A further case of chondrodysplasia with growth failure occurring after hematopoietic stem cell transplantation (HSCT).

There is an emerging body of evidence showing that young patients, post haematopoietic stem cell transplantation (HSCT), can develop skeletal changes that mimic an osteochondrodysplasia process. The key discriminator is that these children have had otherwise normal growth and skeletal development before the therapeutic intervention (HSCT), typically for a haematological malignancy. Herein we present that case of a boy who underwent HSCT for Haemophagocytic Lymphohistiocytosis (HLH) aged 2 years. Following Intervention with HSCT this boy's growth has severely decelerated (stature less than 1st centile matched for age) and he has developed a spondyloepiphyseal dysplasia.

Comparison of multistate model, survival regression, and matched case-control methods for estimating excess length of stay due to healthcare-associated infections.

BACKGROUND: A recent systematic review recommended time-varying methods for minimizing bias when estimating the excess length of stay (LOS) for healthcare-associated infections (HAIs); however, little evidence exists concerning which time-varying method is best used for HAI incidence studies. AIM: To undertake a retrospective analysis of data from a one-year prospective incidence study of HAIs, in one teaching hospital and one general hospital in NHS Scotland. METHODS: Three time-varying methods - multistate model, multivariable adjusted survival regression, and matched case-control approach - were applied to the data to estimate excess LOS and compared. FINDINGS: The unadjusted excess LOS estimated from the multistate model was 7.8 (95% confidence interval: 5.7-9.9) days, being shorter than the excess LOS estimated from survival regression adjusting for the admission characteristics (9.9; 8.4-11.7) days, and the adjusted estimates from matched case-control approach (10; 8.5-11.5) days. All estimates from the time-varying methods were much lower than the crude time-fixed estimates of 27 days. CONCLUSION: Studies examining LOS associated with HAI should consider a design which addresses time-dependent bias as a minimum. If there is an imbalance in patient characteristics between the HAI and non-HAI groups, then adjustment for patient characteristics is also important, where survival regression with time-dependent covariates is likely to provide the most flexible approach. Matched design is more likely to result in data loss, whereas a multistate model is limited by the challenge in adjusting for covariates. These findings have important implications for future cost-effectiveness studies of infection prevention and control programmes.

Epidemiology of healthcare-associated infection reported from a hospital-wide incidence study: considerations for infection prevention and control planning.

BACKGROUND: The measure of disease frequency most widely used to report healthcare-associated infection (HAI) is the point-prevalence survey. Incidence studies are rarely performed due to time and cost constraints; they show which patients are affected by HAI, when and where, and inform planning and design of infection prevention and control (IPC) measures. AIM: To determine the epidemiology of HAI within a general and a teaching hospital in Scotland. METHODS: A prospective observational incidence study was undertaken for one year from April 2018 using data collected as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. A novel, robust approach was undertaken, using record linkage to national administrative data to provide full admission and discharge information. Cases were recorded if they met international HAI definitions. FINDINGS: Incidence of HAI for the combined hospitals was 250 HAI cases per 100,000 acute occupied bed-days (AOBD). Highest frequency was in urinary tract (51.2 per 100,000 AOBD), bloodstream (44.7), and lower respiratory tract infection (42.2). The most frequently reported organisms were Escherichia coli, Staphylococcus aureus, and norovirus. Incidence of HAI was higher in older people and emergency cases. There was an increase in the rate of HAI in summer months (pneumonia, respiratory, surgical, and gastrointestinal infection) and in winter months norovirus gastrointestinal infection (P < 0.0001). The highest incidence specialties were intensive care, renal medicine, and cardiothoracic surgery. HAI occurred at a median of 9 days (interquartile range: 4-19) after admission. Incidence data were extrapolated to provide an annual national estimate of HAI in NHS Scotland of 7437 (95% confidence interval: 7021-7849) cases. CONCLUSION: This study provides a unique overview of incidence of HAI and identifies the burden of HAI at the national level for the first time. Understanding the incidence in different clinical settings, at different times, will allow targeting of IPC measures to those patients who would benefit the most.

Impact of healthcare-associated infection on length of stay.

