The impact of the COVID-19 pandemic on cardiovascular disease prevention and corresponding geographical inequalities in England: interrupted time series analysis.

BACKGROUND: There has been disruption to the detection and management of those with hypertension and atrial fibrillation (AF) during the COVID-19 pandemic. This is likely to vary geographically and could have implications for future mortality and morbidity. We aimed to estimate the change in diagnosed prevalence, treatment and prescription indicators for AF and hypertension and assess corresponding geographical inequalities. METHODS: Using the Quality and Outcomes Framework (2016/17 to 2021/22) and the English Prescribing Datasets (2018 to 2022), we described age standardised prevalence, treatment and prescription item rates for hypertension and AF by geography and over time. Using an interrupted time-series (ITS) analysis, we estimated the impact of the pandemic (from April 2020) on missed diagnoses and on the percentage change in medicines prescribed for these conditions. Finally, we described changes in treatment indicators against Public Health England 2029 cardiovascular risk targets. RESULTS: We observed 143,822 fewer (-143,822, 95%CI:-226,144, -61,500, p = 0.001) diagnoses of hypertension, 60,330 fewer (-60,330, 95%CI: -83,216, -37,444, p = 0.001) diagnoses of AF and 1.79% fewer (-1.79%, 95%CI: -2.37%, -1.22%), p < 0.0001) prescriptions for these conditions over the COVID-19 impact period. There was substantial variation across geography in England in terms of the indirect impact of the COVID-19 pandemic on the diagnosis, prescription, and treatment rates of hypertension and AF. 20% of Sub Integrated Care Boards account for approximately 62% of all missed diagnoses of hypertension. The percentage of individuals who had their hypertension controlled fell from 75.8% in 2019/20 to 64.1% in 2021/22 and the percentage of individuals with AF who were risk assessed fell from 97.2% to 90.7%. CONCLUSIONS: Hypertension and AF detection and management were disrupted during the COVID-19 pandemic. The disruption varied considerably across diseases and geography. This highlights the utility of administrative and geographically granular datasets to inform targeted efforts to mitigate the indirect impacts of the pandemic through applied secondary prevention measures.

Acceleration of cervical cancer diagnosis with human papillomavirus testing below age 30: Observational study.

Several international cervical screening guidelines advise against using high-risk human papillomavirus (HR-HPV) testing in women younger than 30. The rationale for this in young women, lies in the potential for additional detection of both low-grade and high-grade cervical intraepithelial neoplasia (CIN) leading to unnecessary treatments without reducing the burden of cervical cancer. We studied 56 544 women screened at 24 to 29 with HR-HPV testing and 116 858 screened with liquid-based cytology (LBC) in the English HPV screening pilot. They were compared to 528 460 women screened at the age of 30 to 49. We studied the detection of cervical cancer and CIN2/3 across two consecutive screening rounds 3 years apart. At 24 to 29, a positive HR-HPV test detected more cases of cervical cancer in the prevalence round than did a positive LBC test (1.36/1000 screened vs 0.82/1000, ORadj : 1.61, 95% CI: 1.18-2.19). In women with a negative HR-HPV test, cervical cancer was diagnosed before or at the incidence round in 0.07/1000. After a negative LBC test, cancer detection reached 0.47/1000 and 40% of these cases were diagnosed at FIGO stage IB+. HR-HPV testing increased the detection of CIN2/3 diagnoses in two consecutive rounds combined by 30% (71.9/1000 vs 55.2/1000). The patterns of detection of cervical cancer and CIN2/3 were almost identical at older ages. These data support using HR-HPV testing for screening of women younger than 30, which not only accelerates the diagnosis of cervical cancer but leads to a similar relative increase in CIN2/3 diagnosis to that found in women aged 30 to 49.

The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study.

