CERVICAL SCREENING UPDATE Louise Cadman Research Nurse Consultant and Nurse Colposcopist Centre for Cancer Prevention Wolfson Institute of Preventive Medicine
Learning Objectives State the objectives of the cervical screening programme Identify the principles of screening programmes Explain the way the cervical screening programme operates in the UK Understand the prevalence of cervical screening abnormalities Manage cervical screening results correctly Explain colposcopy to a patient
The aim of the NHS Cervical Screening Programme is to reduce the number of women who develop cervical cancer and the number of women who die from the condition NHS Choices http://www.nhs.uk/conditions/cervical-screening-test/pages/introduction.aspx
Principles of screening programmes
Wilson and Jungner classic screening criteria, WHO 1968 1. Condition should be an important health problem 2. Accepted treatment for recognised disease 3. Facilities for diagnosis and treatment should be available 4. Recognisable latent or early symptomatic stage 5. Suitable test or examination 6. Test acceptable to the population 7. Natural history of the condition should be adequately understood 8. Agreed policy on whom to treat as patients 9. Cost of screening, diagnosis and treatment economically viable 10. Case-finding a continuing process Wilson. JMG, Jungner G. Principles and practice of screening for disease. Geneva: WHO; 1968. Available from: http://www.who.int/bulletin/volumes/86/4/07-050112bp.pdf
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, 2011 Number of New Cases, UK Breast Lung Bowel Other Sites Uterus Ovary Malignant Melanoma Non-Hodgkin Lymphoma Brain, Other CNS & Intracranial Tumours Pancreas Kidney Leukaemia Cervix Bladder Oesophagus Stomach Oral Myeloma Thyroid Liver 12 th most common cancer amongst females in the UK 2851 cases/year 972 deaths/year 67% survived five years (2005-2009) 0 10,000 20,000 30,000 40,000 50,000
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
per 100,000 European Age-Standardised Cervical Cancer Incidence & Mortality Rates per 100,000 Female Population, UK 18 16 14 12 10 8 6 4 2 0 Incidence Mortality Prepared by Cancer Research UK Original data sources: Office for National Statistics. Cancer Statistics: Registrations Series MB1. http://www.ons.gov.uk/ons/search/index.html?newquery=series+mb1 Welsh Cancer Intelligence and Surveillance Unit. http://www.wcisu.wales.nhs.uk Information Services Division Scotland. Cancer Information Programme. www.isdscotland.org/cancer Year
1975-1977 1976-1978 1977-1979 1978-1980 1979-1981 1980-1982 1981-1983 1982-1984 1983-1985 1984-1986 1985-1987 1986-1988 1987-1989 1988-1990 1989-1991 1990-1992 1991-1993 1992-1994 1993-1995 1994-1996 1995-1997 1996-1998 1997-1999 1998-2000 1999-2001 2000-2002 2001-2003 2002-2004 2003-2005 2004-2006 2005-2007 2006-2008 2007-2009 2008-2010 2009-2011 Per 100,000 1975-2011 European age-standardised incidence rates of cervical cancer per 100,000 female population, by age in UK 40 35 20 to 24 25 to 34 35 to 49 50 to 64 65 to 79 80+ 30 25 20 15 10 5 0 Years
1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Number of cases by morphology, England 1988-2009 3000 2500 Squamous 2000 1500 Adenocarcinoma Unclassified Epithelial Adenosquamous Neuroendocrine 1000 Other Epithelial Other 500 0 Year of Diagnosis
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 adenocarcinoma screening programmes not achievable in many countries may not detect lesions which progress quickly in time only effective if women attend regularly, when invited
NHS Cervical Screening Programme Coverage
Five year coverage of the target age group (25-64), Primary Care Organisation, England, 31 st March 2013 Source: KC53, Health and Social Care Information Centre.
Cervical screening coverage by London Primary Care Organisation, 2012-13 (% less than 5 years since last adequate test) Kensington & Chelsea PCT Richmond & Twickenham PCT Tower Hamlets PCT Hillingdon PCT Brent Teaching PCT Haringey Teaching PCT Barnet PCT Hammersmith & Fulham PCT Croydon PCT Islington PCT Ealing PCT Lewisham PCT Newham PCT Bromley PCT Lambeth PCT Barking & Dagenham PCT Harrow PCT Redbridge PCT Enfield PCT Sutton & Merton PCT Waltham Forest PCT Bexley Care Trust Southwark PCT Hounslow PCT Kingston PCT Camden PCT Westminster PCT Wandsworth PCT City & Hackney Teaching PCT Havering PCT Greenwich Teaching PCT 70.3 73.2 77.5 76.8 76.5 60.0 65.0 70.0 75.0 80.0 85.0 %
% NHS Cervical Screening Programme, 2003-2013: coverage-less than 5 years (%) 90 85 80 75 70 65 25-64 25-29 30-34 35-39 40-44 45-49 50-64 50-54 55-59 60-64 60 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Five year coverage of the target age group (25-64) England at 31 st 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
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 The Uterine Cervix
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
Types of Transformation Zone Type I TZ completely ectocervical and fully visible Type II TZ partially endocervical but fully visible Type III TZ endocervical and not fully visible
HPV Infection in the Cervix HPV infects cell integrates its DNA into the host cell DNA Persistence cell damage (pre-cancer) Eventually cancer Normal Epithelium HPV Infection CIN I CIN II CIN III Cancer Months Years Decades
Dyskaryosis identified by cytology
CIN 1 CIN 2 CIN 3
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 years 88% 84% 73% 55 69 years 87% 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 histories P Sasieni, J Adams and J Cuzick British Journal of Cancer (2003) 89, 88 93.
