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.

Estimation of HPV prevalence in young women in Scotland; monitoring of future vaccine impact.

BACKGROUND: Estimation of pre-immunisation prevalence of HPV and distribution of HPV types is fundamental to understanding the subsequent impact of HPV vaccination. We describe the type specific prevalence of HPV in females aged 20-21 in Scotland who attended or defaulted from cervical screening using three specimen types; from attenders liquid based cytology and from defaulters urine or self-taken swabs. METHODS: Residual liquid based cytology samples (n = 2148), collected from women aged 20-21 attending for their first smear were genotyped for HPV. A sample (n = 709) from women who had defaulted from screening was also made available for HPV testing through the use of postal testing kits (either urine samples (n = 378) or self-taken swabs (n = 331)). Estimates of prevalence weighted by deprivation, and for the postal testing kit, also by reminder status and specimen type were calculated for each HPV type. The distribution of HPV types were compared between specimen types and the occurrence of multiple high-risk infections examined. The influence of demographic factors on high-risk HPV positivity and multiple infections was examined via logistic regression. RESULTS: The prevalence of any HPV in young women aged 20-21 was 32.2% for urine, 39.5% for self-taken swab, and 49.4% for LBC specimens. Infection with vaccine specific types (HPV 16, 18) or those associated with cross-protection (HPV 31, 33, 45, 51) was common. Individuals were more likely to test positive for high-risk HPV if they resided in an area of high deprivation or in a rural area. The overall distribution of HPV types did not vary between defaulters and attenders. Multiple infections occurred in 48.1% of high-risk HPV positive individuals. Excluding vaccine types the most common pairing was HPV 56 and 66. CONCLUSIONS: Understanding of the pre-immunisation prevalence of HPV in young women puts Scotland in a prime position to assess the early effect of vaccination as the first highly vaccinated cohorts of individuals enter the screening programme. Differences in results with different specimen types must be taken into account when monitoring the impact of vaccination programmes.

Effect of HPV assay choice on perceived prevalence in a population-based sample.

Human papillomavirus (HPV) immunization programs clearly have considerable potential to reduce HPV-associated disease; they are also resource-intense; so, it is essential that their effectiveness is determined accurately and in a timely way. Measuring circulating HPV types in a population can provide an early measure of vaccine impact. We assessed the impact of HPV assay on the observed population prevalence of HPV in women who provided samples as part of a National HPV Immunisation Surveillance Exercise. A total of 1145 liquid-based cytology samples, 326 self-taken swabs, and 371 urine samples were tested with a line-blot assay (the Digene reverse hybridization HPV genotyping assay) and a luminex-based assay (the Mulitmetrix HPV genotyping assay). Assay agreement was determined for the different sample types. Positivity (according to assay) was compared at different levels ranging from positive for HPV 16 and/or 18 to positive for any one of the 18 HPV types common to both assays. The luminex assay consistently detected a higher prevalence of HPV--up to 10% for HPV types common to both assays. In addition, disagreement for HPV 16 and/or 18 was observed in around 9% of the overall sample, with an associated κ score of 0.74. These data indicate that assay choice has a significant impact on observed prevalence of HPV, including vaccine types. The impact of any change of assay during longitudinal surveillance programs should thus be taken into account to avoid confounding the assessment of any vaccine-induced changes.

Acceptability and response to a postal survey using self-taken samples for HPV vaccine impact monitoring.

OBJECTIVE: To assess the feasibility and acceptance of a postal survey to measure human papillomavirus (HPV) prevalence and monitor vaccine impact, using self-taken specimens from young women who do not attend their first cervical screening appointment. METHODS: Focus groups informed the survey design identifying factors that would influence acceptability. Postal testing kits were sent to a nationally representative sample of unscreened women. Overall response rate, the influence of different specimen types (urine or vaginal swab) and the receipt of a reminder letter on participation were calculated. Specimens were tested anonymously for HPV. Individual test results were not provided. RESULTS: Of 5500 kits sent, 725 were returned (13.2%). Fifty-two women actively opted out. There was a higher return rate for urine kits (13.7% vs 12%) and from those who received a reminder letter (15.5% vs 12.2%). Response was influenced by deprivation (10.3% in the most deprived quintile vs 16.2% in the least). Overall weighted HPV prevalence was 35.9% (40.0% from swab specimens and 31.9% from urine). CONCLUSIONS: Some women were willing to participate in anonymised postal testing. However, the low uptake means that HPV prevalence results are difficult to interpret for ongoing surveillance. Monitoring HPV vaccine impact outwith the cervical screening programme remains challenging.