BACKGROUND: Human papillomavirus (HPV) immunisation with a bivalent vaccine (Cervarix) was introduced in England, UK, in Sept 1, 2008: routine vaccination was offered to girls aged 12-13 years with a catch-up programme for females aged 14-18 years in 2008-10. We quantified the early effect of this immunisation programme on cervical cancer and cervical carcinoma in situ, namely grade 3 cervical intraepithelial neoplasia (CIN3), registrations. METHODS: In this observational study, we used an extension of the age-period-cohort Poisson model to estimate the relative risk of cervical cancer in three vaccinated cohorts compared with earlier cohorts that were not eligible for HPV vaccination. Data from a population-based cancer registry were extracted on Jan 26, 2021, and were assessed for diagnoses of cervical cancer and CIN3 from Jan 1, 2006 to June 30, 2019 in women aged 20-64 years and who were a resident in England. We used three vaccinated cohorts to account for differences in the school year in which the vaccine was offered and its national coverage. Adjustment for confounding was made using information on changes in cervical screening policy and historical events that affected cervical cancer incidence. Results were compared across models with different adjustments for confounders. FINDINGS: We used data from a total of 13·7 million-years of follow-up of women aged 20 years to younger than 30 years. The estimated relative reduction in cervical cancer rates by age at vaccine offer were 34% (95% CI 25-41) for age 16-18 years (school year 12-13), 62% (52-71) for age 14-16 years (school year 10-11), and 87% (72-94) for age 12-13 years (school year 8), compared with the reference unvaccinated cohort. The corresponding risk reductions for CIN3 were 39% (95% CI 36-41) for those offered at age 16-18 years, 75% (72-77) for age 14-16 years, and 97% (96-98) for age 12-13 years. These results remained similar across models. We estimated that by June 30, 2019 there had been 448 (339-556) fewer than expected cervical cancers and 17 235 (15 919-18 552) fewer than expected cases of CIN3 in vaccinated cohorts in England. INTERPRETATION: We observed a substantial reduction in cervical cancer and incidence of CIN3 in young women after the introduction of the HPV immunisation programme in England, especially in individuals who were offered the vaccine at age 12-13 years. The HPV immunisation programme has successfully almost eliminated cervical cancer in women born since Sept 1, 1995. FUNDING: Cancer Research UK.

Recovery strategies following COVID-19 disruption to cervical cancer screening and their impact on excess diagnoses.

BACKGROUND: The COVID-19 pandemic has disrupted cervical cancer screening services. Assuming increases to screening capacity are unrealistic, we propose two recovery strategies: one extends the screening interval by 6 months for all and the other extends the interval by 36/60 months, but only for women who have already missed being screened. METHODS: Using routine statistics from England we estimate the number of women affected by delays to screening. We used published research to estimate the proportion of screening age women with high-grade cervical intraepithelial neoplasia and progression rates to cancer. Under two recovery scenarios, we estimate the impact of COVID-19 on cervical cancer over one screening cycle (3 years at ages 25-49 and 5 years at ages 50-64 years). The duration of disruption in both scenarios is 6 months. In the first scenario, 10.7 million women have their screening interval extended by 6 months. In the second, 1.5 million women (those due to be screened during the disruption) miss one screening cycle, but most women have no delay. RESULTS: Both scenarios result in similar numbers of excess cervical cancers: 630 vs. 632 (both 4.3 per 100,000 women in the population). However, the scenario in which some women miss one screening cycle creates inequalities-they would have much higher rates of excess cancer: 41.5 per 100,000 delayed for screened women compared to those with a 6-month delay (5.9 per 100,000). CONCLUSION: To ensure equity for those affected by COVID-19 related screening delays additional screening capacity will need to be paired with prioritising the screening of overdue women.

Impact of screening between the ages of 60 and 64 on cumulative rates of cervical cancer to age 84y by screening history at ages 50 to 59: A population-based case-control study.

