Results

The number of children and young adults in the cohort (those born in Cumbria, 1950–89) remained roughly constant during 1971–89. However, the number of adults (over 25 years) increased steadily from 1975 onwards (see fig 2A). This pattern is reflected in the number of cancer registrations (see fig 2B, C, D).

NHSCR notified us of 720 cases diagnosed during 1971–89, 32 of which did not have specified site or morphology codes or dates of diagnosis, but were confirmed to be malignant.

ACCURACY OF DIAGNOSTIC CODES

The method of review of the remaining 688 cases whose NHSCR site and morphology codes indicated malignancy is summarised in table 2. While 206 (30%) cases were diagnosed in three hospitals in Cumbria, the remaining 482 cases were diagnosed in 113 hospitals throughout the United Kingdom, of which 105 forwarded material for review, 91 sending biological specimens. For three cases, there was insufficient information either to confirm or refute the NHSCR diagnosis, so this was assumed to be correct.

Table 3 shows the level of agreement between the NHSCR and review diagnostic codes and the reasons for disagreement. These codes were in complete agreement for over one third of the cases (38%), in broad agreement for over half the cases (55%) and in different diagnostic groups for 47 (7%) cases, including 26 (4%) that were reclassified on review as non-malignant. The proportion of disagreements was highest in the age group 15–24 years (p for heterogeneity = 0.02, see table 4A) and was non-significantly lower in more recent years (p for trend = 0.08, see table 4B).

Over one third of the disagreements were attributable to failures in data capture and coding by the cancer registration system, (see table3). These were mainly the supply of codes for diagnoses that had not been confirmed by histology, or codes that did not correspond to the diagnosis on the cancer registration form.

Five of the disagreements were attributable to the reviewing pathologist giving a more specific (two cases) or a less specific (two cases) diagnosis than NHSCR or an unspecific diagnosis (one case).

Almost half of the disagreements were attributable to changes in diagnosis (see table 3). Although three cases were reclassified on the basis of histopathology techniques that were not widely available at the time of the original diagnosis, most were reclassified on the basis of standard techniques (see table 3). There was no evidence that the proportion of changes in diagnosis (3% of all notifications) varied over the time period considered.

Table 5 shows the level of agreement between the NHSCR and review diagnostic codes by diagnostic group. The main group of concern was lymphoma, of which 13 cases (10%) were reclassified, three as leukaemia, nine as non-malignant and, for one case, the reviewing pathologist found no evidence from the postmortem report of a malignancy but insufficient evidence to exclude it.

ACCURACY OF DIAGNOSIS DATE

For the 555 cases notified by both NHSCR and another source, which were confirmed as malignant, the dates of diagnosis recorded by NHSCR and the review source were compared: 94% of these were within six weeks of each other and 99% within a year, but for 2% the calendar year of diagnosis was different. For the six for which the dates of diagnoses differed by more than a year, all information was rechecked: for two cases the NHSCR date of diagnosis was correct and the review source was incorrect, for one case NHSCR had used the date of death rather than the date of diagnosis and for three cases the review source (Northern Region Young Persons' Malignant Disease Registry) was correct and had an earlier date of diagnosis than NHSCR.

COMPLETENESS OF ASCERTAINMENT

The 694 cases notified to us by NHSCR and confirmed as malignant represented 94% of the total of 740 confirmed malignancies notified from all sources, (see table 1).

For those aged 0–14 years, we approached three specialist children's cancer registries—two regional and one national; for those aged 15–24 years we approached one specialist regional registry for young people and two regional cancer registries; for those aged over 25 years we approached two regional cancer registries (see table 1). Therefore we expected ascertainment in the younger age groups to be better. This was confirmed by the significantly higher percentage of cases known to us that were not notified by NHSCR in the younger age groups (see table4A: 10%, 6% and 4% in the age groups 0–14, 15–24 and over 25 years respectively, p for heterogeneity=0.02). This under-notification by NHSCR was more marked for cases who had not died (NHSCR failed to notify 16%, 10% and 3% of such cases in the respective age groups, p for heterogeneity =0.006). After stratifying by age group there was little variation in the level of notification over the time period considered (p=0.83, see table 4B).

