Intention to have blood-based multi-cancer early detection (MCED) screening: a cross-sectional population-based survey in England.

BACKGROUND: Trials assessing the clinical utility of blood-based multi-cancer early detection (MCED) tests are underway. Understanding public attitudes towards MCED screening is essential if these tests are to be used. We aimed to quantify MCED screening intention and potential barriers and facilitators to uptake. METHODS: Adults aged 50-77 (n = 958) completed an online survey. The primary outcome was intention to have MCED screening if offered. Psychological variables including barriers and facilitators were assessed. We used logistic regressions to explore associations between socio-demographics and psychological factors and intention. RESULTS: 93.8% of participants said they would 'definitely' or 'probably' have MCED screening if offered. Intention was significantly associated with previous screening participation and general cancer attitudes but not with socio-demographic factors. Participants were more likely to be intenders if they had higher health motivation, and perceived greater benefits of blood tests. Participants were less likely to be intenders if they perceived greater disadvantages of blood tests, more practical barriers, were more worried about the outcome and more concerned about a positive result. CONCLUSIONS AND IMPLICATIONS: MCED screening intention was high. The lack of socio-demographic variation suggests equitable interest in this type of screening; however, future research should consider how intention translates to uptake.

Experiences of Self-Sampling and Future Screening Preferences in Non-Attenders Who Returned an HPV Vaginal Self-Sample in the YouScreen Study: Findings From a Cross-Sectional Questionnaire.

BACKGROUND: We assessed experiences of human papillomavirus (HPV) vaginal self-sampling and future screening preferences in an ethnically and socio-economically diverse group of women overdue for cervical screening. SETTING AND PARTICIPANTS: A postal questionnaire was embedded in the YouScreen self-sampling trial in England: 32.5% (2712/8338) of kit completers returned the survey. Kit non-completers were encouraged to return a questionnaire, but no responses were received. Participants were ethnically diverse (40.3% came from ethnic minority backgrounds), and 59.1% came from the two most deprived quintiles. Differences in confidence in kit completion, trust in the test results and intention to attend a follow-up test if HPV-positive were evaluated using Pearson's χ2 analyses. Binary logistic regression models explored predictors of a future screening choice and preferences for urine versus vaginal self-sampling. RESULTS: Most kit-completers reported high confidence in self-sampling (82.6%) and high trust in the results (79.9%), but experiences varied by ethnicity and screening status. Most free-text comments were positive but some reported difficulties using the device, pain or discomfort. Most women would opt for self-sampling in the future (71.3% vs. 10.4% for a clinician-taken test) and it was more often preferred by ethnic minority groups, overdue screeners and never attenders. Urine self-tests were preferred to vaginal tests (41.9% vs. 15.4%), especially among women from Asian, Black or Other Ethnic backgrounds. CONCLUSIONS: Kit-completers were confident, found the test easy to complete, and trusted the self-sample results. However, experiences varied by ethnic group and some women highlighted difficulties with the kit. Most women would prefer self-sampling in the future, but it was not a universal preference, so offering a choice will be important. PATIENT OR PUBLIC CONTRIBUTION: We did not have direct patient and public involvement and engagement (PPIE) in the questionnaire design. However, patients and public representatives did input into the design of the YouScreen trial and reviewed the wider study materials (e.g. participant information sheet). TRIAL REGISTRATION: This questionnaire study was embedded in the YouScreen trial. The protocol for the YouScreen trial is available at https://www.isrctn.com/ISRCTN12759467. The National Institute for Health Research 43 Clinical Research Network (NIHR CRN) Central Portfolio Management System (CPMS) ID is 4441934.

Attitudes to multi-cancer early detection (MCED) blood tests for population-based screening: A qualitative study in Great Britain.

