CERVICAL SCREENING WALES

Transcription

1 CERVICAL SCREENING WALES Cervical Screening Wales Audit of Cervical Cancer (CSWACC) National Report For more information about this report contact: Dr Rose Fox Director Cervical Screening Wales 18 Cathedral Road Cardiff CF11 9LJ Published: July 2012

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3 Preface This is the first report from the Cervical Screening Wales Audit of Cervical Cancer (CSWACC). The report is intended to be published every three years. The Audit was established in 2006 to collect data prospectively on all cases of invasive cervical cancer and a subset of women who do not have cervical cancer. Uniquely Cervical Screening Wales have been able to provide data retrospectively from 1999 to 2006 and prospectively up to Having access to 11 years of data allows for a comprehensive picture of the cervical screening programme in Wales to be presented. It has also allowed for comparison between the early data (pre 2005) and the later period to assess how the programme has changed since the establishment of Cervical Screening Wales in This Audit is unique in having not only good quality cytology data, but also good quality colposcopy data on all appointments carried out as part of the programme since The Audit continues to collect data on cases and controls diagnosed after December 2009 which will be included in future reports, as will any updates received in relation to cases diagnosed between 1999 and Professor Peter Sasieni Professor of Biostatistics & Cancer Epidemiology Dr Alejandra Castanon Epidemiologist Miss Helen Beer Senior Information Manager & Research Specialist 3

4 ACKNOWLEDGEMENTS The editors are grateful to the following for their comments and suggestions on earlier drafts of this report. Dr Rosemary Fox, Director, Screening Division, Public Health Wales Bryan Rose, Head of Programme, Cervical Screening Wales A large number of individuals across Wales have worked diligently to collect the data presented here. It is impossible to name them all but special thanks are due to the following Jane Evans, Information Governance and Evaluation Manager Dr Jenny Brick, Regional Programme Co-ordinator Dr Anne Hauke, Regional Programme Co-ordinator Dr Louise Pickford, Regional Programme Co-ordinator The editors also gratefully acknowledge research funding from Cancer Research UK (Grants C8162/A9481 and C8162/A10406) Editor(s) Profesor Peter Sasieni Dr Alejandra Castanon Miss Helen Beer Enquiries Alejandra Castanon Centre for Cancer Prevention Wolfson Institute of Preventive Medicine Charterhouse Square, EC1M 6BQ London a.castanon@qmul.ac.uk 4

5 Table of Contents Table of Figures Executive Summary Background Burden of cervical cancer in Wales Epidemiology of HPV and cervical cancer Cervical Screening HPV DNA testing Cervical Screening Wales Cervical screening and HPV vaccination Cervical Screening Wales Audit of Cervical Cancer (CSWACC) Purpose of the audit Audit Protocol Ethical approval Databases and other sources of data Essential Fields Data aggregation Data Completeness and Limitations Cancers and population controls Dealing with missing values Cytology Colposcopy Analysis and Commentary Invasive cervical cancer Age of invasive cervical cancer cases FIGO stage of invasive cervical cancers

6 5.4 Histology of invasive cervical cancers Cervical screening history (cases compared with controls) Proportion of women never screened Classification of screening status Coverage and number of cytology tests in the previous three (or five) years Observed screening interval in women with routine recall Regular screening interval Colposcopy Appendix A: Essential Fields Appendix B: Completion of data for the Essential Fields Glossary Related Publication References Appendix C: Data Tables

7 Table of Figures Table A. Number of cases of cervical cancer included in this report compared with those reported nationally..18 Table B. Number of cases of cervical cancer included in this report compared to those reported nationally ( ) by age group...19 Table C. Number of cases of invasive cervical cancer and controls submitted to the audit by CSW Screening Region.19 Figure 1: FIGO stage of cervical cancer cases: estimated percentage distribution, by age Table D. Number of cervical cancer cases by FIGO stage in audit, by CSW Screening Region...21 Figure 2: FIGO stage of cervical cancer cases: estimated percentage distribution, by age-group...21 Figure 3: FIGO stage of cervical cancers cases: estimated percentage distribution by year in women aged Figure 4: Percentage of cervical cancer cases, by histology...22 Figure 5: Proportion of women with no screening test (other than those taken within six months of diagnosis), by FIGO stage and age..23 Table E. Cervical screening status of cases of invasive cervical cancers and controls under age 65, up to six months prior to diagnosis (percentages)...25 Table F. Proportion of population controls (GP and district) screened 1 in the 3 year interval preceding the date of diagnosis of their matched case and resulting 3 and 5 yearly coverage..26 Table G. Time to previous cytology test among potentially screen-detected cases and their screened controls (percentages)..28 Figure 6: Maximum interval between cytology tests (in the last 8 years) among stage1b+ cases and their population controls, by age 29 Figure 7: Time from cytology indicating referral to colposcopy by year of referral.30 Figure 8: Time from cytology indicating referral to colposcopy for cases and controls, restricted to cytology taken from 2003 onwards.31 7