BACKGROUND: Increased length of stay (LOS) for patients is an important measure of the burden of healthcare-associated infection (HAI). AIM: To estimate the excess LOS attributable to HAI. METHODS: This was a one-year prospective incidence study of HAI observed in one teaching hospital and one general hospital in NHS Scotland as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. All adult inpatients with an overnight stay were included. HAI was diagnosed using European Centres for Disease Prevention and Control definitions. A multi-state model was used to account for the time-varying nature of HAI and the competing risks of death and discharge. FINDINGS: The excess LOS attributable to HAI was 7.8 days (95% confidence interval (CI): 5.7-9.9). Median LOS for HAI patients was 30 days and for non-HAI patients was 3 days. Using a simple comparison of duration of hospital stay for HAI cases and non-cases would overestimate the excess LOS by 3.5 times (27 days compared with 7.8 days). The greatest impact on LOS was due to pneumonia (16.3 days; 95% CI: 7.5-25.2), bloodstream infections (11.4 days; 5.8-17.0) and surgical site infection (SSI) (9.8 days; 4.5-15.0). It is estimated that 58,000 bed-days are occupied due to HAI annually. CONCLUSION: A reduction of 10% in HAI incidence could make 5800 bed-days available. These could be used to treat 1706 elective patients in Scotland annually and help reduce the number of patients awaiting planned treatment. This study has important implications for investment decisions in infection prevention and control interventions locally, nationally, and internationally.

Personalized infection prevention and control: identifying patients at risk of healthcare-associated infection.

BACKGROUND: Few healthcare-associated infection (HAI) studies focus on risk of HAI at the point of admission. Understanding this will enable planning and management of care with infection prevention at the heart of the patient journey from the point of admission. AIM: To determine intrinsic characteristics of patients at hospital admission and extrinsic events, during the two years preceding admission, that increase risk of developing HAI. METHODS: An incidence survey of adults within two hospitals in NHS Scotland was undertaken for one year in 2018/19 as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. The primary outcome measure was developing any HAI using recognized case definitions. The cohort was derived from routine hospital episode data and linkage to community dispensed prescribing data. FINDINGS: The risk factors present on admission observed as being the most significant for the acquisition of HAI were: being treated in a teaching hospital, increasing age, comorbidities of cancer, cardiovascular disease, chronic renal failure and diabetes; and emergency admission. Relative risk of developing HAI increased with intensive care unit, high-dependency unit, and surgical specialties, and surgery <30 days before admission and a total length of stay of >30 days in the two years to admission. CONCLUSION: Targeting patients at risk of HAI from the point of admission maximizes the potential for prevention, especially when extrinsic risk factors are known and managed. This study proposes a new approach to infection prevention and control (IPC), identifying those patients at greatest risk of developing a particular type of HAI who might be potential candidates for personalized IPC interventions.

Bed-days and costs associated with the inpatient burden of healthcare-associated infection in the UK.

BACKGROUND: Healthcare-associated infection (HAI) is associated with increased morbidity and mortality resulting in excess costs. AIM: To investigate the impact of all types of HAI on the inpatient cost of HAI using different approaches. METHODS: The incidence, types of HAI, and excess length of stay were estimated using data collected as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. Scottish NHS reference costs were used to estimate unit costs for bed-days. Variable (cash) costs associated with infection prevention and control (IPC) measures and treatment were calculated for each HAI type and overall. The inpatient cost of HAI is presented in terms of bed-days lost, bed-day costs, and cash costs. FINDINGS: In Scotland 58,010 (95% confidence interval: 41,730-74,840) bed-days were estimated to be lost to HAI during 2018/19, costing £46.4 million (19m-129m). The total annual cost in the UK is estimated to be £774 million (328m-2,192m). Bloodstream infection and pneumonia were the most costly HAI types per case. Cash costs are a small proportion of the total cost of HAI, contributing 2.4% of total costs. CONCLUSION: Reliable estimates of the cost burden of HAI management are important for assessing the cost-effectiveness of IPC programmes. This unique study presents robust economic data, demonstrating that HAI remains a burden to the UK NHS and bed-days capture the majority of inpatient costs. These findings can be used to inform the economic evaluation and decision analytic modelling of competing IPC programmes at local and national level.

Penile cancer and the HPV attributable fraction in Scotland; A retrospective cohort study.

