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- Population, subjects and methods
Objective To examine screening histories of women with invasive cervical cancer in a 12-year period during the introduction of organised screening to assess its effectiveness.
Study Design Screening histories were classified into six categories: no cytology record (1), previous cytology more than 5 years before diagnosis (2) and previous cytology within 5 years of diagnosis (3–6). Categories 3–6 were described as interval cancers and comprised previous negative cytology (3), previous repeats for low-grade cytology (4), previous recommendations for investigation (5) and previous treatment (6).
Setting Southampton and South West Hampshire (SSWH).
Population Women resident in SSWH registered with invasive cervical carcinoma between 1985 and 1996.
Methods Data were held for analysis on an anonymous spreadsheet.
Main outcome measures Association of screening history categories with 3-year time period, age group, type and stage of cancer and route to diagnosis; incidence per 100 000 women aged 25–64 years screened and not screened within 5 years in 1991–93 and 1994–96.
Results Interval cancers increased as a proportion of all cancers from 31.5% in 1985–87 to 48.6% in 1994–96 (P= 0.002) and showed a peak in 1991–93. Their incidence decreased from 20.1 to 10.9 per 100 000 eligible women aged 25–64 years screened within 5 years (P= 0.008) between 1991–93 and 1994–96, while incidence in women not screened within 5 years was unchanged (44.2 and 40.4). Factors other than previous negative smears were recorded in 50.9% of interval cancers. Interval cancers were more likely to be low stage, screen detected and were diagnosed in younger women (P < 0.00001).
Conclusions Interval cancers should be assessed as a proportion of eligible women screened within the same period of time and not as a proportion of all cancers. This audit demonstrates the importance of accurate cytology, appropriate follow up, prompt investigation and effective treatment of high-grade precancerous lesions.
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- Population, subjects and methods
In a previous study of this data set on women resident in Southampton and South West Hampshire (SSWH), we showed that screen-detected cancers became more frequent as screening coverage increased before, during and after the introduction of organised screening in 1988.1 During the study period (1985–87 to 1994–96), incidence fell from 16.8 to 10.4 per 100 000 women, which was similar to England as a whole.2 However, incidence (and mortality) alone does not give the complete picture of the programme’s potential effectiveness.3 Cervical cancer continues to occur in previously screened women, often leading such women to wonder why this happened despite participating in the programme. Audit of their personal history can yield such information and can identify areas of the programme in which procedures or standards could be improved. Such an audit is now recommended by the NHS Cervical Screening Programme (NHSCSP) as a routine component of quality assurance.3
However, it has to be recognised that the greater the screening coverage the higher the proportion of women with cancer who would have previously been screened,4 and this proportion would reach 100% if all women were screened. An audit carried out in Leicestershire showed that 80.3% of women with cancer had previously been screened, but the details of age range, stage of cancer or route to diagnosis were not provided.5 In a previous study of one 3-year period (1991–93) of the current data set, we found that 75.9% of women aged 25–69 years had been screened in the preceding 5.5 years.6
This article is the culmination of a study carried out in SSWH during the 1990s. We now analyse the screening histories of all the cases and believe that our findings provide a useful baseline for the current audits, which the NHSCSP now requires.3
We have already shown that symptomatic, screen-detected fully invasive and screen-detected microinvasive cancers were progressively more likely to be interval cancers.1 We now present the detailed screening histories to determine reasons why cancers were not prevented in a screened population, particularly in the context of the numbers of women screened and not screened within 5 years.
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- Population, subjects and methods
Interval cancers, defined in our study as occurring in women screened within 5.5 years, were significantly more likely to be associated both with early age and early stage at diagnosis. Thus, 86.5% of cancers in women aged 20–34 years were interval cancers as were 83.3% of stage IA cancers, those percentages decreasing with age and stage, respectively (Figure 2). The first of those observations is in accordance with that of Sasieni et al.,12 among whose cases ours were included. Those authors concluded that screening was less effective in younger women while we believe that cancer is more difficult to prevent when it develops early in life because there are less opportunities to detect precancerous changes before invasion develops. Furthermore, screen-detected microinvasive cancers are more likely to occur in previously screened women just as are cases of CIN3 and CGIN, most of which are diagnosed in young women, which we have shown rarely to be detected on the first screening test13—demonstrating the known poor sensitivity of a single test.
