Immune response following a two-dose schedule of bivalent HPV vaccination among girls and boys.

Background: This longitudinal cohort study describes the kinetics in antibody levels after two doses of the bivalent human papillomavirus (HPV) vaccine in girls (birth cohort 2001) vaccinated in the routine Dutch vaccination program at 12 years of age, up to 7.5 years post-vaccination. Also, the antibody response one month post-vaccination of the first cohort of boys (birth cohort 2012, vaccinated at 10 years of age) eligible for HPV vaccination in the Netherlands is presented. Method: Blood samples and questionnaire data were collected of girls and boys. HPV type-specific antibody concentrations (LU/mL) against HPV16/18/31/33/45/52/58 were assessed using a validated virus-like particle (VLP) multiplex immunoassay. For girls, antibody decays over time were modelled using the modified power-law decay model and the exponential decay model. Results: The Geometric Mean Concentrations (GMCs) remained higher for HPV16/18 than for HPV types 31, 33, 45, 52, and 58 among girls up to 7.5 years post-vaccination. The antibody levels of HPV16 and HPV18 reached plateau values of 482 and 159 LU/mL, respectively. Mathematical modelling showed that the half-life values of HPV16/18 were 2.4- to 4.5-fold higher compared with the half-life values of the other HPV types. Among boys (aged 10 years), the GMC for HPV16 was significantly higher than among girls one month post-vaccination (aged 12 years). Conclusion: The GMCs of all HPV types declined over time, although the GMCs of HPV16/18 remained relatively high up to 7.5 years post-vaccination. The GMCs for HPV16/18 among boys were at least equally high as the GMCs among girls at one month post-vaccination. Further follow-up of the cohort of boys is needed to gain knowledge on long-term immune responses of young boys following bivalent HPV vaccination.

Early effect of bivalent human papillomavirus vaccination on cytology outcomes in cervical samples among young women in the Netherlands.

BACKGROUND: The first HPV-vaccine eligible cohorts in the Netherlands will enter the cervical screening program in 2023. However, a substantial number of young women already have had a cervical sample taken before entry into the regular screening program. This study was initiated to explore early effects of HPV vaccination on detection of cytological abnormalities in cervical samples of women younger than the screening age. METHODS: Results of cervical samples were obtained from the Dutch National Pathology Databank (PALGA) and were linked to the women's HPV vaccination status from the national vaccination registry (Praeventis) (N = 42,171). Occurrence of low-grade and high-grade squamous intraepithelial lesions or worse (LSIL and HSIL+) and high-risk HPV positive tests (hrHPV) in the first cervical sample were compared between vaccinated and unvaccinated women by multivariable logistic regression analysis, corrected for age at cervical sampling and age of vaccination (12/13 years, ≥ = 14 years). RESULTS: For fully vaccinated women (three- or two-dose schedule), statistically significant reductions were seen for all outcomes compared to unvaccinated women (hrHPV: adjusted OR, 0.70, 95% CI, 0.63-0.79; LSIL: 0.70, 0.61-0.80; HSIL+: 0.39, 0.30-0.51). CONCLUSIONS: By linking nation-wide registries on pathology and vaccination, we show significant beneficial early effects of HPV-vaccination on LSIL, HSIL+, CIN3/AIS/carcinoma and hrHPV detection in young women upto 24 years of age who have a cervical sample taken before entry into the cervical cancer screening program.

Effects of 2 and 3 Vaccinations With the Bivalent Human Papillomavirus (HPV) Vaccine on the Prevalence and Load of HPV in Clearing and Persistent Infections in Young Women.