There is little empirical data on the absolute benefit of cervical screening between ages 60-64y on subsequent cancer risk. We estimate the incidence of cervical cancer up to age 84y in women with and without a cervical cytology test at age 60-64y, by screening histories aged 50-59y. The current study is a population based case-control study of women born between 1928 and 1956 and aged 60-84y between 2007 and 2018. We included all such women diagnosed with cervical cancer in England and an aged-matched random sample without cancer. Women with a hysterectomy were excluded. Exposure was cervical cytology between ages 50-64y. The main outcome was 25y cumulative risk of cervical cancer between ages 60-84y. We found that eight in every 1000 (8.40, 95%CI: 7.78 to 9.07) women without a screening test between age 50-64y develop cervical cancer between the ages of 60-84y. The risk is half: 3.46 per 1000 (95%CI: 2.75 to 4.36) among women with a test between age 60-64y but no cervical screening test at age 50-59y. The absolute difference in risk is equivalent to one fewer cancer for every 202 such women screened. The highest risk (10.01, 95%CI:6.70 to 14.95) was among women with abnormal screening at ages 50-59y and no tests 60-64y. 25y risk among women with a screening test every five years between age 50-64y was just under two in a 1000 (1.59, 95%CI:1.42 to 1.78). Results suggest the upper age of screening should be dependent on previous screening participation and results.

Impact of disruptions and recovery for established cervical screening programs across a range of high-income country program designs, using COVID-19 as an example: A modelled analysis.

COVID-19 has disrupted cervical screening in several countries, due to a range of policy-, health-service and participant-related factors. Using three well-established models of cervical cancer natural history adapted to simulate screening across four countries, we compared the impact of a range of standardised screening disruption scenarios in four countries that vary in their cervical cancer prevention programs. All scenarios assumed a 6- or 12-month disruption followed by a rapid catch-up of missed screens. Cervical screening disruptions could increase cervical cancer cases by up to 5-6%. In all settings, more than 60% of the excess cancer burden due to disruptions are likely to have occurred in women aged less than 50 years in 2020, including settings where women in their 30s have previously been offered HPV vaccination. Approximately 15-30% of cancers predicted to result from disruptions could be prevented by maintaining colposcopy and precancer treatment services during any disruption period. Disruptions to primary screening had greater adverse effects in situations where women due to attend for screening in 2020 had cytology (vs. HPV) as their previous primary test. Rapid catch-up would dramatically increase demand for HPV tests in 2021, which it may not be feasible to meet because of competing demands on the testing machines and reagents due to COVID tests. These findings can inform future prioritisation strategies for catch-up that balance potential constraints on resourcing with clinical need.

Longitudinal Clinical Performance of the RNA-Based Aptima Human Papillomavirus (AHPV) Assay in Comparison to the DNA-Based Hybrid Capture 2 HPV Test in Two Consecutive Screening Rounds with a 6-Year Interval in Germany.

Longitudinal data on the E6/E7 mRNA-based Aptima human papillomavirus (AHPV) assay exceeding three years in comparison to the gold standard Digene Hybrid Capture 2 (HC2) test are not available. We previously reported the cross-sectional data of the German AHPV Screening Trial (GAST) in which 10,040 women were recruited and tested by liquid-based cytology, the HC2 assay, and the AHPV assay. Four hundred eleven test-positive women were followed for up to six years. In addition, 3,295 triple-negative women were screened after a median time of six years. Overall, 28 high-grade cervical intraepithelial neoplasia (CIN3) cases were detected. The absolute risk of developing high-risk HPV-positive CIN3+ over six years among those women that tested negative at baseline was 2.2 (95% confidence interval [95% CI], 1.0 to 4.9) and 3.1 (95% CI, 1.7 to 5.7) per 1,000 women screened by the HC2 and the AHPV tests; the additional risk for those with AHPV-negative compared with HC2-negative results was 0.9 (95% CI, -0.2 to 2.1) per 1,000. In comparison, the absolute risk following a negative LBC test was 9.3 (95% CI, 2.9 to 30.2). The relative sensitivity of AHPV compared to HC2 was 91.5% for CIN3+, and the negative predictive values were 99.8% (95% CI, 99.5 to 99.9%) for HC2 and 99.7% (95% CI, 99.4 to 99.8%) for AHPV. Our data show that the longitudinal performance of the AHPV test over six years is comparable to the performance of the HC2 test and that the absolute risk of CIN3+ over six years following a negative AHPV result in a screening population is low. (This study is registered at ClinicalTrials.gov under registration number NCT02634190.).