There must inevitably be other cancers, not ascertained by us from any source. If ascertainment from NHSCR cancer registrations and the other sources listed in table 1 were independent, the estimated number of such cancers would be 0.0, 1.9 and 4.4, in those aged 0–14, 15–24 and over 25 years at diagnosis, respectively. Adding these estimates of cancers missed by all sources to the numbers of cancers missed by NHSCR but known from other sources (see above) implies that NHSCR missed a total of 10% (95%CI 6%, 15%), 7% (95%CI 4%, 11%) and 5% (95%CI 3%, 8%) of actual cancers in these age groups and 7% (95%CI 5%, 9%) of cancers overall.

Of the 26 cancer registrations in people over 15 years not notified by NHSCR, 19 (73%) were notified to us by regional cancer registries (Northern Region Cancer Bureau or North Western Regional Cancer Registry), which notify cancers to the National Cancer Intelligence Centre and hence would be expected to be recorded by NHSCR; this proportion did not change significantly over time.

Discussion

A national system of cancer registration, such as National Cancer Intelligence Centre, is a prerequisite for monitoring geographical, social and occupational trends in cancer incidence and for the development and evaluation of policies on prevention and screening of cancer.16 17 However, many epidemiological studies require the linkage of cancer details to individuals. NHSCR provides such a facility for England and Wales, aiding the selection of samples from the entire population for inclusion in cohort or case-control studies. Individuals can be “flagged” for retrospective studies, researchers being informed if their study members have developed cancer, died or emigrated whereas, for prospective studies, researchers are informed if and when these events occur.6 Hence, many epidemiological investigations rely on the timeliness, completeness and accuracy of information passed to researchers by NHSCR,18although for some studies, data obtained directly from regional registries may be more appropriate.19

Although the need for quality assurance of cancer registration data is recognised,20 21 few systematic audits have been carried out to date of the completeness and accuracy of cancer data recorded on NHSCR, (see table 6). Although the cohort considered in this study does not constitute a random sample of cancer cases in England and Wales, being biased towards those diagnosed at a younger age and in more recent years, it extends the findings of previous studies.

ACCURACY OF DIAGNOSTIC CODES

There were substantial disagreements between the NHSCR diagnoses and the review diagnoses in 7% (95%CI 5%, 9%) of cases, approximately half of these disagreements resulting in reclassification as non-malignant on review. These disagreements could have implications for epidemiological studies, either of cancers within specific diagnostic groups or of all malignancies.

Over one third of the disagreements were attributable to failures in data capture by the national cancer registration system. In 3% (95%CI 2%, 5%) of cases, there were genuine differences between the original diagnosis and the review diagnosis. The main areas of concern were lymphomas, of which 10% (95%CI 6%, 17%) were given a different diagnosis on review. Histopathology is the “gold standard” in the diagnosis and typing of the vast majority of tumours. However, its interpretation is to a certain extent subjective, relying on the experience and expertise of the pathologist and hence there will inevitably be occasional differences of opinion. It is worth noting also that better diagnostic criteria may result in changes to a diagnosis made many years ago. Only three disagreements in diagnosis (0.4% of all cancers) resulted from the application of advanced diagnostic techniques available to the pathologists reviewing the cases but not to those making the original diagnoses. However, in some instances the reviewing pathologists had the benefit of hindsight in that they had access to follow up records of the patients.

It is important to note that the diagnosis on which treatment was based was not necessarily the diagnosis reported through NHSCR and we do not know if the discrepancies we observed had any implications for the individual patients concerned.

ACCURACY OF DIAGNOSIS DATE

Agreement on date of diagnosis was generally high, with dates for fewer than 1% of the cancers notified through NHSCR discrepant by over one year.

COMPLETENESS OF NOTIFICATION

In this study, 94% of cancers ascertained during 1971–89 were notified to us by NHSCR by May 1999. This level of ascertainment is compared with other studies in table 6. There is a known delay between diagnosis and recording of a cancer on NHSCR,3 22which would account for the low level of notification observed in studies carried out within three years of diagnosis.23-27 Our study had a minimum period of 10 years between diagnosis and assessment of completeness of NHSCR notifications, longer than that reported in the study of Hawkins and Swerdlow, 1992,3 which may account for its higher level of notification.