BACKGROUND: Human papillomavirus (HPV) viral load (VL) is associated with persistence, which increases cervical cancer risk. The bivalent vaccine protects against oncogenic HPV-16/18 and cross-protects against several nonvaccine types. We examined the effect of 2-dose (2D) and 3-dose (3D) vaccination on HPV prevalence and VL in clearing infections and persistent infections, 6 years and 12 years postvaccination, respectively. METHODS: Vaginal swabs collected from the "HPV Amongst Vaccinated and Non-vaccinated Adolescents" study (HAVANA, 3D-eligible) and HAVANA-2 (2D-eligble) participants were genotyped for HPV with the SPF10-DEIA-LiPA25 system. HPV VL was measured with type-specific quantitative polymerase chain reaction (qPCR). RESULTS: HPV-16, -18, -31, -33, and -45 clearing and/or persistent infection prevalence and HPV-16, -18, and -31 VLs in clearing infections were significantly reduced in 3D-vaccinated women compared to unvaccinated women. Except for HPV-11 and -59 clearing infections, no significant VL differences were observed among vaccinated women, ≤6 and >6 years post-vaccination. Infection numbers were low in 2D-eligible women, with no HPV-16/18 in vaccinated women. No VL differences for the remaining types were found. CONCLUSIONS: 3D vaccination reduces HPV prevalence in clearing infections and persistent infections and decreases HPV VLs in clearing infections, 12 years post-vaccination for vaccine and several nonvaccine types. 2D-eligible women had low infection numbers, with no HPV-16/18 among vaccinated women.

High vaccine effectiveness persists for ten years after HPV16/18 vaccination among young Dutch women.

The current study describes the long-term effectiveness of three-dose HPV16/18 vaccination among Dutch women who were eligible for vaccination during a catch-up campaign and were followed in an observational cohort study. Ten years post vaccination, vaccine effectiveness (VE) was estimated using generalized estimating equation models. VE against persistent infections with vaccine type infections (HPV16/18) was high at 95.8%. For cross protective type persistent infections (HPV31/33/45) this was 64.6%. There were no indications of waning of protection over time. This indicates solid long-term protection is provided by the vaccine and is promising with regard to the future clinical impact.

Approaches to Estimating Clearance Rates for Human Papillomavirus Groupings: A Systematic Review and Real Data Examples.

INTRODUCTION: Approaches to estimating clearance rates, an important metric of human papillomavirus (HPV) clearance, for HPV groupings differ between studies. We aimed to identify the approaches used in the literature for estimating grouped HPV clearance rates. We investigated whether these approaches resulted in different estimations, using data from existing studies. METHODS: In this systematic review, we included articles that reported clearance rates of HPV groupings. We identified approaches to data in the HAVANA cohort, comprising adolescent girls, and the H2M cohort, comprising men who have sex with men. We estimated clearance rates for six HPV groupings (bivalent-, quadrivalent- and nonavalent vaccine-related, and low-risk, high-risk, and any HPV). RESULTS: From 26 articles, we identified 54 theoretically possible approaches to estimating clearance rates. These approaches varied regarding definitions of clearance events and person-time, and prevalence or incidence of infections included in the analysis. Applying the nine most-used approaches to the HAVANA ( n = 1,394) and H2M ( n = 745) cohorts demonstrated strong variation in clearance rate estimates depending on the approach used. For example, for grouped high-risk HPV in the H2M cohort, clearance rates ranged from 52.4 to 120.0 clearances/1000 person-months. Clearance rates also varied in the HAVANA cohort, but differences were less pronounced, ranging from 24.1 to 57.7 clearances/1000 person-months. CONCLUSIONS: Varied approaches from the literature for estimating clearance rates of HPV groupings yielded different clearance rate estimates in our data examples. Estimates also varied between study populations. We advise clear reporting of methodology and urge caution in comparing clearance rates between studies.

Vaccine Effectiveness Following Routine Immunization With Bivalent Human Papillomavirus (HPV) Vaccine: Protection Against Incident Genital HPV Infections From a Reduced-Dosing Schedule.

