Women’s perspectives on Human Papillomavirus self-sampling in the context of the UK cervical screening programme

Background: Testing for human papillomavirus (HPV) is being incorporated into the cervical screening programme, with the probable future introduction of HPV as a primary test and a possibility of HPV self-sampling. In anticipation of this development, we sought to inform future policy and practice by identifying potential barriers to HPV self-sampling. Methods: A cross-sectional survey of 194 women aged 20-64 years was conducted. Logistic regression analysis was used to identify determinants of self-sampling intentions. A purposive subsample of 19 women who reported low self-sampling intentions were interviewed. Interviews were framework-analysed. Results: Most survey participants (N=133, 69.3%) intended to HPV self-sample. Lower intention was associated with lower self-efficacy (OR=24.96, P≤.001), lower education (OR=6.06, P≤.05) and lower perceived importance of HPV as a cause of cervical cancer (OR=2.33, P≤.05). Interviews revealed personal and system-related barriers. Personal barriers included a lack of knowledge about HPV self-sampling, women’s low confidence in their ability to self-sample correctly and low confidence in the subsequent results. System-related factors included a lack of confidence in the rationale for modifying the current cervical screening programme, and concerns about sample contamination and identity theft. Conclusions: Insights gained from this research can be used to guide further enquiry into the possibility of HPV self-sampling and to help inform future policy and practice. Personal and system-related barriers including low confidence in the reasons for changing current cervical screening provision need to be addressed, should HPV self-sampling be incorporated into the cervical screening programme

Impact of human papillomavirus-related genital diseases on quality of life and psychosocial wellbeing: results of an observational, health-related quality of life study in the UK

Background: Data on the psychosocial burden of human papillomavirus (HPV)-related diseases other than cervical cancer are scarce. The objectives of this study were to measure and compare the psychosocial burden and the impact on health-related quality of life (HRQoL) of HPV-related lower genital tract diseases and genital warts (GW) using several generic and disease-specific instruments. Methods. Overall, 842 individuals with normal cervical cytology (n = 241), borderline nuclear abnormalities and/or mild dyskaryosis (n = 23), cervical intraepithelial neoplasia (CIN)1 (n = 84), CIN2/3 (n = 203), vulval intraepithelial neoplasia (VIN)2/3 (n = 43), GW (n = 186) and a history of GW (non-current) (n = 62) were included. The generic European Quality of Life Index Version 5D (EQ-5D) questionnaire was completed by patients with GW and VIN2/3. Sexual functioning was evaluated using the Change in Sexual Functioning Questionnaire (CSFQ). Psychosocial impact was measured in women using the HPV Impact Profile (HIP) questionnaire. HRQoL was assessed using a GW-specific questionnaire, the Cuestionario Especifico en Condilomas Acuminados (CECA) (completed by patients with GW and history of GW). For each instrument, scores were compared between groups using the Student's t-test. In addition, utility loss due to GW and VIN2/3 was evaluated by comparing mean EQ-5D scores weighted by age and sex with the UK general population normal values. Results: A significant psychosocial impact was found in women diagnosed with HPV-related genital diseases, particularly in those with GW. The health state of younger adults with GW was significantly impaired compared with UK normal values (mean EQ-5D index score 0.86 vs 0.94, p < 0.001 for 18-24-year-olds; 0.87 vs 0.93, p = 0.030 for 25-34-year-olds). VIN2/3 was found to have a significant negative impact on sexual functioning, and women with VIN2/3 had a highly impaired health state compared with women in the UK general population (weighted mean EQ-5D index score 0.72 vs 0.89, p < 0.001; weighted mean Visual Analogue Scale score 62 vs 85, p < 0.001). Conclusions: HPV-related lower genital tract lesions and GW significantly impair psychosocial wellbeing and HRQoL. The psychosocial aspects of HPV-related diseases need to be considered when evaluating the potential benefit of HPV vaccination. © 2013 Dominiak-Felden et al.; licensee BioMed Central Ltd

The global burden of disease due to benign gynecological conditions: A call to action

Objective: Focusing on low‐ and middle‐income countries (LMICs), this article uses data from the Global Burden of Disease (GBD) database to highlight the burden of morbidity due to benign gynecological conditions (BGCs). Methods: We analyzed 2019 morbidity data for all BGCs, measured as years lost to disability (YLDs). Disease burden was calculated for individual conditions, BGCs overall, and percentages of overall disease burden from all conditions. The same data extraction was performed for malaria, tuberculosis, and HIV/AIDS for comparison. The data were subcategorized by age and World Bank income level. Results: BGCs are major causes of disease morbidity worldwide. For women aged 15 years and over in high‐income countries (HICs), 3 588 157 YLDs (3.94% of all YLDs) were due to BGC. In LMICs, 18 242 989 YLDs (5.35% of all YLDs) were due to BGCs. The highest burden of BGCs is seen during the reproductive years where conditions driven or exacerbated by reproductive hormones are the major causes of morbidity. In LMICs, for women aged 15–49, 14 574 100 YLDs (7.75% of all YLDs) were due to BGCs, declining to 3 152 313 YLDs (3.04%) in women aged 50–69 and 529 399 YLDs (1.06%) in women age 70+. Conclusion: These data demonstrate a huge burden of morbidity due to BGCs. There is an urgent need for international stakeholders to prioritize the treatment and prevention of BGCs

