Peter Sasieni

• King's College London

Efficient and well‐organised cervical screening programmes have significantly reduced both the incidence and mortality rates of cervical cancer in the population. For optimal performance, such programmes need to incorporate essential quality assurance measures. The International Agency for Research on Cancer (IARC/WHO) organised an expert consultat...

Background Prostate cancer (PCa) is the most common male malignancy in the western world. Many men (40%) are diagnosed with localised low or intermediate-risk PCa, which is suitable for active surveillance (AS). AS affords careful monitoring to identify changes in otherwise non-life-threatening cancers. While AS reduces overtreatment (and quality o...

Background/aims Certain sociodemographic groups are routinely underrepresented in clinical trials, limiting generalisability. Here, we describe the extent to which enriched enrolment approaches yielded a diverse trial population enriched for older age in a randomised controlled trial of a blood-based multi-cancer early detection test (NCT05611632)....

Background Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minori...

Background Human papillomavirus (HPV) testing of self-collected vaginal samples has potential to improve coverage of cervical screening programmes, but current guidelines mostly require those HPV positive on a self-sample to attend for routine screening. Methods and findings A pragmatic modified stepped-wedge implementation feasibility trial was c...

Background Monitoring trends in diseases after the implementation of new public health interventions or policy changes is crucial for public health planning and surveillance. In this study we look at variations in rates of cervical cancer and grade-3 cervical intraepithelial neoplasia (CIN3) incidence between 2006 and 2020 in England and relate the...

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 b...

Objectives To replicate previous analyses on the effectiveness of the English human papillomavirus (HPV) vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia (CIN3) using 12 additional months of follow-up, and to investigate effectiveness across levels of socioeconomic deprivation. Design Observation...

Aims The aim of this study was to examine the safety of e‐cigarettes (EC) and nicotine patches (NRT) when used to help pregnant smokers quit. Design A recent trial of EC versus NRT reported safety outcomes in the randomized arms. We conducted a further analysis based on product use. Setting Twenty‐three hospitals in England and a stop‐smoking ser...

Background Lung cancer screening (LCS) with low-dose CT (LDCT) reduces lung cancer mortality. National implementation is now recommended in England, with government support announced. Following successful UK pilot studies between 2016–2019, NHS England (NHSE) launched the Targeted Lung Health Check (TLHC) programme. This abstract summarises lung ca...

Background We provide a comprehensive view of the impact of alcohol consumption, tobacco smoking, excess body weight, and human papillomavirus (HPV) infection on cancer mortality and years of life lost (YLLs) in Brazil, Russia, India, China, South Africa, the United Kingdom (UK), and United States (US). Methods We collected population attributable...

Background There has been growing interest in the UK and internationally of risk-stratified breast screening whereby individualised risk assessment may inform screening frequency, starting age, screening instrument used, or even decisions not to screen. This study evaluates the cost-effectiveness of eight proposals for risk-stratified screening reg...

Introduction Around 25% of patients with bladder cancer (BCa) present with invasive disease. Non-randomised studies of population-based screening have suggested reductions in BCa-specific mortality are possible through earlier detection. The low prevalence of lethal disease in the general population means screening is not cost-effective and there i...

Background: Lynch syndrome is a hereditary cancer disease resulting in an increased risk of colorectal cancer. Herein, findings are reported from an emergency clinical service implemented during the COVID-19 pandemic utilizing faecal immunochemical testing ('FIT') in Lynch syndrome patients to prioritize colonoscopy while endoscopy services were l...

Background Some pregnant smokers try e-cigarettes, but effectiveness and safety of such use are unknown. Objectives To compare effectiveness and safety of nicotine patches and e-cigarettes in pregnancy. Design A pragmatic multi-centre randomised controlled trial. Setting Twenty-three hospitals across England, and a Stop Smoking Service in Scotla...