BACKGROUND: In the Netherlands, the bivalent human papillomavirus (HPV) vaccine has been offered to preadolescent girls via the National Immunization Program in a 2-dose schedule since 2014. The current study estimates vaccine effectiveness (VE) against HPV infections up to 4 years postvaccination among girls eligible for routine 2-dose immunization. METHODS: A cohort study (HAVANA2) was used in which participants annually filled out an online questionnaire and provided a vaginal self-sample for determination of HPV by the SPF10-LiPA25 assay, able to detect 25 HPV types. VE against incident type-specific infections and pooled outcomes was estimated by a Cox proportional hazards model with shared frailty between the HPV types. RESULTS: In total, 2027 girls were included in the study, 1098 (54.2%) of whom were vaccinated with 2 doses. Highest incidence rate was 5.0/1000 person-years (HPV-51) among vaccinated participants and 9.1/1000 person-years (HPV-74) among unvaccinated participants. Adjusted pooled VE was 84.0% (95% confidence interval [CI], 27.0%-96.5%) against incident HPV-16/18 infections and 86.5% (95% CI, 39.5%-97.08%) against cross-protective types HPV-31/33/45. CONCLUSIONS: Four years postvaccination, 2 doses of bivalent HPV vaccine were effective in the prevention of incident HPV-16/18 infections and provided cross-protection to HPV-31/33/45. Our VE estimates rival those from 3-dose schedules, indicating comparable protection by 2-dose schedules.

Population Impact of Girls-Only Human Papillomavirus 16/18 Vaccination in The Netherlands: Cross-Protective and Second-Order Herd Effects.

BACKGROUND: Human papillomavirus (HPV) vaccination programs achieve substantial population-level impact, with effects extending beyond protection of vaccinated individuals. We assessed trends in HPV prevalence up to 8 years postvaccination among men and women in the Netherlands, where bivalent HPV vaccination, targeting HPV types 16/18, has been offered to (pre)adolescent girls since 2009 with moderate vaccination coverage. METHODS: We used data from the PASSYON study, a survey initiated in 2009 (prevaccination) and repeated biennially among 16- to 24-year-old visitors of sexual health centers. We studied genital HPV positivity from 2009 to 2017 among women, heterosexual men, and unvaccinated women using Poisson generalized estimating equation models, adjusted for individual- and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform. RESULTS: A total of 6354 women (64.7% self-reported unvaccinated) and 2414 heterosexual men were included. Percentual declines in vaccine types HPV-16/18 were observed for all women (12.6% per year [95% confidence interval {CI}, 10.6-14.5]), heterosexual men (13.0% per year [95% CI, 8.3-17.5]), and unvaccinated women (5.4% per year [95% CI, 2.9-7.8]). We observed significant declines in HPV-31 (all women and heterosexual men), HPV-45 (all women), and in all high-risk HPV types pooled (all women and heterosexual men). Significant increases were observed for HPV-56 (all women) and HPV-52 (unvaccinated women). CONCLUSIONS: Our results provide evidence for first-order herd effects among heterosexual men against HPV-16/18 and cross-protective types. Additionally, we show second-order herd effects against vaccine types among unvaccinated women. These results are promising regarding population-level and clinical impact of girls-only bivalent HPV vaccination in a country with moderate vaccine uptake.

Changes in HPV Seroprevalence from an Unvaccinated toward a Girls-Only Vaccinated Population in the Netherlands.

BACKGROUND: In the Netherlands, bivalent human papillomavirus (HPV) vaccination was included in the National Immunization Program for 12-year-old girls in 2010 (vaccination coverage, 45%-60%). We examined possible changes in HPV seroprevalence in the HPV-unvaccinated Dutch population aged 0-89 years, comparing prevaccination data with data of approximately 6 years after implementation of national vaccination. METHODS: Serum samples of men and women were used from two cross-sectional population-based serosurveillance studies performed before (2006-07, n = 6,384) and after (2016-17, n = 5,645) implementation of HPV vaccination in the Netherlands. Seven high-risk HPV-specific antibodies (HPV16, 18, 31, 33, 45, 52, and 58) were tested in a virus-like particle-based multiplex immunoassay. RESULTS: Type-specific HPV seroprevalence increased in women between 2006-07 and 2016-17. Also, a higher seroprevalence for at least one type in women >15 years was found in 2016-17 (31.7%) compared with 2006-07 (25.2%). In men, overall HPV seroprevalence remained similar; however, a lower seroprevalence was found for HPV16 in 2016-17 (7.5%) compared with 2006-07 (10.6%). CONCLUSIONS: Our results indicate an increase in high-risk HPV types in women and a rather stable exposure in men. No clear effects of the strategy of girls-only vaccination were observed in men, probably because of the short time after introduction combined with suboptimal coverage. IMPACT: No herd immunity has been observed yet in a population with suboptimal HPV vaccination coverage.

