An analysis of screen-detected invasive cancers by grade in the English breast cancer screening programme: are we failing to detect sufficient small grade 3 cancers?

OBJECTIVE: Randomised controlled trials have shown a reduction in breast cancer mortality from mammography screening and it is the detection of high-grade invasive cancers that is responsible for much of this effect. We determined the detection rates of invasive cancers by grade, size and type of screen and estimated relative sensitivities with emphasis on grade 3 detection. METHODS: This observational study analysed data from over 11 million screening episodes (67,681 invasive cancers) from the English NHS breast screening programme over seven screening years 2009/2010 to 2015/2016 for women aged 45-70. RESULTS: At prevalent (first) screens (which are unaffected by screening interval), the detection rate of small (< 15 mm) invasive cancers was 0.95 per 1000 for grade 1, but for grade 3 only 0.30 per 1000. The ratio of small (< 15 mm) to large (≥ 15 mm) cancers was 1.8:1 for grade 1 but reversed to 0.5:1 for grade 3. We estimated that the relative sensitivity for grade 3 invasive cancers was 52% of that for grade 1 and the relative sensitivity for small (< 15 mm) grade 3 only 26% of that for small (< 15 mm) grade 1 invasive cancers. CONCLUSIONS: Sensitivity for small grade 3 invasive cancers is poor compared with that for grade 1 and 2 invasive cancers and larger grade 3 malignancies. This observation is likely a limitation of the current technology related to the absence of identifiable mammographic features for small high-grade cancers. Future work should focus on technologies and strategies to improve detection of these clinically most significant cancers. KEY POINTS: • The detection of small high-grade invasive cancers is vital to reduce breast cancer mortality. • We estimate the sensitivity for small grade 3 invasive cancers may be only 26% of that of small grade 1 invasive cancers. This is likely to be associated with the non-specific mammographic features for these cancers. • New technologies and appropriate strategies using current technology are required to maximise the detection of small grade 3 invasive cancers.

Correction to: An analysis of 11.3 million screening tests examining the association between recall and cancer detection rates in the English NHS breast cancer screening programme.

The original version of this article, published on 04 February 2019, unfortunately contained a mistake.

An analysis of 11.3 million screening tests examining the association between recall and cancer detection rates in the English NHS breast cancer screening programme.

OBJECTIVE: To develop methods to model the relationship between cancer detection and recall rates to inform professional standards. METHODS: Annual screening programme information for each of the 80 English NHSBSP units (totalling 11.3 million screening tests) for the seven screening years from 1 April 2009 to 31 March 2016 and some Dutch screening programme information were used to produce linear and non-linear models. The non-linear models estimated the modelled maximum values (MMV) for cancers detected at different grades and estimated how rapidly the MMV was reached (the modelled 'slope' (MS)). Main outcomes include the detection rate for combined invasive/micro-invasive and high-grade DCIS (IHG) detection rate and the low/intermediate grade DCIS (LIG) detection rate. RESULTS: At prevalent screens for IHG cancers, 99% of the MMV was reached at a recall rate of 7.0%. The LIG detection rate had no discernible plateau, increasing linearly at a rate of 0.12 per 1000 for every 1% increase in recall rate. At incident screens, 99% of the MMV for IHG cancer detection was 4.0%. LIG DCIS increased linearly at a rate of 0.18 per 1000 per 1% increase in recall rate. CONCLUSIONS: Our models demonstrate the diminishing returns associated with increasing recall rates. The screening programme in England could use the models to set recall rate ranges, and other countries could explore similar methodology. KEY POINTS: • Question: How can we determine optimum recall rates in breast cancer screening? • Findings: In this large observational study, we show that increases in recall rates above defined levels are almost exclusively associated with false positive recalls and a very small increase in low/intermediate grade DCIS. • Meaning: High recall rates are not associated with increases in detection of life-threatening cancers. The models developed in this paper can be used to help set recall rate ranges that maximise benefit and minimise harm.