8 1 Executive Summary The Cervical Screening Wales Audit of Cervical Cancer (CSWACC) comprises 1,843 women with invasive cervical cancer diagnosed between January 1999 and December 2009 (an estimated 99% of all cervical cancers in Wales). These women are compared with 3,686 women without cervical cancer (referred to as controls). The incidence of cervical cancer peaks between age 35 and 39. Incidence of stage 2 or worse cancer increases with age until age 45 and then it plateaus. Seventy nine percent of cervical cancers in women over the age of 65 were advanced (FIGO stage 2 or worse). There was a shift from stage 3 or worse cancer towards stage 1B cancer particularly in Between 2005 and 2009, 22% of stage 1A cancers and 21% of stage 1B+ occurred despite apparent adherence to screening guidelines. By comparison, 62% of population controls adhered to screening guidelines. The proportion of cancers occurring despite adherence to guidelines has decreased by a third when compared to Approximately 11% of women aged were on short term recall owing to a previous abnormal result. Only 6% of women in the general population were screened within 2.75 years of a normal cytology test. Among women aged 50-64, 60% of those with fully invasive (stage 1B+) cancer had not been screened for the last 7 years, compared with only 16% of the general population. From this we estimate that fully invasive cervical cancer rates in women aged today would be nearly four times higher were it not for the screening undertaken over the last decade. 8

9 9 2 Background 2.1 Burden of cervical cancer in Wales Cervical cancer is a malignant neoplasm of the cervix uteri. Between 1999 and 2009, 1863 cases of cervical cancer were registered in Wales with an average European age-standardised incidence rate (EASR) of 10.3 per 100,000 women [1]. Mortality is substantially lower than incidence of cervical cancer with 735 cases reported between 1999 and 2009 (average EASR mortality rate 4.1 per 100,000) [1]. Relative survival for women diagnosed was 80.2% at 1-year and 65.5% at 5- years [1]. 2.2 Epidemiology of HPV and cervical cancer Human papillomavirus (HPV) is a common, sexually transmitted infection. In rare cases, infection with high-risk forms of this virus can cause a woman to develop cervical cancer. There is consistent evidence from across the world that high-risk (HR) HPV infection is a necessary cause of cervical cancer, and optimal testing systems have identified the virus in all invasive specimens. [2]. 4 HPV is implicated in both squamous cell carcinoma (SCC) and adenocarcinoma (ADC), as well in over 95 % cases of the cancerous precursor, cervical intraepithelial neoplasia, grade 3 (CIN3). Co-factors that appear to increase the risk of developing cervical cancer in HPV-infected women include the use of oral contraceptives, smoking, high parity, unidentified genetic factors possibly related to immunity, and previous exposure to other sexually transmitted diseases, such as Chlamydia trachomatis and herpes virus type 2. Women exposed to human immunodeficiency virus (HIV) are at high risk of HPV infection, HPV persistence, and cervical cancer. Cervical screening and treatment of high-grade CIN have the potential to prevent the development of cervical cancer in HPV-infected women, and screening programmes have had a substantial impact on cervical cancer incidence in many countries [3]. 2.3 Cervical Screening Cervical screening is not a test for cancer, but it is a method of preventing cancer by detecting early abnormalities with cervical cytology, which if left untreated, could lead to cancer in a woman s cervix. Early treatment can prevent nearly 100% of cancers from developing [3]. Although cervical screening may not detect every abnormality before it leads to cancer, screening may lead to the diagnosis of asymptomatic cervical cancer at an early stage, at which point it can be more easily and successfully treated. Virtually all micro-invasive (stage 1A) cancers are diagnosed and these can often be treated with fertility-sparing surgery [4], and can usually be cured (5 year survival >98 %). The cytological screening test involves the collection, staining, and microscopic examination of cells from the cervix. Between 1988 and 2003, conventional smears were used to screen women: samples of cells were taken from around the cervix, the material was wiped onto a glass slide, and the slide was sent to the laboratory for examination. Between 2004 and 2005, liquid-based cytology (LBC) was introduced across Wales as a new way of preparing cervical samples to improve laboratory examination and reduce the proportion of samples that are inadequate for evaluation [5]. The sample is taken with a special device which is