BACKGROUND: Penile cancer (PeC) is a highly morbid disease which is rising in certain settings including Scotland. A component of PeC is associated with Human Papillomavirus (HPV) although its influence on clinical outcomes is debatable as is whether the fraction attributable to HPV is increasing. METHODS: A total of 122 archived tissue samples derived from patients diagnosed with PeC between 2006-2015 were collated and tested for HPV DNA using molecular PCR. HPV positivity was determined for the overall population and by calendar year of diagnosis to determine any temporal trends. The influence of age, deprivation, smoking, tumour stage and tumour grade on likelihood of HPV positivity was determined by logistic regression. In addition, the influence of HPV status and the other clinical and demographics variables on all-cause death and death from PeC was assessed. RESULTS: HPV was detected in 43 % (95 % CI: 34-52) of penile cancers and the majority of infections were HPV 16. The HPV component of PeC did not increase over the time period (p for linear trend - 0.226). No demographic or clinical variables were associated with HPV positivity neither was HPV status associated with improved all-cause or cancer-specific survival during the follow up period. CONCLUSION: The rise in PeC in Scotland may not be attributable to a rise in HPV-associated cancer; this is consistent with oropharyngeal cancer (OPC) in the UK where there is an increase in both HPV positive and negative cancer. This work calls for a larger multi centre study to enable further detailed investigation into the implications of HPV infection in PeC.

Cost burden of Clostridioides difficile infection to the health service: A retrospective cohort study in Scotland.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with high healthcare demands and related costs. AIM: To evaluate the healthcare and economic burden of CDI in hospitalized patients with community- (HOCA-CDI) or hospital-associated CDI (HOHA-CDI) in the National Health Service in Scotland. METHODS: A retrospective cohort study was conducted, examining data between August 2010 and July 2013 from four patient-level Scottish datasets, linked to death data. Data examined included prior antimicrobial prescriptions in the community, hospitalizations, length of stay and mortality. Each CDI case was matched to three hospital-based controls on the basis of age, gender, hospital and date of admission. Descriptive economic evaluations were based on bed-day costs for different types of wards. FINDINGS: Overall, 3304 CDI cases were included in the study. CDI was associated with additional median lengths of stay of 7.2 days for HOCA-CDI and 12.0 days for HOHA-CDI compared with their respective, matched controls. The 30-day mortality rate was 6.8% for HOCA-CDI and 12.4% for HOHA-CDI. Overall, recurrence within 90 days of the first CDI episode occurred in 373/2740 (13.6%) survivors. The median additional expenditure for each initial CDI case compared with matched controls was £1713. In the 6 months after the index hospitalization, the cost associated with a CDI case was £5126 higher than for controls. CONCLUSION: Using routinely collected national data, we demonstrated the substantial burden of CDI on healthcare services, including lengthy hospital stays and readmissions, which increased the costs of managing patients with CDI compared with matched controls.

Droplet digital PCR quantification suggests that higher viral load correlates with improved survival in HPV-positive oropharyngeal tumours.

BACKGROUND: Although HPV-positive oropharyngeal cancer (OPC) patients have improved prognosis compared to HPV negative patients; there remains an HPV-positive group who have poor outcomes. Biomarkers to stratify discrete patient outcomes are thus desirable. Our objective was to analyse viral load (VL) by droplet digital PCR (ddPCR), in HPV-positive patients with OPC on whom clinical outcome data were available. METHODS: In a cohort of patients that had previously tested HPV positive via conventional PCR, VL was determined using ddPCR assays for HPV16 L1 and E6 genes. VL was classed as "medium/high" if more than 5.57 copies or 8.68 copies of the HPV 16 L1 or E6 gene were detected respectively. Effect of VL on overall survival and hazard of death & disease progression was performed with adjustments made for sex, age, deprivation, smoking, alcohol consumption and stage. RESULTS: L1 VL ranged from 0.0014-304 gene copies per cell with a mean of 30.9; comparatively E6 VL ranged from 0.0012-356 copies per cell with a mean of 37.9. Univariate analysis showed those with a medium/high VL had a lower hazard of death; this was significant for L1 (p = 0.02) but not for E6 (p = 0.67). The ratio of E6 to L1 deviated from n = 1 in most samples but had no influence on clinical outcomes. CONCLUSIONS: HPV viral load may be informative for the further stratification of clinical outcomes in HPV positive OPC patients.

A Prospective Cohort Study of Human Papillomavirus-Driven Oropharyngeal Cancers: Implications for Prognosis and Immunisation.