An analysis of 11.3 million screening tests examining the association between needle biopsy rates and cancer detection rates in the English NHS Breast Cancer Screening Programme.

AIM: To examine the association between recall, needle biopsy, and cancer detection rates to inform the setting of target ranges to optimise the benefit to harm ratio of breast screening programmes. MATERIALS AND METHODS: Annual screening programme information from 2009/10 to 2015/16 for the 80 screening units of the English National Health Service Breast Screening Programme (totalling 11.3 million screening tests) was obtained from annual (KC62) returns. Linear regression models were used to examine the association between needle biopsy rates and recall rates and non-linear regression models to examine the association between cancer detection rates and needle biopsy rates. RESULTS: The models show and quantify the diminishing returns for prevalent screens with increasing biopsy rates. A biopsy rate increase from 10 to 20 per 1,000 increases the cancer detection rate by 2.13 per 1,000 with four extra biopsies per extra cancer detected. Increasing the biopsy rate from 40 to 50 per 1,000, increases the cancer detection rate by only 0.25 per 1,000, with 40 extra biopsies per extra cancer detected. Although diminishing returns are also seen at incident screens, screening is generally more efficient. CONCLUSIONS: Increasing needle biopsy rates leads to rapidly diminishing returns in cancer detection and a marked increase in non-malignant/benign needle biopsies. Much of the harms associated with screening in terms of false-positive recall rates and non-cancer biopsies occur at prevalent screens with much lower rates at incident screens. Needle biopsy rate targets should be considered together with recall rate targets to maximise benefit and minimise harm.

Role of performance metrics in breast screening imaging - where are we and where should we be?

The NHS Breast Screening Programme (NHSBSP) was started in 1988 and is a large, organised cancer screening programme. It is delivered by 80 services across England and screens over 2 million women each year. As a screening programme, it must balance the detection of cancers against possible harm to women who do not have cancer. The NHSBSP was therefore designed with detailed information gathering and performance metrics right from the start. In this review paper, we examine how performance metrics in screening mammography have improved the national screening programme and the further developments and challenges that are expected in the years to come.

Disability and participation in breast and bowel cancer screening in England: a large prospective study.

BACKGROUND: There is limited information about participation in organised population-wide screening programmes by people with disabilities. METHODS: Data from the National Health Service routine screening programmes in England were linked to information on disability reported by the Million Women Study cohort participants. RESULTS: Of the 473 185 women offered routine breast or bowel cancer screening, 23% reported some disability. Women with disabilities were less likely than other women to participate in breast cancer screening (RR=0.64, 95% CI: 0.62-0.65) and in bowel cancer screening (RR=0.75, 0.73-0.76). Difficulties with self-care or vision were associated with the greatest reduction in screening participation. CONCLUSION: Participation in routine cancer screening programmes in England is reduced in people with disabilities and participation varies by type of disability.

Nationwide bowel cancer screening programme in England: cohort study of lifestyle factors affecting participation and outcomes in women.

