Epidemiology of a Chronic Disease Exercise By Mary Murphy April 2008 Cervical Cancer Epidemiology of a Chronic Disease Exercise By Mary Murphy April 2008

What is the clinical problem? Epidemiological classification: Cancer/neoplastic disease Site: neck of the womb referred to as the Cervix. The outer and inner cells of the cervix can become cancerous leading to squamous cell cervical cancer or adeno-carcinoma of the cervix. The former, acccountable for 90-95% cervical cancers. The transformation zone is the area where cells are most likely to be abnormal and is the site where cervical screens are taken. Cancer is one of the five major classifications of disease. It is Characterised by abnormal growth of cells that form into a tumours some benign and some malignant Categorised by type of tissue that has been affected and by location Cervical cancer is cancer of the cervix. The area where abnormalities are likely to grow are the transformation zone and for this reason cervical tests are taken from here. Biologically, changes happen in this area and therefore the cells are likely to start to duplicate in an unregulated manner and form tumours. Move to next slide for population at risk Above: diagram female reproductive system Source: http://www.cancerhelp.org.uk assessed 28/3/08

POPULATION AT RISK? It is necessary to have a cervix to cervical cancer, so that rules out men, unless transgender who have kept their reproductive organs.

How big is the problem? World: “Cervical cancer accounts for 1 in 10 of all cancers diagnosed and more than 273,000 deaths in women worldwide every year……In developing countries, cervical cancer is the commonest cancer to affect women, and contributed to 85% of new cases and deaths worldwide in 2002….” Source:http://www.thelancetstudent.com/2007/10/08/reducing-the-burden-of-cervical-cancer-in-the-developing-world/The accessed 14/4/08 UK: About 2,700 women are diagnosed with cervical cancer each year.  Overall, 2 out of every 100 cancers diagnosed in women are cervical cancers.  But it is the second most common cancer in women under 35 years old. In 2005 UK had 8 in 100,000.  Source:http://www.cancerhelp.org.uk/help/default.asp?page=2755#common accessed 16/4/08 In developed countries like the UK Cervical cancer does not have a high incidence - put into perspective there was 8 per 100,0000 in 2005 compared to 123 breast cancers) although it is a very serious disease if you get it - if left unchecked it is fatal. In developing countries it has very high incidence.

Treatment for Cervical Cancer Hysterectomy. Radical trachelectomy. Radiation. Chemotherapy Source: http://www.cnn.com/HEALTH/library/DS/00167.html accessed 29/3/08 Treatment is very expensive and will cause a lot of anxiety and worry. In younger women there is a likelihood they will lose there reproductive ability if not their life.

Risk Factor & Co-factors Infection with some types of HPV virus Low socio-economic status Long-term use of hormonal contraceptives, high parity, tobacco smoking, co-infection with HIV Other STD infections Large number of sexual partners Sexually active before age 18 Early menarche The biggest risk factor for cervical cancer is HPV virus. evidence of the aetiological role of the virus both molecular and through epidemiolgical studies has been discovered, but the mechanism how is still not clear. There are a number of co-factors that are also considered part of the risk – genes have not been identified as being implicated. Many of these risk factors are behavioural and over the last 30 years these will have changed and thus affected incidence of the disease

…….But the real villain 99.7% cases caused by Human papillomavirus (HPV). HPV 16 & 18 especially assocated with cervical cancer. HPV is a very common virus transmitted through direct transmission person to person, to both men and women Up to 75% of people of reproductive age will be infected with HPV at some point in their lives. Majority of women will not get cervical cancer. Cervical cancer is rare while HPV infection is common. Source: http://www.jotrust.co.uk accessed 28/03/08 But the real villain has been found – 99.7% identified cervical cancer implicate strains of HPV – HPV is a common virus that is passed through sexual activity – it has no symptoms – It will clear up after about 18months There are about 100 strains of HPV and about 15 have been implicated in cervical cancer Two in particular in this country are being blamed for the majority of cervical cancers and they are also being implicated in mouth throat and anal cancers too. In epidemiological terms the mode of transmission is direct person to person.  

