Reproducibility of colposcopy quality indicators-A survey among members of the European Federation for Colposcopy.

INTRODUCTION: Colposcopy is an important part of the diagnostic work-up of women with an abnormal cervical screening test as it is used to guide the collection of biopsies. Although quality assurance has been used in the evaluation of screening programs, not much is known about quality indicators for the diagnostics and treatment of screen-positive women. Therefore, the European Federation for Colposcopy developed quality indicators aiming to support colposcopy practice across Europe. We performed a survey of colposcopy cases to determine if the quality indicators are understandable, relevant, and reproducible. MATERIAL AND METHODS: We conducted a survey among all members of the European Federation for Colposcopy Quality and Standards Group from November 2022 to March 2023. Members were asked to collect information on a total of 17 quality indicators for 50 women who had been newly referred for colposcopy due to an abnormal screening test between January 1, 2020 to December 31, 2021. Results were reported descriptively. RESULTS: We included data on 609 cases from 12 members across Europe. The majority of the quality indicators were either achieved or within reach of the agreed standard, often due to few countries with outlying data. One quality indicator had very low performance, although stratified results indicated that two countries had different clinical management of the patient type thereby skewing the results. In addition, discrepancies between the number of cases included in each quality indicator raised concerns regarding potential misunderstanding of the quality indicator and its objective. CONCLUSIONS: Quality indicators on colposcopy must be understandable to those collecting data, highlighting the importance of validating quality indicators before data collection.

Investigating the Impact of Ultra-Radical Surgery on Survival in Advanced Ovarian Cancer Using Population-Based Data in a Multicentre UK Study.

We investigated URS and impact on survival in whole patient cohorts with AOC treated within gynaecological cancer centres that participated in the previously presented SOCQER 2 study. National cancer registry datasets were used to identify FIGO Stage 3,4 and unknown stage patients from 11 cancer centres that had previously participated in the SOCQER2 study. Patient outcomes' association with surgical ethos were evaluated using logistic regression and Cox proportional hazards. Centres were classified into three groups based on their surgical complexity scores (SCS); those practicing mainly low complexity, (5/11 centres with >70% low SCS procedures, 759 patients), mainly intermediate (3/11, 35−50% low SCS, 356 patients), or mainly high complexity surgery (3/11, >35% high SCS, 356 patients). Surgery rates were 43.2% vs. 58.4% vs. 60.9%. across mainly low, intermediate and high SCS centres, respectively, p < 0.001. Combined surgery and chemotherapy rates were 39.2% vs. 51.8% vs. 38.3% p < 0.000 across mainly low, intermediate and high complexity groups, respectively. Median survival was 23.1 (95% CI 19.0 to 27.2) vs. 22.0 (95% CI 17.6 to 26.3) vs. 17.9 months (95% CI 15.7 to 20.1), p = 0.043 in mainly high SCS, intermediate, and low SCS centres, respectively. In an age and deprivation adjusted model, compared to patients in the high SCS centres, patients in the low SCS group had an HR of 1.21 (95% CI 1.03 to 1.40) for death. Mainly high/intermediate SCS centres have significantly higher surgery rates and better survival at a population level. Centres that practice mainly low complexity surgery should change practice. This study provides support for the utilization of URS for patients with advanced OC.

The Impact of COVID-19 Pandemic on Screening Programs for Cervical Cancer Prevention Across Europe.

OBJECTIVE: The aim of the study was to estimate the impact of COVID-19 pandemic on the practice of cervical cancer screening in European countries. MATERIALS AND METHODS: A 3 rounds e-survey was conducted among the 31 European Federation for Colposcopy member countries during 2020. Each representative was asked to answer to each questionnaire for their own country. Questionnaires were not anonymous. The first questionnaire was sent in April 2020 and second and third in June and December 2020, respectively. RESULTS: Twenty five of the 31 European countries solicited responded. A total of 19 countries (70.4%) reported that screening for cervical cancer was suspended at least once during the 3 rounds of questionnaires. In addition, 11 countries reported stopping colposcopy and treatments for cervical precancerous lesions at least once during the 3 rounds of questionnaires. These situations evolved with time, with the highest rate of countries recommending suspension of screening, colposcopy, and treatments during the second round of the survey. At round 3, no country recommended screening, colposcopy, and treatment, and 12 countries (57.5%) reported normal screening was fully implemented. CONCLUSIONS: Our results suggest massive disruption in cervical cancer screening programs across Europe resulting from COVID-19 pandemic. Increase in the incidence of cervical cancer is to be expected.

