Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: A partially-blind randomised placebo-controlled study

In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18–25 years (N = 120) were stratified by CD4⁺ T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix^®; GlaxoSmithKline Vaccines) or placebo (Al[OH]₃) at 0, 1 and 6 months (double-blind). HIV-negative women (N = 30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4⁺ T-cell responses, CD4⁺ T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4⁺ T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4⁺ T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4⁺ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection.     

Immune responses elicited by a fourth dose of the HPV-16/18 AS04-adjuvanted vaccine in previously vaccinated adult women

Background

Vaccines are now available for the prevention of HPV-16/18-related cervical infections and pre-cancers, primarily targeting adolescent girls. Since the risk of HPV exposure potentially persists throughout a woman's sexual life, vaccine-derived immunity should be long-term. The current study, HPV-024 (NCT00546078, http://clinicaltrials.gov), assessed the immune memory in North American women who received three doses of HPV-16/18 AS04-adjuvanted vaccine 7 years earlier in HPV-001 (NCT00689741).

Methods

Women vaccinated in HPV-001 received a 4th-dose of the HPV-16/18 vaccine (024-4DV group, N = 65). Post 4th-dose immune responses were compared with post 1st-dose immune responses in cross-vaccination controls (024-3DV group, N = 50). Reactogenicity was compared between the 4th-dose and the 1st-dose administration.

Results

Pre 4th-dose, 100% of subjects in the 024-4DV group remained seropositive for anti-HPV-16/18 antibodies (ELISA). Compared to pre 4th-dose, GMTs for anti-HPV-16 and anti-HPV-18 antibodies were respectively 9.3-fold and 8.7-fold higher at day 7, and 22.7-fold and 17.2-fold higher at month 1. Compared to post 1st-dose, GMTs for anti-HPV-16 and anti-HPV-18 were respectively 80.5-fold and 205.4-fold higher at day 7, and 11.8-fold and 20.5-fold higher at month 1. Furthermore, 68.2% and 77.3% of women had HPV-16/18 specific memory B-cells, respectively, pre 4th-dose, rising to 100% one month post 4th-dose vaccination. The 4th-dose was generally well tolerated.

Conclusion

A 4th-dose of HPV-16/18 AS04-adjuvanted vaccine triggered a rapid and strong anamnestic response in previously vaccinated women, demonstrating vaccine-induced immune memory.     

Effects of varying antigens and adjuvant systems on the immunogenicity and safety of investigational tetravalent human oncogenic papillomavirus vaccines: Results from two randomized trials

Background

A prophylactic human papillomavirus (HPV) vaccine targeting oncogenic HPV types in addition to HPV-16 and -18 may broaden protection against cervical cancer. Two Phase I/II, randomized, controlled studies were conducted to compare the immunogenicity and safety of investigational tetravalent HPV L1 virus-like particle (VLP) vaccines, containing VLPs from two additional oncogenic genotypes, with the licensed HPV-16/18 AS04-adjuvanted vaccine (control) in healthy 18–25 year-old women.

Methods

In one trial (NCT00231413), subjects received control or one of 6 tetravalent HPV-16/18/31/45 AS04 vaccine formulations at months (M) 0,1,6. In a second trial (NCT00478621), subjects received control or one of 5 tetravalent HPV-16/18/33/58 vaccines formulated with different adjuvant systems (AS04, AS01 or AS02), administered on different schedules (M0,1,6 or M0,3 or M0,6).

Results

One month after the third injection (Month 7), there was a consistent trend for lower anti-HPV-16 and -18 geometric mean antibody titers (GMTs) for tetravalent AS04-adjuvanted vaccines compared with control. GMTs were statistically significantly lower for an HPV-16/18/31/45 AS04 vaccine containing 20/20/10/10 μg VLPs for both anti-HPV-16 and anti-HPV-18 antibodies, and for an HPV-16/18/33/58 AS04 vaccine containing 20/20/20/20 μg VLPs for anti-HPV-16 antibodies. There was also a trend for lower HPV-16 and -18-specific memory B-cell responses for tetravalent AS04 vaccines versus control. No such trends were observed for CD4⁺ T-cell responses. Immune interference could not always be overcome by increasing the dose of HPV-16/18 L1 VLPs or by using a different adjuvant system. All formulations had acceptable reactogenicity and safety profiles. Reactogenicity in the 7-day post-vaccination period tended to increase with the introduction of additional VLPs, especially for formulations containing AS01.