BACKGROUND: In 2006, the National Health Service Bowel Cancer Screening Programme in England (NHSBCSP) began offering routine population-based biennial faecal occult blood testing (FOBt) at ages 60-69. There is, however, limited information on how characteristics of individuals affect participation and outcomes of screening, and we studied this association by linking NHSBCSP data to a large prospective cohort of women. METHODS: Electronic linkage of the NHSBCSP and Million Women Study records identified 899 166 women in the study cohort with at least one invitation for screening. NHSBCSP provided information on screening acceptance, FOBt results, screen-detected colorectal cancer and other outcomes. The Million Women Study provided prospectively collected information on personal and lifestyle factors. Multiple regression was used to estimate relative risks (RRs) of factors associated with acceptance and outcomes of screening. RESULTS: Overall, 70% of women (628 976/899 166) accepted their first invitation for bowel cancer screening, of whom 9133 (1.5%) were FOBt-positive, 743 (0.1%) had screen-detected colorectal cancer and 3056 (0.5%) had screen-detected colorectal adenoma. Acceptance was lower in women from the most than the least deprived tertile, in South Asians and in Blacks than in Whites, in current than in never smokers and in obese than in normal weight women: adjusted RRs (95% confidence interval) for acceptance vs not, 0.90 (0.90-0.90); 0.77 (0.75-79); 0.94 (0.92-0.96); 0.78 (0.77-0.78); and 0.88 (0.88-0.89), respectively: P<0.001 for each. These factors were also associated with an increased risk of being FOBt-positive and of having screen-detected adenoma, but were not strongly associated with the risk of screen-detected colorectal cancer. Relative risks for screen-detected adenoma were 1.22 (1.12-1.34), 2.46 (1.75-3.45), 1.61 (1.05-2.48), 1.53 (1.38-1.68) and 1.77 (1.60-1.95), respectively (P<0.001 for all, except for Blacks vs Whites P=0.03). Use of hormone therapy for menopause was associated with reduced risk of screen-detected adenoma, RR ever vs never use, 0.87 (0.81-0.93), P<0.001 and colorectal cancer, 0.78 (0.68-0.91), P=0.001. INTERPRETATION: Among women in England, socioeconomic and lifestyle factors strongly affect participation in routine bowel cancer screening, risk of being FOBt-positive and risk of having screen-detected colorectal adenoma. However, screen-detected colorectal cancer risk is not strongly related to these factors.

Longer mean colonoscopy withdrawal time is associated with increased adenoma detection: evidence from the Bowel Cancer Screening Programme in England.

BACKGROUND AND STUDY AIMS: Increasing colonoscopy withdrawal time (CWT) is thought to be associated with increasing adenoma detection rate (ADR). Current English guidelines recommend a minimum CWT of 6 minutes. It is known that in the Bowel Cancer Screening Programme (BCSP) in England there is wide variation in CWT. The aim of this observational study was to examine the relationship between CWT and ADR. PATIENTS AND METHODS: The study examined data from 31 088 colonoscopies by 147 screening program colonoscopists. Colonoscopists were grouped in four levels of mean CWT ( < 7, 7 - 8.9, 9 - 10.9, and ≥ 11 minutes). Univariable and multivariable analysis (binary logistic and negative binomial regression) were used to explore the relationship between CWT, ADR, mean number of adenomas and number of right-sided and advanced adenomas. RESULTS: In colonoscopists with a mean CWT < 7 minutes, the mean ADR was 42.5 % compared with 47.1 % in the ≥ 11-minute group (P < 0.001). The mean number of adenomas detected per procedure increased from 0.77 to 0.94, respectively (P < 0.001). The increase in adenoma detection was mainly of subcentimeter or proximal adenomas; there was no increase in the detection of advanced adenomas. Regression models showed an increase in ADR from 43 % to 46.5 % for mean CWT times ranging from 6 to 10 minutes. CONCLUSIONS: This study demonstrates that longer mean withdrawal times are associated with increasing adenoma detection, mainly of small or right-sided adenomas. However, beyond 10 minutes the increase in ADR is minimal. Mean withdrawal times longer than 6 minutes are not associated with increased detection of advanced adenomas. Withdrawal time remains an important quality metric of colonoscopy.

An observational study to evaluate the performance of units using two radiographers to read screening mammograms.