BACKGROUND: Trials are underway to test the clinical utility of multi-cancer early detection (MCED) blood tests for screening asymptomatic individuals. We sought to understand the acceptability of MCED blood test screening and potential barriers and facilitators to participation among the general public. METHODS: We conducted eleven semi-structured online focus groups with 50-77-year-olds (n = 53) in April-November 2022. Participants were purposefully sampled to include a mix of socio-economic and ethnic backgrounds as well as people who would not want 'a blood test for cancer'. Participants were shown information about MCED blood tests. Transcripts were analysed using reflexive thematic analysis. RESULTS: Participants showed enthusiasm for MCED screening. Perceived benefits included procedural familiarity and the potential to screen for many cancers. Enthusiasm was driven by beliefs that cancer is a real and increasing risk (both at population level and personally with age) and that early detection reduces treatment burden and cancer mortality. Some felt they would not want to know if they had cancer. The potential for MCED tests to raise anxiety was a concern, especially in a false-positive scenario. Participants wanted to avoid unpleasant and unnecessary procedures. The initial blood test was deemed "less invasive" than current screening tests, but potential follow-up procedures were a concern. Views on MCED screening were influenced by wider factors including dislike of uncertainty, desire for choice and control over one's health, and existing relationships with the NHS. CONCLUSION: The introduction of MCED screening is likely to be appealing due to the simplicity and familiarity of the primary test procedure. Test accuracy needs to be high to facilitate acceptability and should be communicated from the outset. Some people would rather not know if they have cancer, and MCEDs will not appeal to all.

Patient-Derived Tumor Xenograft Study with CDK4/6 Inhibitor Plus AKT Inhibitor for the Management of Metastatic Castration-Resistant Prostate Cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive malignancy with poor outcomes. To investigate novel therapeutic strategies, we characterized three new metastatic prostate cancer patient derived-tumor xenograft (PDTX) models and developed 3D spheroids from each to investigate molecular targeted therapy combinations including CDK4/6 inhibitors (CDK4/6i) with AKT inhibitors (ATKi). Metastatic prostate cancer tissue was collected and three PDTX models were established and characterized using whole-exome sequencing. PDTX 3D spheroids were developed from these three PDTXs to show resistance patterns and test novel molecular-targeted therapies. CDK4/6i's were combined with AKTi's to assess synergistic antitumor response to prove our hypothesis that blockade of AKT overcomes drug resistance to CDK4/6i. This combination was evaluated in PDTX three-dimensional (3D) spheroids and in vivo experiments with responses measured by tumor volumes, PSA, and Ga-68 PSMA-11 PET-CT imaging. We demonstrated CDK4/6i's with AKTi's possess synergistic antitumor activity in three mCRPC PDTX models. These models have multiple unique pathogenic and deleterious genomic alterations with resistance to single-agent CDK4/6i's. Despite this, combination therapy with AKTi's was able to overcome resistance mechanisms. The IHC and Western blot analysis confirmed on target effects, whereas tumor volume, serum PSA ELISA, and radionuclide imaging demonstrated response to therapy with statistically significant SUV differences seen with Ga-68 PSMA-11 PET-CT. These preclinical data demonstrating antitumor synergy by overcoming single-agent CDK 4/6i as well as AKTi drug resistance provide the rational for a clinical trial combining a CDK4/6i with an AKTi in patients with mCRPC whose tumor expresses wild-type retinoblastoma 1.

The genomic and evolutionary landscapes of anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.

The impact of age-relevant and generic infographics on knowledge, attitudes and intention to attend cervical screening: A randomized controlled trial.