Conclusions

HPV-16 and -18 antibody responses were lower when additional HPV L1 VLPs were added to the HPV-16/18 AS04-adjuvanted vaccine. Immune interference is a complex phenomenon that cannot always be overcome by changing the antigen dose or adjuvant system.     

Immunogenicity of bivalent HPV vaccine among partially vaccinated young adolescent girls in Uganda

Background

Investigations of vaccine efficacy and immunogenicity for adult females receiving fewer than three doses of human papillomavirus (HPV) vaccine have suggested protection against infection and precancerous lesions. We investigated the immunogenicity of bivalent HPV vaccines among adolescent girls from Uganda who received one, two, or three vaccine doses.

Methods

Young girls vaccinated through a government program in Uganda were invited to participate. HPV16- and HPV18-specific antibodies were measured at ≥24 months after the last vaccine dose using an enzyme linked immunoassay in girls who received one (n = 36), two (n = 145), or three (n = 195) doses.

Results

Nearly all subjects (99%) were HPV16 and HPV18 seropositive at the time of blood-draw. Geometric mean antibody levels (GMTs) were: HPV16_1-dose = 230 EU/mL, HPV16_2-dose = 808 EU/mL, and HPV16_3-dose = 1607 EU/mL; HPV18_1-dose = 87 EU/mL, HPV18_2-dose = 270 EU/mL, and HPV18_3-dose = 296 EU/mL. The GMT ratio for 2:3 doses was 0.50 (HPV16) and 0.68 (HPV18) and did not meet the non-inferiority criteria (i.e., lower bound of 97.5% confidence interval of the GMT ratio greater than 0.50). The GMT ratio for 1:3 doses for HPV16 and HPV18 was inferior, but absolute GMTs for one dose were higher than adult women who received one dose (HPV16 = 124 EU/mL, HPV18 = 69 EU/mL) where efficacy has been demonstrated.

Conclusions

Even though immunogenicity with less than three doses did not meet a priori non-inferiority thresholds, antibody levels measured ≥24 months after last dose were similar to those of adult women who have been followed for more than eight years for efficacy.     

Immune response after one or two doses of pandemic influenza A (H1N1) monovalent,AS03-adjuvanted vaccine in HIV infected adults

Introduction

Continued research is needed to evaluate and improve the immunogenicity of influenza vaccines in HIV infected patients. We aimed to determine the antibody responses after one or two doses of the AS03-adjuvanted pandemic influenza A (H1N1) vaccine in HIV infected patients.

Method

Following the influenza season 2009/2010, 219 HIV infected patients were included and divided into three groups depending on whether they received none (n = 60), one (n = 31) or two (n = 128) doses of pandemic influenza A (H1N1) vaccine. At inclusion, antibody titers for all patients were analyzed and compared to pre-pandemic antibody titers analyzed from serum samples in a local storage facility.

Results

4–9 months after a single immunization, we found a seroprotection rate of 77.4% and seroconversion rate of 67.7%. After two immunizations the rates increased significantly to seroprotection rate of 97.7% and seroconversion rate of 86.7%.

Conclusion

A single dose of AS03-adjuvanted pandemic influenza A (H1N1) vaccine created an adequate immune response in HIV infected patients lasting as long as 4–9 months. Two doses improved the immunogenicity further.     

Incidence and variables associated with inadequate antibody titers after pre-exposure rabies vaccination among veterinary medical students

Background

This study sought to determine the proportion of subjects with inadequate antibody titers at two years after pre-exposure rabies vaccination and identify variables associated with inadequate antibody titers.