AIM: To examine the performance of screening units in which a proportion of mammograms were double read using "non-discordant radiographer only (double) reading" (NDROR). MATERIALS AND METHODS: NDROR was used by seven pilot units between 2006 and 2009, and six further units in 2009 only. There were 51 comparison units. Screening performance outcome measures were calculated, and logistic regression was used to compare performance between the pilot and comparison units. RESULTS: Phase 1 pilot units read between on average 15 and 48% of mammograms per year using NDROR between 2006 and 2009 (median, 33%) and in 2009, phase 2 pilot units used NDROR to read between 4 and 77% of mammograms (median, 34%). The results showed an increase in recall rates in the phase 1 pilot units relative to the comparison units at both prevalent and incident screens (adjusted OR 1.09, 95% CI 1.05, 1.14; and adjusted OR 1.10, 95% CI 1.07, 1.14, respectively). There were also increases in the phase 2 pilot units relative to the comparison units; adjusted OR 1.08 (95% 1.00, 1.17) at prevalent screens, and adjusted OR 1.07 (95% CI 1.02, 1.14) at incident screens. There was no evidence to suggest a difference in cancer-detection rates between the pilot units and the comparison units. CONCLUSIONS: Evidence from the present study suggests that recall rates may increase as a result of units using radiographers to double read a proportion of their mammograms. However, there is little evidence to suggest that NDROR, as practiced by the pilot units in the present study, is likely to have major impacts on performance in the UK National Health Service Breast Screening Programme (NHSBSP), particularly if it is fully supported and closely monitored (particularly recall rates).

ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England.

The new Achievable Standards, Benchmarks for Reporting, and Criteria for Evaluating Cervical Cytopathology, 3rd edn (ABC3) includes radical changes in the criteria for evaluating cervical cytology. First, they include a new mission statement 'the objective of cervical screening is to reduce cervical cancer incidence and mortality by screening with a high sensitivity for the detection of CIN2 or worse, whilst maintaining a high specificity'. Second, the original four performance measurement criteria where laboratories were examined further if they were below the 10th or above the 90th percentile has been changed to three and laboratories are only mandatorily examined if they fall below the 5th or above the 95th percentile. The old criteria related to the percentage of samples that were inadequate, the percentage of all adequate samples reported as moderate dyskaryosis or worse (equivalent to high-grade squamous intraepithelial lesion or cancer), the percentage of adequate samples reported as mild dyskaryosis or borderline (equivalent to low-grade squamous intraepithelial lesion or atypical squamous/glandular cells) and the positive predictive value. The new criteria are percentage of inadequate samples, positive predictive value and a new measure termed referral value. These changes mean that far fewer laboratories will require mandatory examination. Third, a raft of optional performance measures have been introduced to help laboratories examine their annual statistical return to the Department of Health in comparison with other laboratories. These measures have been designed to produce a more uniform national programme, and to help laboratories decide whether they are maximizing the benefit of screening while minimizing the harm, which is the goal of all screening programmes. This review examines in detail the new criteria and explains in more detail some of the thinking behind them.

Estimation of disease severity in the NHS cervical screening programme. Part I: artificial cut-off points and semi-quantitative solutions.

OBJECTIVE: Current cytology and histology classifications are based on ordered categories and have a strong emphasis on providing information that decides a woman's management rather than the best estimate of disease severity. This two-part paper explores the use of a quantitative approach to both cytology and histology disease severity measurements. METHODS: In Part I the problem of artificial cut-off points is discussed and a simple semi-quantitative solution to the problem is proposed. This closely relates to the revised British Society for Clinical Cytology (BSCC) terminology. The estimates of disease severity are designed as extensions of the existing methods, with an emphasis on probability rather than certainty, as a more natural way of approaching the problem. Borderline changes are treated as categorical variables, but koilocytosis, mild, moderate and severe dyskaryosis, and ?invasive as quasi-continuous and the disease severity estimated as a grade number (GN) with any value between 0-4 and the margin of error as a calculated grade range (CGR). RESULTS: As an example, if the reader is unsure between moderate dyskaryosis (HSIL favouring CIN2) and mild dyskaryosis (LSIL favouring CIN1) they can register this uncertainty as a probability, such as 60%/40% moderate/mild. With 2 and 1 as the mid-points of the grade numbers for moderate and mild dyskaryosis the GN value is ((60 × 2)+(40 × 1))/100 = 1.6. The CGR is 1.5 - 0.4 to 1.5 + 0.6 = 1.1 to 2.1. The GN (CGR) estimate of disease severity is therefore 1.6 (1.1-2.1). In a similar manner the disease severity from all slides showing koilocytosis or dyskaryosis can be estimated as a number between 0 and 4 with an associated error. Histology can be treated in a similar way. CONCLUSIONS: This semi-quantitative approach provides a framework more suitable for research and audit of disease severity estimates. It avoids the paradox inherent in the current systems using artificial cut-points to produce categories whereby increasing agreement can only be achieved by losing information.