Our study also shows that numbers and to a lesser extent percentages of cancers in women who had not been screened within 5.5 years decreased as screening coverage increased reaching steady levels in the final two periods of the study (Figure 1). However, that proportion will decrease further with time as more previously screened (and treated) women enter the older age groups; and there will be progressively fewer women in the population who have never been screened. The Leicester audit5 showed that less than 20% of cancers were in women who had never been screened, which was taken as an indication that screening had been ineffective. Cancers in women who have never been screened should be taken in the context of the number of women in the same population who have never been screened and not as a proportion of cancers. Unfortunately, records do not accurately separate women who have never been screened from those who have been screened more than 5 years before diagnosis, although an attempt to separate these groups was made in a previous study.6 In the third and fourth periods of our present study, when screening coverage was relatively constant, incidence was unchanged at 44.0 and 42.2 per 100 000 women aged 25–64 years who had not been screened within 5 years. Cancers in such women comprised 19.2% (14 of 73) and 37.5% (18 of 48) of cancers in women aged 25–64 years in 1991–93 and 1994–96, respectively (Table 4). The first figure is similar to the Leicester study, whose age range was not presented.
More importantly, interval cancers should be related to the population of women screened within 5 years, which is relatively easy to calculate from Department of Health’s Annual Statistics Bulletins.8 In our study, incidence in previously screened eligible women decreased significantly during the third and fourth periods of the study from 20.1 to 10.9 per 100 000 women. Incidence in women screened within 5 years is an overestimate for the majority of well-screened women. We showed in a previous study that incidence was significantly lower in women screened within 3.5 years, who comprised the majority (75%) compared with 3.5–5.5 years.6 Nevertheless, it is important to question why interval cancers were so frequent in the third period of our study.
We believe that there were several reasons. Those women were previously screened during a decade when workload increased steadily, but sometimes in sudden bursts, almost doubling during the 1980s, resulting in recurring backlogs in screening and waiting lists for colposcopy (unpubl obs.). Although resources eventually followed those demands, there was often a delay in appointing and training new staff leading to considerable pressure on the workforce, while many aspects of quality control had yet to be introduced. Although there was a certificate of competence for cytology screeners, the test was not mandatory for qualified biomedical scientists; there was no rapid review or preview of negative smears; there was no external quality control; there were no standards for cytology reporting rates. All these measures were introduced in Southampton early in the 1990s. The interval cancers detected in 1991–93, many of which were screen-detected microinvasive cancers, resulted from improved quality control as much if not more than from increased screening coverage, which had increased steadily during the whole of the previous decade. The time period 1991–93 also coincided with the introduction of excisional biopsies instead of local ablation for high-grade CIN, so it is possible that some microinvasive cancers might not have been recognised in previous years.14 However, the 65 interval cancers during 1991–93 should be placed in the context of high-grade CIN and CGIN successfully detected. The figures for CIN2 are not recorded, but there were 700 women with CIN3 and 14 with CGIN (3 of the latter were mixed CIN3/CGIN) reported in SSWH 1991–93.13
Another reason for the high rate of interval cancers was the risk of cancer in women aged 35–49 years, who comprised 83/173 (48.0%) of all women with interval cancers. Women in that age band in 1991–93 were born between 1942 and 1958, representing a birth cohort that has been shown across Europe to be at increased risk of cervical cancer15 almost certainly because of the sexual freedom allowed by the availability of reliable contraception.16 Our study suggests that screening in the 1980s was failing to control that increased risk but that increased screening coverage and improved quality control in the 1990s rapidly reversed the trend. Overall incidence had fallen to 10.4 per 100 000 women in 1994–96, at which time incidence of interval cancers in eligible women aged 25–64 years was 10.9 per 100 000 women. The latter figure could provide a useful baseline for the increasing proportion of cancers that are interval cancers in young women, now that cancers in older women have so successfully been prevented and would undoubtedly be more helpful than relating the number of interval cancers to the overall number of cancers, which largely reflects the number of older unscreened women in the population.