AIMS: Oropharyngeal cancer (OPC) is increasing on a global scale, including the component driven by high-risk human papillomavirus (HR-HPV); contemporary data that provides insight into the prognosis of this disease in addition to the fraction attributable to HR-HPV are essential to inform primary and secondary disease management strategies. MATERIALS AND METHODS: A population-based cohort of 235 patients diagnosed with OPC between 2013 and 2015 in Scotland was assessed for HPV status using molecular genotyping. Associations between HR-HPV status and key clinical and demographic variables were estimated using the Pearson chi-squared test. Rates of overall survival and progression-free survival were estimated and visualised using Kaplan-Meier curves. RESULTS: HPV DNA (largely HPV 16) was identified in 60% of cases. After adjustment for age, gender, deprivation, smoking, alcohol consumption and tumour stage, patients with HR-HPV-positive OPC had an 89% reduction in the risk of death (hazard ratio = 0.11, 95% confidence interval 0.05-0.25) and an 85% reduction in the risk of disease progression (hazard ratio = 0.15, 95% confidence interval 0.07-0.30). HPV positivity was not associated with age, deprivation or smoking status, whereas those who reported excess alcohol consumption were less likely to be positive for HR-HPV. CONCLUSIONS: The prevalence of HR-HPV-associated OPC is high in Scotland and strongly associated with dramatically improved clinical outcomes, including survival. Demographic/behavioural variables did not reliably predict HPV positivity in this cohort, which underlines the importance of laboratory confirmation. Finally, the dominance of HPV 16 in OPC indicates the significant impact of prophylactic immunisation on this disease.

Residual effect of community antimicrobial exposure on risk of hospital onset healthcare-associated Clostridioides difficile infection: a case-control study using national linked data.

BACKGROUND: Associations between antimicrobial exposure in the community and community-associated Clostridioides difficile infection (CA-CDI) are well documented but associations with healthcare-associated CDI (HA-CDI) are less clear. This study estimates the association between antimicrobial prescribing in the community and HA-CDI. METHODS: A matched case-control study was conducted by linking three national patient level datasets covering CDI cases, community prescriptions and hospitalizations. All validated cases of HA-CDI (August 2010 to July 2013) were extracted and up to three hospital-based controls were matched to each case on the basis of gender, age, hospital and date of admission. Conditional logistic regression was applied to estimate the association between antimicrobial prescribing in the community and HA-CDI. A sensitivity analysis was conducted to consider the impact of unmeasured hospital antimicrobial prescribing. RESULTS: Nine-hundred and thirty unique cases of HA-CDI with onset in hospital and no hospital discharge in the 12 weeks prior to index admission were linked with 1810 matched controls. Individuals with prior prescription of any antimicrobial in the community had an odds ratio (OR) = 1.41 (95% confidence interval (CI) 1.13-1.75) for HA-CDI compared with those without. Individuals exposed to high-risk antimicrobials (cephalosporins, clindamycin, co-amoxiclav or fluoroquinolones) had an OR = 1.86 (95% CI: 1.33-2.59). After accounting for the likely impact of unmeasured hospital prescribing, the community exposure, particulary to high-risk antimicrobials, was still associated with elevated HA-CDI risk. CONCLUSIONS: Community antimicrobial exposure is an independent risk factor for HA-CDI and should be considered as part of the risk assessment of patients developing diarrhoea in hospital.

Enhancing dysphonia clinic consultations through a focus on patients' expectations: streamlining and validation of a new tool ('ACaPELa-R' questionnaire).

OBJECTIVE: The Assessing and Caring for Patients' Expectations in Laryngology ('ACaPELa') questionnaire was developed to guide laryngology clinic consultations. This study aimed to audit its use, revise it depending on outcomes and validate it. METHODS: The questionnaire was completed by all new patients attending a laryngology clinic over one year. The questionnaire was refined and validated in a new cohort of patients over a six-month period. RESULTS: Thirty-seven of 242 patients (15.3 per cent) incorrectly gave the same ranking to more than one question. Questions with similar content were collapsed to cover broader themes, and an outcome question was added, resulting in the five-item Assessing and Caring for Patients' Expectations in Laryngology - Revised ('ACaPELa-R') questionnaire. Using this revised questionnaire, there was a significant reduction in the number of same-ranked questions (4.4 vs 15.3 per cent; p = 0.003) and high patient satisfaction post-consultation (95.7 per cent). CONCLUSION: The Assessing and Caring for Patients' Expectations in Laryngology - Revised questionnaire makes patients' rank ordering of questions easier. It can be used to inform how different topics should be approached during the consultation and utilised for clinician self-audit.