Estimation of disease severity in the NHS cervical screening programme. Part II: quantitative methods of estimating disease severity and progression potential.

OBJECTIVE: This is the second of a two-part paper exploring the use of a more quantitative approach to both cytology and histology disease severity measurements. In Part I the problem of artificial cut-off points was discussed and a semi-quantitative solution to the problem proposed. In Part II quantitative methods are proposed that are used to predict the estimated progression probability (EPP) to invasive cancer. METHODS: Based on models derived from published data the grade number (GN) is related to the EPP to invasive cancer over the next 10 years for both cytology (CEPP) and histology (HEPP) using a look-up table. CEPP and HEPP are then adjusted by other factors such as age, persistence, HPV result, number of cells and lesion size to obtain the adjusted CEPP and HEPP (ACEPP and (AHEPP). The two factors can be combined to produce an adjusted weighted estimated progression potential using the formula AWEPP √((ACEPP + AHEPP)/2) × AHEPP) using a two to one bias in favour of the histology. RESULTS: As an example of the methodology consider a slide estimated as showing a 60% probability of moderate dyskaryosis (HSIL favouring CIN2) and 40% probability of mild dyskaryosis (LSIL favouring CIN1). The GN number would be 1.6 (as described in Part I) and the EPP over the next 10 years 0.78%. For a woman aged 52 years (correction factor ×2.0) with a second mildly dyskaryotic smear (correction factor ×1.25) and >50 dyskaryotic cells (correction factor 1.5) the ACEPP would be 0.78 × 2.00 × 1.25 × 1.5 = 2.9%. If the HEPP on histology was 50:50 between CIN1 and CIN2, the AHEPP can be calculated as 1.4%. The AWEPP would be √((2.9 + 1.4)/2 × 1.4) = 1.7%. The final estimate of disease progression potential based on both cytology and histology is 1.7% over 10 years. CONCLUSIONS: These quantitative approaches based on adjusted and weighted EPP provide a framework suitable for research, audit and comparison between screening centres, and for tailoring criteria for colposcopy referral and treatment. Further research is required to improve the estimates given in the paper.

Using a graph of the abnormal predictive value versus the positive predictive value for the determination of outlier laboratories in the National Health Service cervical screening programme.

OBJECTIVE: The positive predictive value (PPV) for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse of referral to colposcopy from moderate dyskaryosis or worse (equivalent to high-grade squamous intraepithelial lesion or worse) is a standard performance measure in the National Health Service cervical screening programme. The current target is to examine 'outlier' laboratories with PPVs outside the 10th-90th percentile, which automatically identifies 20% of laboratories for further investigation. A more targeted method of identifying outliers may be more useful. METHODS: A similar measure to the PPV, the abnormal predictive value (APV), can be defined as the predictive value for CIN2 or worse for referrals from borderline (includes atypical squamous and glandular cells) and mild dyskaryosis (equivalent to low-grade squamous intraepithelial lesion) combined. A scatter plot of the APV versus the PPV can be produced (the APV-PPV diagram). Three kinds of 'outlier' can be defined on the diagram to help determine laboratories with unusual data. These are termed a true outlier value (TOV) or an extreme value (EV) for either PPV or APV, or a residual extreme value (REV) from the APV-PPV best line of fit. RESULTS: Using annual return information for 2007/8 from 124 laboratories, two were defined as having EVs for PPV (both had a relatively low PPV of 62%). For APV, four laboratories were considered to have EVs of 34%, 34%, 34% and 4% and one was considered to be a TO with an APV of 45%. Five were identified as REV laboratories, although three of these were also identified as having extreme or outlier values, leaving two that had not been identified by the other methods. A total of eight (6%) laboratories were therefore identified as meriting further investigation using this methodology. CONCLUSIONS: The method proposed could be a useful alternative to the current method of identifying outliers. Slide exchange studies between the identified laboratories, particularly those at opposing ends of the diagram, or other further investigations of such laboratories, may be instructive in understanding why such variation occurs, and could therefore potentially, lead to improvements in the national programme.

