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.

Impact of an influenza information pamphlet on vaccination uptake among Polish pupils in Edinburgh, Scotland and the role of social media in parental decision making.

BACKGROUND: In Edinburgh, Scotland, lower influenza vaccine uptake has been observed in primary school children in the Polish community. METHODS: To address this disparity, the Polish-language version of the NHS Health Scotland influenza information pamphlet was updated and distributed in 2018 to all identified Polish pupils attending three pilot schools. The impact of the revised pamphlet was evaluated by examining changes in vaccine uptake in these schools as compared to a control group of schools, and a questionnaire was issued to all Polish parents in the pilot schools to explore their opinions of the pamphlet and preferred sources of immunisation information. RESULTS: On average uptake was 7.4% (95% CI 1.0-13.8%, p < 0.05) higher in the three pilot schools in which the Polish-language pamphlet was distributed (28.7%) than control schools (21.3%). The questionnaire feedback was that 37.3% of respondents felt better-informed about the influenza vaccine following the pamphlet. The respondents reported that the most important information source in deciding whether to vaccinate is previous experience. Healthcare professionals were ranked lower in importance when making a decision. Parents, who refused consent (n = 65) were more likely to source information from social media, friends and family, and Polish websites compared with those who consented (n = 45). CONCLUSIONS: These findings suggest that issuing new Polish health literature was associated with a large increase in consent form return rate and a modest increase in uptake of the influenza vaccine by Polish pupils in the pilot schools. Social media and Polish websites were found to have a greater influence over Polish parents' decision to immunise than UK healthcare staff and health authority information. Intensive effort is required to encourage parents towards information sources where more accurate pro-vaccination messages can be promulgated by national health services and independent expert groups. The role of social media for migrant communities requires careful consideration, especially for vaccine programmes not delivered in their country of birth.

Comparing vaccination hesitancy in Polish migrant parents who accept or refuse nasal flu vaccination for their children.

This study investigates the background to low uptake of nasal influenza vaccination in Polish pupils in Edinburgh, Scotland. In autumn 2018, one week after their child's nasal flu vaccination sessions, 365 Polish parents were sent a questionnaire exploring influences on their vaccination choices. The questionnaire included a series of 10 vaccine hesitancy questions recommended by the WHO SAGE Working Group on Vaccine Hesitancy. 128 questionnaires were returned representing 43.4% of vaccinated, 41.9% of refusing and 23.8% of non-consent form returning parents. Responses highlighted concerns about side effects, new vaccines and the accuracy of professional advice and information sources. There was complacency expressed about vaccination against diseases that are not common any more. Vaccine refusers were consistently more negative about all aspects vaccination and more likely to answer 'don't know'. Almost half of refusers were uncertain about the quality of health information offered to them. Polish migrants in Scotland come with their beliefs about vaccination and modify these as they acculturate to the UK system. They also continue to be influenced by developments and opinions, norms and values from their home country, as well as diaspora media. We have highlighted issues of concern among Polish migrants as a group and gained additional insights by comparing responses of parents who have refused or accepted vaccination. These insights can inform and target messages and strategies to build confidence and encourage immunisation, which should lead to improved vaccine uptake among ethnic population groups.

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.

A qualitative study of vaccination behaviour amongst female Polish migrants in Edinburgh, Scotland.

Vaccine hesitancy is increasing and failure to vaccinate is well-recognised in Europe as a contributing factor to outbreaks of infectious diseases. In Lothian and Scotland, low vaccine uptake has been seen in migrants - notably in the Polish group who have arrived since 2004. The recent Vaccine Confidence in European Union report highlights a concerning recent decline in vaccine confidence in Poland. We held three focus groups containing 13 Polish women about the childhood vaccination programme in Lothian, with specific focus on influenza and Human Papillomavirus vaccinations. Key emergent themes were: trust in the national vaccination policy, trust in the vaccination providers (health professionals), trust in the individual vaccines, balancing the risk of disease, and language and communication. Polish norms, beliefs and behaviours shape how Polish migrants navigate the UK health system and its vaccination programme. While not confident in the Scottish primary care model and its generalist practitioners, the participants liked the ethos of informed consent in Scotland and compared this favourably with the compulsory vaccination policy in Poland. There was a belief that vaccines in Scotland were of higher quality than Poland and with fewer adverse effects. Respondents reported returning to Poland for specialist clinical appointments and diagnostic testing. They regularly access Polish clinical expertise and their opinions about health are influenced by Polish friends and family. They say they have difficulty finding official UK Government and health authority vaccination material and often access Polish media, online resources and information. They are familiar with anti-vaccination activities in Poland. Consequently, there are important unmet information needs for this group of parents who may not be making truly informed choices about vaccination. This requires further investigation especially as migration continues and declining immunisation uptake is reported in many countries across Europe.