Methods

A retrospective chart review of vaccination records of veterinary students in Michigan, 2004–2009, was conducted. Antibody titers <0.5 IU/ml as estimated by rapid fluorescent focus inhibition test were classified as inadequate. Variables were compared between the two groups to identify factors associated with inadequate titers at two years.

Results

A total of 603 subjects (mean age 24.1 ± 4.2 years, male:female 106:497) were included. Nearly one third (177/603, 29.4%) had inadequate titers at two years. Male gender (adjusted odds ratio (AOR) 1.87, 1.07–3.27; p = 0.029), vaccine manufacturer (AOR 1.49, 1.16–1.92; p = 0.002), BMI >25 (AOR 1.61, 1.02–2.54; p = 0.043), and duration between first and third doses of vaccine >21 days (AOR 2.49, 1.26–4.97; p = 0.009) were independently associated with inadequate titers.

Conclusions

Twenty-nine percent of subjects had inadequate antibody titers against rabies at 2 years. Gender, vaccine type/manufacturer, BMI of 25 or greater, and more than 21 days between the first and third doses of vaccine were independently associated with inadequate antibody titers at two years. Our data would support modifying the recommendations, so the third dose is recommended at 21 days rather than 21–28 days.     

Impact of human papillomavirus (HPV) vaccination on HPV 16/18-related prevalence in precancerous cervical lesions

Background

Vaccination against human papillomavirus (HPV) types 16 and 18 is recommended for girls aged 11 or 12 years with catch-up vaccination through age 26 in the U.S. Cervical intraepithelial neoplasia (CIN) grade 2 or 3 and adenocarcinoma in situ (CIN2+) are used to monitor HPV vaccine impact on cervical disease. This report describes vaccination status in women diagnosed with CIN2+ and examines HPV vaccine impact on HPV 16/18-related CIN2+.

Methods

As part of a vaccine impact monitoring project (HPV-IMPACT), females 18–31 years with CIN2+ were reported from pathology laboratories in CA, CT, NY, OR, TN from 2008 to 2011. One diagnostic block was selected for HPV DNA typing with Roche Linear Array. Demographic, abnormal Papanicolaou (Pap) test dates and vaccine status information were collected. The abnormal Pap test immediately preceding the CIN2+ diagnosis was defined as the ‘trigger Pap’.

Results

Among 5083 CIN2+ cases reported to date, 3855 had vaccination history investigated; 1900 had vaccine history documented (vaccinated, with trigger Pap dates, or unvaccinated). Among women who initiated vaccination >24 months before their trigger Pap, there was a significantly lower proportion of CIN2+ lesions due to 16/18 compared to women who were not vaccinated (aPR = .67, 95% CI: .48–.94). Among the 1900 with known vaccination status, 20% initiated vaccination on/after their trigger screening. Women aged 21–23 years were more likely to initiate vaccination on/after the trigger Pap compared to 24–26 year olds (29.0% vs. 19.6%, p = .001), as were non-Hispanic blacks compared to non-Hispanic whites (27.3% vs. 19.0%, p = .001) and publicly compared to privately insured women (38.1% vs. 17.4%, p < .0001).

Conclusion

We found a significant reduction in HPV 16/18-related lesions in women with CIN2+ who initiated vaccination at least 24 months prior to their trigger Pap. These preliminary results suggest early impact of the HPV vaccine on vaccine-type disease, but further evaluation is warranted.     

Increases in HPV-16/18 antibody avidity and HPV-specific memory B-cell response in mid-adult aged men post-dose three of the quadrivalent HPV vaccine