OBJECTIVES: Cervical screening uptake in England is falling. Infographics could strengthen intention to attend, increase positive attitudes and improve knowledge. Age targeting could improve these outcomes further. We tested the impact of generic and age-targeted infographics. DESIGN: A randomized controlled trial using an age-stratified, parallel-group design. METHODS: Women aged 25-64 (n = 2095) were recruited through an online panel and randomized to see one of the three infographics. We tested: (i) impact of a generic cervical screening infographic compared to a control infographic on an unrelated topic with all screening age women and (ii) impact of an age-targeted infographic compared to a generic cervical screening infographic with older women (50-64 years). Intentions, knowledge and attitudes were measured. RESULTS: Women aged 25-64 years who viewed the generic infographic had significantly higher intentions [F(1, 1513) = 6.14, p = .013, η p 2 = .004], more accurate beliefs about the timeline of cervical cancer development (OR: 5.18, 95% CI: 3.86-6.95), more accurate social norms (OR: 3.03, 95% CI: 2.38-3.87) and more positive beliefs about screening benefits (OR: 2.23, 95% CI: 1.52-3.28) than those viewing the control infographic. In the older age group, there was no significant difference in intention between those viewing the generic versus age-targeted versions [F(1, 607) = .03, p = .853, η p 2 < .001], but the age-targeted version was more engaging [F(1, 608) = 9.41, p = .002, η p 2 = .015]. CONCLUSIONS: A cervical screening infographic can result in more positive attitudes and better knowledge and may have a small impact on intentions. Although age targeting did not affect intention, it had a positive impact on engagement and may therefore be useful in encouraging women to read and process materials.

"Knowing that I had HPV, I literally just shut down": A qualitative exploration of the psychosocial impact of human papillomavirus (HPV) in women living with mental health conditions.

OBJECTIVE: Psychological distress after testing positive for human papillomavirus (HPV) at cervical cancer screening is well documented in the general population. However, little is known about the impact of an HPV-positive result on those with pre-existing mental health conditions, who may be at higher risk of experiencing clinically significant distress. This study explored the psychosocial impact of HPV in women with co-morbid mental health conditions, as well as their experience of cervical screening during the COVID-19 pandemic. METHODS: Semi-structured telephone interviews were conducted with 22 women aged 27-54 who had tested positive for HPV at routine cervical screening in England, and who reported having at least one mental health condition. Data were analysed using thematic analysis. RESULTS: Being informed of an HPV-positive result increased distress and heightened pre-existing psychological challenges. Psychosocial response and duration of HPV-related distress appeared to be influenced by the ability to regulate emotions, number of consecutive HPV-positive results, interactions with health care professionals, and other life stressors. The experience added further complexity to many women's perceptions of self and self-esteem. Women who had received psychological treatment for their mental health condition were best able to self-manage HPV-related distress by applying learned coping skills. CONCLUSIONS: Receiving an HPV-positive result at cervical screening appears to be a distressing experience for women with co-morbid mental health conditions. Future hypothesis-driven research is needed to confirm findings and develop effective interventions to reduce psychosocial burden.

CDK4 phosphorylation status and rational use for combining CDK4/6 and BRAF/MEK inhibition in advanced thyroid carcinomas.

Background: CDK4/6 inhibitors (CDK4/6i) have been established as standard treatment against advanced Estrogen Receptor-positive breast cancers. These drugs are being tested against several cancers, including in combinations with other therapies. We identified the T172-phosphorylation of CDK4 as the step determining its activity, retinoblastoma protein (RB) inactivation, cell cycle commitment and sensitivity to CDK4/6i. Poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinomas, the latter considered one of the most lethal human malignancies, represent major clinical challenges. Several molecular evidence suggest that CDK4/6i could be considered for treating these advanced thyroid cancers. Methods: We analyzed by two-dimensional gel electrophoresis the CDK4 modification profile and the presence of T172-phosphorylated CDK4 in a collection of 98 fresh-frozen tissues and in 21 cell lines. A sub-cohort of samples was characterized by RNA sequencing and immunohistochemistry. Sensitivity to CDK4/6i (palbociclib and abemaciclib) was assessed by BrdU incorporation/viability assays. Treatment of cell lines with CDK4/6i and combination with BRAF/MEK inhibitors (dabrafenib/trametinib) was comprehensively evaluated by western blot, characterization of immunoprecipitated CDK4 and CDK2 complexes and clonogenic assays. Results: CDK4 phosphorylation was detected in all well-differentiated thyroid carcinomas (n=29), 19/20 PDTC, 16/23 ATC and 18/21 thyroid cancer cell lines, including 11 ATC-derived ones. Tumors and cell lines without phosphorylated CDK4 presented very high p16CDKN2A levels, which were associated with proliferative activity. Absence of CDK4 phosphorylation in cell lines was associated with CDK4/6i insensitivity. RB1 defects (the primary cause of intrinsic CDK4/6i resistance) were not found in 5/7 tumors without detectable phosphorylated CDK4. A previously developed 11-gene expression signature identified the likely unresponsive tumors, lacking CDK4 phosphorylation. In cell lines, palbociclib synergized with dabrafenib/trametinib by completely and permanently arresting proliferation. These combinations prevented resistance mechanisms induced by palbociclib, most notably Cyclin E1-CDK2 activation and a paradoxical stabilization of phosphorylated CDK4 complexes. Conclusion: Our study supports further clinical evaluation of CDK4/6i and their combination with anti-BRAF/MEK therapies as a novel effective treatment against advanced thyroid tumors. Moreover, the complementary use of our 11 genes predictor with p16/KI67 evaluation could represent a prompt tool for recognizing the intrinsically CDK4/6i insensitive patients, who are potentially better candidates to immediate chemotherapy.