Background Screening programmes utilising blood-based multi-cancer early detection (MCED) tests, which can detect a shared cancer signal from any site in the body with a single, low false-positive rate, could reduce cancer burden through early diagnosis. Methods A natural history (‘interception’) model of cancer was previously used to characterise...

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental pa...

Extending screening intervals in ongoing cancer screening programmes can lead to challenging year‐on‐year variations in the number of screening tests. We explored how such variation could be diminished with a managed transition to the extended interval. We defined three extension scenarios: immediate extension for the entire target population; step...

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 coll...

Background Lynch Syndrome (LS) is an inherited cancer predisposition syndrome defined by pathogenic variants in the mismatch repair (MMR) or EPCAM genes. In the United Kingdom, people with LS are advised to undergo biennial colonoscopy from as early as 25 until 75 years of age to mitigate a high lifetime colorectal cancer (CRC) risk, though the con...

We report the design of the NHS-Galleri trial (ISRCTN91431511), aiming to establish whether a multi-cancer early detection (MCED) test that screens asymptomatic individuals for cancer can reduce late-stage cancer incidence. This randomised controlled trial has invited approximately 1.5 million persons and enrolled over 140,000 from the general popu...

Introduction The NHS Bowel Cancer Screening Programme (BCSP) faces endoscopy capacity challenges from the COVID-19 pandemic and plans to lower the screening starting age. This may necessitate modifying the interscreening interval or threshold. Methods We analysed data from the English Faecal Immunochemical Testing (FIT) pilot, comprising 27,238 in...

Background Primary HPV screening, due to its low specificity, requires an additional liquid-based cytology (LBC) triage test. However, even with LBC triage there has been a near doubling in the number of patients referred for colposcopy in recent years, the majority having low-grade disease. Methods To counter this, a triage test that generates a...

Background: There is uncertainty about overdiagnosis in mammography screening. Methods: We aimed to estimate the effect of screening on breast cancer incidence and overdiagnosis in the NHS Breast Screening Programme in England. The study included 57,493 cases and 105,653 controls, with cases defined as women diagnosed at ages 47-89 with primary...

We aimed to explore the underlying reasons that estimates of overdiagnosis vary across and within low‐dose computed tomography (LDCT) lung cancer screening trials. We conducted a systematic review to identify estimates of overdiagnosis from randomised controlled trials of LDCT screening. We then analysed the association of Ps (the excess incidence...

Background Long-term projections of cancer incidence and mortality estimate the future burden of cancer in a population, and can be of great use in informing the planning of health services and the management of resources. We aimed to estimate incidence and mortality rates and numbers of new cases and deaths up until 2044 for all cancers combined a...

TPS6606 Background: Cancer is a leading cause of premature death globally. Early detection can reduce cancer mortality by reducing the number of cancers diagnosed at a late stage. A blood-based MCED test (Galleri) was developed that can detect cancer signals and predict cancer origin with a single blood draw. The NHS-Galleri trial is a randomized c...

10606 Background: Lynch syndrome (LS) is an inherited disorder characterized by pathogenic variants within mismatch repair genes resulting in an increased risk of colorectal cancer (CRC). In England, the fecal immunochemical test for Haemoglobin (FIT) is currently used in non-LS symptomatic and screening populations to guide subsequent colonoscopy....

Introduction Screening for Barrett’s oesophagus (BO) is a consideration due to the high mortality from oesophageal adenocarcinoma (OAC). The aim of this study was to utilise data from the randomised controlled Barrett’s oEsophagus Screening Trial 3 (BEST3) to estimate: 1) the optimal age for screening of BO/OAC; and 2) the number of missed cases un...

Background The English national bowel cancer screening programme(NHSBCSP) offering a guaiac faecal occult blood test (gFOBT) began in July 2006. In randomised controlled trials of gFOBT screening, reductions in mortality were accompanied by reductions in advanced stage colorectal cancer (CRC). We aimed to evaluate the effect of participation in the...