10 used to brush cells from the neck of the womb, which are placed into a small vial containing preservative fluid. This vial is then sent to the laboratory where a glass slide is prepared from the cells in the fluid. This method was designed to produce a more representative sample of the specimen and reduce the presence of distracting background material. 2.4 HPV DNA testing There are over 100 types of Human Papillomavirus (HPV). Most do not cause significant disease in humans. However, around 15 HPV types have been implicated in cervical cancer, notably types 16 and 18 which give rise to some 70% of all cervical cancers. Research has shown that women with no evidence of high risk HPV infection are extremely unlikely to have concurrent precursor disease or to develop such disease or cervical cancer over the next 6 years [6]. HPV testing has been evaluated in various settings: to triage women with borderline changes or with mild dyskaryosis on cytology; as a test of cure to reduce the duration of surveillance following treatment for CIN; To replace cytology as the primary screening test. At the time of this publication, no form of HPV testing has been introduced as part of the cervical screening programme in Wales. 2.5 Cervical Screening Wales Cervical screening began in Britain in the mid-1960s. By the mid-1980s, although many women were having regular cytology tests, there was concern that those at greatest risk were not being tested, and that those who had positive results were not being followed up and treated effectively. The NHS Cervical Screening programme was set-up in 1988 when the Department of Health instructed all health authorities to introduce computerised call-recall systems and to meet certain quality standards. Cervical Screening Wales (CSW) is responsible for the NHS Cervical Screening Programme (NHSCSP) in Wales. CSW was launched in 1999 to provide women with equal access to a uniform and high quality cervical screening service across Wales [7]. The programme aims to reduce the incidence of and mortality from invasive cervical cancer [8]. It does this by regularly screening all women at risk so that conditions which might otherwise develop into invasive cancer can be identified and treated. Cervical Screening Wales invites women aged for a cytology test every three years. Cervical screening is free for all eligible women. Screening is not offered to women who have had a total hysterectomy. Cervical Screening Intervals Age group Frequency of screening (years) 20 First invitation yearly 65+ Screen those who have recent abnormal tests until these have been resolved The NHS call-and-recall system invites women who are registered with a GP. It also keeps track of any follow-up investigation, and, if all is well, recalls the woman for screening after three years. Women should receive their first invitation for routine screening at or just before 10

11 their 20 th birthday. Migrants should receive their first invitation (between the ages of 20 and 64) soon after registering with an NHS GP. The programme screens on average around 223,500 women in Wales each year. For clinical reasons some women have more than one test during the course of a year thus around 236,800 samples are examined by pathology laboratories every year[9]. Whilst no cervical screening can be 100 percent effective, cervical screening programmes have been shown to dramatically reduce the incidence of cancer in a population of women. Since the introduction of the NHSCSP in the UK in 1988, the number of diagnoses has halved, from 16.5 per 100,000 women in 1988 to 8.5 per 100,000 women in 2008 despite increased rates of underlying disease[10]. Percentage of cancers prevented by a single negative cytology test Screening interval years years years 3-yearly 41% 69% 73% 5-yearly 30% 63% 73% Adapted from Sasieni P, Adams, Cuzick[11] The effectiveness of the programme can partly be judged by coverage. Coverage is defined as the percentage of women in the target age group (20-64) who have received an adequate test in the last three years. In 2008/2009, screening coverage of women aged was 65.5% in the last three years and 75.5% in the last five [12]. 2.6 Cervical screening and HPV vaccination Two prophylactic HPV vaccines have been shown to be highly efficacious at preventing persistent HPV infection and the high-grade disease (CIN3) caused by infection. In September 2008 a national programme was introduced to vaccinate girls against HPV 16 and 18. This covers girls aged 12-13, with a catch-up programme for those born The NHS cervical screening programme will continue to play an important part in screening women who have not been vaccinated, including all those born before The role of cervical screening for vaccinated women remains to be clarified but will depend on the age at which the woman was vaccinated, the cross-protection given by the vaccine for other HPV types and the duration of protection provided. The impact of HPV vaccination will in due course need to be monitored alongside the cervical screening programme. In the interim, continued work is needed to determine the most effective means of monitoring the impact of both vaccination and cervical screening. 11

12 3 Cervical Screening Wales Audit of Cervical Cancer (CSWACC) Despite the provision of an effective population-based screening programme in Wales, there are several reasons why screened women may develop cervical cancer. These reasons were recognised before the NHSCSP was implemented in 1988[13], and were taken into account in previous recommendations for the Audit [14]. Five year cervical screening coverage between 1999 and 2009 has been on average 77% (and has been increasing in recent years), so it is likely that the majority of cancers detected in the screening age group will occur in women who have been screened at some point during their lives. Monitoring incidence and mortality rates is an important element in establishing whether the programme is achieving its objectives. It does not give the complete picture, however, and it certainly does not indicate how effective screening would be if its activities were optimised. 3.1 Purpose of the audit The purpose of the Cervical Screening Wales Audit of Cervical Cancer (CSWACC) (hereafter the Audit) is to monitor the effectiveness of the screening programme, identify areas of good practice and indicate where improvements might be made. It also aims to monitor cases where the programme fails to prevent cervical cancer, which can be particularly revealing at a time when changes are being made to the technology used and to the age and frequency with which women are called for screening. The Audit offers the opportunity to explain why some cases occurred, for example in previously unscreened women or if colposcopic treatment has failed, and what proportion were screen detected. It is also able to indicate in a timely fashion whether the alterations in screening ages and frequencies have affected the incidence of cervical cancer. It is intended that all cervical cancers be included in the Audit, irrespective of clinical stage or the age of the woman at the time of diagnosis. The CSWACC is based on the successful audit model established in England by the NHSCSP. Judgement about the effectiveness of the programme depends on accurate data on incidence and prognosis or mortality, linked to individual level information on screening uptake and outcome. In an attempt to obtain consistently reported data, all parties in the NHSCSP are advised to follow the national protocol for audit of cases of invasive cervical cancer (audit protocol) [13]. 3.2 Audit Protocol Specific individuals within Cervical Screening Wales (CSW) have been identified as having key roles. Wales is divided into three screening regions for administrative and audit purposes; each region is the responsibility of a designated Regional Programme Co-ordinator, who has responsibility for the conduct of the Audit within their locality. Identification of cases with histologically confirmed invasive cervical cancer is done by CSW on a quarterly basis. CSW holds the national coordination of the cervical screening history review, which includes validating local cytology, histology, and colposcopy review processes according to internal protocols (which follow the 2006 national audit guidelines)[13]. CSW work very closely with the Welsh Cancer Intelligence and Surveillance Unit (WCISU) to ensure that all cervical cancers diagnosed in Wales are registered in both databases. Very rarely cancers are registered in the Audit which are not included in the Registry and vice versa (but numbers are very small, Table A). 12