Strong quantitative and functional antibody responses to the quadrivalent human papillomavirus (HPV) vaccine were reported in mid-adult aged men, but there are limited data on the avidity of the antibody response and the memory B-cell response following vaccination. Although circulating antibodies induced by vaccination are believed to be the main mediators of protection against infection, evaluation of avidity of antibodies and memory B cell responses are critical for a better understanding of the vaccine immunogenicity mechanisms. Both the modified enzyme-linked immunosorbent assay (ELISA) and the enzyme-linked immunosorbent spot (ELISpot) assay are tools to measure the humoral and cellular immune responses post vaccination to characterize vaccine immunogenicity. The avidity of HPV-16 and HPV-18 specific IgG in the serum of mid-adult aged men (N = 126) who received three quadrivalent HPV vaccine doses was examined using a modified ELISA. HPV-16 memory B-cell responses were assessed via ELISpot at month 0 (prior to vaccination) and 1-month post-dose three of the vaccine (month 7). The quadrivalent vaccine induced an increase in HPV-16 and HPV-18 antibody avidity at month 7. HPV-18 avidity levels moderately correlated with anti-HPV-18 antibody titers, but no association was observed for HPV-16 antibody titers and avidity levels. The HPV-16-specific memory B-cell response was induced following three vaccine doses, however, no association with anti-HPV-16 antibody avidity was observed. Three doses of quadrivalent HPV vaccine increased antibody affinity maturation for HPV-16/18 and increased the frequency of anti-HPV-16 memory B-cells in mid-adult aged men.     

Human papillomavirus,lichen sclerosus and penile cancer: A study in Belgium

Purpose

The prevalence of penile cancer varies between 1.5 (industrialized countries) and 4.5 per 100,000 men (non-industrialized countries). Predominant histological subtype is squamous cell carcinoma (SCC). Human papillomavirus (HPV) is found in 40–46% of cases: penile cancer is considered to behave as vulvar cancer. Non HPV related risk factors are lack of circumcision, phimosis, chronic inflammation, and smoking. The role of lichen sclerosus (LS) is unclear. Clinical diagnosis is difficult and treatment often mutilating. Preventive measures can be taken since the risk factors are known: the use of the prophylactic HPV vaccines may contribute. We measured the prevalence of HPV and LS in penile cancer in Belgium.

Materials and methods

We found 76 samples of penile lesions in the archives of the departments of Histology of four university hospitals in Belgium. Real-time PCR of type-specific HPV DNA was performed targeting 18 HPV types.

Principal results

Patients with penile intraepithelial neoplasia (PeIN) were 56.1 years of age: patients with invasive penile cancer (IPC) 68.5 (p = 0.009). Fifty-five samples (55/76) were adequate for HPV targeting. Overall HPV DNA was 70.9%: 89.5% in samples of PeIN (n = 19) and 61.1% in samples of IPC (n = 36). Invasive penile cancer samples were less likely to be HPV infected (p = 0.028). HPV 16 was most prevalent: 48.3%: 20% PeIN, and 28.3% IPC. HPV DNA of the types, included in the prophylactic vaccines, was found in 33% of PeIN and 31.7% of IPC samples. Thrice, low risk HPV (lrHPV) types 6 (1 IPC) and 11 (1 PeIN, 1 IPC) were solely present. There was no difference in the presence of LS between HPV positive and HPV negative samples (p = 0.944).

Conclusions

Prevalence of HPV DNA in penile lesions in Belgium is high. However, the prophylactic vaccines may contribute to primary prevention of only a subset of cases. The role of LS remains unclear.     

Engaging parents and schools improves uptake of the human papillomavirus (HPV) vaccine: Examining the role of the public health nurse

Background

Nova Scotia has the highest rate of cervical cancer in Canada, and most of these cases are attributed to the Human Papillomavirus (HPV). In 2007, Gardasil^® was approved and implemented in a successful school-based HPV immunization program. Little is known, however, which strategies (if any) used within a school-based program help to improve vaccine uptake.

Methods

A retrospective, exploratory correlation study was conducted to examine the relationship between school-based strategies and uptake of HPV vaccine. Data was analyzed through Logistic regression, using PASW Statistics 17 (formerly SPSS 17).

Results

HPV vaccine initiation was significantly associated with Public Health Nurses providing reminder calls for: consent return (p = 0.017) and missed school clinic (p = 0.004); HPV education to teachers (p < 0.001), and a thank-you note to teachers (p < 0.001). Completion of the HPV series was associated with vaccine consents being returned to the students’ teacher (p = 0.003), and a Public Health Nurse being assigned to a school (p = 0.025).