Nicotine replacement therapy, in the form of nicotine patches, is commonly offered to pregnant women who smoke to help them to stop smoking, but this approach has limited efficacy in this population. Electronic cigarettes (e-cigarettes) are also used by pregnant women who smoke but their safety and efficacy in pregnancy are unknown. Here, we report...

Objectives This study assessed preferences for human papillomavirus (HPV) self-sampling if offered as an alternative to clinician-based screening at the point of invitation for cervical screening. Setting and Methods An online questionnaire was completed by screening-eligible women living in England (n = 3672). Logistic regressions explored associ...

OBJECTIVES The BEST3 trial demonstrated the efficacy and safety of the Cytosponge-trefoil factor 3, a cell collection device coupled with the biomarker trefoil factor 3, as a tool for detecting Barrett’s oesophagus, a precursor of oesophageal adenocarcinoma (OAC), in primary care. In this nested study, our aim was to understand patient experiences....

Jiao and colleagues have developed an estimation framework for measuring the benefits of a multi-cancer screening test, notably in terms of cancer detection and deaths prevented. The approach is clear and attractive. Further developments are likely to include more flexible modeling of sensitivities and specificities. See related article by Jiao et...

Introduction Lynch syndrome (LS) is an autosomal dominant inherited disorder characterised by pathogenic variants within the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, PMS2, and a variant in EPCAM, which regulates MSH2 expression and results in an increased risk of several cancers, particularly colorectal cancer with an annual incidence rate of...

Background Current guidelines recommend endoscopic surveillance for Barrett oesophagus (BE), but the value of surveillance is still debated. Using a combination of primary care, secondary care and cancer registry datasets, we examined the impact of a prior BE diagnosis, clinical and risk factors on survival from oesophageal cancer and adenocarcinom...

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 cervic...

Introduction Lynch syndrome (LS) is an autosomal dominant inherited disorder characterised by pathogenic variants within the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, PMS2, and a variant in EPCAM, which regulates MSH2 expression and results in an increased risk of several cancers, particularly colorectal cancer with an annual incidence rate of...

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. Design and setting: Pragmatic randomised control trial conduct...

p>The first step in evaluating the effectiveness of cervical screening is defining exposure to screening. Our aim was to describe the spectrum of screening exposure definitions used in studies of the effectiveness of cervical screening. This systematic review included case-control studies in a population-based screening setting. Outcome was inciden...

Background Esophageal adenocarcinoma has a very poor prognosis unless detected early. The Cytosponge-trefoil factor 3 (TFF3) is a non-endoscopic test for Barrett esophagus, a precursor of esophageal adenocarcinoma. Randomised controlled trial data from the BEST3 trial has shown that an offer of Cytosponge-TFF3 in the primary care setting in Englan...

Awareness of the link between human papillomavirus (HPV) and oral cancer varies across populations. Levels of awareness and factors may impact HPV vaccine uptake in women and the intent to obtain the vaccine in men if it becomes available. A cross-sectional survey of 1415 UK university students (495 men and 920 women) aged 18–25 years was conducted...

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 wom...

Background Population-based cancer registries strive to cover all cancer cases diagnosed within the population, but some cases will always be missed and no register is 100 % complete. Many cancer registries use death certificates to identify additional cases not captured through other routine sources, to hopefully add a large proportion of the miss...

Background There is currently a lack of information on full anogenital evaluation of women with a previous history of anogenital neoplasia. Methods Retrospective analysis of the Homerton Anogenital Neoplasia Service records from January 2012 to March 2017, to identify all new referrals of women with previous anogenital neoplasia, who had had at le...

Introduction Oesophageal cancer is the sixth most common cause for cancer related deaths with over 450,000 new cases and 400,000 resulting deaths per year globally. Most cases in the UK are adenocarcinoma with some of the poorest outcomes from this cancer type in Europe -- mainly due to late diagnosis. The main risk factor for oesophageal adenocarc...