13 The Director of the Screening Division, Public Health Wales has the final say on updates and recommendations on the data and results generated from this project and on which data items are provided to the authors of this document Ethical approval Data for cases of invasive cervical cancer and their controls in Wales are an anonymous selection of routinely collected data that is regarded as service evaluation and is exempt from research ethics review[15] Databases and other sources of data The audit aims to collect data on age, stage, call/recall status, cytology, histology, and colposcopy data from a number of sources. Information on screening history of invitations, results, and action codes on cytology are obtained from the Exeter system, which is a database that provides these data to Health Boards and NHS trusts, GP practices, and laboratories. This Exeter system (aka NHAIS) is used to invite women for screening and stores screening records (since 1988) of all women registered with the NHS; the system is used to derive the screening history for the purpose of the Audit. In Wales, cervical screening databases can be accessed nationally by Cervical Screening Wales (CSW). CSW is responsible for maintaining a centralised colposcopy database (CANISC) which contains all colposcopy data since CSW also has direct access agreements with Health Boards for cervical cytology and histopathology reports and related information held in Laboratory Information Management systems (LIMS) across Wales. Regional Programme Coordinators are charged with verifying and collecting missing data on stage and histology. All audit data is collated and formatted in accordance to published guidelines (audit protocol) and submitted to the authors for analysis Essential Fields To generate a minimum dataset, information must be entered in a number of essential fields. These are listed at Appendix A. Every field in this list is expected to be completed for each case of cervical cancer included in the Audit SELECTION OF CONTROLS To permit rigorous evaluation of the programme, women who did not develop cancer were used as controls for the cases identified. These age-matched controls were selected from among women who were not known to have had a hysterectomy and who were registered with a GP in the same administrative district as the case. Controls were selected from four groups (i) GP controls were selected from the same group practice (ii) district controls were selected from the same area (with the same first half of the postcode) but from a different GP (iii) screened controls were selected only for cases whose cancer is believed to have been diagnosed as a direct result of the screening programme, and the control was required to have had cytology tests in roughly the same time period as the case (iv) abnormal controls were selected only for cases with an abnormal cytology test history prior to diagnosis; the control was required to have had an abnormal cytology test. 13

14 Each case was assigned two population controls (one GP control and one district control). In addition, some cases (see section 6.1) were assigned controls whose screening history was partially matched. This was designed to facilitate the audit of screen-detected cancers and cancers that develop despite the women having been referred to colposcopy some considerable time before diagnosis following an abnormal screening result. Controls were selected by specially written software within the Exeter call and recall system CYTOLOGY SCREENING HISTORY Before 2003 cytology samples took the form of conventional smears. Between 2004 and 2005 laboratories in Wales converted from conventional to liquid-based cytology (LBC); all tests within the programme are now collected through LBC. To reflect the use of both technologies in the audit period, cytology samples are referred to here as tests rather than smears. Details of every cytology test taken and recorded for both cases and controls were downloaded from the Exeter system. Records included all samples taken on eligible women within Cervical Screening Wales (or within the NHSCSP). The following information was obtained for both cases and controls date the test was taken result of the test action code resulting from the test The action code is the national code used to define the woman s recall type, the type of notifications required, and the period of time between recalls. It determines the management action for each woman in the light of her latest test result and records any additional clinical input, automatically generating a specific recall type. The following additional information was collected for cases date of birth date of cancer diagnosis FIGO stage of the tumour histology of the tumour For controls, information was collected only on date of birth COLPOSCOPY Colposcopy data were obtained for both cases and controls. The data obtained on colposcopy visits included date of appointment attendance at appointment whether the examination was satisfactory surgical procedure performed Non-essential fields included colposcopic impression pathological diagnosis whether the woman was pregnant time to next follow-up appointment 14