Quality of life from cytoreductive surgery in advanced ovarian cancer: Investigating the association between disease burden and surgical complexity in the international, prospective, SOCQER-2 cohort study.

OBJECTIVE: To investigate quality of life (QoL) and association with surgical complexity and disease burden after surgical resection for advanced ovarian cancer in centres with variation in surgical approach. DESIGN: Prospective multicentre observational study. SETTING: Gynaecological cancer surgery centres in the UK, Kolkata, India, and Melbourne, Australia. SAMPLE: Patients undergoing surgical resection (with low, intermediate or high surgical complexity score, SCS) for late-stage ovarian cancer. MAIN OUTCOME MEASURES: Primary: change in global score on the European Organisation for Research and Treatment of Cancer (EORTC) core quality-of-life questionnaire (QLQ-C30). Secondary: EORTC ovarian cancer module (OV28), progression-free survival. RESULTS: Patients' preoperative disease burden and SCS varied between centres, confirming differences in surgical ethos. QoL response rates were 90% up to 18 months. Mean change from the pre-surgical baseline in the EORTC QLQ-C30 was 3.4 (SD 1.8, n = 88) in the low, 4.0 (SD 2.1, n = 55) in the intermediate and 4.3 (SD 2.1, n = 52) in the high-SCS group after 6 weeks (p = 0.048), and 4.3 (SD 2.1, n = 51), 5.1 (SD 2.2, n = 41) and 5.1 (SD 2.2, n = 35), respectively, after 12 months (p = 0.133). In a repeated-measures model, there were no clinically or statistically meaningful differences in EORTC QLQ-C30 global scores between the three SCS groups (p = 0.840), but there was a small statistically significant improvement in all groups over time (p < 0.001). The high-SCS group experienced small to moderate decreases in physical (p = 0.004), role (p = 0.016) and emotional (p = 0.001) function at 6 weeks post-surgery, which resolved by 6-12 months. CONCLUSIONS: The global QoL of patients undergoing low-, intermediate- and high-SCS surgery improved at 12 months after surgery and was no worse in patients undergoing extensive surgery. TWEETABLE ABSTRACT: Compared with surgery of lower complexity, extensive surgery does not result in poorer quality of life in patients with advanced ovarian cancer.

Early Welsh cervical screening programme learning as a consequence of the coronavirus pandemic.

BACKGROUND: The coronavirus pandemic has had a profound impact on the cervical screening programme in Wales for the eligible women, sample takers, and laboratory and colposcopy services. AIMS: To explore what changes due to the pandemic have adversely affected screening outcomes in Wales and what lessons can be learned to improve cervical screening in Wales and elsewhere. METHODS: A review of the screening performance in 2020 and the first quarter of 2021 in Wales as well as a comparison with other cervical screening programme responses to the pandemic. RESULTS: A 3 month pause of screening together with a change in a variety of working practices, including social distancing, use of personal protective equipment, use of virtual meetings, and home working have been implemented. The combination of a pause to the issuing of invitations, plus reduced services in primary and secondary care, together with population lockdown, have contributed to longer waiting times for colposcopy and potentially delayed cancer diagnoses. Some programme changes which were being evaluated prior to the pandemic could be developed now to mitigate the impact of the pandemic such as improved information, increased screening intervals for human papillomavirus-based screening programmes, and home working for call and recall staff. CONCLUSIONS: Despite a considerable short-term interruption to the cervical screening programme, some changes introduced as a result of the coronavirus pandemic could provide key lessons learnt for improvement for cervical cancer prevention services.

Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.

BACKGROUND: Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS. METHODS: In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032. FINDINGS: Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1-17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (-41·8 to -2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (-21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group. INTERPRETATION: The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended. FUNDING: National Institute for Health Research, Cancer Research UK, and The Eve Appeal.