Conclusions

These findings can be used to help guide school-based immunization programs for optimal uptake of the HPV vaccine among the student population.     

Differences in avidity of IgG antibodies to pertussis toxin after acellular pertussis booster vaccination and natural infection

Background

Pertussis toxin (PT) is a specific virulence factor of Bordetella pertussis and it is included in all acellular pertussis vaccines (aP). Although immunity after infection seems to persist longer than that after vaccination, the exact mechanism(s) is not known. Primary aim of this study was to develop an ELISA method for measuring avidity index (AI) of IgG-anti-PT antibodies and to compare antibody responses after booster vaccination and infection. Secondary aim was to evaluate if the AI-ELISA has potential in the serodiagnosis of pertussis.

Material

Serum samples from a total of 409 subjects were included in the study. Paired sera were taken from 97 adolescents who received booster vaccine ten years ago (dTpa-004) and from 80 young adults who received a second booster dose ten years after the previous booster vaccine (dTpa-040). Thirty-two paired sera from culture-confirmed pertussis patients, 161 single sera from serologically diagnosed patients and 39 single sera from healthy controls were included. AI of IgG-anti-PT antibodies were determined with newly developed ELISA using diethylamine (DEA) as a bond breaking agent. The IgG-anti-PT antibodies were measured by standardized ELISA.

Results

A significant increase was found in antibody concentrations and AI between PRE and one month POST vaccination ten years ago [GMC for antibody: 7.9 IU/ml vs. 98.3 IU/ml (p = 0.0001); for AI: 40.4% vs. 56.1% (p = 0.0001)]. Similar result was observed after the second booster dose [GMC for antibody: 9.2 IU/ml vs. 92.4 IU/ml (p = 0.0001); for AI: 36.1% vs. 59.5% (p = 0.0001)] and between the first and second sera of culture-confirmed patients [GMC for antibody: 6.9 IU/ml vs. 285.1 IU/ml (p = 0.0001); for AI: 40.5% vs. 68.4% (p = 0.0001)]. Healthy controls showed lower levels of both antibodies and AI.

Conclusions

Our results suggest that there may be difference in quality and quantity of antibodies to PT after vaccination and after infection. Furthermore, AI could be a help for vaccine studies.     

The impact of differential uptake of HPV vaccine by sexual risks on health inequalities: A model-based analysis

Background

Differences in sexual behaviour are partly responsible for significant inequalities in human papillomavirus (HPV)-related diseases between sub-populations. Our aim was to illustrate how differential HPV vaccine uptake by sexual behaviour can impact population-level vaccination effectiveness and inequalities in HPV prevalence.

Methods

We used a multi-type individual-based transmission-dynamic model of HPV infection. The modelled population is stratified into 4 sexual activity levels (low = L0, high = L3). The model was calibrated to Canadian epidemiological data, including the proportion of sexually active individuals by gender and type-specific HPV prevalence by level of sexual activity. Vaccine uptake by sexual activity level was varied in one-way sensitivity analyses. Uncertainty in model predictions is presented using the median [10-90th percentiles] of simulations.

Results

In our pre-vaccination calibrated modelled population, the most sexually active risk groups (L2–L3) account for 43% of prevalent HPV-16/18 infections while only representing 20% of the population. Under base case assumptions (age at vaccination = 12 years, vaccine efficacy = 100%, average duration of protection = 20 years, overall coverage = 50%), vaccinating girls is predicted to reduce HPV-16/18 prevalence by 56% [46–69] at equilibrium (70 years post-vaccination) when uptake is uniform across sexual activity levels, and by 35% [28–40] when uptake is maldistributed (L0: 100%, L1: 55%, L2: 0%, L3: 0%). At uniform 50% vaccination coverage across risk groups, HPV-16/18 prevalence is predicted to be reduced by 62% [52–73], 74% [57–82], 40% [24–60], and 28% [7–54] at equilibrium among women in levels of sexual activity L0, L1, L2 and L3, respectively.

