Opportunistic offering of self-sampling to non-attenders within the English cervical screening programme: a pragmatic, multicentre, implementation feasibility trial with randomly allocated cluster intervention start dates (YouScreen).

Background: Self-sampling has game-changing potential to tackle the declining participation and inequities seen in many organised cervical screening programmes. Wide variation in uptake between settings and mode of kit offer highlight the importance of local piloting. Furthermore, harnessing the benefits of self-sampling in real-world settings has been surprisingly challenging.

Considerations for using potential surrogate endpoints in cancer screening trials.

The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Review aims to highlight the issues underlying the choice and use of surrogate endpoints for cancer screening trials, to propose criteria for when and how we might use such endpoints, and to suggest possible candidates.

Years of life lost due to cancer in the United Kingdom from 1988 to 2017.

Background: We investigated the application of years of life lost (YLL) in routine cancer statistics using cancer mortality data from 1988 to 2017.

Methods: Cancer mortality data for 17 cancers and all cancers in the UK from 1988 to 2017 were provided by the UK Association of Cancer Registries by sex, 5-year age group, and year. YLL, age-standardised YLL rate (ASYR) and age-standardised mortality rate (ASMR) were estimated.

Predictors of the experience of a Cytosponge test: analysis of patient survey data from the BEST3 trial.

Background: The Cytosponge is a cell-collection device, which, coupled with a test for trefoil factor 3 (TFF3), can be used to diagnose Barrett's oesophagus, a precursor condition to oesophageal adenocarcinoma. BEST3, a large pragmatic, randomised, controlled trial, investigated whether offering the Cytosponge-TFF3 test would increase detection of Barrett's. Overall, participants reported mostly positive experiences.

Non-speculum clinician-taken samples for human papillomavirus testing: a cross-sectional study in older women.

Background: Cervical cancer incidence and mortality are high in women aged ≥65 years, despite the disease being preventable by screening. Speculum-based screening can become more uncomfortable after the menopause.

Aim: To examine test performance and acceptability of human papillomavirus (HPV) testing on clinician-collected vaginal samples without a speculum (non-speculum).

Use of a Cytosponge biomarker panel to prioritise endoscopic Barrett's oesophagus surveillance: a cross-sectional study followed by a real-world prospective pilot.

Background: Endoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. However, repeated endoscopy has associated harms and access has been limited during the COVID-19 pandemic. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett's oesophagus.

Non-speculum sampling approaches for cervical screening in older women: randomised controlled trial.

Background: Cervical cancer disproportionately affects women ≥65 years, especially those not screened regularly. Speculum use is a key barrier.

Aim: To assess if offering non-speculum clinician-taken sampling and self-sampling increases uptake for lapsed attenders aged 50-64 years.

A case-control study to evaluate the impact of the breast screening programme on mortality in England.

Background: Over the past 30 years since the implementation of the National Health Service Breast Screening Programme, improvements in diagnostic techniques and treatments have led to the need for an up-to-date evaluation of its benefit on risk of death from breast cancer. An initial pilot case-control study in London indicated that attending mammography screening led to a mortality reduction of 39%.

Methods: Based on the same study protocol, an England-wide study was set up.

Intraoperative radiotherapy for early breast cancer - insufficient evidence to change practice.

We argue that the evidence remains insufficient for use of intraoperative radiotherapy (IORT) in women with early stage breast cancer outside of a clinical trial, as the recently reported TARGIT-A trial does not provide sufficient evidence to conclude that IORT is superior to no radiotherapy.

A state-wide population-based evaluation of cervical cancers arising during opportunistic screening in the United States.

Objective: Despite widespread cervical screening, an estimated 13,800 women will be diagnosed with cervical cancer in the United States in 2020. To inform improvements, the screening histories of women diagnosed with cervical cancer in New Mexico were assessed.

Methods: Data were collected on all cervical screening, diagnostic tests and treatment procedures for all women diagnosed with cervical cancer aged 25-64 yrs.

Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial.

Background: The appropriate age range for breast cancer screening remains a matter of debate. We aimed to estimate the effect of mammographic screening at ages 40-48 years on breast cancer mortality.

Methods: We did a randomised, controlled trial involving 23 breast screening units across Great Britain.

Impact of screening on cervical cancer incidence: A population-based case-control study in the United States.

Cervical cancer is widely preventable through screening, but little is known about the duration of protection offered by a negative screen in North America. A case-control study was conducted with records from population-based registries in New Mexico. Cases were women diagnosed with cervical cancer in 2006-2016, obtained from the Tumor Registry.

Absolute risks of cervical precancer among women who fulfill exiting guidelines based on HPV and cytology cotesting.

US guidelines recommend that most women older than 65 years cease cervical screening after two consecutive negative cotests (concurrent HPV and cytology tests) in the previous 10 years, with one in the last 5 years. However, this recommendation was based on expert opinion and modeling rather than empirical data on cancer risk. We therefore estimated the 5-year risks of cervical precancer (cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ [CIN3]) after one, two and three negative cotests among 346,760 women aged 55-64 years undergoing routine cotesting at Kaiser Permanente Northern California (2003-2015).

Challenges in risk estimation using routinely collected clinical data: The example of estimating cervical cancer risks from electronic health-records.

Electronic health-records (EHR) are increasingly used by epidemiologists studying disease following surveillance testing to provide evidence for screening intervals and referral guidelines. Although cost-effective, undiagnosed prevalent disease and interval censoring (in which asymptomatic disease is only observed at the time of testing) raise substantial analytic issues when estimating risk that cannot be addressed using Kaplan-Meier methods. Based on our experience analysing EHR from cervical cancer screening, we previously proposed the logistic-Weibull model to address these issues.

What cervical screening is appropriate for women who have been vaccinated against high risk HPV? A simulation study.

Women vaccinated against HPV16/18 are approaching the age for cervical screening; however, an updated screening algorithm has not been agreed. We use a microsimulation model calibrated to real published data to determine the appropriate screening intensity for vaccinated women. Natural histories in the absence of vaccination were simulated for 300,000 women using 10,000 sets of transition probabilities.

Risk stratification of Barrett's oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study.

Background: Barrett's oesophagus predisposes to adenocarcinoma. However, most patients with Barrett's oesophagus will not progress and endoscopic surveillance is invasive, expensive, and fraught by issues of sampling bias and the subjective assessment of dysplasia. We investigated whether a non-endoscopic device, the Cytosponge, could be coupled with clinical and molecular biomarkers to identify a group of patients with low risk of progression suitable for non-endoscopic follow-up.

Range of pathologies diagnosed using a minimally invasive capsule sponge to evaluate patients with reflux symptoms.

Aims: Reflux symptoms are highly prevalent and non-specific; hence, in the absence of alarm symptoms, endoscopy referral decisions are challenging. This study evaluated whether a non-endoscopic Cytosponge could detect benign oesophageal pathologies and thus have future potential in triaging patients with persistent symptoms.

Methods And Results: Two complementary cohorts were recruited: (i) patients with reflux symptoms and no prior endoscopy (n = 409), and (ii) patients with reflux symptoms referred for endoscopy (n = 411).