15 CYTOLOGY AND HISTOLOGY REVIEWS Audit guidelines covering the period of this report suggest that all cytology samples and histology specimens obtained in the 10 years preceding diagnosis, including those that diagnosed or led to diagnosis, should be reviewed for all women with cervical cancer. Although Wales does perform cytology and histology reviews regularly this data has not been provided as part of this Audit. The Director is considering whether to provide this data in the future Data aggregation Names, addresses and unique identifiers such as NHS numbers are not recorded within the data transferred to the national audit database. The only personal identifier the Audit receives (both for cancer cases and their controls) is the date of birth. This personal identifier is not sufficient to identify a given individual and the data are thus considered to be anonymous. 15

16 4 Data Completeness and Limitations Data completeness is critical when interpreting audit results, and the findings presented in this report should thus be approached with a degree of caution. Appendix B highlights data completeness in the essential fields. Where data are reported as missing, this may not mean that they are unavailable but merely that they have not yet been recorded as part of the Audit. For this reason the term none recorded has been used, although reference is also made to missing values. For some fields the information simply may not exist: on a death certificate, for example, the cancer will not have been staged. Such instances are rare, however, and cannot be distinguished from incomplete records. The difficulties in ensuring data completeness for specific sections of the essential fields are described below. 4.1 Cancers and population controls Cases are identified primarily by the Welsh Cancer Intelligence and Surveillance Unit (WCISU), but the Screening Division Informatics Team reviews all cases coded as cervical cancer to identify the small proportion of cancers that the WCISU miss. These cases are notified to WCISU. Nonetheless, a small proportion of cancers may remain unidentified and not recorded. Additionally a very small number of cases are excluded from the Audit because the women are not registered with an NHS GP. Table A (Section 6.1) compares the number of registrations for cervical cancer in a given calendar year with the number of cases in this Audit in each calendar year. There are slight differences in the way CSW and the Cancer Registry define the date of diagnosis for each cancer, therefore cancers are not always registered on the same year in both sources. Therefore a small number of cases were included in the Cancer registry (n=20) that were not included in the Audit over the 11 year period. Controls are selected randomly (subject to matching) from women registered with an NHS GP. All those selected are included in the Audit. 4.2 Dealing with missing values In general, estimates are reported on the assumption that the data are missing at random. For example, if 40 women were reported with FIGO stage 1A, 60 with stage 1B+ and 25 with stage unknown, it would be estimated that 40% of the 25 unknown (ie 10 women) were, in fact, stage 1A. Where this approach has been adopted the label estimated proportion is used. 4.3 Cytology Since data on cytological tests are downloaded directly from the Exeter system, it is assumed that the data are complete for all cases and controls. This is because cytology tests (as noted above) are recorded for all women who participate in the CSW programme. The Audit does not attempt to capture screening events that take place outside the UK and will miss a very small proportion of tests taken privately. 4.4 Colposcopy The quality and completeness of the colposcopic data are good. A centralised colposcopy database has been in place since The database is populated by the colposcopist during or after each colposcopic appointment. Clinicians have access through the colposcopy database to the record of any colposcopy appointment in Wales attended by 16

17 women under their care. Details of the histology result (when a sample has been taken) are recorded at a later date by the colposcopy clinic staff. The best indicator of whether a woman should have had colposcopy is whether or not there is a suspend code in her cytology record (see Appendix B, table 4). Similarly a record in the histology laboratory is suggestive of a sample having been taken at colposcopy. Unfortunately, we have not collected data from the histology laboratories independently from those reported at the colposcopy clinics, so we are unable to include those histology specimens not taken in a colposcopy setting. Nevertheless, neither the cytology nor the histology record provides conclusive information regarding colposcopy. In future we will be receiving data from the histology laboratories from Cervical Screening Wales. 17

18 5 Analysis and Commentary Commentary on select analyses is presented. Detailed data are presented in Appendix C. 5.1 Invasive cervical cancer In the period , 1,843 cases of invasive cervical cancer and 3,686 women without cancer were included in the Audit. Table A shows the number of cases of invasive cervical cancer included in each audit year compared to those reported nationally. Table B shows the number of cases of invasive cervical cancer included in the audit in five year age groups compared to those reported nationally. From 2006 onwards CSW routinely compares all cases reported to them with those reported to the cancer registry (and have done this retrospectively to 1999). Therefore with the exception of a small number of cases (n=20) which were included in the Cancer Registry data but not registered in the Audit, the Audit includes data on 99% of cancers diagnosed in Wales. It is evident from table A that cancers in both sources are not registered in the same calendar year; the most likely reason for this is that the date of diagnosis recorded at the cancer registry differs from the date recorded by CSW. Further evidence of this can be observed in table B which suggests that the differences between the Audit and the Cancer Registrations are due to slight differences in the dates of diagnosis and not to a systematic under reporting of cancers in a certain demographic. Work is ongoing to align these dates for future reporting. Table A. Number of cases of cervical cancer included in this report compared with those reported nationally Calendar Year No of cases in Audit Cancer Registrations Total 1,843 1,863 1 Source: Trends in incidence, Welsh Cancer Intelligence & Surveillance Unit. [16] 18

