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, 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 0 10,000 12th most common cancer amongst females in the UK 2851 cases/year 972 deaths/year 67% survived ≥ five years (2005-2009) 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 European Age-Standardised Cervical Cancer Incidence & Mortality Rates per 100,000 Female Population, UK 18 Incidence 16 Mortality per 100,000 14 12 10 8 6 4 2 0 Year 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 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 population, by age, females, Great Britain 40 20 to 24 25 to 34 35 to 49 35 50 to 64 65 to 79 80+ 30 25 20 15 10 5 0 Years Number of cases by morphology, England 1988-2009 3000 2500 Squamous 2000 Adenocarcinoma 1500 Unclassified Epithelial Adenosquamous Neuroendocrine 1000 Other Epithelial Other 500 Year of Diagnosis 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989 1988 0 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, 31st 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 60.0 77.5 76.8 76.5 73.2 70.3 65.0 70.0 75.0 % 80.0 85.0 NHS Cervical Screening Programme, 20032013: coverage-less than 5 years (%) 90 85 25-64 25-29 80 30-34 % 35-39 40-44 75 45-49 50-64 70 50-54 55-59 60-64 65 60 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 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 Columnar epithelium Usually on ectocervix Cells are multilayered Usually appears as smooth, shiny, pale pink 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 HPV infects cell integrates its DNA into the host cell DNA Persistence cell damage (pre-cancer) Eventually cancer Normal Epithelium HPV Infection Months CIN I CIN II CIN III Years Cancer 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 3and 5-yearly screening Annual 3 yearly 5 yearly 76% 61% 30% (39%) 88% 84% 73% 87% 87% 83% 20–39 years 40–54 years 55–69 years * 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 Additional cervical screening is not In women who have had justified in any of the multiple following situations sexual providing the woman partners has undergone screening within the previous three to five years and is on routine In women with recall: pelvic infection In women with vaginal discharge In women with genital warts On starting or taking HRT Antenatally, postnatally or after termination of pregnancy Would you like to empty your bladder before we start? Be realistic in the length of time it should take This should not take longer than five minutes but I will keep you informed Some women may wish to agree a non-verbal sign Prior to the examination Please indicate if you would like to stop and I will be guided by you You are unlikely to be able to relax but try to avoid lifting your bottom off the couch Avoid the word relax! 31 You may experience some discomfort but let me know if it is unbearable 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 Explain that spotting following the test is possible and to be expected Ensure that the woman knows how and when she will receive her results. Complete the sample request form accurately 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 Severe dyskaryosis or worse Moderate dyskaryosis Mild dyskaryosis 84 Borderline changes 82 Negative 80 Cytological referral for colposcopy or further assessment URGENT Suggestion of invasive carcinoma (x1) to be seen within 2 weeks Suggestion of glandular lesion (x1) Severe dyskaryosis (x1) URGENT Moderate dyskaryosis (x1) to be seen within 4 weeks Mild/borderline and hr HPV +ve (x1) ROUTINE Persistent unsatisfactory smears (x3) to be seen within 8 weeks 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 Cytology terminology and result codes Previous terminology (BSCC 1986) New Terminology 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 Low-grade dyskaryosis (not HPV Tested) 3 Low-grade dyskaryosis (HPV tested) M High-grade dyskaryosis (moderate) High-grade dyskaryosis (severe) High-grade dyskaryosis ?Invasive squamous carcinoma 7 4 5 ?Glandular Neoplasia endocervical type ?Glandular Neoplasia (non-cervical) (not HPV Tested) 6 0 ?Glandular Neoplasia (non-cervical) (HPV tested) G Negative (Not HPV tested) Negative (HPV tested) Inadequate 2 N 1 Mild dyskaryosis Borderline changes with koilocytosis Moderate dyskaroysis Severe dyskaroysis Severe dyskaryosis? Invasive ?Glandular neoplasia Negative Inadequate Result code Referral for colposcopy or further assessment Clinically suspicious cervix Post-menopausal bleeding Symptoms → gynaecologist → colposcopy Not using HRT URGENT to be seen within 2 weeks 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 Direct referral for colposcopy Sample taken Sample taken Sample processed and cytology results available Sample processed and cytology results available Sample taker receives results and made aware of direct referral Smear taker referral for colposcopy Sample taker receives results and refers to colposcopy Direct referral from laboratory 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 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 IODINE COLOUR VESSELS 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) 100 90 80 Percent 70 60 Other 50 Ablation with biopsy 40 Ablation without biopsy Excision 30 Diagnostic biopsy No procedure 20 10 0 All referrals Inadequate Low Grade High Grade Reason for referral Clinical Clinical Indication - Indication Urgent 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 Future developments Prophylactic Vaccines Gardasil Cervarix (Sanofi Pasteur MSD) (GSK) Quadrivalent Bivalent HPV HPV types 6,11,16 and 18 Adjuvant – aluminium salts 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? Swab Median duration time of HPV infection Tampon (months) Vaginal Any 9.8washings Brush hrHPV 9.3 lrHPV 8.4 16 12.4 18 9.8 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 64 www.cancerscreening.nhs.uk www.bsccp.org.uk www.jostrust.org.uk