Performance Characteristics of the Ultrasound Strategy during Incidence Screening in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

Randomised controlled trials of ovarian cancer (OC) screening have not yet demonstrated an impact on disease mortality. Meanwhile, the screening data from clinical trials represents a rich resource to understand the performance of modalities used. We report here on incidence screening in the ultrasound arm of UKCTOCS. 44,799 of the 50,639 women who were randomised to annual screening with transvaginal ultrasound attended annual incidence screening between 28 April 2002 and 31 December 2011. Transvaginal ultrasound was used both as the first and the second line test. Participants were followed up through electronic health record linkage and postal questionnaires. Out of 280,534 annual incidence screens, 960 women underwent screen-positive surgery. 113 had ovarian/tubal cancer (80 invasive epithelial). Of the screen-detected invasive epithelial cancers, 37.5% (95% CI: 26.9-49.0) were Stage I/II. An additional 52 (50 invasive epithelial) were diagnosed within one year of their last screen. Of the 50 interval epithelial cancers, 6.0% (95% CI: 1.3-16.5) were Stage I/II. For detection of all ovarian/tubal cancers diagnosed within one year of screen, the sensitivity, specificity, and positive predictive values were 68.5% (95% CI: 60.8-75.5), 99.7% (95% CI: 99.7-99.7), and 11.8% (95% CI: 9.8-14) respectively. When the analysis was restricted to invasive epithelial cancers, sensitivity, specificity and positive predictive values were 61.5% (95% CI: 52.6-69.9); 99.7% (95% CI: 99.7-99.7) and 8.3% (95% CI: 6.7-10.3), with 12 surgeries per screen positive. The low sensitivity coupled with the advanced stage of interval cancers suggests that ultrasound scanning as the first line test might not be suitable for population screening for ovarian cancer. Trial registration: ISRCTN22488978. Registered on 6 April 2000.

Options for triage and implications for colposcopists within European HPV-based cervical screening programmes.

The development of human papillomavirus (HPV)-based screening should detect more pre-cancerous changes and so reduce the incidence and mortality from cervical squamous carcinoma and cervical adenocarcinoma. However, many more women are high risk HPV (hrHPV) screen positive compared to cytology-based screening, especially in younger age-women. A variety of tests have become available which may triage into those hrHPV test-positive women who need immediate referral to colposcopy from those who need early repeat HPV tests or recall on the basis of their disease status. We performed a literature review of publications and a manual search from 2010, reporting cytology, HPV partial genotyping, dual-staining and DNA methylation for triage of hrHPV positive tests, including their comparative performance between these methods as well as the effectiveness of some triage combinations with reference to HPV-based screening services in Europe. Cost effectiveness and the structure of triage algorithms for colposcopists also have been considered. From one report evaluating four options for triage as single options or as combined algorithms, partial genotyping for HPV 16 and 18 with dual-staining yielded the highest risk of cervical intraepithelial neoplasia grade three or worse within an HPV positive population and with an acceptable colposcopy rate. From a separate paper, this option appeared cost effective. However, publications were difficult to compare objectively. All options have their merits but a combination triage involving any two of cytology, HPV partial genotyping or dual-staining seems most efficient at present. HPV vaccination may impact upon the performance of future partial genotyping. DNA Methylation may become an acceptable future option.

Using technology to harmonise treatment approaches in colposcopy in the face of a changing environment.

The overall numbers of precancerous lesions are expected to fall as human papillomavirus (HPV) vaccinated women enter the cervical screening programme. Juxtaposed against an increase in referrals from the introduction of primary high-risk HPV screening, colposcopists expect to see a decreasing incidence of high-grade cervical intraepithelial neoplasia (CIN). Correct identification of lesions will become more challenging, as the prevalence of high-grade lesions becomes minimal and conventional colposcopy is subject to a lower sensitivity. In this review, we explore the scenarios where adjunct technologies could support colposcopists to manage referrals and diagnose treatable lesions with more confidence.

Identification of European-wide clinical priorities for guideline development in the management of pre-invasive cervical disease.