High prevalence of HPV 51 in an unvaccinated population and implications for HPV vaccines

Human papillomavirus (HPV) is detected in 99.7% of cervical cancers. Current vaccines target types 16 and 18. Prior to vaccination implementation, a prospective cohort study was conducted to determine baseline HPV prevalence in unvaccinated women in Wales; after HPV16 and HPV18, HPV 51 was found to be most prevalent. This study aimed to re-assess the unexpected high prevalence of HPV 51 and consider its potential for type-replacement. Two hundred HPV 51 positive samples underwent re-analysis by repeating the original methodology using HPV 51 GP5+/6+ PCR-enzyme immunoassay, and additionally a novel assay of HPV 51 E7 PCR. Data were correlated with age, social deprivation and cytology. Direct repeat of HPV 51 PCR-EIA identified 146/195 (75.0%) samples as HPV 51 positive; E7 PCR identified 166/195 (85.1%) samples as HPV 51 positive. HPV 51 prevalence increased with cytological grade. The prevalence of HPV 51 in the pre-vaccinated population was truly high. E7 DNA assays may offer increased specificity for HPV genotyping. Cross-protection of current vaccines against less-prevalent HPV types warrants further study. This study highlights the need for longitudinal investigation into the prevalence of non-vaccine HPV types, especially those phylogenetically different to vaccine types for potential type-replacement. Ongoing surveillance will inform future vaccines

Human Papillomavirus DNA methylation predicts response to treatment using cidofovir and imiquimod in Vulval Intraepithelial Neoplasia 3

Purpose: Response rates to treatment of vulval intraepithelial neoplasia (VIN) with imiquimod and cidofovir are approximately 57% and 61%, respectively. Treatment is associated with significant side effects and, if ineffective, risk of malignant progression. Treatment response is not predicted by clinical factors. Identification of a biomarker that could predict response is an attractive prospect. This work investigated HPV DNA methylation as a potential predictive biomarker in this setting. Experimental Design: DNA from 167 cases of VIN 3 from the RT3 VIN clinical trial was assessed. HPV-positive cases were identified using Greiner PapilloCheck and HPV 16 type-specific PCR. HPV DNA methylation status was assessed in three viral regions: E2, L1/L2, and the promoter, using pyrosequencing. Results: Methylation of the HPV E2 region was associated with response to treatment. For cidofovir (n = 30), median E2 methylation was significantly higher in patients who responded (P ≤ 0.0001); E2 methylation >4% predicted response with 88.2% sensitivity and 84.6% specificity. For imiquimod (n = 33), median E2 methylation was lower in patients who responded to treatment (P = 0.03; not significant after Bonferroni correction); E2 methylation <4% predicted response with 70.6% sensitivity and 62.5% specificity. Conclusions: These data indicate that cidofovir and imiquimod may be effective in two biologically defined groups. HPV E2 DNA methylation demonstrated potential as a predictive biomarker for the treatment of VIN with cidofovir and may warrant investigation in a biomarker-guided clinical trial

Talking about human papillomavirus and cancer:development of consultation guides through lay and professional stakeholder coproduction using qualitative, quantitative and secondary data

Background High-risk human papillomaviruses (HPVs) cause all cervical cancer and the majority of vulvar, vaginal, anal, penile and oropharyngeal cancers. Although HPV is the most common sexually transmitted infection, public awareness of this is poor. In addition, many clinicians lack adequate knowledge or confidence to discuss sexual transmission and related sensitive issues. Complex science needs to be communicated in a clear, digestible, honest and salient way. Therefore, the aim of this study was to coproduce with patients who have cancer appropriate resources to guide these highly sensitive and difficult consultations. Methods A matrix of evidence developed from a variety of sources, including a systematic review and telephone interviews with clinicians, supported the production of a draft list of approximately 100 potential educational messages. These were refined in face-to-face patient interviews using card-sorting techniques, and tested in cognitive debrief interviews to produce a ‘fast and frugal’ knowledge tool. Results We developed three versions of a consultation guide, each comprising a clinician guidance sheet and patient information leaflet for gynaecological (cervical, vaginal, vulvar), anal or oropharyngeal cancers. That cancer could be caused by a sexually transmitted virus acquired many years previously was surprising to many and shocking to a few patients. However, they found the information clear, helpful and reassuring. Clinicians acknowledged a lack of confidence in explaining HPV, welcomed the clinician guidance sheets and considered printed information for patients particularly useful. Conclusion Because of the ‘shock factor’, clinicians will need to approach the discussion of HPV with sensitivity and take individual needs and preferences into account, but we provide a novel, rigorously developed and tested resource which should have broad applicability in the UK National Health Service and other health systems