Is the recent increase in cervical cancer in women aged 20-24years in England a cause for concern?

The rates of cervical cancer (CxCa) in England among women aged 20-24yrs increased from 2.7 in 2012 to 4.6 per 100,000 in 2014 (p=0.0006). There was concern that the sudden increase was linked to the withdrawal of cervical screening in women aged 20-24 (a policy that affected women born since 1984). We analyse granular data on age and FIGO stage at diagnosis using a generalised linear model to see whether the unprecedented increase in CxCa in young women in 2014 was linked to the change in 2012 to the age at which the first invitation to screening was sent (from 25.0 to 24.5). Annual rates of CxCa per 100,000 women aged 20.0-24.5yrs decreased gradually over time, whereas at age 24.5-25.0yrs they increased from an average of 16 pre-2013 to 49 in 2015. An increase of 20.3 per 100,000 women aged 24.5-25.0yrs (95% CI: 15.2-25.4) was associated with inviting women for screening at age 24.5yrs instead of at age 25.0. At age 25.0-25.5yrs, rates decreased by 23.7 per 100,000 after women were invited at age 24.5yrs (p<0.001). All these changes were limited to stage I CxCa. There was a dramatic increase in diagnoses at age 25yrs in 2009-2011 associated with changing the age at first invitation from 20yrs to 25yrs. No changes were observed at age 26.0-27.0yrs. The increase in CxCa aged 20-24 is attributable to an increase in the proportion of women first screened aged 24.5yrs. The increase was limited to stage I CxCa. There is no evidence of a lack of screening leading to increasing rates.

Is cervical screening preventing adenocarcinoma and adenosquamous carcinoma of the cervix?

While the incidence of squamous carcinoma of the cervix has declined in countries with organised screening, adenocarcinoma has become more common. Cervical screening by cytology often fails to prevent adenocarcinoma. Using prospectively recorded cervical screening data in England and Wales, we conducted a population-based case-control study to examine whether cervical screening leads to early diagnosis and down-staging of adenocarcinoma. Conditional logistic regression modelling was carried out to provide odds ratios (ORs) and 95% confidence intervals (CIs) on 12,418 women with cervical cancer diagnosed between ages 30 and 69 and 24,453 age-matched controls. Of women with adenocarcinoma of the cervix, 44.3% were up to date with screening and 14.6% were non-attenders. The overall OR comparing women up to date with screening with non-attenders was 0.46 (95% CI: 0.39-0.55) for adenocarcinoma. The odds were significantly decreased (OR: 0.22, 95% CI: 0.15-0.33) in up to date women with Stage 2 or worse adenocarcinoma, but not for women with Stage1A adenocarcinoma 0.71 (95% CI: 0.46-1.09). The odds of Stage 1A adenocarcinoma was double among lapsed attenders (OR: 2.35, 95% CI: 1.52-3.62) compared to non-attenders. Relative to women with no negative cytology within 7 years of diagnosis, women with Stage1A adenocarcinoma were very unlikely to be detected within 3 years of a negative cytology test (OR: 0.08, 95% CI: 0.05-0.13); however, the odds doubled 3-5 years after a negative test (OR: 2.30, 95% CI: 1.67-3.18). ORs associated with up to date screening were smaller for squamous and adenosquamous cervical carcinoma. Although cytology screening is inefficient at preventing adenocarcinomas, invasive adenocarcinomas are detected earlier than they would be in the absence of screening, substantially preventing Stage 2 and worse adenocarcinomas.

Impact of cervical screening on cervical cancer mortality: estimation using stage-specific results from a nested case-control study.

