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.

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.

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.

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.

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.

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.

Patterns of anxiety and distress over 12 months following participation in HPV primary screening.

OBJECTIVES: Many countries are now using primary human papillomavirus (HPV) testing for cervical screening, testing for high-risk HPV and using cytology as triage. An HPV-positive result can have an adverse psychological impact, at least in the short term. In this paper, we explore the psychological impact of primary HPV screening over 12 months. METHODS: Women were surveyed soon after receiving their results (n=1133) and 6 (n=762) and 12 months (n=537) later. Primary outcomes were anxiety (Short-Form State Anxiety Inventory-6) and distress (General Health Questionnaire-12). Secondary outcomes included concern, worry about cervical cancer and reassurance. Mixed-effects regression models were used to explore differences at each time point and change over time across four groups according to their baseline result: control (HPV negative/HPV cleared/normal cytology and not tested for HPV); HPV positive with normal cytology; HPV positive with abnormal cytology; and HPV persistent (ie, second consecutive HPV-positive result). RESULTS: Women who were HPV positive with abnormal cytology had the highest anxiety scores at baseline (mean=42.2, SD: 15.0), but this had declined by 12 months (mean=37.0, SD: 11.7) and was closer to being within the 'normal' range (scores between 34 and 36 are considered 'normal'). This group also had the highest distress at baseline (mean=3.3, SD: 3.8, scores of 3+ indicate case-level distress), but the lowest distress at 12 months (mean=1.9, SD: 3.1). At 6 and 12 months, there were no between-group differences in anxiety or distress for any HPV-positive result group when compared with the control group. The control group were less concerned and more reassured about their result at 6 and 12 months than the HPV-positive with normal cytology group. CONCLUSIONS: Our findings suggest the initial adverse impact of an HPV-positive screening result on anxiety and distress diminishes over time. Specific concerns about the result may be longer lasting and efforts should be made to address them.

Testing the content for a targeted age-relevant intervention to promote cervical screening uptake in women aged 50-64 years.

OBJECTIVES: Low uptake of cervical screening in women in their 50s and 60s leaves them at elevated risk of cancer in older age. An age-targeted intervention could be an effective way to motivate older women to attend cervical screening. Our primary objective was to test the impact of different candidate messages on cervical screening intention strength. DESIGN: A cross-sectional online survey with randomized exposure to different candidate messages. METHODS: Women aged 50-64 years who were not intending to be screened when next invited were recruited through an online panel. Those meeting the inclusion criteria (n = 825) were randomized to one of three groups: (1) control group, (2) intervention group 1, (3) intervention group 2. Each intervention group saw three candidate messages. These included a descriptive social norms message, a diagram illustrating the likelihood of each possible screening outcome, a response efficacy message, a risk reduction message and an acknowledgement of the potential for screening discomfort. We tested age-targeted versions (vs. generic) of some messages. The primary outcome was screening intention strength. RESULTS: After adjusting for baseline intention, social norms (p = .425), outcome expectancy (p = .367), risk reduction (p = .090), response efficacy (p = .136) and discomfort acknowledgement messages (p = .181) had no effect on intention strength. Age-targeted messages did not result in greater intention than generic ones. CONCLUSIONS: There was no evidence that a single message used to convey social norms, outcome expectancy, risk reduction or response efficacy had an impact on intention strength for older women who did not plan to be screened in future.

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.

Improving postal survey response using behavioural science: a nested randomised control trial.

BACKGROUND: Systematic reviews have identified effective strategies for increasing postal response rates to questionnaires; however, most studies have isolated single techniques, testing the effect of each one individually. Despite providing insight into explanatory mechanisms, this approach lacks ecological validity, given that multiple techniques are often combined in routine practice. METHODS: We used a two-armed parallel randomised controlled trial (n = 2702), nested within a cross-sectional health survey study, to evaluate whether using a pragmatic combination of behavioural science and evidenced-based techniques (e.g., personalisation, social norms messaging) in a study invitation letter increased response to the survey, when compared with a standard invitation letter. Participants and outcome assessors were blinded to group assignment. We tested this in a sample of women testing positive for human papillomavirus (HPV) at cervical cancer screening in England. RESULTS: Overall, 646 participants responded to the survey (response rate [RR] = 23.9%). Logistic regression revealed higher odds of response in the intervention arm (n = 357/1353, RR = 26.4%) compared with the control arm (n = 289/1349, RR = 21.4%), while adjusting for age, deprivation, clinical site, and clinical test result (aOR = 1.30, 95% CI: 1.09-1.55). CONCLUSION: Applying easy-to-implement behavioural science and evidence-based methods to routine invitation letters improved postal response to a health-related survey, whilst adjusting for demographic characteristics. Our findings provide support for the pragmatic adoption of combined techniques in routine research to increase response to postal surveys. TRIAL REGISTRATION: ISRCTN, ISRCTN15113095 . Registered 7 May 2019 - retrospectively registered.

Vaccine acceptability, uptake and completion amongst men who have sex with men: A systematic review, meta-analysis and theoretical framework.