Correction: Effectiveness of a Web-Based Tailored Intervention With Virtual Assistants Promoting the Acceptability of HPV Vaccination Among Mothers of Invited Girls: Randomized Controlled Trial.

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High seroprevalence of multiple high-risk human papillomavirus types among the general population of Bonaire, St. Eustatius and Saba, Caribbean Netherlands.

BACKGROUND: Incidence and mortality of human papillomavirus (HPV)-related cancers differs geographically, with high rates in Caribbean countries. Seroepidemiological data provide information on lifetime cumulative HPV exposure and contributing risk factors, but has not been available yet for Caribbean Netherlands (CN), comprising the islands Bonaire, St. Eustatius and Saba. Therefore, a cross-sectional population-based serosurveillance study was performed in this (recently girls-only HPV-vaccinated) population in 2017. METHODS: Blood samples from participants (n = 1,823, 0-90 years) were tested for seven high-risk (hr)-HPV-specific IgG-antibodies using a VLP-based multiplex-immunoassay. Risk factors for HPV-seropositivity were analysed among persons unvaccinated aged ≥ 15 years who ever had sex (n = 1,080). RESULTS: Among unvaccinated individuals aged ≥ 15 years, overall seropositivity was high (34%), with over half of them being seropositive for ≥ 2 hr-HPV types, and HPV16 and 52 being most prevalent (13%). Seroprevalence was substantial higher in unvaccinated women (51%) than men (18%), predominantly peaking in women aged 20-59 years, and was highest on St. Eustatius (38%). Besides age and sex, sexual risk factors were associated with HPV-seropositivity. CONCLUSIONS: In accordance with the Caribbean region, seroprevalence of multiple hr-HPV types was high in CN. These data corroborate the decision regarding introduction of a sex-neutral HPV-vaccination program and the relevance for considering a population-based cervical cancer screening program.

Persisting Antibody Response 9 Years After Bivalent Human Papillomavirus (HPV) Vaccination in a Cohort of Dutch Women: Immune Response and the Relation to Genital HPV Infections.

The bivalent human papillomavirus (HPV) vaccine is highly effective and induces robust serological responses. Using a Dutch prospective cohort initiated in 2009, including 744 vaccinated and 294 unvaccinated girls (1993-1994) who provide a vaginal self-swab sample, serum sample, and questionnaire yearly, we report a high, persisting antibody response up to 9 years after vaccination for vaccine types HPV-16 or HPV-18. Antibodies against nonvaccine HPV types 31, 33, 45, 52, and 58 were lower but still significantly higher than in unvaccinated individuals. This was also reflected in the seroprevalence. We compared participant characteristics and antibody levels between vaccinated women with and those without HPV infections 1 year before infection (204 incident and 64 persistent infections), but we observed no consistent difference in type-specific antibody levels. Having a high-risk HPV infection was associated with sexual risk behavior and smoking 1 year before infection. Although high antibody levels are necessary for protection, our study suggests that on the individual level other factors such as HPV exposure or antibody avidity could be important.

Long-term HPV-specific immune response after one versus two and three doses of bivalent HPV vaccination in Dutch girls.