Awareness and knowledge about HPV and primary HPV screening among women in Great Britain: An online population-based survey.

OBJECTIVES: Human papillomavirus (HPV) primary testing for cervical screening is being implemented around the world. We explored HPV awareness, and knowledge about primary screening in Great Britain (England, Scotland and Wales), where it has been in place for several years, ahead of extended screening intervals being implemented in England. SETTING/METHODS: Women aged 18-70 (n = 1995) were recruited by YouGov from their online panel in August 2022. The weighted sample (n = 1930) was population-representative by age, region, education and social grade. We measured HPV awareness, knowledge (excluding those unaware of HPV) using eight true/false items, and understanding of the role of HPV testing in cervical screening. RESULTS: Overall, 77.6% (1499/1930) of women were aware of HPV. When asked to identify the statement describing how cervical screening works, only 12.2% (236/1930) correctly selected the statement reflecting HPV primary screening (13.5% (194/1436) in screening-eligible women). Excluding those unaware of HPV, most participants had heard about the virus in the context of cervical screening (981/1596; 61.5%) or HPV vaccination (1079/1596; 67.6%). Mean knowledge score was 3.7 out of 8 (SD = 2.2) in this group. Most knew that an HPV-positive result does not mean a woman will definitely develop cervical cancer (1091/1499; 72.8%) but far fewer were aware of the long timeline for HPV to develop into cervical cancer (280/1499; 18.7%). CONCLUSIONS: Only three-quarters of women in Britain are aware of HPV, and knowledge of primary screening is very low, even among screening-age women. This points to continued need for awareness-raising campaigns to ensure informed choice about screening and mitigate public concern when screening intervals are extended.

Psychological Impact of the Galleri test (sIG(n)al): protocol for a longitudinal evaluation of the psychological impact of receiving a cancer signal in the NHS-Galleri trial.

INTRODUCTION: Multi-cancer early detection (MCED) blood tests look for cancer signals in cell-free deoxyribonucleic acid. These tests have the potential to detect cancers at an earlier (asymptomatic) stage, improving cancer outcomes. Any screening method needs careful consideration of the psychological harms prior to implementation. The aim of this research is to explore the psychological impact of having a cancer signal detected following an MCED blood test. METHODS AND ANALYSIS: The project is embedded in the NHS-Galleri trial (ISRCTN91431511; NCT05611632), a large clinical trial in eight Cancer Alliances in England. In the trial, over 140 000 members of the general population aged 50-77 have been randomised 1:1 to either the intervention (blood tested with MCED test) or control (blood stored) arm. The proposed project focuses on participants in the intervention arm, who have a cancer signal detected. All participants who have a cancer signal detected (expected to be around 700 assuming a 1% test positive rate) will be sent a questionnaire at three timepoints: soon after receiving their result, 6 months and approximately 12 months later. The primary outcome is anxiety, assessed using the short-form 6-item Spielberger State Trait Anxiety Inventory. We will also assess the psychological consequences of screening (using the Psychological Consequences of Screening Questionnaire), reassurance/concern about the test result, understanding of results and help/health-seeking behaviour. A subsample of 40 participants (20 with a cancer diagnosis and 20 for whom no cancer was found) will be invited to take part in a one-to-one semistructured interview. ETHICS AND DISSEMINATION: Ethical approval for this work has been granted by the Wales Research Ethics Committee as part of the NHS-Galleri trial (Ref 21/WA/0141). Consent to be sent questionnaires is collected as part of the main trial. A separate consent form will be required for interview. Results will be disseminated via peer-reviewed publication and conference presentations.