BACKGROUND: It is well established that screening can prevent cervical cancer, but the magnitude of the impact of regular screening on cervical cancer mortality is unknown. METHODS: Population-based case-control study using prospectively recorded cervical screening data, England 1988-2013. Case women had cervical cancer diagnosed during April 2007-March 2013 aged 25-79 years (N=11 619). Two cancer-free controls were individually age matched to each case. We used conditional logistic regression to estimate the odds ratio (OR) of developing stage-specific cancer for women regularly screened or irregularly screened compared with women not screened in the preceding 15 years. Mortality was estimated from excess deaths within 5 years of diagnosis using stage-specific 5-year relative survival from England with adjustment for age within stage based on SEER (Surveillance, Epidemiology and End Results, USA) data. RESULTS: In women aged 35-64 years, regular screening is associated with a 67% (95% confidence interval (CI): 62-73%) reduction in stage 1A cancer and a 95% (95% CI: 94-97%) reduction in stage 3 or worse cervical cancer: the estimated OR comparing regular (⩽5.5yearly) screening to no (or minimal) screening are 0.18 (95% CI: 0.16-0.19) for cancer incidence and 0.08 (95% CI: 0.07-0.09) for mortality. It is estimated that in England screening currently prevents 70% (95% CI: 66-73%) of cervical cancer deaths (all ages); however, if everyone attended screening regularly, 83% (95% CI: 82-84%) could be prevented. CONCLUSIONS: The association between cervical cancer screening and incidence is stronger in more advanced stage cancers, and screening is more effective at preventing death from cancer than preventing cancer itself.

Head-to-Head Comparison of the RNA-Based Aptima Human Papillomavirus (HPV) Assay and the DNA-Based Hybrid Capture 2 HPV Test in a Routine Screening Population of Women Aged 30 to 60 Years in Germany.

Testing for E6/E7 mRNA in cells infected with high-risk (HR) human papillomavirus (HPV) might improve the specificity of HPV testing for the identification of cervical precancerous lesions. Here we compared the RNA-based Aptima HPV (AHPV) assay (Hologic) and the DNA-based Hybrid Capture 2 (HC2) HPV test (Qiagen) to liquid-based cytology (LBC) for women undergoing routine cervical screening. A total of 10,040 women, 30 to 60 years of age, were invited to participate in the study, 9,451 of whom were included in the analysis. Specimens were tested centrally by LBC, the AHPV test, and the HC2 test, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all HR-HPV-positive samples. Test characteristics were calculated based on histological review. As a result, we identified 90 women with cervical intraepithelial neoplasia grade 2+ (CIN2+), including 43 women with CIN3+. Sensitivity differences between the AHPV test and the HC2 test in detecting CIN2+ (P = 0.180) or CIN3+ (P = 0.0625) lesions were statistically nonsignificant. Of three CIN3 cases that were missed with the AHPV test, two cases presented lesion-free cones and one had a non-HR HPV67 infection. The specificity (

How many preterm births in England are due to excision of the cervical transformation zone? Nested case control study.

BACKGROUND: Preterm births (as a proportion of all births) have been increasing in many countries. There is growing evidence of increased risk of preterm birth following excisional treatment of the cervix. We estimate the number of preterm births attributable to excisional treatments with a length of 10 mm or more in England. METHODS: Case-control study nested in a record linkage cohort of women with a histological sample at 13 hospitals in England. We combined observed age at first excisional treatment in our cohort with the weighted distribution of excision length from the case-control study to estimate the length distribution by age at first treatment among the cohort. The number of births after excision for each 5-year age group was estimated using national fertility data; published absolute risks of preterm (<37 gestational weeks) and very preterm birth (<32 weeks) were applied to these to estimate the number of preterm births per 100 women treated. Excess preterm births were estimated assuming all treatments were small. The attributable risk of preterm birth following excisional treatment in England was estimated. RESULTS: The majority of first excisional treatments at colposcopy were small (47.5%) or medium (39.1%), 9.5% were large and 4.1% were very large excisions. 4.0% of women treated before birth had more than one excisional treatment. Thus based on our cohort of 10,711 treated women and the length of treatment observed in the case control study we estimate an excess of 240 preterm births (including 57 very preterm) or 2.2 (including 0.5 very preterm) per 100 women treated. At a population level (for England) we estimate that 39,101 women aged 20-39 would be treated each year and that these treatments will lead to an excess of 840 preterm births (including 196 very preterm) in England each year. CONCLUSIONS: Assuming associations between preterm birth and treatment for cervical disease are causal; we estimate that an excess 840 (2.5%) preterm birth in England each year are due to excisional treatments of 10 mm or more. Those that go on to become pregnant should be closely monitored during antenatal period to reduce their risk of preterm birth.