19 Table B. Number of cases of cervical cancer included in this report compared to those reported nationally ( ) by age group Age group No of cases in Audit Cancer Registrations Total 1,843 1,863 1 Source: Trends in incidence, Welsh Cancer Intelligence & Surveillance Unit. [16] All cases bar one submitted to the audit have two age matched populations controls (GP and district). For a defined subset of cases, up to two further controls were selected, resulting in 666 screened and 866 abnormal controls (see Section ). Table C. Number of cases of invasive cervical cancer and controls submitted to the audit by CSW Screening Region 1 CSW Screening Region Case One Population Controls Two Population Controls Abnormal control Screened control North Wales Mid & West Wales South East Wales Total Cancers diagnosed 01/01/1999 to 31/12/

20 5.2 Age of invasive cervical cancer cases Figure 1 shows the estimated percentage distribution of cases of cervical cancer by age in the audit with a peak number of cases in the age group (12%). Seventy four percent of all cases of invasive cervical cancer fall within the eligible cervical screening age group (20-64 years, table 3, Appendix C). Age and stage at diagnosis have a strong correlation. For example, as a proportion of all cancers, invasive cervical cancer stage 1A is more likely to be diagnosed in women under age 45, than in those over age 45. The correlation is particularly evident in women over the age of 65, where over 75% of cancers are stage 2+. Surprisingly 9.6% of cancers are diagnosed in women 80 years or older. The large proportion of cancers observed in this age group is most likely due to very complete ascertainment of cervical cancers reported on death certificates, since very few of these women would have been invited for screening when the programme started in Figure 1 FIGO stage of cervical cancer cases: estimated percentage distribution, by age 14% 12% 10% 8% 6% 4% 2% 0% Stage 2+ Stage 1B Stage 1A 5.3 FIGO stage of invasive cervical cancers Table D shows the number of cervical cancer cases by FIGO stage for each screening region. Percentages are presented in table 5a. The majority are stage 2 or worse, representing forty five percent of all cases with known FIGO stage. Even when restricting the analysis to cases aged at diagnosis we see that 29% of cases with known stage were micro-invasive (1A), 36% stage 1B and 35% stage 2 or worse. This has implications on prognosis and survival as advance stage cancers require aggressive treatment and 5 year survival is generally poor (5-year relative survival for stage 2 cancer is 60.7% and decreases steeply to 15.8% for stage IV cancer). In comparison 5-year relative survival for stage 1A carcinoma is 98.1% and for stage 1B cancer it is 88.2% [4]. However there has been a decrease in the number and proportion of cancers diagnosed as stage 3 or 4 from to (see figure 3 and table 8). We are unable to say how many of the cases with missing stage are due to the lack of clinical staging, but 48% (123/254) of those with missing stage were cancers in women over age 64 at diagnosis. 20

21 Table D. Number of cervical cancer cases by FIGO stage in audit, by CSW Screening Region CSW Screening Region 1A 1B 2+ None recorded Total North Wales Mid & West Wales South East Wales Total ,843 Figure 2 shows the estimated percentage distribution of invasive cervical cancer cases by age and FIGO stage. A decreasing proportion of cases with FIGO Stage 1A are found with increasing age. In contrast, an increasing proportion of cases with FIGO Stage 2+ are found with increasing age. Note that there are only 40 cancers diagnosed in women under age 25. There is clearly a benefit of screening in diagnosing cervical cancer early (as stage 1A or 1B) even when it fails to prevent cancer per se. Treatment of stage 1A cancer generally has fewer side effects and is more likely to be curative. Figure 2 FIGO stage of cervical cancer cases: estimated percentage distribution, by age-group 1A 1B < Figure 3 shows the estimated percentage distribution of cases of cervical cancer by FIGO stage and year in women aged There has been a general shift from stage 2 or worse cancers towards stage 1B cancers particular in (Table 8a). No change was seen in the proportion of cancers stage 1A in the 11 year period. 21

22 Figure 3 FIGO stage of cervical cancers cases: estimated percentage distribution by year in women aged A 1B Histology of invasive cervical cancers Figure 4 shows the distribution of invasive cervical cancer cases by histology. Almost three quarters of cases of cervical cancer are of squamous histology followed by adenocarcinoma and adeno-squamous carcinoma. The proportion of cancers recorded as having other histology is higher than expected because those cancers where the histological type was unclear or not recorded have been included in this category. Figure 4 Percentage of cervical cancer cases, by histology Other/Unknown 8.6 Undifferentiated 0.1 Adeno-Squamous 3.4 Adenocarcinoma 17.1 Squamous