Exploring the psychosexual impact and disclosure experiences of women testing positive for high-risk cervical human papillomavirus.

OBJECTIVES: To examine the psychosexual impact and disclosure experiences of women testing HPV-positive following cervical screening. DESIGN: In-depth semi-structured interviews. METHODS: Interviews were conducted with 21 women of screening age (i.e. those aged 24-65 years) in England who self-reported testing HPV-positive in the context of cervical screening in the last 12 months. Data were analysed using Framework Analysis. RESULTS: The sexually transmitted nature of HPV, and aspects relating to the transmission of HPV and where their HPV infection had come from, had an impact on women's current, past and future interpersonal and sexual relationships. Most women had disclosed their HPV infection to others, however the factors influencing their decision, and others' reactions to disclosure differed. The magnitude and extent of psychosexual impact was influenced by how women conceptualized HPV, their understanding of key aspects of the virus, concerns about transmitting HPV and having a persistent HPV infection. CONCLUSIONS: Increasing knowledge of key aspects of HPV, such as its high prevalence and spontaneous clearance, and the differences between HPV and other STIs, may increase women's understanding of their screening result and reduce any negative psychosexual consequences of testing HPV-positive. Referring to HPV as an infection that is passed on by skin-to-skin contact during sexual activity, rather than an STI, may help to lessen any psychosexual impact triggered by the STI label.

Do age-targeted messages increase cervical screening intentions in women aged 50-64 years with weak positive intentions? A randomised control trial in Great Britain.

Over 20% of women aged 50-64 in Britain have not attended cervical screening within the recommended 5-year interval. The aim of the present study was to investigate the impact of five messages, informed using strategies from the Behaviour Change Wheel, on strength of intention to attend cervical screening in women aged 50-64 with weak positive intentions to be screened when next invited. Women were randomised (2:2:1), into one of two intervention groups or a control group. The control group saw basic information about cervical screening. Intervention group 1 saw a social norms message and an outcome expectancy message. Intervention group 2 saw a risk reduction message and a response efficacy message. There was further randomisation within the two intervention groups (1:1) to test the effectiveness of message framing and age-targeted information. Lastly, both intervention groups were randomised (1:1) to see a message acknowledging the possible discomfort associated with screening and offering support, or the support message only. Data were included from 475 women, collected using an online survey in March 2022. Adjusting for baseline intention, social norms (p = .84), outcome expectancy (p = .51), risk reduction (p = .19), response efficacy (p = .23) and discomfort acknowledgement messages (p = .71) had no effect on intention strength. However, there was a significant increase in intention after reading multiple messages. These results suggest that although no single message has a significant impact on intentions, when combined, they may act together to increase intention strength. Further research will understand the impact of these messages when combined in information materials.