BACKGROUND: In view of further reduction of HPV vaccination schedules, gaining more insight into humoral and cellular immune responses after a single HPV vaccine is of great interest. Therefore, these responses were evaluated after different doses of the bivalent (2v) HPV-vaccine in girls. METHODS: Blood was collected yearly up to seven years post-vaccination with one-, two- or three-doses of the 2vHPV vaccine (N = 890). HPV-type-specific IgG and IgA-antibody levels, IgG-isotypes and avidity indexes were measured by a virus-like-particle-based multiplex-immuno-assay for two vaccine and five non-vaccine HPV types. HPV-type-specific memory B-cell numbers- and T-cell cytokine responses were determined in a subpopulation. RESULTS: HPV-type-specific antibody concentrations were significantly lower in one- than in two- and three-dose vaccinated girls but remained stable over seven years. The lower antibody response coincided with reduced HPV-type-specific B- and T-cell responses. There were no differences in both the IgG subtypes and the avidity of the HPV16-specific antibodies between the groups. CONCLUSIONS: One-dose of the 2vHPV vaccine is immunogenic, but results in less B- and T-cell memory and considerable lower antibody responses when compared with more doses. Therefore, at least of some of girls receiving the one-dose of the vaccination might be at higher risk for waning immunity to HPV in the long-term.

Disease burden of varicella versus other vaccine-preventable diseases before introduction of vaccination into the national immunisation programme in the Netherlands.

IntroductionEstimating burden of disease (BoD) is an essential first step in the decision-making process on introducing new vaccines into national immunisation programmes (NIPs). For varicella, a common vaccine-preventable disease, BoD in the Netherlands was unknown.AimTo assess national varicella BoD and compare it to BoD of other vaccine-preventable diseases before their introduction in the NIP.MethodsIn this health estimates reporting study, BoD was expressed in disability-adjusted life years (DALYs) using methodology from the Burden of Communicable Diseases in Europe (BCoDE)-project. As no parameters/disease model for varicella (including herpes zoster) were available in the BCoDE toolkit, incidence, disease progression model and parameters were derived from seroprevalence, healthcare registries and published data. For most other diseases, BoD was estimated with existing BCoDE-parameters, adapted to the Netherlands if needed.ResultsIn 2017, the estimated BoD of varicella in the Netherlands was 1,800 (95% uncertainty interval (UI): 1,800-1,900) DALYs. Herpes zoster mainly contributed to this BoD (1,600 DALYs; 91%), which was generally lower than the BoD of most current NIP diseases in the year before their introduction into the NIP. However, BoD for varicella was higher than for rotavirus gastroenteritis (1,100; 95%UI: 440-2,200 DALYs) and meningococcal B disease (620; 95%UI: 490-770 DALYs), two other potential NIP candidates.ConclusionsWhen considering the introduction of a new vaccine in the NIP, BoD is usually estimated in isolation. The current approach assesses BoD in relation to other vaccine-preventable diseases' BoD, which may help national advisory committees on immunisation and policymakers to set vaccination priorities.

Persistence of immune response following bivalent HPV vaccination: A follow-up study among girls routinely vaccinated with a two-dose schedule.

BACKGROUND: In this cohort study, we examined antibody levels and avidity after a two-dose schedule (0, 6 months) of the bivalent HPV-vaccine in girls routinely vaccinated in the Dutch HPV-vaccination program, up to 2 years following vaccination. METHODS: A blood sample at 7, 12 and 24 months after the first dose and questionnaire data were collected (n = 56). HPV type-specific antibody concentrations (lU/ml) against seven types (HPV16/18/31/33/45/52/58) were assessed using a validated virus-like particles (VLP) multiplex immunoassay. Avidity was tested using a modification of this assay. RESULTS: Seropositivity for vaccine types HPV 16 and 18 was 100% up to month 24, but declined for HPV-types 31/33/45/52/58, although not statistically significant for HPV45. All Geometric Mean Concentrations (GMCs) declined by months 12 and 24, but remained high for HPV16/18. Between month 7 and 12, GMCs declined more for other types. High avidity antibodies were induced up to 24 months for vaccine types (75%, 76-78% and 81-82% at months 7, 12 and 24, respectively), but for other types antibody avidity was 16-29% at month 7, 20-32% at month 12 and 19-32% at month 24. CONCLUSIONS: GMCs declined over time for HPV-types 16/18/31/33/45/52/58, but remained high for vaccine-types HPV16/18 up to 24 months of follow-up. Antibody avidity was >75% for vaccine types but <35% for other HPV-types. Further follow-up of this cohort will provide insight into antibody and avidity kinetics over time.