Multi-drug resistant Escherichia coli in diarrhoeagenic foals: Pulsotyping, phylotyping, serotyping, antibiotic resistance and virulence profiling.

Extraintestinal pathogenic E. coli (ExPEC) possess the ability to cause extraintestinal infections such as urinary tract infections, neonatal meningitis and sepsis. While information is readily available describing pathogenic E. coli populations in food-producing animals, studies in companion/sports animals such as horses are limited. In addition, many antimicrobial agents used in the treatment of equine infections are also utilised in human medicine, potentially contributing to the spread of antibiotic resistance determinants among pathogenic strains. The aim of this study was to phenotypically and genotypically characterise the multidrug resistance and virulence associated with 83 equine E. coli isolates recovered from foals with diarrhoeal disease. Serotyping was performed by both PCR and sequencing. Antibiotic resistance was assessed by disc diffusion. Phylogenetic groups, virulence genes, antibiotic resistance genes and integrons were determined by PCR. Thirty-nine (46%) of the isolates were classified as ExPEC and hence considered to be potentially pathogenic to humans and animals. Identified serogroups O1, O19a, O40, O101 and O153 are among previously reported human clinical ExPEC isolates. Over a quarter of the E. coli were assigned to pathogenic phylogroups B2 (6%) and D (23%). Class 1 and class 2 integrons were detected in 85% of E. coli, revealing their potential to transfer MDR to other pathogenic and non-pathogenic bacteria. With 65% of potentially pathogenic isolates harbouring one or more TEM, SHV and CTX-M-2 group ß-lactamases, in addition to the high levels of resistance to fluoroquinolones observed, our findings signal the need for increased attention to companion/sport animal reservoirs as public health threats.

Changes in microvascular density differentiate metabolic health outcomes in monkeys with prior radiation exposure and subsequent skeletal muscle ECM remodeling.

Radiation exposure accelerates the onset of age-related diseases such as diabetes, cardiovascular disease, and neoplasia and, thus, lends insight into in vivo mechanisms common to these disorders. Fibrosis and extracellular matrix (ECM) remodeling, which occur with aging and overnutrition and following irradiation, are risk factors for development of type 2 diabetes mellitus. We previously demonstrated an increased incidence of skeletal muscle insulin resistance and type 2 diabetes mellitus in monkeys that had been exposed to whole body irradiation 5-9 yr prior. We hypothesized that irradiation-induced fibrosis alters muscle architecture, predisposing irradiated animals to insulin resistance and overt diabetes. Rhesus macaques (Macaca mulatta, n = 7-8/group) grouped as nonirradiated age-matched controls (Non-Rad-CTL), irradiated nondiabetic monkeys (Rad-CTL), and irradiated monkeys that subsequently developed diabetes (Rad-DM) were compared. Prior radiation exposure resulted in persistent skeletal muscle ECM changes, including a relative overabundance of collagen IV and a trend toward increased transforming growth factor-ß1. Preservation of microvascular markers differentiated the irradiated diabetic and nondiabetic groups. Microvascular density and plasma nitrate and heat shock protein 90 levels were lower in Rad-DM than Rad-CTL. These results are consistent with a protective effect of abundant microvasculature in maintaining glycemic control within radiation-induced fibrotic muscle.

Reduced Intestinal Motility, Mucosal Barrier Function, and Inflammation in Aged Monkeys.

OBJECTIVE: We aimed to examine the general health and intestinal physiology of young and old non-human primates with comparable life histories and dietary environments. DESIGN: Vervet monkeys (Chlorcebus aethiops sabaeus) in stable and comparable social and nutritional environments were selected for evaluation. Health phenotype, circulating cytokines and biomarkers of microbial translocation (MT) were measured (n=26-44). Subsets of monkeys additionally had their intestinal motility, intestinal permeability, and fecal microbiomes characterized. These outcomes document age-related intestinal changes present in the absence of nutritional stressors, which are all known to affect gastrointestinal motility, microbiome, and MT. RESULTS: We found that old monkeys have greater systemic inflammation and poor intestinal barrier function as compared to young monkeys. Old monkeys have dramatically reduced intestinal motility, and all changes in motility and MT are present without large differences in fecal microbiomes. CONCLUSION: We conclude that deteriorating intestinal function is a feature of normal aging and could represent the source of inflammatory burden yet to be explained by disease or diet in normal aging human primate populations. Intestinal changes were seen independent of dietary influences and aging within a consistent environment appears to avoid major microbiome shifts. Our data suggests interventions to promote intestinal motility and mucosal barrier function have the potential to support better health with aging.