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). DESIGN AND SETTING: Cross-sectional study in 11 GP practices and four colposcopy clinics in London, UK, between August 2017 and January 2019. METHOD: Non-speculum and conventional (speculum) samples were collected from women aged ≥50 years attending for a colposcopy (following a speculum HPV-positive screening result) or women aged ≥35 years (with confirmed cervical intraepithelial neoplasia (CIN) 2+), and women aged 50-64 years attending routine screening. Sensitivity to CIN2+ was assessed among women with confirmed CIN2+ (colposcopy). Specificity to HPV relative to speculum sampling and overall concordance was assessed among women with negative cytology (routine screening). RESULTS: The sensitivity of non-speculum sampling for detecting CIN2+ was 83.3% (95% confidence interval [CI] = 60.8 to 94.2) (n = 15/18). There was complete concordance among women with positive CIN2+ who had a speculum sample ≤91 days prior to the non-speculum sample (n = 12). Among 204 women with negative cytology, the specificity to HPV was 96.4% (95% CI = 92.7 to 98.5), with 96.6% concordant results (κ 72.4%). Seventy-one percent (n = 120/170) of women preferred a non-speculum sample for their next screen. CONCLUSION: HPV testing on non-speculum clinician-taken samples is a viable approach that warrants further exploration in larger studies. Overall test performance was broadly comparable with that of self-sampling.

Acceptability of extending HPV-based cervical screening intervals from 3 to 5 years: an interview study with women in England.

OBJECTIVES: The introduction of primary Human Papillomavirus (HPV) testing in the National Health Service (NHS) Cervical Screening Programme in England means the screening interval for 25-49 years can be extended from 3 to 5 years. We explored women's responses to the proposed interval extension. METHODS: We conducted semi-structured phone/video interviews with 22 women aged 25-49 years. Participants were selected to vary in age, socioeconomics and screening history. We explored attitudes to the current 3-year interval, then acceptability of a 5-year interval. Interviews were transcribed verbatim and analysed using framework analysis. RESULTS: Attitudes to the current 3-year interval varied; some wanted more frequent screening, believing cancer develops quickly. Some participants worried about the proposed change; others trusted it was evidence based. Frequent questions concerned the rationale and safety of longer intervals, speed of cancer development, the possibility of HPV being missed or cell changes occurring between screens. Many participants felt reassured when the interval change was explained alongside the move to HPV primary screening, of which most had previously been unaware. CONCLUSIONS: Communication of the interval change should be done in the context of broader information about HPV primary screening, emphasising that people who test negative for HPV are at lower risk of cell changes so can safely be screened every 5 years. The long time needed for HPV to develop into cervical cancer provides reassurance about safety, but it is important to be transparent that no screening test is perfect.

Testing key messages about extending cervical screening intervals.

OBJECTIVES: We tested the impact of different messages about the rationale for extended cervical screening intervals on acceptability of an extension. METHODS: Women in England aged 25-49 years (n = 2931) were randomised to a control group or one of 5 groups given different messages about extending cervical screening intervals from 3 to 5 years. Outcome measures were general acceptability and six components from the Theoretical Framework of Acceptability (TFA). RESULTS: The groups who saw additional messages (47-63%) were more likely to find the change acceptable than controls (43%). Messages about interval safety, test accuracy and speed of cell changes resulted in more positive affective-attitudes, higher ethicality beliefs, a better understanding of the reasons for extended intervals and greater belief in the safety of 5-year intervals. Being up-to-date with screening and previous abnormal results were associated with finding 5-yearly screening unacceptable. CONCLUSIONS: Emphasising the slow development of cell changes following an HPV negative result and the safety of longer intervals, alongside the accuracy of HPV primary screening is important. PRACTICAL IMPLICATIONS: Campaigns explaining the rationale for extended cervical screening intervals are likely to improve acceptability. Though women who feel at increased risk, may remain worried even when the rationale is explained.

Self-sampling for cervical screening offered at the point of invitation: A cross-sectional study of preferences in England.

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 associations between demographic characteristics and screening preferences, stratified by previous screening attendance. Reasons for preferences were also assessed. RESULTS: Half of participants (51.4%) intended to choose self-sampling, 36.5% preferred clinician screening, 10.5% were unsure, and <2% preferred no screening. More irregular and never attenders chose self-sampling, compared with regular attenders (71.1% and 70.1% vs. 41.0% respectively). Among regular attenders, self-sampling was preferred more frequently by the highest occupational grade, older and lesbian, gay and bisexual women, and those with experience of blood self-tests. In the irregular attender group, older women and those with experience of blood self-tests were more likely to choose self-sampling. In 'never attenders', self-sampling was less popular in ethnic minority groups. CONCLUSIONS: If offered a choice of screening, around half of women in England may choose self-sampling, but a substantial proportion would still opt for clinician screening. Screening providers will need to manage a high take-up of self-sampling if many regular attenders switch to self-sampling.