Conclusions

A low vaccine uptake in girls at highest risk of future HPV acquisition may substantially limit population effectiveness of vaccination. Vaccination effectiveness is lower in more sexually active groups due to smaller herd effects. Uniform vaccination coverage across sub-populations may not be able to decrease existing inequalities in HPV infection and disease unless coverage is high enough to produce herd effects in higher risk groups.     

Immunogenicity of a 7-valent pneumococcal conjugate vaccine (PCV7) and impact on carriage in Venezuelan children at risk of invasive pneumococcal diseases

Background and aims

We evaluated the immunogenicity of the 7-valent pneumococcal conjugate vaccine (PCV7), and its impact on pneumococcal carriage in Venezuelan children at high risk for invasive pneumococcal disease (IPD).

Methods

82 children (age 2–59 months) with sickle cell anemia (n = 22), chronic heart disease (n = 19), HIV infection (n = 12), immune-suppressive therapy (n = 11) and other IPD-predisposing conditions (n = 18) were vaccinated with PCV7 according to CDC-recommended age-related immunization schedules. Blood samples were taken to determine the concentration of IgG antibody, and nasopharyngeal swabs were obtained to isolate Streptococcus pneumoniae, before the first vaccine dose and 1 month after completion of the vaccination schedule.

Results

Pneumococcal carriage prior to the first immunization was 27% (n = 22), with the most frequently carried serotypes being vaccine serotypes 6B (22%) and 14 (13%). One month after completion of the vaccination scheme pneumococcal carriage was 22% (n = 17), dominated by non-vaccine serotypes 19A (24%) and 7F (12%). Before immunization, 65% of the subjects had IgG antibody titers >0.35 μg/mL for five serotypes tested. Post-vaccination, 100% of the subjects showed titers >1.0 μg/mL for all PCV7 serotypes with geometric mean concentrations (GMC) ranging from 1.75 μg/mL (serotype 23F) to 17.16 μg/mL (serotype 14). Children previously colonized with serotype 6B had a significantly lower GMC to this serotype following immunization than children not carrying 6B prior to the first PCV dose (p < 0.05).

Conclusions

PCV7 is highly immunogenic in Venezuelan children at high-risk for IPD. Vaccination was associated with an immediate shift in nasopharyngeal carriage toward non-PCV7 serotypes. Finally, we observed serotype-specific hyporesponsiveness to immunization after natural carriage with the same serotype in high-risk children.     

Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls

Background

To evaluate co-administration of GlaxoSmithKline Biologicals’ human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB).

Methods

This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV (n = 247), HepB (n = 247) or HPV co-administered with HepB (HPV + HepB; n = 247) at Months 0, 1 and 6. Antibodies against hepatitis B surface antigen (HBs), HPV-16 and HPV-18 were measured, and reactogenicity and safety monitored. Co-primary objectives were to demonstrate non-inferiority of hepatitis B and HPV-16/18 immune responses at Month 7 for co-administered vaccines, compared with vaccines administered alone, in the according-to-protocol cohort.

Results

The pre-defined criteria for non-inferiority were met for all co-primary immunogenicity endpoints at Month 7. Anti-HBs seroprotection rates ≥10 mIU/mL were achieved by 97.9% and 100% of girls, respectively, following co-administration or HepB alone. Anti-HBs geometric mean titers (GMTs) (95% confidence interval) were 1280.9 (973.3-1685.7) and 3107.7 (2473.1-3905.1) milli-international units/mL, respectively. Anti-HPV-16 and -18 seroconversion rates were achieved by ≥99% of girls following co-administration or HPV alone. Anti-HPV-16 GMTs were 19819.8 (16856.9-23303.6) and 21712.6 (19460.2-24225.6) ELISA units (ELU)/mL, respectively. Anti-HPV-18 GMTs were 8835.1 (7636.3-10222.1) and 8838.6 (7948.5-9828.4) ELU/mL, respectively. Co-administration was generally well tolerated.

Conclusions

The study results support the co-administration of HPV-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine in adolescent girls aged 9-15 years.

Clinical trials registration

ClinicalTrials.gov registration number NCT00652938.     