Ten most frequent HPV types in women with invasive cervical cancer in United Kingdom as compared to Northern Europe and the World This slide shows just how prevalent some of the HPV viruses are in the UK compared to other countries. As you can see the rate for 16 is very high compared to other parts of the world. This slide was taken from the WHO site – they provide information that is reasonably uptodate. There are international agreements about provision of particular types of data. There is an information centre on HPV and they have their own magazine. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Summary report on HPV and cervical cancer statistics in United Kingdom. 2007. [6/4/08]. Available at www. who. int/ hpvcentre

Prevalance of Cervical Cancer I was able to get raw data from National Statistics for england, the intelligence centre in wales and the common services agency in scotland. I would then have had to age standardise the data after aggregating it – so instead I took this from the cancer research site who do all the work for you. They have epidemiological experts who provide all sorts of stat reports on incidence and mortality and it would be difficult not to use what they have available. I did do a quality check on some of it just to make sure. Anyway, here we have prevalance across the uk and you can see that Wales and scotland appear to have a much high rate than england and ireland. Source: http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/?a=5441#age assessed 30/3/08

Incidence Rates of Invasive Cervical Cancer From 1990’s you can see that the incidence rate for all ages groups has been steadily reducing and this trend is continuing. Source: http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/?a=5441#age assessed 30/3/08

Invasive Cervical cancer incidence by age When we look at age specific rates for invasive cancer there are two peaks. Epidemiologists believe these reflect a cohort effect. There are two peaks in the incidence rates for cervical cancer, both reaching around 16 or 17 per 100,000 women. The first peak in the cervical cancer incidence rates is for women in their thirties and the second is for women in their eighties. Women in there Source:http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/?a=5441#age accessed 30/3/2008

Mortality Rates for Cervical Cancer 2005 In the most uptodate stats we know there was 1061 death from cervical cancer in the UK in 2005. Out of interest I checked this slide against an estimated figure in a bulletin the doh released on cervical statistics for England and on the next slide check the estimated mortality deaths for 2005. You can see here the figure is 841 and on the next slide. 837 Source:http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/?a=5441#age accessed 30/3/2008

UK Cervical Cancer Incidence & Mortality This has been taken directly from the latest figures of the DOH KC62. (5) Source: National Cancer Intelligence Centre, ONS; data are for year commencing 1 January Registration and death rates are Directly Age Standardised Rates using the European Standard Population (DAS(E)) (6) Figures for mortality for 2005 are provisional. Source: Office for National Stats. Bulletin: 2007/14/HSCIC –Cervical Screening Programme England 2006-07

Cervical cancer mortality trends mortality rates in 2005 are over 60% lower than they were 30 years earlier Source:http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/?a=5441#age accessed 30/3/2008

Age-standardised incidence & mortality rates, Of cervical cancer by region of the world, 2002 estimates Wordlwide mortality rates …….we are in with Northern Europe on this slide. It’s not particularly uptodate and of course not all of the developing countries have their sophisticated system of cancer registries such as ours, despite that you can tell they have a problem Developed countries have a high incidence of HPV, but because of cervical screening programmes we catch precancerous cells and treat them. This data was also from cancer research all aggregated but it had a hypertextlink to Cancer Monidal. This website provides access to information on the occurrence of cancer world-wide held by the Descriptive Epidemiology Groups of IARC. One in ten female cancers diagnosed worldwide are cancers of the cervix and it is the most commonly diagnosed cancer among women in Southern Africa and Central America. There is a huge variation in the incidence of cervical cancer between the different regions of the world  1. Incidence data collected by cancer registries worldwide : CI5 (Cancer Incidence in Five Continents) Volumes I to IX.  2. The data on incidence and survival of children and adolescents in Europe;(the ACCIS project)  3. Mortality data extracted from the World Health Organization (WHO) databank.    4. The most recent estimates of the cancer incidence, mortality and prevalence, by sex and cancer site, for all the countries of the world (GLOBOCAN 2002). Source:http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/?a=5441#age accessed 30/3/2008

European age-standardised incidence of and mortality,cervical cancer by deprivation category, England and Wales, 1990-93 I’m sure it comes a no surprise to anyone that that cervical cancer both incidence and mortality have a strong positive association with high deprivation scores. Carstairs deprivation category Women living in the most deprived areas have rates more than three times as high as those in the least deprived areas. . Source: http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/?a=5441#age assessed 30/3/08

The graph below shows the incidence rates in the U. S The graph below shows the incidence rates in the U.S. for cervical cancer from 1975–2004 by race and ethnicity. Cervical Cancer I found it very hard to get Uk rates for differences in ethnicity - Although we know there are differences in uptake for diff ethnic groups most data is now very old. Exeter Systems we currently have in place don’t do ethnic monitoring This is an american slide taken from the SEERS site and it shows that all those incidence is decreasing most ethinic groups it is still higher in hispanic and African-American women. 1 ‡Source: Surveillance, Epidemiology, and End Results (SEER) Program, National Cancer Institute, NCI accessed 16/4/08