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. DESIGN AND SETTING: Pragmatic randomised control trial conducted at 10 general practices in East London, UK. METHOD: Participants were 784 women aged 50-64 years, last screened 6-15 years before randomisation. Intervention participants received a letter offering the choice of non-speculum clinician- or self-sampling. Control participants received usual care. The main outcome measure was uptake within 4 months. RESULTS: Screening uptake 4 months after randomisation was significantly higher in the intervention arm: 20.4% (n = 80/393) versus 4.9% in the control arm (n = 19/391, absolute difference 15.5%, 95% confidence interval [CI] = 11.0% to 20.0%, P<0.001). This was maintained at 12 months: intervention 30.5% (n = 120/393) versus control 13.6% (n = 53/391) (absolute difference 17.0%, 95% CI = 11.3% to 22.7%, P<0.001). Conventional screening attendance within 12 months was very similar for both intervention 12.7% (n = 50/393) and control 13.6% (n = 53/391) arms. Ethnic differences were seen in screening modality preference. More White women opted for self-sampling (50.7%, n = 38/75), whereas most Asian and Black women and those from other ethnic backgrounds opted for conventional screening. CONCLUSION: Offering non-speculum clinician-taken sampling and self-sampling substantially increases uptake in older lapsed attendee women. Non-speculum clinician sampling appeals to women who dislike the speculum but still prefer a clinician to take their sample. Providing a choice of screening modality may be important for optimising cervical screening uptake.

Distinct Illness Representation Profiles Are Associated With Anxiety in Women Testing Positive for Human Papillomavirus.

BACKGROUND: Testing positive for human papillomavirus (HPV) at cervical cancer screening has been associated with heightened anxiety. To date, the cognitive determinants of heightened anxiety remain unclear, making it difficult to design effective interventions. PURPOSE: This study investigated latent illness representation profiles in women testing positive for HPV with no abnormal cells (normal cytology) and explored associations between these profiles and anxiety. METHODS: Women aged 24-66 (n = 646) who had tested HPV-positive with normal cytology at routine HPV primary screening in England completed a cross-sectional survey shortly after receiving their result. RESULTS: Latent profile analysis identified three distinct profiles of illness representations (termed "adaptive," "negative," and "negative somatic"), which differed significantly in their patterns of illness perceptions. Hierarchal linear regression revealed that these latent illness representation profiles accounted for 21.8% of the variance in anxiety, after adjusting for demographic and clinical characteristics. When compared with adaptive representations (Profile 1), women with negative representations (Profile 2) and negative somatic representations (Profile 3) had significantly higher anxiety, with clinically meaningful between-group differences (mean difference [MD] = 17.26, confidence interval [CI]: 14.29-20.22 and MD = 13.20, CI: 9.45-16.96 on the S-STAI-6, respectively). CONCLUSION: The latent illness representation profiles identified in this study provide support for the role of negative beliefs contributing to anxiety in women testing HPV-positive with normal cytology. Characteristics specific to subgroups of highly anxious women (Profiles 2 and 3) could be used by policymakers to target information in routine patient communications (e.g., test result letters) to reduce unnecessary burden. Future research should adopt longitudinal designs to understand the trajectory of illness representations from HPV diagnosis through to clearance versus persistence.

Western Blot Processing Optimization: The Perfect Blot.

Western blot processing is a well-established procedure that includes protein extraction from tissues and cells, gel electrophoresis separation, transfer to a membrane, and immunodetection with specific antibodies. Here, we show that optimization of washing helps to maximize the specific interactions of antigens and antibodies. Performing all washing steps at 4 °C ensures a maximal signal to noise ratio and reduces nonspecific signals.