Reduction in colposcopy workload and associated clinical activity following human papillomavirus (HPV) catch-up vaccination programme in Scotland: an ecological study.

OBJECTIVE: To measure patterns of clinical activity at colposcopy before and after vaccinated women entered the Scottish Cervical Screening Programme (SCSP). DESIGN: Population-based observational study using nationally collected data. SETTING: Scottish colposcopy clinics. SAMPLE: All women with a date of birth on or after 1 January 1985 who attended colposcopy in Scotland between 2008 and 2014. METHODS: Routinely collected data from the Scottish National Colposcopy Clinical Information Audit System (NCCIAS) were extracted, including: referral criteria, referral cervical cytology, colposcopic findings, clinical procedures, and histology results. Analysis was restricted to those referred to colposcopy at age 20 or 21 years. MAIN OUTCOME MEASURES: Referral criteria, positive predictive value of colposcopy, default rates, and rates of cervical biopsies and treatments. RESULTS: A total of 7372 women referred for colposcopy at age 20 or 21 years were identified. There was a downward trend in the proportion of those referred with abnormal cytology (2008/9, 91.0%; 2013/14, 90.3%; linear trend P = 0.03). Women were less likely to have diagnostic or therapeutic interventions. The proportion with no biopsy (2008/9, 19.5%; 2013/14, 26.9%; linear trend P < 0.0001) and no treatment (2008/9, 74.9%; 2013/14, 91.8%; linear trend P < 0.0001) increased over the period of observation. CONCLUSIONS: A reduction in clinical activity related to abnormal screening referrals is likely to be associated with the human papillomavirus (HPV) catch-up immunisation programme. Referral criteria and the service provision of colposcopy needs to be planned carefully, taking account of the increasing number of women who have been immunised against HPV that will be entering cervical screening programmes worldwide. TWEETABLE ABSTRACT: Colposcopy referral criteria and service planning need attention following HPV immunisation programme.

The impact of human papillomavirus type on colposcopy performance in women offered HPV immunisation in a catch-up vaccine programme: a two-centre observational study.

OBJECTIVE: To determine whether human papillomavirus (HPV) immunisation has affected the prevalence of HPV genotypes and colposcopic features of cervical intraepithelial neoplasia (CIN) in young women referred for colposcopy. DESIGN: A two-centre observational study including vaccinated and unvaccinated women. SETTING: Colposcopy clinics serving two health regions in Scotland, UK. POPULATION: A total of 361 women aged 20-25 years attending colposcopy following an abnormal cervical cytology result at routine cervical screening. METHODS: Cervical samples were obtained from women for HPV DNA genotyping and mRNA E6/E7 expression of HPV 16, 18, 31, 33, and 45. Demographic data, cytology, and histology results and colposcopic features were recorded. Chi-square analysis was conducted to identify associations between vaccine status, HPV genotypes, and colposcopic features. MAIN OUTCOME MEASURES: Colposcopic features, HPV genotypes, mRNA expression, and cervical histology. RESULTS: The prevalence of HPV 16 was significantly lower in the vaccinated group (8.6%) compared with the unvaccinated group (46.7%) (P = 0.001). The number of cases of CIN2+ was significantly lower in women who had been vaccinated (P = 0.006). The HPV vaccine did not have a statistically significant effect on commonly recognised colposcopic features, but there was a slight reduction in the positive predictive value (PPV) of colposcopy for CIN2+, from 74% (unvaccinated) to 66.7% (vaccinated). CONCLUSIONS: In this group of young women with abnormal cytology referred to colposcopy, HPV vaccination via a catch-up programme reduced the prevalence of CIN2+ and HPV 16 infection. The reduced PPV of colposcopy for the detection of CIN2+ in women who have been vaccinated is at the lower acceptable level of the UK national cervical screening programme guidelines. TWEETABLE ABSTRACT: Reduction of hrHPV positivity and CIN in immunised women consistent with lower PPV of colposcopy for CIN2+.

Impact of partial bivalent HPV vaccination on vaccine-type infection: a population-based analysis.