Cost-effectiveness of screening for chronic hepatitis B and C among migrant populations in a low endemic country.

BACKGROUND: Chronic infection with hepatitis B or C virus (HBV/HCV) can progress to cirrhosis, liver cancer, and even death. In a low endemic country as the Netherlands, migrants are a key risk group and could benefit from early diagnosis and antiviral treatment. We assessed the cost-effectiveness of screening foreign-born migrants for chronic HBV and/or HCV using a societal perspective. METHODS: The cost-effectiveness was evaluated using a Markov model. Estimates on prevalence, screening programme costs, participation and treatment uptake, transition probabilities, healthcare costs, productivity losses and utilities were derived from the literature. The cost per Quality Adjusted Life Year (QALY) gained was estimated and sensitivity analyses were performed. RESULTS: For most migrant groups with an expected high number of chronically infected cases in the Netherlands combined screening is cost-effective, with incremental cost-effectiveness ratios (ICERs) ranging from €4,962/QALY gained for migrants originating from the Former Soviet Union and Vietnam to €9,375/QALY gained for Polish migrants. HBV and HCV screening proved to be cost-effective for migrants from countries with chronic HBV or HCV prevalence of ≥0.41% and ≥0.22%, with ICERs below the Dutch cost-effectiveness reference value of €20,000/QALY gained. Sensitivity analysis showed that treatment costs influenced the ICER for both infections. CONCLUSIONS: For most migrant populations in a low-endemic country offering combined HBV and HCV screening is cost-effective. Implementation of targeted HBV and HCV screening programmes to increase early diagnosis and treatment is important to reduce the burden of chronic hepatitis B and C among migrants.

Systematically Developing a Web-Based Tailored Intervention Promoting HPV-Vaccination Acceptability Among Mothers of Invited Girls Using Intervention Mapping.

Background: Currently, the eHealth field calls for detailed descriptions of theory-based interventions in order to support improved design of such interventions. This article aims to provide a systematic description of the design rationale behind an interactive web-based tailored intervention promoting HPV-vaccination acceptability. Methods: The 6-step Intervention Mapping (IM) protocol was used to describe the design rationale. After the needs assessment in Step 1, intervention objectives were formulated in Step 2. In Step 3, we translated theoretical methods into practical applications, which were integrated into a coherent intervention in Step 4. In Step 5, we anticipated future implementation and adoption, and finally, an evaluation plan was generated in Step 6. Results: Walking through the various steps of IM resulted in a detailed description of the intervention. The needs assessment indicated HPV-vaccination uptake remaining lower than expected. Mothers play the most important role in decision-making about their daughter's immunization. However, they generally feel ambivalent after they made their decisions, and their decisions are based on rather unstable grounds. Therefore, intervention objectives were to improve HPV-vaccination uptake and informed decision-making, and to decrease decisional conflict among mothers of invited girls. Computer-tailoring was chosen as the main method; virtual assistants were chosen as a practical application to deliver interactive tailored feedback. To maximize compatibility with the needs of the target group, a user-centered design strategy by means of focus groups and online experiments was applied. In these, prototypes were tested and sequentially refined. Finally, efficacy, effectiveness, and acceptability of the intervention were tested in a randomized controlled trial. Results showed a significant positive effect of the intervention on informed decision-making, decisional conflict, and nearly all determinants of HPV-vaccination uptake (P < 0.001). Mothers evaluated the intervention as highly positive. Discussion: Using IM led to an innovative effective intervention for promoting HPV-vaccination acceptability. The intervention maps will aid in interpreting the results of our evaluation studies. Moreover, it will ease the comparison of design rationales across interventions, and may provide leads for the development of other eHealth interventions. This paper adds to the plea for systematic reporting of design rationales constituting the process of developing interventions.

Changes in (risk) behavior and HPV knowledge among Dutch girls eligible for HPV vaccination: an observational cohort study.

