Kimberley Kavanagh

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis.

BACKGROUND Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations. METHODS We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure. FINDINGS We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects. INTERPRETATION Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement. FUNDING The Canadian Institutes of Health Research.

Introduction and sustained high coverage of the HPV bivalent vaccine leads to a reduction in prevalence of HPV 16/18 and closely related HPV types

Background:In 2008, a national human papillomavirus (HPV) immunisation programme began in Scotland for 12–13 year old females with a three-year catch-up campaign for those under the age of 18. Since 2008, three-dose uptake of bivalent vaccine in the routine cohort aged 12–13 has exceeded 90% annually, while in the catch-up cohort overall uptake is 66%.Methods:To monitor the impact of HPV immunisation, a programme of national surveillance was established (pre and post introduction) which included yearly sampling and HPV genotyping of women attending for cervical screening at age 20. By linking individual vaccination, screening and HPV testing records, we aim to determine the impact of the immunisation programme on circulating type-specific HPV infection particularly for four outcomes: (i) the vaccine types HPV 16 or 18 (ii) types considered to be associated with cross-protection: HPV 31, 33 or 45; (iii) all other high-risk types and (iv) any HPV.Results:From a total of 4679 samples tested, we demonstrate that three doses (n=1100) of bivalent vaccine are associated with a significant reduction in prevalence of HPV 16 and 18 from 29.8% (95% confidence interval 28.3, 31.3%) to 13.6% (95% confidence interval 11.7, 15.8%). The data also suggest cross-protection against HPV 31, 33 and 45. HPV 51 and 56 emerged as the most prevalent (10.5% and 9.6%, respectively) non-vaccine high-risk types in those vaccinated, but at lower rates than HPV 16 (25.9%) in those unvaccinated.Conclusions:This data demonstrate the positive impact of bivalent vaccination on the prevalence of HPV 16, 18, 31, 33 and 45 in the target population and is encouraging for countries which have achieved high-vaccine uptake.

Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland

Background:In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established.Methods:We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20–21 in 2008–2012.Results:By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58; P<0.0001) for women who received three doses of vaccine compared with unvaccinated women.Conclusions:To our knowledge, this is one of the first studies to show a reduction of low- and high-grade CIN associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake.

Achieving high and equitable coverage of adolescent HPV vaccine in Scotland

Background and methods The national immunisation records of over 220 000 girls offered vaccine in the routine or catch-up programme of the Human papillomavirus (HPV) programme in Scotland were analysed. Descriptive statistics and multilevel modelling were used to determine individual and organisational factors associated with uptake. Age, school year, school denomination, deprivation and, for school-leavers, mode of delivery were explored. Additional aggregate data were used to examine the effect of late uptake of missed doses in the routine vaccination programme. Results School-based delivery initially achieved over 80% uptake of complete courses in routine and catch-up age groups. Within this context of generally high coverage, there was an association between individual level deprivation and lower uptake, and a decline in in-year course completion over time. However, later uptake of missed doses in the following year substantially decreased these effects. There was no influence on uptake of the type of school (non-denominational/denominational). Vaccination of school-leavers in the catch-up campaign had lower coverage, with 50% starting and 30% completing the course in-year. There was no clear advantage of vaccination through general practice or through Board-run clinics in reaching this group. Conclusions School-based vaccination can achieve high and equitable uptake of a multidose vaccine in a routine immunisation programme. Sustained high coverage with HPV vaccine across Scotland provides a stable platform for planning future strategies for cervical screening and understanding the impact of the vaccination at a population level.

Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009-2013

Prevalence was reduced, and early evidence indicates herd immunity.