Samples examined by source of sample, 2012-13
In women who are heavy cigarette smokers On taking or starting to take an oral contraceptive On insertion of an IUCD or IUS In women who have had multiple sexual partners In women with pelvic infection Additional cervical screening is not justified in any of the following situations providing the woman has undergone screening within the previous three to five years and is on routine recall: On starting or taking HRT Antenatally, postnatally or after termination of pregnancy In women with vaginal discharge In women with genital warts
Be realistic in the length of time it should take This should not take longer than five minutes but I will keep you informed You are unlikely to be able to relax but try to avoid lifting your bottom off the couch Would you like to empty your bladder before we start? Prior to the examination Please indicate if you would like to stop and I will be guided by you Some women may wish to agree a non-verbal sign You may experience some discomfort but let me know if it is unbearable 35 Avoid the word relax! Would you like to have anyone else in the room with us? Would you like me to tell you what I am doing as we go along? Some women prefer it if you just get on with it
Taking a sample Wash hands and wear gloves. Close the speculum before starting and then gently insert into the vagina and aim for the posterior vault Open the blades approximately 5mm and guide speculum until the anterior lip of cervix can be seen. Only open the speculum wide enough to reveal the whole cervix Do not over-expose the cervix and vagina as this may cause discomfort to the woman If you cannot visualise the cervix, consider repositioning the woman by raising her hips, adjust the speculum rotating it so locking ratchet faces up or down or using a condom to support vaginal walls Inspect the cervix; noting appearance, colour, amount and colour of vaginal secretions and the location of the transformation zone Obtain the sample using the appropriate sampling device ensuring all the transformation zone is sampled and ensure sample placed in LBC vial as per protocol Remove speculum it may be necessary to open it slightly first to release the cervix before removing it and ensure safe disposal of all equipment in accordance with local health and safety guidelines
Following the examination 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 Ensure that the woman knows how and when she will receive her results. Complete the sample request form accurately Explain that spotting following the test is possible and to be expected If additional tests or swabs were taken these should be discussed and arrangements made for her to receive these results and any follow-up treatment Reassurance should be given about what will happen if a result is abnormal and what will happen next 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, 2012-13 100 98 96 94 92 90 88 86 84 82 80 Severe dyskaryosis or worse Moderate dyskaryosis Mild dyskaryosis Borderline changes Negative
Summary of referral/waiting time standards Cytology/HPV NHSCSP standard 3 consecutive inadequate samples Offered an appointment Borderline change or low grade / HR-HPV positive with a colposcopist within 6 weeks High-grade (moderate) or high-grade (severe)? Invasive squamous carcinoma? Glandular neoplasia of endocervical type or not otherwise specified? Glandular neoplasia cells of other origin referral outside NHSCSP Abnormal cervix (outside the NHSCSP) Symptomatic (outside NHSCSP) Offered an appointment with a colposcopist within 2 weeks Offered an appointment with a gynaecologist within 2 weeks
Direct referral for colposcopy Smear taker referral for colposcopy Sample taken Sample taken Sample taker receives results and made aware of direct referral Sample processed and cytology results available Direct referral from laboratory to colposcopy Sample processed and cytology results available Sample taker receives results and refers to colposcopy Referral from GP to colposcopy. Patient sent appointment 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
Test of Cure After treatment for all grades of CIN women invited for cervical cytology at 6 months Negative, borderline change or low-grade dyskaryosis => HR-HPV test HPV negative => screening test in three years (irrespective of age) => returned to routine recall if the subsequent test negative; HPV positive => referred back to colposcopy. Cytology high grade or worse => straight to colposcopy
COLPOSCOPY Louise Cadman Research Nurse Consultant and Nurse Colposcopist Centre for Cancer Prevention Wolfson Institute of Preventative Medicine
Aims of Colposcopy 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
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 MARGINS COLOUR IODINE VESSELS
Normal Colposcopy with acetic acid with iodine
CIN I with acetic acid with iodine
Percent 2012-3 Procedure at colposcopy by reason for referral (N=3,320,389) 100 90 80 70 60 50 40 30 20 10 Other Ablation with biopsy Ablation without biopsy Excision Diagnostic biopsy No procedure 0 All referrals Inadequate Low Grade High Grade Reason for referral Clinical Indication - Urgent Clinical Indication - Non urgent
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
Depth/length of excision Type I TZ: 7mm (95%) aim to remove <10 mm in women of reproductive age Type II TZ: 10-15mm, depending on the position of the scj within endocervical canal. When Type I or II (for CIN) 15mm (85%) Type III TZ: 15-25mm
Information for women after outpatient treatment Avoid tampons for four weeks Abstain from vaginal intercourse for four weeks Avoid swimming for two weeks May consume alcohol in moderation after treatment Other normal activities, including light exercise, may continue Although there are no known health grounds for avoiding travel following treatment problems may not be covered by insurance May be a temporary change in menstrual pattern Single excision <10mm not associated with any increased incidence of preterm labour and preterm pre-labour rupture of membrane Single excision not associated with any increased risk of infertility but may increase the risk of mid-trimester miscarriage.
Future developments
Prophylactic Vaccines Gardasil (Sanofi Pasteur MSD) Quadrivalent HPV types 6,11,16 and 18 Adjuvant aluminium salts Bivalent Cervarix (GSK) HPV types 16 and 18 Adjuvant ASO4 UK vaccination programme introduced in September 2008
Recent results for HPV prevalence in England 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 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 Tampon (months) Any 9.8 hrhpv 9.3 lrhpv 8.4 16 12.4 18 9.8 Swab 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 websites 68 www.cancerscreening.nhs.uk www.bsccp.org.uk www.jostrust.org.uk