BACKGROUND: Implementation of human papillomavirus (HPV) vaccination raised concerns that vaccination could lead to riskier sexual behavior. This study explored how possible differences in sexual behavior and HPV knowledge developed over time between HPV-vaccinated and unvaccinated girls. METHODS: A random sample of 19,939 girls (16-17 year olds) eligible for the catch-up HPV vaccination campaign in the Netherlands was invited for a longitudinal study with questionnaires every 6 months over a two-year follow-up period. Possible differences over time between vaccinated and unvaccinated participants were studied using generalized equations estimation (GEE). RESULTS: A total of 2989 girls participated in round one, of which 1574 participated (52.7%) in the final 5th round. Vaccinated girls were more likely to live in more urban areas (OR 1.28, 95%CI 1.10-1.47) and to use alcohol (OR 1.46, 95%CI 1.24-1.70) and contraceptives (OR 1.69, 95%CI 1.45-1.97). Vaccinated and unvaccinated girls showed comparable knowledge on HPV, HPV vaccination, and transmission. Vaccinated girls were more likely to be sexually active (OR 1.19, 95%CI 1.02-1.39), and this difference increased over time (OR for interaction 1.06, 95%CI 1.00-1.12). However, they had a slightly lower number of lifetime sexual partners (mean difference - 0.20, 95%CI -0.41-0.00). Vaccinated girls were less likely to use a condom with a steady partner (aOR 0.71, 95%CI 0.56-0.89). However, the difference between vaccinated and unvaccinated girls with regard to condom use with casual or steady partner(s) did not significantly change over time. CONCLUSION: Overall, we did not find indications that vaccination influenced sexual behavior in girls during 2 years of follow-up. The few differences found may be related to existing disparities in the socio-demographic characteristics of the young population pointing to the importance and improvement of education with regard to safe sex practices. Our findings do not suggest that vaccination status is associated with changes in sexual risk behavior and thus it is unlikely that this might influence the effectiveness of the vaccination program.

Bivalent Vaccine Effectiveness Against Type-Specific HPV Positivity: Evidence for Cross-Protection Against Oncogenic Types Among Dutch STI Clinic Visitors.

Background: Observational postmarketing studies are important to assess vaccine effectiveness (VE). We estimated VE from the bivalent human papillomavirus (HPV) vaccine against HPV positivity of vaccine and nonvaccine types in a high-risk population. Methods: We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional survey in Dutch sexually transmitted infection clinics. Vaginal swabs were analyzed using a polymerase chain reaction-based assay (SPF10-LiPA25) able to detect the 12 high-risk HPV (hrHPV) types 16/18/31/33/35/39/45/51/52/56/58/59. We compared hrHPV positivity between self-reported vaccinated (≥1 dose) and unvaccinated women, and estimated VE by a logistic mixed model. Results: We included 1087 women of which 53% were hrHPV positive and 60% reported to be vaccinated. The adjusted pooled VE against HPV-16/18 was 89.9% (81.7%-94.4%). Moreover, we calculated significant VE against nonvaccine types HPV-45 (91%), HPV-35 (57%), HPV-31 (50%), and HPV-52 (37%). Among women who were offered vaccination 5/6 years ago, we estimated similar VE against HPV-16/18 (92%) and all hrHPV types (35%) compared to women who were offered vaccination <5 years ago (83% and 33%, respectively). Conclusion: We demonstrated high VE of the bivalent vaccine against HPV-16/18 and cross-protection against HPV-45/35/31/52. Protection against HPV-16/18 was sustained up to 6 years postvaccination.

Effectiveness of a Web-Based Tailored Intervention With Virtual Assistants Promoting the Acceptability of HPV Vaccination Among Mothers of Invited Girls: Randomized Controlled Trial.