BACKGROUND: Data on the effectiveness of one dose of HPV vaccine are lacking, particularly in population-based settings. Data from a national HPV immunisation catch-up programme of 14-18-year-old girls were used to assess the effectiveness of<3 doses of the bivalent vaccine on vaccine-type and cross-reactive-type HPV infection. METHODS: Cervical samples from women attending for their first cervical smear, which had been genotyped for HPV as part of a longitudinal HPV surveillance programme were linked to immunisation records to establish the number of vaccine doses (0, 1, 2 and 3) administered. Vaccine effectiveness (VE) adjusted for deprivation and age at first dose, was assessed for prevalent HPV 16/18 and HPV 31/33/45 infection. RESULTS: VE for prevalent HPV 16/18 infection associated with 1, 2 and 3 doses was 48.2% (95% CI 16.8, 68.9), 54.8% (95% CI 30.7, 70.8) and 72.8% (95% CI 62.8, 80.3). Equivalent VE for prevalent HPV 31/33/45 infection was -1.62% (95% CI -85.1, 45.3), 48.3% (95% CI 7.6, 71.8) and 55.2% (95% CI 32.6, 70.2). CONCLUSIONS: Consistent with recent aggregated trial data, we demonstrate the potential effectiveness of even one dose of HPV vaccine on vaccine-type infection. Given that these women were immunised as part of a catch-up campaign, the VE observed in this study is likely to be an underestimate of what will occur in girls vaccinated at younger ages. Further population-based studies which look at the clinical efficacy of one-dose schedules are warranted.

HPV immunisation and cervical screening--confirmation of changed performance of cytology as a screening test in immunised women: a retrospective population-based cohort study.

BACKGROUND: To document the effect of bivalent HPV immunisation on cervical cytology as a screening test and assess the implications of any change, using a retrospective analysis of routinely collected data from the Scottish Cervical Screening Programme (SCSP). METHODS: Data were extracted from the Scottish Cervical Call Recall System (SCCRS), the Scottish Population Register and the Scottish Index of Multiple Deprivation. A total of 95 876 cytology records with 2226 linked histology records from women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. The performance of cervical cytology as a screening test was evaluated using the key performance indicators used routinely in the English and Scottish Cervical Screening Programmes (NHSCSP and SCSP), and related to vaccination status. RESULTS: Significant reductions in positive predictive value (16%) and abnormal predictive value (63%) for CIN2+ and the mean colposcopy score (18%) were observed. A significant increase (38%) in the number of women who had to be referred to colposcopy to detect one case of CIN2+ was shown. The negative predictive value of negative- or low-grade cytology for CIN2+ increased significantly (12%). Sensitivity and specificity, as used by the UK cervical screening programmes, were maintained. CONCLUSIONS: The lower incidence of disease in vaccinated women alters the key performance indicators of cervical cytology used to monitor the quality of the screening programme. These findings have implications for screening, colposcopy referral criteria, colposcopy practice and histology reporting.

HPV immunisation and increased uptake of cervical screening in Scottish women; observational study of routinely collected national data.

BACKGROUND: To measure the uptake of first invitation to cervical screening by vaccine status in a population-based cohort offered HPV immunisation in a national catch-up campaign. METHODS: A retrospective observational study of routinely collected data from the Scottish Cervical Screening Programme. Data were extracted and linked from the Scottish Cervical Call Recall System, the Scottish Population Register and the Scottish Index of Multiple Deprivation. Records from 201 023 women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. Attendance for screening was within 12 months of the first invitation at age 20 years. RESULTS: There was a significant decline in overall attendance from the 1988 cohort to the 1993 cohort with the adjusted attendance ratio of the 1988 cohort being 1.49 times (95% CI 1.46-1.52) that of the 1993 cohort. Immunisation compensated for this decrease in uptake with unvaccinated individuals having a reduced ratio of attendance compared with those fully vaccinated (RR=0.65, 95% CI 0.64-0.65). Not taking up the opportunity for HPV immunisation was associated with an attendance for screening below the trend line for all women before the availability of HPV immunisation. CONCLUSIONS: HPV immunisation is not associated with the reduced attendance for screening that had been feared. Immunised women in the catch-up cohorts appear to be more motivated to attend than unimmunised women, but this may be a result of a greater awareness of health issues. These results, while reassuring, may not be reproduced in routinely immunised women. Continued monitoring of attendance for the first smear and subsequent routine smears is needed.