A population-based record linkage study of mortality in hepatitis C-diagnosed persons with or without HIV coinfection in Scotland.

Infection with the hepatitis C virus (HCV) is known to increase the risk of death from severe liver disease and, because HCV status is strongly associated with a history of injecting drug use, the effect of a key disease progression cofactor, infection with human immunodeficiency virus (HIV), is of interest. We examined all-cause, liver-related and drug-related mortality and excess risk of death from these causes in a large cohort of HCV-monoinfected and HIV-coinfected persons in Scotland. The study population consisted of 20,163 persons confirmed to be infected with hepatitis C through laboratory testing in Scotland between 1991 and 2005. Records with sufficient identifiers were linked to the General Register Office for Scotland death register to retrieve associated mortality data, and were further linked to a national database of HIV-positive individuals to determine coinfection status. A total of 1715 HCV monoinfected and 305 HIV coinfected persons died of any cause during the follow-up period (mean of 5.4 and 6.4 years, respectively). Significant excess mortality was observed in both HCV monoinfected and HIV coinfected populations from liver-related underlying causes (standardised mortality ratios of 25, 95% CI = 23-27; and 37, 95% CI = 26-52 for the two groups, respectively) and drug-related causes (25, 95% CI = 23-27; 39, 95% CI = 28-53. The risk of death from hepatocellular carcinoma, alcoholic or non-alcoholic liver disease, or from a drug-related cause, was greatly increased compared with the general Scottish population, with the highest standardised mortality ratio observed for hepatocellular carcinoma in the monoinfected group (70, 95% CI = 57-85). This study has revealed considerable excess mortality from liver- and drug-related causes in the Scottish HCV-diagnosed population; these data are crucial to inform on the clinical management, and projected future public health burden, of HCV infection.

Increasing incidence of mumps in Scotland: options for reducing transmission.

BACKGROUND: There has been a dramatic increase in mumps in Scotland since November 2003, with cases primarily in adolescents and young adults. OBJECTIVES: This paper describes mumps epidemiology in Scotland, undertakes a risk assessment and considers option for reducing transmission. RESULTS: Mumps is primarily a risk for the 13-25 year age group, as they have neither been offered two routine doses of measles, mumps and rubella MMR vaccine, nor been exposed to wild virus. Transmission is facilitated by a high degree of social mixing, with enclosed settings (school, universities etc.) being higher risk. On the basis of susceptibility and risk of transmission, three categories of higher (17-20 years), intermediate (21-22; 15-16 years), and low (23-25; 13-14 years) risk were defined, all in higher risk enclosed settings. Herd immunity would be very difficult to achieve, as it would require unrealistically high MMR uptake (an additional 45-80% in 17-20 year olds). A risk management strategy of reducing transmission and decreasing the likelihood of outbreaks was therefore proposed. Action would be targeted at the higher risk group (17-20 years) in higher risk settings. Three options were considered: do nothing; opportunistic immunisation through GPs; a mass campaign. The 'do nothing' option was discounted. The preferred option was to alert GPs to the need to offer MMR vaccine to 17-20 year olds in higher risk settings. The rationale for this was that it had the lowest cost, avoided disruption to services, and primarily that it would reduce the probability of mumps transmission in higher risk settings. CONCLUSIONS: The Chief Medical Officer issued a letter to all health professionals in Scotland encouraging them to offer MMR vaccine to 13-15 year olds, who had not previously received two doses, and particularly those aged 17-20 years in higher risk settings.