BACKGROUND: In 2010, the human papillomavirus (HPV) vaccination was introduced in the Dutch National Immunization Program for 12-year-old girls, aiming to reduce the incidence of cervical cancer in women. HPV vaccination uptake turned out to be lower than expected: 61% versus 70%, respectively. Mothers were shown to play the most important role in the immunization decision about this vaccination. They had also expressed their need for interactive personal information about the HPV vaccination over and above the existing universal general information. To improve the effectiveness of the existing education about the HPV vaccination, we systematically developed a Web-based tailored intervention with virtual assistants providing mothers of girls to be invited with tailored feedback on their decision making about the HPV vaccination. OBJECTIVE: The aim of this study was to evaluate the effectiveness of the Web-based tailored intervention for promoting HPV vaccination acceptance by means of a randomized controlled trial (RCT). METHODS: Mothers were recruited via the Dutch vaccination register (Praeventis) (n=36,000) and three Web-based panels (n=2483). Those who gave informed consent (N=8062) were randomly assigned to the control (n=4067) or intervention condition (n=3995). HPV vaccination uptake, as registered by Praeventis once the HPV vaccination round was completed, was used as the primary outcome. Secondary outcomes were differential scores across conditions between baseline (before the provided access to the new tailored intervention) and follow-up (just before the first vaccination) regarding the mothers' degree of informed decision making (IDM), decisional conflict, and critical determinants of HPV vaccination uptake among which are intention, attitude, risk perception, and outcome beliefs. RESULTS: Intention-to-treat analysis (N=8062) showed a significant positive effect of the intervention on IDM, decisional conflict, and nearly all determinants of HPV vaccination uptake (P<.001). No effect was found on uptake (P=.60). This may be attributed to the overall high uptake rates in both conditions. Mothers evaluated the intervention as highly positive, including the website as well as the virtual assistants that were used to deliver the tailored feedback. CONCLUSIONS: This computer-tailored intervention has the potential to improve HPV vaccination acceptability and IDM and to decrease decisional conflict among mothers of invited girls. Implications for future research are discussed. TRIAL REGISTRATION: Trialregister.nl NTR4935; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4935 (Archived by WebCite at http://www.webcitation.org/6srT7l9EM).

Long-term mortality after IPD and bacteremic versus non-bacteremic pneumococcal pneumonia.

BACKGROUND: Short-term mortality after invasive pneumococcal disease (IPD) and pneumococcal pneumonia is high but data on long-term mortality (including the comparison between bacteremic and non-invasive/non-bacteremic pneumococcal pneumonia) within the first years after diagnosis are scarce. METHODS: Adult patients with 'non-pneumonia' IPD and 'invasive pneumonia' (from 2004 to 2012) and with 'bacteremic' vs 'non-invasive/non-bacteremic (NI/NB)' pneumococcal pneumonia (from 2008 to 2012) diagnosed by negative blood culture but a positive urinary antigen test (UAT) were identified in a Dutch hospital. Mortality of patients up to 10years after diagnosis was compared with age- and sex-matched life-expectancy data of the general population. Multivariable Cox regression analysis was used to study predictors for mortality in invasive pneumonia patients and to adjust for confounders comparing mortality between bacteremic and NI/NB/UAT-positive pneumonia patients. RESULTS: Of 228 invasive pneumonia patients 17% died within 30days and in 30-day survivors cumulative long-term mortality at 1 and 5years were 16% and 39% as compared with 3% and 15% in age- and sex-matched persons. High mortality was largely dependent on pre-existent comorbidities. In invasive pneumonia patients who survived the first 30days, age, male gender, chronic cardiovascular disease, malignancy and PCV7 serotype disease were independent predictors for higher long-term mortality. For bacteremic pneumonia patients (n=128) 30-day mortality was 16% and almost similar to 14% in NI/NB/UAT-positive pneumococcal pneumonia patients (n=170). In 30-day survivors of bacteremic pneumonia (n=108, median age 66years), cumulative mortality at 1 and 3years were 13% and 29% as compared with 18% and 40% in NI/NB/UAT-positive pneumococcal pneumonia patients (n=146, median age 67years) without a significant difference in mortality. CONCLUSIONS: Approximately 40% of all patients, who survived the first 30days after presentation with non-pneumonia IPD and pneumococcal pneumonia died within the following 5years. High long-term mortality was largely dependent on pre-existent comorbidity.