Nasal Swab Screening for Methicillin-Resistant Staphylococcus aureus—How Well Does It Perform? A Cross-Sectional Study

OBJECTIVE To determine the proportion of methicillin-resistant Staphylococcus aureus (MRSA) detections identified by nasal swabbing using agar culture in comparison with multiple body site testing using agar and nutrient broth culture. DESIGN Cross-sectional study. PATIENTS Adult patients admitted to 36 general specialty wards of 2 large hospitals in Scotland. METHODS Patients were screened for MRSA via multiple body site swabs (nasal, throat, axillary, perineal, and wound/invasive device sites) cultured individually on chromogenic agar and pooled in nutrient broth. Combined results from all sites and cultures provided a gold-standard estimate of true MRSA prevalence. RESULTS This study found that nasal screening performed better than throat, axillary, or perineal screening but at best identified only 66% of true MRSA carriers against the gold standard at an overall prevalence of 2.9%. Axillary screening performed least well. Combining nasal and perineal swabs gave the best 2-site combination (82%). When combined with realistic screening compliance rates of 80%-90%, nasal swabbing alone probably detects just over half of true colonization in practice. Swabbing of clinically relevant sites (wounds, indwelling devices, etc) is important for a small but high-prevalence group. CONCLUSIONS Nasal swabbing is the standard method in many locations for MRSA screening. Its diagnostic efficiency in practice appears to be limited, however, and the resource implications of multiple body site screening have to be balanced against a potential clinical benefit whose magnitude and nature remains unclear.

Changes in the prevalence of human papillomavirus following a national bivalent human papillomavirus vaccination programme in Scotland: a 7-year cross-sectional study

BACKGROUND On Sept 1, 2008, Scotland launched routine vaccination for human papillomavirus (HPV) types 16 and 18, targeted at 12-13-year-old girls, of whom 92·4% were fully vaccinated in 2008-09. In this study, we report on vaccine effectiveness of the bivalent vaccine in these vaccinated women who attended for routine cervical screening at age 20-21 years. METHODS In this 7-year cross-sectional study (covering birth cohorts 1988-1995), we sampled approximately 1000 samples per year from those attending cervical screening at age 20-21 years and tested each for HPV. By linkage to vaccination records we ascertained prevalence by birth cohort and vaccination status. Estimates of vaccine effectiveness for HPV types 16 and 18, HPV types 31, 33, and 45, other high-risk types, and any HPV were calculated using logistic regression. FINDINGS In total, 8584 samples were HPV genotyped. Prevalence of HPV types 16 and 18 reduced substantially from 30·0% (95% CI 26·9-33·1) in the 1988 cohort to 4·5% (3·5-5·7) in the 1995 cohort, giving a vaccine effectiveness of 89·1% (85·1-92·3) for those vaccinated at age 12-13 years. All cross-protective types showed significant vaccine effectiveness (HPV type 31, 93·8% [95% CI 83·8-98·5]; HPV type 33, 79·1% [64·2-89·0]; HPV type 45, 82·6% [61·5-93·9]). Unvaccinated individuals born in 1995 had a reduced odds of HPV types 16 and 18 infection compared with those born in 1988 (adjusted odds ratio 0·13 [95% CI 0·06-0·28]) and reduced odds of HPV types 31, 33, and 45 (odds ratio 0·45 [0·23-0·89]). INTERPRETATION Bivalent vaccination has led to a startling reduction in vaccine and cross-protective HPV types 7 years after vaccination. There is also evidence of herd protection against the vaccine-specific and cross-protective types in unvaccinated individuals born in 1995. These findings should be considered in cost-effectiveness models informing vaccine choice and models to shape the future of cervical screening programmes. FUNDING Scottish Government and Chief Scientists Office.

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.

The Burden of HPV-Associated Anogenital Cancers

The epidemiology of anogenital cancers is under going substantial change. Cervical cancer remains a major public health concern, particular in resource-limited settings. Cancers of the anus, penis, vagina and vulva are relatively uncommon cancers, but may be increasing in incidence. The change in occurrence of anogenital cancers may be due to increasing HPV transmission secondary to changes in sexual behaviour. Screening programmes and the HPV vaccine offer optimism that anogenital cancers can be prevented. This article reviews the epidemiology of anogenital cancers with a focus on Scottish data.

Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes

After introduction of vaccination, some prevalences of nonvaccine types changed, without clear evidence for type replacement.