It is of concern that 19 (73%) of the 26 cancers not notified by NHSCR in those over 15 years were known to the relevant regional registry (Northern Region Cancer Bureau or North Western Regional Cancer Registry) indicating difficulties at some point in the flow of information from regional registries to the National Cancer Intelligence Centre and hence to NHSCR and researchers.22Some records may not have been sent by the regional registries to the National Cancer Intelligence Centre, some records may not have been sent from National Cancer Intelligence Centre to NHSCR at the time of our study or may have gone astray between them, some flagged cases may not have been notified to researchers and some cases may have been wrongly flagged.

It is clear that, as noted by other researchers,28ascertainment of cancers is likely to be inadequate for epidemiological studies unless registrations are sought from several sources: six of the seven sources that we approached notified details of cancers unknown to all other registries.

There were almost certainly some cancers not registered by any of the sources we approached. The numbers of such cancers were estimated by two methods. Firstly, assuming independence of ascertainment by NHSCR and other sources, the proportion missed was estimated to be 7%. This is likely to be an underestimate, as the assumption of independence of sources is not valid, as NHSCR is informed of cancers registered by the regional registries, which exchange information with the specialist children's and young persons' registries. Secondly, the apparently worse notification by NHSCR of children's cancers is almost certainly an artefact attributable to our more thorough ascertainment of childhood cancers from regional and national specialist children's cancer registries. Hence the proportion missed in all age groups is likely to be at least 10% (95% CI 6%, 15%), as in the youngest age group, despite a generous interval of at least 10 years between diagnosis and notification. In this series of 694 cancers diagnosed at all ages and notified by NHSCR, 10% missed would represent 77 cases.

It is clear that overall case ascertainment was superior for the younger age group, as a consequence of the availability of specialist children's cancer registries, which are an important resource for epidemiological studies of these rare tumours.

REPRESENTATIVENESS OF STUDY

There is varying under-ascertainment of cases by regional cancer registries.2 About half the cases in this study were diagnosed within the area covered by the Northern Region Cancer Bureau, which was one of the few regional registries in the United Kingdom whose data were not included in Cancer Incidence in Five Continents, 29 which has stringent data quality criteria. Hence it is possible that the level of notification might have been higher if the study had been based on a different geographical cohort. On the other hand, there are many steps in the supply of information where cases may have been lost and NHSCR failed to notify us of cases known to the Northern Region Cancer Bureau. It is therefore unclear whether geographical bias has affected the level of notification.

Information for diagnostic review was obtained from over 100 hospitals throughout the UK in addition to the two major regional referral centres for children's cancers (Newcastle in the northern region and Manchester in the north western region). About half of the disagreements in diagnosis were for cases diagnosed outside the area covered by the Northern Region Cancer Bureau, corresponding roughly to the distribution of diagnoses. Therefore the 3% disagreement in diagnosis is likely to be typical of the country as a whole.

Although the age distribution in our cohort changed over time, it consisted predominantly of children and young people and included no one aged over 40 years (see fig 2). This was reflected in the distribution of tumours (see table 5), in particular the high proportion of lymphomas (18% of all tumours but 28% of those reclassified). While the incidence of cancer increases dramatically with age, the proportion of lymphomas declines; hence the rate of disagreement for a sample with an age distribution representative of all cancer cases might be lower than that found in our cohort.

In conclusion, we estimate that NHSCR notified us of 90% (95%CI 85%, 94%) of all incident cancers and that this is likely to be typical of notification of cancers diagnosed under 40 years of age throughout England and Wales. Among the cancers notified by NHSCR as malignant, 7% (95%CI 5%, 9%) had diagnostic codes that differed substantially from those assigned by our pathology review, 4% (95%CI 2%, 5%) being reclassified as non-malignant.

Completeness of ascertainment of cancers from NHSCR alone may not be adequate for epidemiological studies and registrations should be sought from several additional sources where possible. Likewise, researchers should be aware that a small fraction of site and morphology codes notified by NHSCR may not be accurate and diagnostic review should be attempted.

The National Cancer Intelligence Centre is the largest national cancer registry in the world. By linking this information on cancers to individuals and combining it with information on deaths and emigrations, NHSCR provides a uniquely powerful resource for medical research. It is therefore critical that checks on its accuracy and completeness are assured through regular audit and administrative excellence. Adequate funding is clearly of national importance, not only for NHSCR but for the entire cancer registration infrastructure, including primary data suppliers in hospitals and pathology laboratories, regional registries and the National Cancer Intelligence Centre.