Understanding context in knowledge translation: a concept analysis study protocol

AimTo conduct a concept analysis of clinical practice contexts (work environments) that facilitate or militate against the uptake of research evidence by healthcare professionals in clinical practice. This will involve developing a clear definition of context by describing its features, domains and defining characteristics.BackgroundThe context where clinical care is delivered influences that care. While research shows that context is important to knowledge translation (implementation), we lack conceptual clarity on what is context, which contextual factors probably modify the effect of knowledge translation interventions (and hence should be considered when designing interventions) and which contextual factors themselves could be targeted as part of a knowledge translation intervention (context modification).DesignConcept analysis.MethodsThe Walker and Avant concept analysis method, comprised of eight systematic steps, will be used: (1) concept selection; (2) determination of aims; (3) identification of uses of context; (4) determination of defining attributes of context; (5) identification/construction of a model case of context; (6) identification/construction of additional cases of context; (7) identification/construction of antecedents and consequences of context; and (8) definition of empirical referents of context. This study is funded by the Canadian Institutes of Health Research (January 2014).DiscussionThis study will result in a much needed framework of context for knowledge translation, which identifies specific elements that, if assessed and used to tailor knowledge translation activities, will result in increased research use by nurses and other healthcare professionals in clinical practice, ultimately leading to better patient care.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111196/1/jan12574.pd

Recurrence of vulval intraepithelial neoplasia following treatment with cidofovir or imiquimod: results from a multi-centre, randomised, phase II trial (RT3VIN)

Objective To compare the recurrence rates after complete response to topical treatment with either cidofovir or imiquimod for vulval intraepithelial neoplasia (VIN) 3. Design A prospective, open, randomised multicentre trial. Setting 32 general hospitals located in Wales and England. Population or Sample 180 patients were randomised consecutively between 21 October 2009 and 11 January 2013, 89 to cidofoovir (of whom 41 completely responded to treatment) and 91 to imiquimod (of whom 42 completely responded to treatment). Methods After 24 weeks of treatment, complete responders were followed up at 6‐monthly intervals for 24 months. At each visit, the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was assessed and any new lesions were biopsied for histology. Main outcome measures Time to histologically confirmed disease recurrence (any grade of VIN). Results The median length of follow up was 18.4 months. At 18 months, more participants were VIN‐free in the cidofovir arm: 94% (95% CI 78.2–98.5) versus 71.6% (95% CI 52.0–84.3) [univariable hazard ratio (HR) 3.46, 95% CI 0.95–12.60, P = 0.059; multivariable HR 3.53, 95% CI 0.96–12.98, P = 0.057). The number of grade 2+ events was similar between treatment arms (imiquimod: 24/42 (57%) versus cidofovir: 27/41 (66%), χ2 = 0.665, P = 0.415), with no grade 4+. Conclusions Long‐term data indicates a trend towards response being maintained for longer following treatment with cidofovir than with imiquimod, with similar low rates of adverse events for each drug. Adverse event rates indicated acceptable safety of both drugs Tweetable abstract Long‐term follow up in the RT3VIN trial suggests cidofovir may maintain response for longer than imiquimod

Identification of Human Papillomavirus Type 58 Lineages and the Distribution Worldwide

Background. Human papillomavirus type 58 (HPV-58) accounts for a much higher proportion of cervical cancers in East Asia than other types. A classification system of HPV-58, which is essential for molecular epidemiological study, is lacking. Methods and results. This study analyzed the sequences of 401 isolates collected from 15 countries and cities. The 268 unique concatenated E6-E7-E2-E5-L1-LCR sequences that comprised 57% of the whole HPV-58 genome showed 4 distinct clusters. L1 and LCR produced tree topologies that best resembled the concatenated sequences and thus are the most appropriate surrogate regions for lineage classification. Moreover, short fragments from L1 (nucleotides 6014–6539) and LCR (nucleotides 7257–7429 and 7540–52) were found to contain sequence signatures informative for lineage identification. Lineage A was the most prevalent lineage across all regions. Lineage C was more frequent in Africa than elsewhere, whereas lineage D was more prevalent in Africa than in Asia. Among lineage A variants, sublineage A2 dominated in Africa, the Americas, and Europe, but not in Asia. Sublineage A1, which represents the prototype that originated from a patient with cancer, was rare worldwide except in Asia. Conclusions. HPV-58 can be classified into 4 lineages that show some degree of ethnogeographic predilection in distribution. The evolutionary, epidemiological, and pathological characteristics of these lineages warrant further study

Risk of newly detected infections and cervical abnormalities in adult women seropositive or seronegative for naturally acquired HPV-16/18 antibodies

Funder: GlaxoSmithKline Biologicals SAPeer reviewedPublisher PD