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. Method...

Objectives The National Health Service Bowel Cancer Screening Programme (NHS BCSP) in England has replaced guaiac faecal occult blood testing by faecal immunochemical testing (FIT). There is interest in fully exploiting FIT measures to improve bowel cancer (CRC) screening strategies. In this paper, we estimate the relationship of the quantitative h...

Objective: To determine the demand for colposcopy in the Cervical Screening Wales programme after the introduction of human papillomavirus (HPV) cervical screening, which coincided with the start of screening of women vaccinated against HPV types 16/18. Design: The study used a computational model that assigns screening and screening-related col...

Background For some common cancers, survival is lower in the UK than in comparable high-income countries. Aim To assess the effectiveness of a targeted postal intervention (to promote awareness of cancer symptoms and earlier help seeking) on patient consultation rates. Design and setting A two-arm randomised controlled trial was carried out on pa...

Background Data from population-based cancer registries are often used to compare cancer survival between countries or regions. The ICBP SURVMARK-2 study is an international partnership aiming to quantify and explore the reasons behind survival differences across high-income countries. However, the magnitude and relevance of differences in cancer s...

Background Cervical cancer screening services in England have been disrupted by the COVID-19 pandemic. Methods Using routine statistics we estimate 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...

In the context of opportunistic cervical cancer screening settings of low‐and‐middle‐income countries, little is known about the benefits of high‐risk human papillomavirus (hrHPV) testing on high‐grade cervical abnormality detection among women with atypical squamous cells of undetermined significance (ASC‐US) cytology in routine clinical practice....

Background There remains disagreement on the long-term effect of mammographic screening in women aged 40–49 years. Objectives The long-term follow-up of a randomised controlled trial that offered annual mammography to women aged 40–49 years. The estimation of the effect of these mammograms on breast cancer and other-cause mortality, and the effect...

Pre-clinical models have shown that targeting pancreatic stellate cells with all-trans-retinoic-acid (ATRA) reprograms pancreatic stroma to suppress pancreatic ductal adenocarcinoma (PDAC) growth. Here, in a phase Ib, dose escalation and expansion, trial for patients with advanced, unresectable PDAC (n = 27), ATRA is re-purposed as a stromal-target...

Background English cervical screening programme guidelines changed between 2009 and 2012. We explore the impact on the age and intervals at which women receive a cytology test. Methods Eligible women were controls from a population-based case–control study in England. Tests taken between 1980 and 2017 were extracted from the call/recall database....

Background Differences in registration practices across population-based cancer registries may contribute to international variation in survival estimates. In particular, there are variations in recorded date of incidence (DOI) as cancer registries have access to different sources of information and use different rules to determine an official DOI....

Background Treatment of dysplastic Barrett's oesophagus prevents progression to adenocarcinoma; however, the optimal diagnostic strategy for Barrett's oesophagus is unclear. The Cytosponge-trefoil factor 3 (TFF3) is a non-endoscopic test for Barrett's oesophagus. The aim of this study was to investigate whether offering this test to patients on med...

Age at which women are first invited to attend cervical screening in England has changed twice: in 2004, women under 25 years were no longer invited; and in 2012, first invitations were sent six months earlier (at age 24.5 years). Concomitantly, a dramatic increase in screen-detected cervical cancer was observed, and their survival had not been doc...

Cervical screening in low-resource settings remains an unmet need. Lectins are naturally occurring sugar-binding glycoproteins whose binding patterns change as cancer develops. Lectins discriminate between dysplasia and normal tissue in several precancerous conditions. We explored whether lectins could be developed for cervical screening via visual...

The COVID-19 epidemic can probably be ended and normal life restored, perhaps quite quickly, by weekly SARS-CoV-2 RNA testing together with household quarantine and systematic contact tracing. Isolated outbreaks could then be contained by contact tracing, supplemented if necessary by temporary local reintroduction of population testing or lockdown....