OBJECTIVE: Addressing management controversies in the treatment of pre-invasive cervical disease is a key priority for the European Federation for Colposcopy/European Society of Gynaecologic Oncology who aim to develop a practical handbook of European centred guidelines to address areas where there is a lack of high-quality evidence or identifiable practice variation. Clinical opinion across the EFC network was sought to identify topics likely to have the most impact on clinical practice for systematic review and development of practice recommendations. STUDY DESIGN: A scoping exercise comprising of a three-iteration modified Delphi with representation from each member society of the EFC was conducted in 2018. Round one identified 19 potential topics which were scored for importance using a five-point Likert scale by EFC members in round two and ranked. Results from round two were discussed at an open EFC satellite meeting resulting in exclusion of five topics. A third round of the 14 remaining topics was conducted to allow members to modify scores after viewing the second-round rankings. Responses were analysed and topics were allocated a weighted score. RESULTS: Strategies for management of persistent HPV infection in the context of normal colposcopy and negative cytology was the highest overall weighted topic (4.40) followed by identification of appropriate length of follow up for ASCUS or LSIL prior to excisional treatment (3.95) and the impact of length of excision on patient outcomes (3.95). Topics to identify best practice for management of challenging topics scored highly including optimising follow up strategies for cervical stenosis (3.91) and management of HSIL in the under 25 year olds (3.64) or pregnancy (3.64). CONCLUSION: A European wide systematic modified-Delphi has prioritised six topics for systematic review and generation of clinical practice recommendations aiming to assist management in areas of controversy in pre-invasive cervical disease.

UK national survey of the management of vaginal intraepithelial neoplasia.

Vaginal intraepithelial neoplasia (VaIN) is less common than intraepithelial neoplasia at other non-cervical sites and can be challenging to manage. This survey describes current clinical practice by colposcopists in the UK. An online questionnaire was emailed to all the lead colposcopists in U.K. A total of 86 (43%) responses were obtained. The median number of cases of VaIN seen in a year was five (range 0-100. Most clinics (95%) managed low grade VaIN conservatively. Local vaginal mucosal excision was the most common surgical procedure. Half of respondents adopted observation, although 64% of the units referred cases to a cancer centre. More than half used a combination of cytology and colposcopy for follow-up; only two reported using Human papilloma virus testing. Seventy-seven of eighty-six lead colposcopists did not have a local guideline and would support national guidance. Treatment differed across the UK with no agreed management guidelines.Impact statementWhat is already known on the subject? Vaginal intraepithelial neoplasia (VaIN) is a pre-cancerous condition of lower genital tract and usually co-exists with cervical intraepithelial neoplasia (CIN) rather than in isolation. Unlike CIN, VaIN can be extremely challenging to manage in view of its anatomical proximity to bladder and bowel and also difficulty in accessing fornices. If diagnosed during the definitive management of CIN at the time of hysterectomy and confined to the upper vagina, it could be surgically treated at the same time. VaIN can be more challenging post-hysterectomy, especially following a failed medical and conservation option. Various treatment options are adopted for management of VaIN with no standardisation of care.What do the results of this study add? A national survey was conducted to assess the management of VaIN amongst lead colposcopists. The national survey has added valuable results, despite a response rate of only 43%. The survey confirmed conservative approach to low grade VaIN but differing treatment for high grade VaIN.What are the implications of these findings for clinical practice and/or further research? This clearly calls for the implementation of a national guideline in the UK to standardise management of VaIN, though it may be quite challenging. The survey could help inform implementation of HrHPV testing in recurrent or persistent VaIN.

Evaluating Colposcopy with Dynamic Spectral Imaging During Routine Practice at Five Colposcopy Clinics in Wales: Clinical Performance.

BACKGROUND: The diagnostic accuracy of colposcopy is poor for detecting precancerous cervical lesions. OBJECTIVES: We assessed the performance of colposcopy for identifying cervical intraepithelial neoplasia grade 2 or worse (CIN2+), before and after including a dynamic spectral imaging (DSI) map that quantifies and maps acetowhitening to assist subsequent biopsy of suspicious lesions. METHODS: Four hundred and twenty-five women were examined at a multi-center setting in Wales, of which 393 women were included in the final analysis. RESULTS: For all referrals, the sensitivity of conventional colposcopy for histologically confirmed CIN2+ was 51.5%, the specificity was 92.0%, the positive predictive value was 56.7%, and the negative predictive value (NPV) was 90.4%. With the incorporation of the DSI map in predicting CIN2+, these became 84.8, 61.5, 30.8, and 95.3% respectively. The increase of sensitivity was statistically significant (p < 0.001). For the 236 women having colposcopy after low-grade (LG) cytology, with the incorporation of DSI, the sensitivity for CIN2+ increased from 27.3 to 86.4% (p < 0.001) and the NPV from 92.6 to 97.8%. CONCLUSIONS: Colposcopy with DSI results in improved sensitivity to detect CIN2+ and maintains a high NPV for all referrals and especially for those with LG referral cytology.