BACKGROUND: Due to an increased risk of sexually transmitted infections (STIs), gay, bisexual and other men who have sex with men (MSM) have been recommended to receive vaccinations against human papillomavirus, meningitis C and hepatitis A/B. This review aimed to compare the rates of vaccine acceptability, uptake and completion, and to identify determinants of vaccine outcomes specific to MSM to inform a theoretical framework. METHODS: In January 2020 four databases were explored to identify vaccination behaviours and associated factors among MSM. A narrative systematic review and meta-analysis were performed. Data were synthesised for theoretical modelling. RESULTS: Seventy-eight studies, mostly from the USA, were included. The average vaccine acceptability was 63% (median = 72%, range: 30%-97%), vaccine uptake 45% (median = 42%, range: 5%-100%) and vaccine completion 47% (median = 45%, range: 12%-89%). Six categories of factors associated with vaccination acceptability, uptake and completion were conceptualised: Individual (e.g., demographic and psychosocial); Interpersonal (e.g., peer education); Healthcare provider (e.g., vaccine recommendation); Organisational and practice setting (e.g., routine collection of patient sexual orientation information that is integrated into a clinical decision support system); Community environment (e.g., targeted health promotion campaigns); and National, state and local policy environment (e.g., public health guidelines targeting MSM). CONCLUSION: Despite overall high levels of acceptability, uptake and completion rates were below targets predicted by cost-effectiveness modelling across all recommended vaccines. These parameters may need to be adjusted for more precise estimations of cost-effectiveness. Addressing the multiple levels of determinants, as outlined in our theoretical framework, will help guide interventions to increase vaccine completion among MSM.

Emotional response to testing positive for human papillomavirus at cervical cancer screening: a mixed method systematic review with meta-analysis.

Tens-of-millions of women every year test positive for human papillomavirus (HPV) at routine cervical screening. We performed a mixed-methods systematic review using a results-based convergent design to provide the first comprehensive overview of emotional response to testing positive for HPV (HPV+). We mapped our findings using the cognitive behavioural framework. Six electronic databases were searched from inception to 09-Nov-2019 and 33 papers were included. Random-effects meta-analyses revealed that HPV+ women with abnormal or normal cytology displayed higher short-term anxiety than those with normal results (MD on State-Trait Anxiety Inventory = 7.6, 95% CI: 4.59-10.60 and MD = 6.33, CI: 1.31-11.35, respectively); there were no long-term differences. Psychological distress (general/sexual/test-specific) was higher in HPV+ women with abnormal cytology in the short-term and long-term (SMD = 0.68, CI: 0.32-1.03 and SMD = 0.42, CI: 0.05-0.80, respectively). Testing HPV+ was also related to disgust/shame, surprise and fear about cancer. Broadly, adverse response related to eight cognitive constructs (low control, confusion, cancer-related concerns, relationship concerns, sexual concerns, uncertainty, stigma, low trust) and six behavioural constructs (relationship problems, social impact, non-disclosure of results, idiosyncratic prevention, indirect clinical interaction, changes to sexual practice). Almost exclusive use of observational and qualitative designs limited inferences of causality and conclusions regarding clinical significance.

Exploring reasons for variations in anxiety after testing positive for human papillomavirus with normal cytology: a comparative qualitative study.

OBJECTIVE: To explore reasons for variations in anxiety in women testing positive for human papillomavirus (HPV) with normal cytology at routine HPV primary cervical cancer screening. METHODS: In-depth interviews were conducted with 30 women who had tested HPV-positive with normal cytology, including 15 with low-to-normal anxiety and 15 with high anxiety. Data were analysed using Framework Analysis to compare themes between low and high anxiety groups. RESULTS: Several HPV-related themes were shared across anxiety groups, but only highly anxious women expressed fear and worry, fatalistic cognitions about cancer, fertility-related cognitions, adverse physiological responses and changes in health behaviour(s). In comparison to those with low anxiety, women with high anxiety more strongly voiced cognitions about the 12-month wait for follow-up screening, relationship infidelity, a lower internal locus of control and HPV-related symptom attributions. CONCLUSIONS: Receiving an HPV-positive with normal cytology result related to various emotional, cognitive, behavioural and physiological responses; some of which were specific to, or more pronounced in, women with high anxiety. If our observations are confirmed in hypothesis-driven quantitative studies, the identification of distinct themes relevant to women experiencing high anxiety can inform targeted patient communications and HPV primary screening implementation policy.

Countering Vaccine Hesitancy among Pregnant Women in England: The Case of Boostrix-IPV.

This study explored the effects of message framing on vaccine hesitancy for the antenatal whooping cough vaccine. The study also assessed whether the Theory of Planned Behaviour (TPB) constructs had any explanatory utility for vaccine intentions and behaviours in pregnant women. A between-subjects, cross-sectional design was employed. Participants (n = 282) were women who were pregnant (mean = 28 weeks, SD = 7.0), living in England and between 18 and 44 years of age. A self-report web-based survey was used to collect data. Participants were randomly assigned to read either (i) disease risk, (ii) myth busting, or (iii) control information before answering questions based on the TPB. No significant effects of message framing were found. Attitudes (Beta = 0.699; p < 0.001) and subjective norms (Beta = 0.262, p < 0.001) significantly predicted intention to vaccinate but perceived behavioural control did not. The TPB constructs accounted for 86% and 36% of the variance in vaccine intention and vaccine history respectively. Disease risk information did not influence vaccine acceptability in this sample of English pregnant women. The study offered preliminary evidence that interventions targeting constructs from the TPB may promote vaccine acceptability among pregnant women.