Evidence of decreased HPV vaccine acceptance in Polish communities within Scotland.

Human papillomavirus (HPV) vaccines are currently utilised globally in national immunisation programmes. Many new European migrants have settled in the United Kingdom (UK) since the 2004 European Union expansion with approximately 91,000 Polish people resident in Scotland. Following anecdotal reports from several NHS Boards within Scotland of lower HPV vaccine uptake in Polish communities compared with other ethnic minorities, an extract containing both forename and surname, was taken from the Scottish Immunisation Recall System (SIRS) for all girls in S2 and S3 in school years 2014/15 to 2016/17. We then used the OnoMap algorithm software to derive ethnicity. OnoMap identified between 289 and 321 age-eligible girls as Polish with significant disparity noted for completed HPV vaccine uptake between UK (87.2-89.8%) and Polish ethnicities (69.7-77.2%) (P < 0.01). Preliminary discussions with Polish families suggest that vaccine programme differences, trust in medical/healthcare practitioners, and cultural influences may be important drivers of acceptance.

Low uptake of nasal influenza vaccine in Polish and other ethnic minority children in Edinburgh, Scotland.

Failure to vaccinate is well-recognised in Europe as a contributing factor to outbreaks of infectious diseases. Low immunisation rates are often associated with religious, social and ethnic minorities, including refugees or migrant groups. Polish people form Scotland's newest and largest migrant group. They have moved to Scotland since 2004, joining established ethnic minorities from China, the Indian subcontinent and Africa. Scotland has had a seasonal influenza nasal vaccination programme for all primary school children since 2013. We investigated three primary schools in Edinburgh, which had reported low influenza vaccination uptake rates in 2016 and 2017 and found that these schools contained many pupils from ethnic minorities, the majority of whom were Polish. Pupils were categorized as one of three ethnic groupings: White British, Polish and Other Identified Ethnic Minority (OIEM). We ascertained ethnicity using NHS and Education Department information sources and name recognition. We examined vaccine acceptance, declination and non-return of consent forms. In 2017, nasal influenza vaccine uptake was 70.7% (65.2-75.6%, p < 0.001) in White British, 60.9% (53.9-67.6%%, p < 0.001) in other identified ethnic minorities and 25.0% (20.9-29.6%, p > 0.001) in Polish children. White British children were more likely to return completed forms (78.9%) than other groups (OIEM 68.2% and Polish 61.8%). 36.8% of Polish families completed a consent form declining vaccination compared to 6.2% of White British families. These findings demonstrate that significant differences exist in nasal influenza vaccination uptake rates, which have important implications for the trans-national study of vaccine hesitancy. Further qualitative work and an investigation of uptake rates of other childhood immunisations in Polish and other migrant groups is required to assess differences in uptake and behaviours.

HPV vaccine uptake in men who have sex with men in Scotland.

Human papillomavirus (HPV) vaccines are currently utilised globally in national immunisation programmes. In July 2017, a national HPV vaccine programme for men who have sex with men (MSM) was initiated across Scotland with vaccine being offered in the sexual health clinic setting. During the first year of this targeted vaccination programme, there were 5905 individuals who received at least one dose of HPV vaccine, representing 63.7% of eligible MSM attendees in this period. Vaccine uptake was relatively stable across all age groups (range 49.8-55.5%). The vaccination programme appears to have dovetailed well with pre-existing sexual health services and appears to be popular with MSM attending the service. The MSM HPV vaccine programme is a robust adjunct to the national girls programme but gender-neutral immunisation will reduce stigma and inequality in HPV-driven disease.

An outbreak of mumps with genetic strain variation in a highly vaccinated student population in Scotland.

An outbreak of mumps within a student population in Scotland was investigated to assess the effect of previous vaccination on infection and clinical presentation, and any genotypic variation. Of the 341 cases, 79% were aged 18-24. Vaccination status was available for 278 cases of whom 84% had received at least one dose of mumps containing vaccine and 62% had received two. The complication rate was 5·3% (mainly orchitis), and 1·2% were admitted to hospital. Genetic sequencing of mumps virus isolated from cases across Scotland classified 97% of the samples as genotype G. Two distinct clusters of genotype G were identified, one circulating before the outbreak and the other thereafter, suggesting the virus that caused this outbreak was genetically different from the previously circulating virus. Whilst the poor vaccine effectiveness we found may be due to waning immunity over time, a contributing factor may be that the current mumps vaccine is less effective against some genotypes. Although the general benefits of the measles-mumps-rubella (MMR) vaccine should continue to be promoted, there may be value in reassessing the UK vaccination schedule and the current mumps component of the MMR vaccine.

