September 2008

Previous calculation: number of cancers could be reduced to 1000

6000 cytology screening samples + pathology samples HPV 16 and 18 found in

76.4% of squamous cell cancers 81.9% of adenocarcinomas 63% of CIN 3 91% of high grade glandular lesions

Frequently found multiple HPV types in a lesion Number of cancers could be reduced to 700

Recent results for HPV prevalence in England

Howell-Jones R, et al Br J Cancer 2010:103;209-16; doi:10.1038/sj.bjc.6605747

Monitoring after vaccination

Monitoring essential: type-specific HPV tests needed

Duration of protection 15 - 30 years?

booster needed?

Relevance of antibody levels

Detection of non-vaccine HPV types

Cuzick J, et al. Vaccine 2008; 26S:K29–K41 Fraser C, et al. Vaccine. 2007; 25:4324–4333

David MP, et al. Gynecol Oncol. 2009

Screening in the era of vaccination:challenges and possibilities

HPV as primary screen?

Increase screening interval to ?5 years

Transience of infection At what age to start?

Maybe age 30? Triage using cytology?

When to refer for colposcopy?

Median duration time of HPV infection (months)

Any 9.8

hrHPV 9.3

lrHPV 8.4

16 12.4

18 9.8

Swab Tampon Vaginal

washings Brush

New developments

Nonavalent human papillomavirus (HPV) vaccine, including HPV-types 6/11/16/18/31/33/45/52/58

Therapeutic vaccine: ProCervix - bivalent HPV 16 and 18

therapeutic vaccine

Useful websites64

www.jostrust.org.ukwww.bsccp.org.uk

www.cancerscreening.nhs.uk