Seroprevalence of seven high-risk HPV types in The Netherlands

Background

To obtain insight into the age-specific seroprevalence for seven high-risk human papillomavirus (hr-HPV) serotypes (HPV16, 18, 31, 33, 45, 52, and 58) among the general population in the pre-vaccination era in The Netherlands.

Methods

From a cross-sectional population-based study (ISRCTN 20164309) performed in 2006/2007 6384 sera of men, women and children were tested for seven hr-HPV specific antibodies using a fluorescent bead-based multiplex immunoassay with virus-like particles of the seven HPV serotypes.

Results

An increase in seroprevalence was observed in adolescents, especially for the most prevalent HPV type 16 (up to 11.3%). The increase was most pronounced in women, but was less clear for the other six HPV serotypes. Relatively stable seroprevalences were found in the middle aged cohorts and a slight decrease in the elderly. For the age cohorts >14 years, the seroprevalence among women (25.2%) was higher compared with men (20.3%) (p = 0.0002). We found that 10.1% of the population was seropositive for multiple HPV serotypes.

Conclusions

The HPV vaccination program is targeted at preadolescents as is justified by the results in this study in which a step-up in HPV seroprevalence is observed at ages of sexual debut. Although direct interpretation of seroprevalence data are hampered by cross-reactivity and seroconversion rate, these data are useful as baseline to evaluate long-term population effects of the HPV16/18 vaccination program.     

HPV vaccination among lesbian and bisexual women: Findings from a national survey of young adults

Background

Human papillomavirus (HPV) infection and associated cervical disease are common among all women, regardless of sexual identity, yet limited research has examined HPV vaccination among lesbian and bisexual women.

Methods

A national sample of lesbian and bisexual women ages 18–26 (n = 543) completed our online survey during Fall 2013. We used multivariable logistic regression to identify correlates of HPV vaccine initiation (receipt of at least 1 dose) and completion (receipt of all 3 recommended doses among initiators).

Results

Overall, 45% of respondents had initiated HPV vaccine and 70% of initiators reported completing the series. HPV vaccine initiation was higher among respondents who were students, had received a healthcare provider's recommendation, perceived greater positive social vaccination norms, or anticipated greater regret if they did not get vaccinated and later got HPV. Initiation was lower among those who perceived greater HPV vaccine harms or greater barriers to getting the vaccine (all p < .05). HPV vaccine completion was higher among initiators who had a college degree while it was lower among those who perceived a greater likelihood of acquiring HPV or who anticipated greater regret if they got the vaccine and fainted (all p < .05). Among HPV vaccine initiators who had not yet completed the series, about half (47%) intended to get the remaining doses.

Conclusions

Many lesbian and bisexual women are not getting vaccinated against HPV. Healthcare provider recommendations and women's health beliefs may be important leverage points for increasing vaccination among this population.     

Vaccine induced Hepatitis A and B protection in children at risk for cystic fibrosis associated liver disease

Objectives

Hepatitis A (HAV) and Hepatitis B (HBV) infections can cause serious morbidity in patients with liver disease, including cystic fibrosis associated liver disease (CFALD). HAV and HBV vaccinations are recommended in CFALD, and maintenance of detectable antibody levels is also recommended with chronic liver disease. A better understanding of factors predicting low HAV and HBV antibodies may help physicians improve protection from these viruses in CFALD patients.

Methods

We examined HAV and HBV vaccine protection in children at risk for CFALD. Clinical and vaccine histories were reviewed, and HAV and HBV antibody titers measured. Those with no vaccination history or low HAV or HBV titers received primary or booster vaccinations, and responses were measured.

Results

Thirty-four of 308 children were at risk for CFALD per project criteria. Ten had previous HAV vaccination, of which 90% had positive anti-HAV antibodies. Thirty-three of 34 had previously received primary HBV vaccination (most in infancy), but only 12 (35%) had adequate anti-HBs levels (≥10 mIU/mL). Children with adequate anti-HBs levels were older at first HBV vaccine (median 2.3 vs. 0.1 years, p < 0.01), and at final HBV vaccine (median 4.0 vs. 0.8 years, p = 0.01). Fourteen of 19 (74%) responded to HBV boosters. Z-scores for BMI at HBV booster were significantly lower in booster non-responders (p = 0.04).