23 5.5 Cervical screening history (cases compared with controls) Proportion of women never screened Figure 5 shows the proportion of cases and controls with no recorded screening history up to six months prior to diagnosis. Cases (n=254) with no information on stage are excluded from this figure. Note that we have excluded 3 women aged with FIGO stage 1A cancer because there the lack of routine screening for women in this age group means that it is unlikely that these cancers were screen-detected. Instead, this small number of cancers (8 out of 239 in women aged 65-79) may represent rare instances of incidental cancer diagnosis. Overall cases with stage 1A cervical cancer are as likely as controls to have no adequate tests up to six months prior to diagnosis, suggesting that the majority of these cancers are in fact screen detected. Interestingly only in the age group are women with invasive cervical cancer stage 1B more likely to have been previously screened than controls. For all other age groups women with stage 1B or worse cancer are more likely to have no screening tests than controls. Figure 5 Proportion of women with no screening test (other than those taken within six months of diagnosis), by FIGO stage and age Population Controls Stage 1A 30 Stage 1B Stage Classification of screening status Table E summarises the screening status of women with cervical cancer and their controls six months before the cancer was diagnosed. The table has been divided into women diagnosed between and those diagnosed to allow for comparison between the two time periods. Numbers can be found in table 12 and pooled results can be found in table 13 and 14. All tests taken by women over the age of 66 have been excluded. Results in women aged 65 are included to allow for repeat tests in women with a low grade abnormality at age 64. The action code shown on the Exeter database has been used to determine whether the last cytology test led to a routine recall, early recall or suspension from the call and recall programme. After a routine recall interval, screening is considered to be up-to-date when the diagnosis occurred within 3.5 years of the routine cytology test. For women aged 65 or older (Table 14) up-to-date means that there 23

24 was a cytology result at age After an early repeat action code, screening is considered to be up-todate if diagnosis occurred within 1.25 years of the early repeat test (or 0.25 years if that test was inadequate). Those that were suspended more than 6 months before diagnosis and are not followed by any negative tests are considered to be lapsed. The proportion of stage 1A and 1B+ cancers that occurred in women whose screening was apparently upto-date and in line with national guidelines has reduced to about one third in when compared to the previous period (22% vs 32% and 21% vs 26% respectively) (this comprises up-to-date routine screening plus up-to-date early recall screening and up-to-date last test suspended screening). When compared with cases more than double the proportion of controls adhered to screening guidelines (62% of controls compared to 22% of cases in ). However the proportion of controls that adhered to screening guidelines has decreased by 4% between periods (66% in and 62% in ), this corresponds with the drop in coverage observed over the same period. The proportion of women never screened (except within six months of diagnosis) has doubled for cases with stage 1A cancer (8% in , 16% in ) and increased by 15% in the general population (8.6% in , 9.9% in ). However, it has remained almost unchanged for cases with stage 1B+ cancer (26% in , 27% in ). The proportion of cases stage 1A scheduled for early repeat screening has decreased from 22% in to 16% Another substantial change is the decrease in the proportion of women with stage 1B+ cancer who are diagnosed more than 6 months after they have been referred to colposcopy; it was 11.2% in and 8.2% in Coverage and number of cytology tests in the previous three (or five) years Table F presents a snapshot of the coverage achieved by the screening programme by age group. They can be compared to coverage data presented in the Cervical Screening Wales KC53/61/65 Statistical Report([12], table 1) (3-year coverage in women aged was 65.5%, and 5-year coverage for women aged was 75.5% for 2008/09). Results in five-year age groups are presented in table 15/15a using 3- year and 5-year coverage for women aged Comparable national data have been extracted ([12], table 1) and included in table 15/15a. Coverage figures here are based on whether or not a sample of the population has been screened, whereas national coverage figures are based on the total number of women screened and the total population in the age group. The Audit s figures are thus subject to sampling error but are not compromised by a disconnection between the coverage denominator and numerator. Table F quantifies the number of women attending for screening more than once during the recommended interval (3 yearly) and reveals that 11% ie (115+90)/( ) of those screened aged had had two or more cytology tests in the previous three years. This figure may be compared with the proportion of screened women on early repeat or suspended screening (Table 13): in women aged this is 9.8%. For women aged 65+ it shows how many had at least one test between age 60 and 65 (i.e ). Those screened three or more times in the previous interval reflect those women having an early repeat test due to an abnormal result (this estimate is also very similar to the one reported in the KC53: 2.4% for 2008/09[12], table 5b 1. Women over the age of 80 have low coverage because they would have been over 60 when the screening programme started in Although more recent reports have been published by CSW, was have chosen the 2008/09 report so that it ties in with the last year of data provided to the Audit (2009). 24

25 Table E. Cervical screening status of cases of invasive cervical cancers and controls under age 65, up to six months prior to diagnosis (percentages) Cervical screening history up to six months prior to diagnosis Population Controls Stage 1A Stage 1B+ Stage not recorded Population Controls Stage 1A Diagnosed Diagnosed No cytology test (except within six months of diagnosis) Last smear routine and Up to date Lapsed Last smear early repeat and Up to date Lapsed Last smear suspend (not followed by any negative(s)) Lapsed Last smear suspend (followed by at least one negative) Up to date Lapsed Total Stage 1B+ Stage not recorded 25