Cancers may develop in screened populations for a number of reasons, which were described by Chamberlain17 and supported by later observations.18 These reasons have been used in our study to categorise screening histories as recommended in the first edition of ‘Achievable standards, benchmarks for reporting and criteria for evaluating cervical cytopathology’.19 The most frequent and clinically important category among interval cancers comprised the 49.1% that occurred in women who had negative smears within the previous screening round. Most (70.6%) of those cancers were symptomatic and only 41.1% of negative smears were confirmed as such on review, which is consistent with other studies.20–22 Cancers also occurred in women who had repeat tests recommended for low-grade or inadequate cytology, some of whom had not been followed up as recommended. That category represented 21.3% of interval cancers, and about half of the slides were considered to be high-grade on review. There had been a delay of 8–23 months, for a variety of reasons, since a recommendation for colposcopy in 11.8% of women with interval cancers. Most of those cancers were screen detected (83.3%). Previous treatment for CIN had been carried out in 19.0% of women with interval cancers, which were described in more detail in a separate publication.11 All except one had high-grade CIN, of which most was CIN3 or CGIN but nine of 32 (28.1%) had CIN2.11 In the present study, two of 61 women screened more than 5.5 years before diagnosis were also known to have received treatment for CIN and defaulted from follow up. Overall, 35 of 382 (9.1%) cancers were in women previously treated for CIN. These should be placed in the context of the total number of women treated for high-grade CIN. If the percentage of cases in our study is representative of the country as a whole, 202 (9.1%) of 2221 cancers in 2004 might have been in women who had previous treatment. In that year, 17 345 cases of CIN3 alone were registered and probably a similar number of cases of CIN2, for which there is no national figure. Thus, 1.2% of women with treated CIN3 and probably about half that percentage of those treated for CIN2 and CIN3 combined may have developed invasive cancer. As with cancers in unscreened women and interval cancers, it is the denominator that counts.
Audit of all aspects of screening draws attention to reasons why many of these cancers were not prevented—and demonstrates the importance of accurate cytology, appropriate follow up (and compliance with recommendations), prompt investigation and effective treatment of high-grade CIN. We believe that our study will provide a useful baseline for later audits in the UK and also for countries introducing organised screening on a background of opportunistic screening.
Disclosure of interest
None of the authors have interests that conflict with the study.
Contribution to authorship
A.H. conceived and carried out the initial 12-year audit, while employed as Lead Cytopathologist at Southampton University Hospitals Trust (SUHT). Anshu, while a Commonwealth Fellow at Guy’ and St Thomas’ (GSTT) NHS Foundation Trust helped write the paper and prepared the tables and graphs from the spreadsheet. S.S.G. carried out the statistical analysis. M.G. led the Southampton Cytology Laboratory throughout the time of the study and collaborated in collecting the information about screening at that time. N.S. is now the Lead Cytopathologist at SUHT and helped with this study and was co-author of the previous study of the same data set when it was transferred to an anonymous spreadsheet.
Details of ethics approval
Approval for this audit was gained at the time the project was started in January 1992 when a 3-year grant was successfully applied for and Catherine Breen appointed as a research assistant.
Wessex Cancer Trust and Cansearch, which was the campaigning arm of the British Society for Clinical Cytology, jointly provided the grant that enabled the original project to be set up and carried out. GSTT Charity provided a grant for A.H. to carry out the final analysis of the data set as a baseline for a GSTT cervical cancer audit.