Cervical screening at age 50-64 years and the risk of cervical cancer at age 65 years and older: population-based case control study.

BACKGROUND: There is little consensus, and minimal evidence, regarding the age at which to stop cervical screening. We studied the association between screening at age 50-64 y and cervical cancer at age 65-83 y. METHODS AND FINDINGS: Cases were women (n = 1,341) diagnosed with cervical cancer at age 65-83 y between 1 April 2007 and 31 March 2012 in England and Wales; age-matched controls (n = 2,646) were randomly selected from population registers. Screening details from 1988 onwards were extracted from national databases. We calculated the odds ratios (OR) for different screening histories and subsequent cervical cancer. Women with adequate negative screening at age 65 y (288 cases, 1,395 controls) were at lowest risk of cervical cancer (20-y risk: 8 cancers per 10,000 women) compared with those (532 cases, 429 controls) not screened at age 50-64 y (20-y risk: 49 cancers per 10,000 women, with OR = 0.16, 95% CI 0.13-0.19). ORs depended on the age mix of women because of the weakening association with time since last screen: OR = 0.11, 95% CI 0.08-0.14 at 2.5 to 7.5 y since last screen; OR = 0.27, 95% CI 0.20-0.36 at 12.5 to 17.5 y since last screen. Screening at least every 5.5 y between the ages 50 and 64 y was associated with a 75% lower risk of cervical cancer between the ages 65 and 79 y (OR = 0.25, 95% CI 0.21-0.30), and the attributable risk was such that in the absence of screening, cervical cancer rates in women aged 65+ would have been 2.4 (95% CI 2.1-2.7) times higher. In women aged 80-83 y the association was weaker (OR = 0.49, 95% CI 0.28-0.83) than in those aged 65-69 y (OR = 0.12, 95% CI 0.09-0.17). This study was limited by an absence of data on confounding factors; additionally, findings based on cytology may not generalise to human papillomavirus testing. CONCLUSIONS: Women with adequate negative screening at age 50-64 y had one-sixth of the risk of cervical cancer at age 65-83 y compared with women who were not screened. Stopping screening between ages 60 and 69 y in women with adequate negative screening seems sensible, but further screening may be justifiable as life expectancy increases.

RWE ready for reimbursement? A round up of developments in real-world evidence relating to health technology assessment: part 16.

In this update, we discuss recent US FDA guidance offering more specific guidelines on appropriate study design and analysis to support causal inference for non-interventional studies and the launch of the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) public electronic catalogues. We also highlight an article recommending assessing data quality and suitability prior to protocol finalization and a Journal of the American Medical Association-endorsed framework for using causal language when publishing real-world evidence studies. Finally, we explore the potential of large language models to automate the development of health economic models.

R WE ready for reimbursement? A round up of developments in real-world evidence relating to health technology assessment: part 15.

In this latest update we discuss real-world evidence (RWE) guidance from the leading oncology professional societies, the American Society of Clinical Oncology and the European Society for Medical Oncology, and the PRINCIPLED practical guide on the design and analysis of causal RWE studies.

HPV16 L1 and L2 DNA methylation predicts high-grade cervical intraepithelial neoplasia in women with mildly abnormal cervical cytology.