Secondary prevention -Cervical Screening Screening ages (years) 25-64; (previously 20-65) 3.4m screened 06/07 Screening interval (years) 3 years for ages 25-49, every 5 years for ages 50-64 Lifetime number of recommended smears 12? 79.2% in 2006 of eligible women had Pap test in last 5 years. Compared with 79.5% last year and 82% in 1997 Smear taker - General practitioners or general practice nurses Cervical screening - including the cost of treating cervical abnormalities - has been estimated to cost around £157 million a year in England To solve the mystery why incidence and mortality have got so much better in this country we must look at the public health initiative – which is an example of secondary prevention the cervical screening programme. The programme started in 1988 – but it was never based on any RCT trials and therefore has a bit of a reputation. Previously opportunistic tests were being done and they were picking up so much pre cancerous cells that it was decided it would be a good thing!! The cervical screen is not a diagnostic test, if a woman has an abnormal test she is sent for colposcopy where the abnormality will be diagnosed. Treatments for precancerous cells are much cheaper and obviously less invasive and cause less anxiety. Its not fatal. The programme is dogged by controversy! The age group was recently reduced because of a paper written by Sasieni etc al who said many young women were being treated for abnormalities that would have righted themselves if left alone. Because incidence is now so low many people have asked do we need it now – but a paper by peto et al in the Lancet modelled what would have happened with incidence if the programme hadn’t been in existence and he said an epidemic had been averted. Sources: Office for National Stats. Bulletin: 2007/14/HSCIC –Cervical Screening Programme England 2006-07 & http://www.cancerscreening.nhs.uk/cervical/ accessed 6/4/08

Primary prevention – HPV Vaccine difficult to prevent HPV infections. Most adults will have had HPV at some time in their lives. Direct Transmission mode person to person Condoms are not effective - because HPV has a field effect, it found on skin not covered by the condom and skin-to-skin contact transmits HPV. Available vaccines for HPV 16 & 18. They may provide protectection against a few other types, but not all types of HPV. Cost - £100m a year routine programme vaccinate girls 12-13 from September 2008 Catch up programme £200m over 2009/10 and 2010/11. But there’s more – a new public health initiative that starts in September 08 is about to kick off, and of course it’s the vaccine for From September in the UK we will routinely vaccinate girls aged 12 - 13 years of age against cervical cancer, Will be a two-year catch up campaign starting in Autumn 2009, for girls up to 18 years. The routine programme could cost up to £100m a year and the catch up programme could cost up to £200m in 2009/10 and 20010/11, but the Department of Health aims to negotiate a reduction in vaccine price during the procurement process. Cervical cancer vaccination Although the vaccine is a great leap forward in the prevention of cervical cancer it is important to remember that it is not a cure-all and will only protect against certain strains of the Human Papillomavirus (HPV). Also, at this time we do not know how long the immunity given by the vaccine will last: so far we know it gives protection for five years. Women should continue to have routine cervical screening tests.

Targeted vs. universal vaccinations HPV VACCINE ISSUES Very expensive Targeted vs. universal vaccinations the age and gender of vaccine recipients the acceptability of this vaccine to health care providers, adolescents, and parents the effect of this vaccine on cervical cancer screening. HPV vaccine has created a great deal of debate on key issues, some of them up here. It will be girls of pre sexual activity age. – this is the problem. Gay pressure groups of been putting pressure on asking why are boys not being vaccinated as evidence is being uncovered re other cancers The question everyone wants to know will it be effective. In the short term, many people will not have been vaccinated, and even those who have will still have to be screened until they know how effective the vaccine is.

About Data from Cancer Registries!! It is dynamic and only ever a snapshot in time. It is mandatory for deaths to be registered within five days. It is not mandatory for incidence data to be reported. It comes from a number of sources, it is usually 2 years National coverage in UK was not achieved until 1962 ……………and lots of other things too!! In the meantime about data from cancer registries!! Mortality is usually more complete and timely than incidence data, because it is mandatory to report a death within five days.

New – Invasive Cancer Audit Future Developments - For all newly diagnosed cervical cancers a review will be conducted of a woman’s complete screening history by Quality Assurance Reference Centres across England. It’s purpose - to measure the effectiveness of cervical screening programme, to identify areas of good practice and identify where improvements can be made

Thank you for listening!