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  12 th most common cancer amongst females in the UK  2851 cases/year  972 deaths/year  67% survived ≥ five years ( )

Age-specific incidence rates and number of cases diagnosed by five year age group, England 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 UK Original data sources: Office for National Statistics. Cancer Statistics: Registrations Series MB1. Welsh Cancer Intelligence and Surveillance Unit. Information Services Division Scotland. Cancer Information Programme.

European age-standardised incidence rates of cervical cancer per 100,000 population, by age, females, Great Britain

Number of cases by morphology, England

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

Source: KC53, Health and Social Care Information Centre. Five year coverage of the target age group (25-64), Primary Care Organisation, England, 31 st March 2013

Cervical screening coverage by London Primary Care Organisation, (% less than 5 years since last adequate test)

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

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

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 IICIN III Cancer 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 Annual3 yearly5 yearly 20–39 years 76%61%30% (39%) 40–54 years 88%84%73% 55–69 years 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,

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 taking or starting to take an oral contraceptive On insertion of an IUCD or IUS On starting or taking HRT Antenatally, postnatally or after termination of pregnancy In women with genital warts In women with vaginal discharge In women with pelvic infection In women who have had multiple sexual partners In women who are heavy cigarette smokers

Would you like to empty your bladder before we start? Please indicate if you would like to stop and I will be guided by you You may experience some discomfort but let me know if it is unbearable Would you like me to tell you what I am doing as we go along? Would you like to have anyone else in the room with us? You are unlikely to be able to relax but try to avoid lifting your bottom off the couch This should not take longer than five minutes but I will keep you informed 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

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 Taking a sample

Following the examination 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 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, Total number of results: 3,283, % 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,

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 changesBorderline 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 dyskaryosis Borderline changes with koilocytosis Low-grade dyskaryosis (not HPV Tested)3 Low-grade dyskaryosis (HPV tested)M Moderate dyskaroysisHigh-grade dyskaryosis (moderate)7 Severe dyskaroysisHigh-grade dyskaryosis (severe)4 Severe dyskaryosis? Invasive High-grade dyskaryosis ?Invasive squamous carcinoma5 ?Glandular neoplasia?Glandular Neoplasia endocervical type6 ?Glandular Neoplasia (non-cervical) (not HPV Tested)0 ?Glandular Neoplasia (non-cervical) (HPV tested)G NegativeNegative (Not HPV tested)2 Negative (HPV tested)N 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 

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

Treatment Methods

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 L ight A mplification S timulated E mission of R adiation

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: /sj.bjc

Monitoring after vaccination  Monitoring essential:  type-specific HPV tests needed  Duration of protection 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) Any9.8 hrHPV9.3 lrHPV  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

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