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.

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.

Adverse event monitoring of the human papillomavirus vaccines in Scotland.

BACKGROUND: Human papillomavirus (HPV) vaccines are currently utilised globally in national immunisation programmes. While evidence from clinical trials and epidemiological studies suggest that the HPV vaccines are both effective and safe, concerns about the safety of the vaccine and scientifically unproven associations with severe adverse events following immunisation have led to dramatic decreases in vaccine uptake in Japan and acceptance issues in other countries. AIM: In Scotland, we utilised hospital admissions data to assess the impact of the HPV immunisation programme on the incidence of 60 diagnoses between 2004 and 2014 in both girls and boys; with boys acting as a comparator group. METHODS: Tabular and graphical outputs of the number of admissions, the incidence and the incidence ratio of 59 diagnoses were created to assess trends before and after the introduction of the HPV vaccine. Data linkage was utilised to investigate further the increase in Bell palsy diagnoses. RESULTS: Fifty-four diagnoses showed no change in incidence following the introduction of the national immunisation programme, and while small increases in incidence were observed for Bell palsy, coeliac disease, ovarian dysfunction, juvenile onset of type 1 diabetes, demyelinating disease and juvenile rheumatoid arthritis, none was statistically significant. CONCLUSIONS: Consistent with previous evidence, we present disaggregate data that reiterate the safety of both HPV vaccines.

Comparison of Legionella longbeachae and Legionella pneumophila cases in Scotland; implications for diagnosis, treatment and public health response.

The reported incidence of Legionnaires' disease caused by Legionella longbeachae has increased since 2008 in Scotland. While microbiological and epidemiological studies have identified exposure to growing media as a risk factor for infection, little is known about the differences regarding disease risk factors, clinical features and outcomes of infection with L. longbeachae when compared with L. pneumophila. A nested case-case study was performed comparing 12 L. longbeachae cases with 25 confirmed L. pneumophila cases. Fewer L. longbeachae infected patients reported being smokers [27% (95% CI 2-52%) vs. 68% (95% CI 50-86%), P = 0.034] but more L. longbeachae patients experienced breathlessness [67% (95% CI 40-94%) vs. 28% (95% CI 10-46%), P = 0.036]. Significantly more L. longbeachae-infected patients received treatment in intensive care [50% (95% CI 22-78%) vs. 12% (95% CI 0-25%), P = 0.036]. However, the differences in diagnostic methods between the two groups may have led to only the most severe cases of L. longbeachae being captured by the surveillance system. No differences were observed in any of the other pre-hospital symptoms assessed. Our results highlight the similarity of Legionnaires' disease caused by L. pneumophila and L. longbeachae, and reinforce the importance of diagnostic tools other than the urinary antigen assays for the detection of non-L. pneumophila species. Unfortunately, cases of community-acquired pneumonia caused by Legionella species will continue to be underdiagnosed unless routine testing criteria changes.

Molecular characterization of Cryptosporidium parvum isolates from human cryptosporidiosis cases in Scotland.

Cryptosporidium parvum (C. parvum) is one of the most prevalent protozoan pathogens responsible for inducing human and animal disease worldwide. In this study, the glycoprotein-60 (gp60) subtyping tool was employed to assess the molecular diversity of C. parvum from human feces throughout Scotland during potential outbreaks. Over a 24-month period, microscopy analysis revealed 1139 positive feces containing Cryptosporidium species with 256 identified by molecular methods specifically as C. parvum. Cryptosporidium parvum was shown to be more prevalent in rural areas of Scotland and subtyping of 87 isolates demonstrated the predominant family as IIa, which occurred in 94% (n=82) of isolates. The IIaA15G1R1 subtype was most common, being isolated from 47% (n=41) of Scottish human cases. Non-IIa strains constituted a total of 5 isolates and included subtypes from the IIc, IId and IIg families. This information contributes significantly to existing knowledge and understanding of C. parvum subtypes in Scotland which is vital in assisting with the management of future local and national outbreaks.

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.

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.