2017 update of the European Federation for Colposcopy (EFC) performance standards for the practice of colposcopy.

A refinement of quality indicators (QIs) is described whereby the quality of care can be measured across colposcopy services in different countries and healthcare settings. A five-round Delphi process was conducted at successive satellite meetings from 2011 to 2015 of leading European colposcopists to refine the most high-scoring QIs relevant to colposcopic practice. A review and refinement of the wording of the standards and their criteria was undertaken by national society representatives. Six quality indicators were identified and refined. "Documentation of whether the squamocolumnar junction (SCJ) has been visible or not" was changed into "for cervical colposcopy transformation zone (TZ) type (1, 2 or 3) should be documented". The standard "percentage of cases having a colposcopic examination prior to treatment for abnormal cytology" was changed to "percentage of cases having a colposcopic examination prior to treatment for abnormal cervical screening test". The standard "percentage of all excisional treatments/conizations containing CIN2+ (cervical intra-epithelial neoplasia grade two or worse)" was changed into "percentage of excisional treatments/conizations having a definitive histology of CIN2+. Definitive histology is highest grade from any diagnostic or therapeutic biopsies". The standard "percentage of excised lesions/conizations with clear margins" was unchanged. The remaining two QIs define the minimum caseloads required for colposcopists. However, "cytology" was replaced by "screening results" to acknowledge the introduction of human papillomavirus testing to European screening programmes. Six QIs were identified to define good practice in colposcopy.

Trial of Optimal Personalised Care After Treatment-Gynaecological Cancer (TOPCAT-G): A Randomized Feasibility Trial.

OBJECTIVE: This study aimed to evaluate the feasibility of completing a parallel-group randomized controlled trial to compare usual follow-up care for women who have completed treatment of gynecological cancer against a nurse-led telephone intervention, known as Optimal Personalised Care After Treatment-Gynaecological. METHODS: The unblinded trial aimed to recruit patients who had completed treatment of cervical, endometrial, epithelial ovarian, or vulval cancer within the previous 3 months at 3 North Wales hospitals. We randomized participants to either usual hospital-based follow-up or specialist nurse-led telephone education, empowerment, and structured needs assessment follow-up. The primary outcomes assessed the feasibility of running a larger trial including patient eligibility, recruitment and retention rates, and outcome measure completion. Secondary outcomes were generic and health-related quality of life and a patient self-report health service use (Client Service Receipt Inventory) data collected at 3 time points (baseline, 3 months, and 6 months). RESULTS: Of the 58 women screened, 44 were eligible (76%) and 24 (55%) were recruited and randomized (12:12 to control and intervention, respectively). One participant was lost to follow-up. Recruited participants had a mean (SD) age of 60 (11.2) years and were approximately 5 months from their initial diagnosis (mean [SD], 159 [58] days). Seventeen (71%) of the participants had an endometrial cancer diagnosis. All outcome measure completion rates exceeded 96%. Although not a core feasibility objective, analyses of outcome measures indicated positive changes in quality of life and well-being within the Optimal Personalised Care After Treatment-Gynaecological group; exploratory cost consequence analysis indicated that the nurse-led intervention had a mean total service use cost of £27 per patient (bootstrapped 95% confidence interval, -£290 to £240) lower than did the standard care group. CONCLUSION: Eligibility, recruitment, and retention rates as well as outcome measure completion showed that the trial is feasible.

Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis.

