WHO : when is screening effective? World health organisation, regional office for Europe Assessing a screening procedure 1986 Wilson and Junge

principles for early detection: the condition sought should be an important health problem there should be an accepted treatment for patients with the recognised disease facilities for diagnosis and treatment should be available there should be a recognisable latent or early symptomatic stage “the person being screened should have a reasonable chance of benefiting”

principles for early detection there should be a suitable test or examination this test should be acceptable for the population the natural history of the disease, including the development from latent to disease should understood there should be an agreed policy on whom to treat as patients the cost of case-finding (including diagnosis and treatment) should be economically balanced in relation to possible expenditure and medical care as a whole case-finding should be a continuing process, and not a “once and for all” project

we want a test that is: Valid and reliable Specific and sensitive

National cancer plan Fall of 20% in cancer deaths in under 75’s Screening for cervix, breast, bowel. No screening for prostate cancer at present

No screening for prostate cancer at present Passes 1st requirement - Is 2nd biggest killer, mainly in over 50s – but fails all the others Would use prostate specific antigen (PSA) - 2\3 men with raised PSA will not have cancer, whilst others with ca will not be identified Treatment for ca prostate may be unnecessary Treatment has side effects

Screening for bowel cancer NHS bowel screening programme has been rolled out from 2006 is organised with regional hubs, each working with up to 20 local screening centres each hub operates “call and recall” system, sends out FOBt kits, analyses specs and post results local centres provide nurse-led endoscopy clinics

Facts and figures - Cervical cancer World wide 1\10 female cancers diagnosed is CaCx Rate varies seven fold around the world Highest rate is Zimbabwe, 67.21 per 100,000 women yrs Lowest rate in China, 2-3 per 100,000 women yrs In UK is 9.3 per 100,000 women yrs, Was about 15-16

Facts and figures Cervical cancer is the 11th most common cause of cancer deaths in the UK In 2000 there were 2,424 new registrants for invasive cancer, in 2002 there were 927 deaths, the first time that deaths had fallen below 1,000 1988-97 there was a 42% fall in deaths from this cancer

Cervical cancer Usually a primary Squamous cell cancer \ carcinoma Adenocarcinoma Lymphoma Symptoms include abnormal vaginal bleeding discomfort during sex abnormal vaginal discharge.

Effectiveness of screening In England screening prevents approximately 4,500 cancers pa In UK screening prevents approx 3,900 deaths Programme costs approx £150 million Or £37.00 per woman screened Or £33,000 per life saved

The epidemic that never was Without screening, CaCx would have killed 1\65 U.K. women born since 1950 = 6,000 deaths a year Are preventing 80% (5,000 of them)

Risk Factors Viruses and cancer HPV cervical cancer Hepatitis B virus liver cancer Epstein Barr Virus lymphoma and Hodgkins disease HIV and cancer ??Mouse mammary tumour virus (MMTV)/breast cancer ??? from musculus domesticus MMTV ? Transmitted from cancerous mothers to offspring via milk ( mice studies)

HPV subtypes Are 100 different subtypes, are mostly harmless Type 16 is greatest threat Also types 18, 31, 33, 45 These are not associated with genital warts

Transcriptional units E6 and E7 both oncoproteins that prevent tumour suppression E6 is an oncoprotein that binds to and inactivates tumour suppressor gene p53 (“guardian of the genome”) E7 binds to and inactivates retinoblastoma gene Rb, also p53 and p21 Transcription is 1st step of gene expression – DNA copied by RNA Oncoprotein – coded by an oncogene( which is agene with potential to cause cancer) and the protein is involved in regulation of timourgenic cell growth

How common are “High risk” HPVs ? 1\5 of all 20-25 year olds will test positive type16 Figure for over 50s is 1\20 World wide between 28-40 million women 7% of all women in developed world and 15% in developing world Problem is persistence of infection (eg over 6 months) Needs to be present for 10 yrs for cellular changes to occur.

Other risk factors Early (before 16yrs) sexual activity High number (over 4) sexual partners Cigarette smoking (including passive) Immuno suppression and HIV Early first pregnancy Multiple pregnancies

Risk factors: contraception Barrier methods of contraception should be protective Use of combined oral contraceptive seems to increase risk: if taking COC for > 5yrs, rr1.1 if taking COC for 5-9yrs rr1.6yrs if taking COC for > 10yrs rr2.2

Do we know in time? 60% of all cancers are diagnosed when changes confined to cervix 25% changes extended to vagina 10% changes in pelvic wall (symptoms) 5% changes extended beyond pelvis

BUT what do we do if we find it???? Should we screen for HPV? Cancer research UK did a trial, offering 11,000 women screening for HPV and cytology 9% had HPV (900 women) 10% of them required treatment (90) All those identified at cytology had HPV 97% of those requiring treatment would have been identified by HPV alone 76% would have been identified by cytology alone So smears alone would have missed 8\11,000 HPV would have missed none BUT what do we do if we find it????

Predications: 120,000 borderline\mild changes pa in UK Of these, 10-20% will have CIN3 Expect 56% to be referred to colposcopy This would give a rate of: 96% sensitivity 99.5% negative predictive value Rebello G et al Human papillomavirus testing and the management of women with mildly abnormal smears: an observational study BMJ 2001;322:893-94

Could we prevent HPV? Now offering immunisation against types 16 and 18, which together cause 70% of all cervical cancer Will need to do it before they become sexually active May also protect against anal and oral cancers

BUT Current screening programmes identify cancers “vaccine overload” and multiple immunisations Immunising against STD is controversial A backlash could affect other immunisation programmes What about vertical transmission? Both immunisations require multiple jabs Long term results not available yet More than 80% of all cervical cancer occurs in resource deprived countries Offers no protection to those already colonised