Comparison of cytology and histology results in English cervical screening laboratories before and after liquid-based cytology conversion: do the data provide evidence for a single category of high-grade dyskaryosis?

OBJECTIVE: To determine whether the difference between the positive predictive value (PPV) for cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) of referral from moderate dyskaryosis and from severe dyskaryosis was reduced after laboratories converted from conventional to liquid-based cytology (LBC). Furthermore, to explore the cytology/histology agreement after LBC conversion, and to determine post-LBC whether there was increased support for the use of one single category of high-grade dyskaryosis (equivalent to high-grade squamous intraepithelial lesion). METHODS: The association between cytology and histology has been examined using annual Korner return data (KC61 returns) collected by laboratories from the English National Health Service cervical screening programme. The study compares return data before and after LBC conversion. RESULTS: The study examined data from 102 laboratories that converted from conventional cytology to LBC. Before conversion the PPV for CIN2+ of severe dyskaryosis was 88% and after increased to 90% (P = 0.003). For moderate dyskaryosis the PPV for CIN2+ increased from 70% to 72% (P = 0.06). The absolute difference of 18% between severe and moderate dyskaryosis was therefore the same pre- and post-LBC conversion. The PPV of mild dyskaryosis for CIN2+ before and after conversion reduced from 23% to 19% (P < 0.001). The agreement between cytology and histology measured using a weighted Kappa statistic increased from 0.52 to 0.60 after conversion to LBC because of small increases in the proportions of severe dyskaryosis or worse with CIN3+ outcomes and mild dyskaryosis with CIN1 or less outcomes. CONCLUSIONS: Following LBC conversion there was evidence of a modest increase in the agreement between cytology and histology but no evidence of a change in the absolute difference in PPV for CIN2+ between moderate and severe dyskaryosis. The data support the conclusion that women referred with moderate dyskaryosis will on average have a lower risk of progression to invasive cancer than women referred with severe dyskaryosis. If the data were considered to support the categories of high-grade dyskaryosis (moderate) and high-grade dyskaryosis (severe) before LBC conversion then it can be strongly argued that they also support these categories after conversion.

Evaluation of extension of breast screening to women aged 65-70 in England using screening performance measures.

The objective of this study was to investigate screening performance measures in the English screening units that began inviting women aged 65-70 between 1 April 2001 and 1 April 2004. We analysed results after each unit commenced inviting women aged 65-70. In addition, we analysed data from units that invited this age group for a second time between 1 April 2004 and 31 March 2007. Results for women aged 65-70 were compared to women aged 50-64 and 60-64. Average uptake was 72.8% for women aged 65-70 and 76.7% for women aged 50-64. For women screened within the last 5 years, uptake was 88.7% for older women and 89.1% for younger women. For women previously screened within 5 years the invasive cancer detection rate was 17% higher in the 65-70 age group than in the 60-64 age group. The rates of recall to assessment and PPV were 3.5 and 27.6% in women aged 65-70 and 3.4 and 24.6% in women aged 50-64 respectively. These results suggest that, as in the earlier demonstration studies, uptake rates remain high in older women, and many more older women attend following an invitation than had previously self-referred. The cancer detection rate is higher in this older age group, whereas rates of recall are generally similar to those in younger women; consequently the PPV is also higher in older women.