BACKGROUND: Incomplete excision of cervical precancer is associated with therapeutic failure and is therefore considered as a quality indicator of clinical practice. Conversely, the risk of preterm birth is reported to correlate with size of cervical excision and therefore balancing the risk of adequate treatment with iatrogenic harm is challenging. We reviewed the literature with an aim to reveal whether incomplete excision, reflected by presence of precancerous tissue at the section margins, or post-treatment HPV testing are accurate predictors of treatment failure. METHODS: We did a systematic review and meta-analysis to assess the risk of therapeutic failure associated with the histological status of the margins of the tissue excised to treat cervical precancer. We estimated the accuracy of the margin status to predict occurrence of residual or recurrent high-grade cervical intraepithelial neoplasia of grade two or worse (CIN2+) and compared it with post-treatment high-risk human papillomavirus (HPV) testing. We searched for published systematic reviews and new references from PubMed-MEDLINE, Embase, and CENTRAL and did also a new search spanning the period Jan 1, 1975, until Feb 1, 2016. Studies were eligible if women underwent treatment by excision of a histologically confirmed CIN2+ lesion, with verification of presence or absence of CIN at the resection margins; were tested by cytology or HPV assay between 3 months and 9 months after treatment; and had subsequent follow-up of at least 18 months post-treatment including histological confirmation of the occurrence of CIN2+. Primary endpoints were the proportion of positive section margins and the occurrence of treatment failure associated with the marginal status, in which treatment failure was defined as occurrence of residual or recurrent CIN2+. Information about positive resection margins and subsequent treatment failure was pooled using procedures for meta-analysis of binomial data and analysed using random-effects models. FINDINGS: 97 studies were eligible for inclusion in the meta-analysis and included 44 446 women treated for cervical precancer. The proportion of positive margins was 23·1% (95% CI 20·4-25·9) overall and varied by treatment procedure (ranging from 17·8% [12·9-23·2] for laser conisation to 25·9% [22·3-29·6] for large loop excision of the transformation zone) and increased by the severity of the treated lesion. The overall risk of residual or recurrent CIN2+ was 6·6% (95% CI 4·9-8·4) and was increased with positive compared with negative resection margins (relative risk 4·8, 95% CI 3·2-7·2). The pooled sensitivity and specificity to predict residual or recurrent CIN2+ was 55·8% (95% CI 45·8-65·5) and 84·4% (79·5-88·4), respectively, for the margin status, and 91·0% (82·3-95·5) and 83·8% (77·7-88·7), respectively, for high-risk HPV testing. A negative high-risk HPV test post treatment was associated with a risk of CIN2+ of 0·8%, whereas this risk was 3·7% when margins were free. INTERPRETATION: The risk of residual or recurrent CIN2+ is significantly greater with involved margins on excisional treatment; however, high-risk HPV post-treatment predicts treatment failure more accurately than margin status. FUNDING: European Federation for Colposcopy and Institut national du Cancer (INCA).

The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

BACKGROUND: To assess the within-trial cost-effectiveness of an NHS ovarian cancer screening (OCS) programme using data from UKCTOCS and extrapolate results based on average life expectancy. METHODS: Within-trial economic evaluation of no screening (C) vs either (1) an annual OCS programme using transvaginal ultrasound (USS) or (2) an annual ovarian cancer multimodal screening programme with serum CA125 interpreted using a risk algorithm (ROCA) and transvaginal ultrasound as a second-line test (MMS), plus comparison of lifetime extrapolation of the no screening arm and the MMS programme using both a predictive and a Markov model. RESULTS: Using a CA125-ROCA cost of £20, the within-trial results show USS to be strictly dominated by MMS, with the MMS vs C comparison returning an incremental cost-effectiveness ratio (ICER) of £91 452 per life year gained (LYG). If the CA125-ROCA unit cost is reduced to £15, the ICER becomes £77 818 per LYG. Predictive extrapolation over the expected lifetime of the UKCTOCS women returns an ICER of £30 033 per LYG, while Markov modelling produces an ICER of £46 922 per QALY. CONCLUSION: Analysis suggests that, after accounting for the lead time required to establish full mortality benefits, a national OCS programme based on the MMS strategy quickly approaches the current NICE thresholds for cost-effectiveness when extrapolated out to lifetime as compared with the within-trial ICER estimates. Whether MMS could be recommended on economic grounds would depend on the confirmation and size of the mortality benefit at the end of an ongoing follow-up of the UKCTOCS cohort.