26 Table F. Proportion of population controls (GP and district) screened 1 in the 3 year interval preceding the date of diagnosis of their matched case and resulting 3 and 5 yearly coverage. 5 yearly coverage 2 3 yearly coverage 3 Not screened in previous 3yrs Screened once in previous 3 yrs Screened twice in previous 3yrs Screened 3 times in Age previous 3yrs (>=1 test in interval) % % N % N % N % N % Total For women aged 65+ it is the number of samples taken in the five years before their 65 th birthday. 2 Coverage in women aged is about half (33%) of coverage in women aged (64%) 3 Coverage in women aged is about half (29%) of coverage in women aged (47%) 26

27 5.5.4 Observed screening interval in women with routine recall For the purposes of this report, a screen-detected cancer is defined as a cancer that is diagnosed after a referral to colposcopy, where that referral is due to a cytology test taken at least 3 weeks, and no more than 4 months, prior to diagnosis. However, there is no national record of the reason for taking the original cytology test, i.e. whether it arose from routine screening, or from a test to investigate suspicious symptoms. Therefore, some women whose cancers are defined as screen-detected will have gone to their GP with symptoms and been offered a cytology test as an alternative to rapid referral for suspected cancer. Conversely, some stage 1A cancers may not be included if, for instance, a woman went to see a gynaecologist without a screening-based referral, following a borderline cytology test. In this section we aim to establish whether women with screen detected cancer were screened less often than screened women who do not have cervical cancer. Table G shows the interval between the previous screening test and the test that led to diagnosis for screen-detected cases, and compares this to the interval between screening episodes for controls. If a previous test result was recorded for cases, the interval was taken to have started after an action code specifying routine recall; if there was no previous adequate test, the time to the previous screen is shown as none within 9.5 years.2 Compliance with three yearly screening in women of all ages was poor, reaching a maximum level of 58% among screened controls aged Additionally 15% of women aged did not attend screening within 3.5 years of their previous test but were in fact screened between 3.5 and 4.75 years later. By contrast, the majority (81 %) of screened controls aged had been screened in the previous 5-year period, with 58 % of this group tested in the previous 3 years, and the other 23% tested in the previous 5 years. For women aged 50-64, the difference between cases who had not been screened in the last 9.5 years and controls was striking 45% compared with 6% and similarly for women aged In women aged 2024 the opposite is observed, 68% of controls had not been screened compared to 32% of cases. This suggests that a high proportion of the cancers detected in this age group are been detected on the woman s first cytology test. Fewer than 6% of women on routine recall were screened at an interval of under 2.75 years (see Table 17). Of the women with a routine screen between 1999 and 2009, 73% had had an earlier screen in the previous 5.5 years. This suggests that the 5-year coverage of 77% does reflect women attending due to an invitation rather than reflecting coverage among women with early recall and post-colposcopy (except in women under age 35). 2 When discussing controls, these intervals are informally referred to as the actual interval after routine recall, although, in fact, the calculation looks back from a current test rather than forwards from one resulting in routine recall. 27

28 Table G. Time to previous cytology test among potentially screen-detected cases and their screened controls (percentages) Time to previous screen Age <3.5 yrs yrs yrs yrs No previous cytology within 9.5 yrs Total <5.5 yrs Cases Controls Cases Controls Cases Controls Cases Controls Cases Controls Cases Controls Cases Controls Total

29 5.5.5 Regular screening interval Figure 6 presents the maximum interval between cytology tests taken over the 8 years preceding diagnosis for women with stage 1B or worse cervical cancer, and for their population controls. The numbers are presented in Table 18. Women aged under 28 are not included, because they would not have been eligible for screening for the whole of the previous 8 years. Results by year of diagnosis are presented in table In all age groups, women with stage 1B+ cervical cancer are less likely to have been screened at least every 3.5 years (during the last 8 years) than are controls. Over 70% of controls have been screened at least every 5.5 years (during the last 8 years), compared to 58% women with stage 1B+ cancer under age 35, 42% age and 34% age The proportion of women with a maximum interval of more than 7 years between cytology tests, or with no cytology recorded, is greatest among women aged 50 64, where 60% of those with stage 1B+ cancer were in this category, compared with 16% of controls. This corresponds to a relative risk of 8.21 in women with a maximum interval of over 7 years between screening episodes. Since 16% of controls are in this category, the relative risk of the this population compared to those screened at more frequent intervals is (0.17*8.21)+0.84 = This means that cervical cancer rates in women aged today would be more than three times higher (8.21/2.15=3.8) were it not for the screening undertaken over the last decade. Figure 6 Maximum interval between cytology tests (in the last 8 years) among stage 1B+ cases and their population controls, by age Maximum Interval <3.5 yrs yrs yrs yrs 7+ yrs Cases Controls Cases Controls Cases Controls yrs yrs yrs 29