Risk of cervical abnormality after age 50 in women with previously negative smears.

There is discussion over the benefit of continuing cervical screening in women over the age of 50 with a history of negative cytology. We aimed to determine the risk of abnormal cytology in such women. Screening history data from 1985 to 2003 were obtained for a cohort of 2 million women from the NHS cervical screening programme from four Health Authorities in England. The 57,651 women in the cohort who reached age 40 between 1 January 1985 and 31 December 1990 and had at least one routine or opportunistic smear between ages 50 and 54 were included in the analysis. Exposure groups (negative cytology history, negative but including inadequate smears, and positive history) were defined on the basis of screening histories from ages 40 to 49. Sixty-four percent (134/206) (95% CI: 57-71%) of the moderate dyskaryosis or worse lesions at ages over 50 were detected from women in the negative smear history group. After allowance for time since last negative smear, the relative risk for the first primary smear over the age of 50 having moderate dyskaryosis or worse decreased from 0.60 (95% CI: 0.41-0.84) for two negative smear episodes to 0.25 (95% CI: 0.10-0.56) for four negative smear episodes, compared with the positive history group. If screening were discontinued for all women over 50 with a negative history, the majority of cytological abnormalities now being detected at these ages that lead directly to referral to colposcopy would be missed.

The use of screening episodes linked to CIN3 and invasive cancer registrations to study outcomes from the NHS Cervical Screening Programme.

UNLABELLED: The use of screening episodes linked to CIN3 and invasive cancer registrations to study outcomes from the NHS Cervical Screening ProgrammeObjective: To examine how NHS cervical screening data can be collected and analysed in order to evaluate women's screening histories as episodes rather than as individual smears. DESIGN: Analysis of routine cervical screening data grouped into screening episodes for a cohort of women regarding episodes starting in a given year. SETTING: NHS Cervical Screening Programme. POPULATION: Data from four Health Authorities (now eight Primary Care Trusts) from the NHS Cervical Screening Programme with primary smears (first in an episode) taken between 1 April 1999 and 31 March 2000. METHODS: Cytology information obtained from the call/recall ('Exeter') computer system was linked to cervical intraepithelial neoplasia (CIN) 3 and invasive cancer outcome information obtained from cancer registries. Screening histories were divided into episodes, each starting with a primary smear that was followed up to episode closure or, for episodes still open followed for an average 4.25 years, from the primary smear. The episode was divided into two parts (up to referral to colposcopy and following the referral). The outcomes of the episodes are described including referral rate to colposcopy and CIN3 and invasive cancer rates by factors such as age. MAIN OUTCOME MEASURES: Episode histories and rates of referral to colposcopy, CIN3 and invasive cancer. RESULTS: There were 176 923 episodes from 176 319 women (1.003 episodes per woman) followed up to March 2004, the date at which the first phase of information accrual ceased. Of these episodes, 172 100 (97.3%) were closed either by a negative smear referring the woman back to routine recall or by default (defined as no smear recorded within 21 months following a smear requiring an action of repeat or refer to colposcopy). The remaining 4823 (2.7%) of episodes were still open, of which in 3121 (1.8%) the woman had been referred to colposcopy and in 1702 (1.0%) no referral decision had been made. Referral rates to colposcopy varied by age from 5.7% in women aged 20-24 years down to 0.9% in women aged 60-64 years. The overall efficiency of screening was highest for woman aged about 30 years, with a CIN3 detection rate of eight per 1000 women and a positive predictive value (for CIN3 or worse) of referral to colposcopy of 21%. CONCLUSION: The study has shown that routinely collected NHS cervical screening data can be combined to give information on complete episodes, allowing important performance measures to be studied. We suggest that in future information in the NHS screening system should be structured to facilitate such analysis and to allow cytology and histology information to be readily linked.