NOW PUBLISHED OPEN ACCESS IN BJGP - https://doi.org/10.3399/bjgp20X713489 Objective To assess the effectiveness of a targeted postal promotion for improving cancer symptom awareness and increasing help-seeking in general practice, on subsequent general practitioner (GP) consultation rates in a population which has made infrequent use of consultati...

Cause-specific and relative survival estimates differ. We aimed to examine these differences in common cancers where by possible identifying the most plausible sources of error in each estimate. Ten-year cause-specific and relative survival were estimated for lung, breast, prostate, ovary, oesophagus and colorectal cancers. The cause-specific survi...

Background Randomised controlled trials demonstrating improved longevity are needed to justify high-dose vitamin D supplementation for older populations. Objectives To demonstrate the feasibility of a large trial ( n ≈ 20,000) of high-dose vitamin D in people aged 65–84 years through general practitioner (GP) practices, and to cluster randomise pa...

BACKGROUND: Screening for Barrett's oesophagus relies on endoscopy, which is invasive and few who undergo the procedure are found to have the condition. We aimed to use machine learning techniques to develop and externally validate a simple risk prediction panel to screen individuals for Barrett's oesophagus. METHODS: In this prospective study, mac...

Introduction The NLST and NELSON studies demonstrated lung cancer mortality reduction from low-dose CT (LDCT) lung cancer screening. Local implementation pilots of ‘Lung Health Checks’ indicate feasibility in the NHS. NHS England will now fund 10 aligned projects for a national Lung Health Check pilot as a major centre-piece of the early diagnosis...

Background: Screening for Barrett's Oesophagus (BE) relies on endoscopy which is invasive and has a low yield. This study aimed to develop and externally validate a simple symptom and risk-factor questionnaire to screen for patients with BE. Methods: Questionnaires from 1299 patients in the BEST2 case-controlled study were analysed: 880 had BE i...

Background Rare and uncommon diseases are difficult to study in clinical trials due to limited recruitment. If the incidence of the disease is very low, international collaboration can only solve the problem to a certain extent. A consequence is a disproportionately high number of deaths from rare diseases, due to unclear knowledge of the best way...

Background Preclinical data demonstrated that we can effectively target pancreatic stellate cells, with measurement of subsequent changes within the stroma, using all trans retinoic acid (ATRA). In a phase I trial we have repurposed ATRA as a stromal targeting agent in combination with gemcitabine and nab-paclitaxel (G-nP). Methods Patients with l...

Aim: To evaluate the cost-effectiveness of e-cigarettes as a smoking cessation aid used in routine stop smoking services in England. Design: Cost-effectiveness analysis was performed from the National Health Service (NHS) and Personal Social Services (PSS) perspective for 12-month periods and life-time. Costs, including that of both treatments,...

Background Over the past few years, a large number of smokers in the UK have stopped smoking with the help of e-cigarettes. So far, UK Stop Smoking Services (SSSs) have been reluctant to include e-cigarettes among their treatment options because data on their efficacy compared with the licensed medications are lacking. Objective The objective was...

Background: A key challenge in phase I trials is maintaining rapid escalation in order to avoid exposing too many patients to sub-therapeutic doses, while preserving safety by limiting the frequency of toxic events. Traditional rule-based designs require temporarily stopping recruitment whilst waiting to see whether enrolled patients develop toxic...

Introduction Barrett’s oesophagus (BO) is the only known precursor of esophageal adenocarcinoma. The current gold-standard test for diagnosing BO is endoscopy which is expensive and impractical as a population screening tool. We aimed to develop a robust questionnaire that could be used in routine clinical practice to identify patients with differe...

Lung cancer screening is receiving increasing attention worldwide, both in the medical community and the general public. Multiple randomised trials — including the US National Lung Screening Trial (NLST), the Multicentric Italian Lung Detection trial, and preliminary results from the Dutch-Belgian NELSON trial — have provided definitive evidence th...