Trial of Optimal Personalised Care After Treatment for Gynaecological cancer (TOPCAT-G): a study protocol for a randomised feasibility trial.

BACKGROUND: Gynaecological cancers are diagnosed in over 1000 women in Wales every year. We estimate that this is costing the National Health Service (NHS) in excess of £1 million per annum for routine follow-up appointments alone. Follow-up care is not evidence-based, and there are no definitive guidelines from The National Institute for Health and Care Excellence (NICE) for the type of follow-up that should be delivered. Standard care is to provide a regular medical review of the patient in a hospital-based outpatient clinic for a minimum of 5 years. This study is to evaluate the feasibility of a proposed alternative where the patients are delivered a specialist nurse-led telephone intervention known as Optimal Personalised Care After Treatment for Gynaecological cancer (OPCAT-G), which comprised of a protocol-based patient education, patient empowerment and structured needs assessment. METHODS: The study will recruit female patients who have completed treatment for cervical, endometrial, epithelial ovarian or vulval cancer within the previous 3 months in Betsi Cadwaladr University Health Board (BCUHB) in North Wales. Following recruitment, participants will be randomised to one of two arms in the trial (standard care or OPCAT-G intervention). The primary outcomes for the trial are patient recruitment and attrition rates, and the secondary outcomes are quality of life, health status and capability, using the EORTC QLQ-C30, EQ-5D-3L and ICECAP-A measures. Additionally, a client service receipt inventory (CSRI) will be collected in order to pilot an economic evaluation. DISCUSSION: The results from this feasibility study will be used to inform a fully powered randomised controlled trial to evaluate the difference between standard care and the OPCAT-G intervention. TRIAL REGISTRATION: ISRCTN45565436.

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.

BACKGROUND: Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. METHODS: In this randomised controlled trial, we recruited postmenopausal women aged 50-74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. FINDINGS: Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202,638 women: 50,640 (25·0%) to MMS, 50,639 (25·0%) to USS, and 101,359 (50·0%) to no screening. 202,546 (>99·9%) women were eligible for analysis: 50,624 (>99·9%) women in the MMS group, 50,623 (>99·9%) in the USS group, and 101,299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345,570 MMS and 327,775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0-12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p=0·10) with MMS and 11% (-7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (-20 to 31) in years 0-7 and 23% (1-46) in years 7-14, and in the USS group, of 2% (-27 to 26) in years 0-7 and 21% (-2 to 42) in years 7-14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favour of MMS. INTERPRETATION: Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7-14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening. FUNDING: Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal.

Utility of EFC quality indicators for colposcopy in daily practice: results from an independent, prospective multicenter trial.

OBJECTIVES: The accuracy of colposcopy as the gold standard to manage abnormal screening tests depends on qualification and well defined standards. A recent survey of the European Federation for Colposcopy (EFC) found strong heterogeneity in the practice of colposcopy across Europe. EFC defined four quality indicators (QIs) to enable quality assessment in colposcopy as one tool to harmonize colposcopy standards. We undertook a pilot project to estimate the utility of these QIs for an independent external quality assessment in daily routine colposcopy. STUDY DESIGN: Participating colposcopy clinics used newly developed software for data collection. Data were automatically anonymized, encrypted and stored in a secure relational database located within the clinics' network and allowed for an independent external benchmarking comparing the performance of participating clinics according to EFC QIs. RESULTS: 10,869 patients referred for routine colposcopy were included. On average none of the four EFC QIs was fulfilled. One target was almost met with 83.3% instead of 85% excisional treatments/conizations containing CIN2+ and for another QI the difference of 94.4% instead of 100% cases having a colposcopic examination prior to treatment for abnormal cervical cytology was mainly explained by wrong documentation. For a third QI, visibility of the squamocolumnar junction (SCJ) was only reported in 90.9% instead of 100% but reporting improved to 94.7% after a consensus meeting. The last QI, >80% clear margins in excised lesions/conizations were not considered as useful by some clinics and therefore not documented. DISCUSSION AND CONCLUSIONS: At least 3 out of 4 QIs seemed to be useful for quality assessment in colposcopy but will need rewording and readjustment. All tools for an independent electronic quality assessment with the use of EFC-QI are available and could be used to achieve a high quality standard in colposcopy across Europe.