Coverage in the National Health Service Breast Screening Programme, 1996-2005: correcting for the first invitation of women between 50 and 52 years.

BACKGROUND: Coverage measures the ability of the National Health Service Breast Screening Programme (NHSBSP) to reach the eligible population and has a target of 70%. OBJECTIVE: To estimate coverage accurately for women aged 50-64. METHODS: Routine data from the KC63 return were used to calculate coverage for women aged 50-64 using an adjusted method that allows for the fact that women receive a first invitation to screening between 50 and 52.9 years. RESULTS: The adjusted average coverage between 1996 and 2005, for women aged 50-64 was 74.3% and the standard unadjusted average measure for the same period was 68.3%. Therefore, previous measures of coverage for this age group have underestimated coverage by approximately 9% and the adjusted figure is actually well above the target. CONCLUSION: In terms of coverage the programme has been performing better than previously reported. It is important to monitor the effect of an increasing workload on the programmes ability to re-invite women within three years of their last screen as maintaining coverage is an important factor in ensuring that the NHSBSP is effective in reducing mortality from breast cancer.

The development of the referral outcome diagram and an analysis of laboratory cancer detection rates in the English NHS cervical screening programme--is there an optimum level of detection of CIN 1 and CIN 2 lesions?

OBJECTIVE: To use routine annual data from the English cervical screening laboratories (KC61 returns) to evaluate individual laboratory return characteristics with particular reference to factors associated with sensitivity and specificity. METHODS: A graphical technique has been developed using data on referral to colposcopy and histological outcomes called a referral outcome (ROUT) diagram. The average grade of cervical intraepithelial neoplasia (CIN) detected (the mean CIN score, MCS) is plotted against the odds of a false-positive referral. Further analysis has been conducted to examine the relationship between the MCS and screen-detected invasive cancer rate. RESULTS: There are large variations in ROUT diagram positions of individual laboratories and the diagram can be used to identify laboratories for further investigation. These variations are strongly influenced by substantial differences in the rate of low-grade referrals and the MCS (and positive predictive value) are inversely related to the referral rate for low-grade cytology (P < 0.001). There is a strong association between high MCS values and increased screen-detected cancer rates (P < 0.001) particularly above an MCS of 2.2. The data can be re-formulated in terms of CIN 2 and CIN 3 only where it can be shown that the invasive cancer rate rapidly increases if the numbers of CIN 2 lesions detected drops below 50% of the number of CIN 3 lesions. Given the complexity of cervical screening this may best be viewed as a hypothesis generating observation, best tested by interventional studies. CONCLUSIONS: The ROUT diagram represents a new and potentially interesting way of presenting annual return data. The national programme in England needs to balance the prevention of cancer against too many unnecessary referrals to colposcopy and the ROUT diagram, and associated data given in this paper may help toward this. Further research is required including examining the role of referral policy and threshold criteria in influencing low-grade referrals and the relationship between MCS and cancer detection rate.

Should a standard be defined for the Positive Predictive Value (PPV) of recall in the UK NHS Breast Screening Programme?

The UK NHSBSP defines standards for both cancer detection rate and recall rate for assessment but has not explicitly set a defined standard for positive predictive value (PPV) of recall. However, as PPV is defined as the percentage of women who are recalled and have a final diagnosis of cancer, a standard for PPV is an implicit consequence of the standards for cancer detection rate and recall rate. The standards are defined in terms of a lower level of acceptability known as the 'minimum standard' and a higher level of acceptability referred to as the 'target'. The target can be shown to be a PPV of more than 5.1% for prevalent screens and more than 8.4% for incident screens. This paper will explore the role of PPV as a performance measure and show how making moderate increases in PPV for programmes with the lowest PPVs could lead to major improvements in the overall efficiency of the programme.