DNA methylation changes in human papillomavirus type 16 (HPV16) DNA are common and might be important for identifying women at increased risk of cervical cancer. Using recently published data from Costa Rica we developed a classification score to differentiate women with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) from those with no evident high-grade lesions. Here, we aim to investigate the performance of the score using data from the UK. Exfoliated cervical cells at baseline and 6-months follow-up were analyzed in 84 women selected from a randomized clinical trial of women undergoing surveillance for low-grade cytology. Selection of women for the methylation study was based on detectable HPV16 in the baseline sample. Purified DNA was bisulfite converted, amplified and pyrosequenced at selected CpG sites in the viral genome (URR, E6, L1 and L2), with blinding of laboratory personnel to the clinical data. The primary measure was a predefined score combining the mean methylation in L1 and any methylation in L2. At the second follow-up visit, 73/84 (87%) women were HPV16 positive and of these 25 had a histopathological diagnosis of CIN2/3. The score was significantly associated with CIN2/3 (area under curve = 0.74, p = 0.002). For a cutoff with 92% sensitivity, colposcopy could have been avoided in 40% (95% CI 27-54%) of HPV16 positive women without CIN2/3; positive predictive value was 44% (32-58%) and negative predictive value was 90% (71-97%). We conclude that quantitative DNA methylation assays could help to improve triage among HPV16 positive women.

Pregnancy outcomes after treatment for cervical intraepithelial neoplasia in a single NHS hospital.

OBJECTIVE: The objective of this study was to assess the adverse pregnancy outcomes in women who had treatment for cervical intraepithelial neoplasia. METHODS: This was a retrospective cohort using data linkage. Pathology databases from Whipps Cross University Hospital were used to identify women with a histological sample taken at colposcopy between 1995 and 2009. Births for these women were identified through the hospitals' obstetric database. A total of 876 births (from 721 women) were identified. Logistic regression was used to assess the relationship between adverse pregnancy outcomes and treatment for cervical intraepithelial neoplasia before delivery. Results were adjusted by ethnicity, deprivation, and parity. RESULTS: After taking into account parity, socioeconomic status, and ethnicity, receiving any type of excisional treatment (single or multiple) before birth increased the risk of preterm labor compared with having a punch biopsy only (adjusted relative risk, 1.61; 95% confidence interval, 1.11-2.32). Preterm deliveries that occurred after a spontaneous onset of labor were found to be more likely after treatment for cervical disease (adjusted relative risk, 1.68; 95% confidence interval, 1.11-2.52). CONCLUSIONS: Women receiving any type of excisional treatment before delivery are at increased risk of preterm delivery when compared with women attending colposcopy but not treated. Although we took into account the effects of parity, socioeconomic status, and ethnicity, residual confounding factors may be unidentified.

audit_cc: A Stata command for the analysis of matched case-control audits of cervical cancer screening.

Background and objectives: Cervical screening programmes are crucial for the early diagnosis and prevention of cancer of the cervix. Regular auditing is vital for ensuring that these programmes achieve their full potential and meet their objectives in practice. Unfortunately, the time and skills required for the statistical analysis of the data collected are often important limiting factors. Comparisons across countries and over time have also been particularly difficult due to a lack of standardized definitions and methodology. We aimed to overcome these problems. Methods: Using the statistical software Stata, we developed a new command called audit_cc for the analysis of matched case-control audits of cervical cancer screening. Analyses are reported for two measures of screening history: time since last test and time since last negative test. Results: The command carries out the data manipulation which is required for the analysis and allows to save the resulting data set in an external file for further investigations. It promotes consistent evaluations of screening programmes over time and across studies and facilitates the creation of automatic publication-quality reports, which are especially useful in the context of routine audits. Conclusions: audit_cc is a valid tool that not only simplifies the analysis and reporting of cervical screening audits but also allows meaningful international comparisons. Although it is specific for cervical cancer, it can be seen as an example of how the standardisation of exposure definitions and key methodological issues can enable consistent and comparable evaluations of screening programmes across different countries and settings.