Conclusions

Children at increased risk of CFALD have inadequate HAV and HBV antibody levels, and HBV antibody protection can be enhanced through vaccine boosters. HBV antibody titers should be assessed in CFALD patients with a history of vaccination, particularly in those who received HBV vaccines in infancy or who are malnourished.     

HPV vaccination: Are we initiating too late?

Background

Human papillomavirus (HPV) vaccination is recommended in early adolescence. While limited data suggest that patients frequently delay initiation of the three-dose series, age-based variability in initiation of HPV vaccination and its clinical relevance are not well described. Thus, this study aims to characterize HPV vaccination delay among adolescent and young adult females.

Methods

This retrospective cohort study examined age at HPV vaccination initiation and missed opportunities for receipt of the first vaccine dose (HPV1) among 11–26 year-old females (n = 22,900) receiving care at 16 urban academically-affiliated ambulatory care clinics between 2007 and 2011. Predictors of timely vaccination and post-licensure trends in age at HPV1 receipt were assessed using multivariable logistic regression and a generalized linear mixed model, respectively. Chlamydia trachomatis and Papanicolaou screening before HPV vaccination initiation, as markers of prior sexual experience and associated morbidity, were examined in a subcohort of subjects (n = 15,049).

Results

The proportion of 11–12 year-olds who initiated HPV vaccination increased over time (44.4% [2007] vs. 74.5% [2011], p < 0.01). Initiation rates also improved among 13–26 year-olds. Thus, the mean age at HPV1 receipt remained unchanged between 2007 and 2011 (16.0 ± 2.7 vs. 15.9 ± 4.0 years, p = 0.45). Spanish language was a positive predictor (AOR 1.62, 95% CI 1.05–2.48) of HPV vaccination initiation among 11–12 year-olds in 2011. The majority (70.8–76.4%) of unvaccinated subjects experienced missed vaccination opportunities. Of the subcohort, 36.9% underwent Chlamydia screening before HPV1 receipt (19.1% with ≥1 positive result). Of those with prior Papanicolaou screening (16.6%), 32.1% had ≥1 abnormal result.

Conclusions

These low-income, minority females frequently delayed initiation of HPV vaccination. Many had evidence of prior sexual experience and associated morbidity, placing them at risk of HPV-related complications. Promoting timely HPV vaccination and reducing missed vaccination opportunities are crucial.     

Factors associated with human papillomavirus vaccination among young adult women in the United States

Background

Human papillomavirus (HPV) vaccination is recommended to protect against HPV-related diseases.

Objective

To estimate HPV vaccine coverage and assess factors associated with vaccine awareness, initiation and receipt of 3 doses among women age 18–30 years.

Methods

Data from the 2010 National Health Interview Survey were analyzed to assess associations of HPV vaccination among women age 18–26 (n = 1866) and 27–30 years (n = 1028) with previous HPV exposure, cervical cancer screening and selected demographic, health care and behavioral characteristics using bivariate analysis and multivariable logistic regression.

Results

Overall, 23.2% of women age 18–26 and 6.7% of women age 27–30 years reported receiving at least 1 dose of HPV vaccine. In multivariable analyses among women age 18–26 years, not being married, having a regular physician, seeing a physician or obstetrician/gynecologist in the past year, influenza vaccination in the past year, and receipt of other recommended vaccines were associated with HPV vaccination. One-third of unvaccinated women age 18–26 years (n = 490) were interested in receiving HPV vaccine. Among women who were not interested in receiving HPV vaccine (n = 920), the main reasons reported included: not needing the vaccine (41.3%); concerns about safety of the vaccine (12.5%); not knowing enough about the vaccine (11.9%); not being sexually active (8.2%); a doctor not recommending the vaccine (7.6%); and already having HPV (2.7%). Among women with health insurance, 10 or more physician contacts within the past year and no contraindications, 74.5% reported not receiving HPV vaccine.

Conclusions

HPV vaccination coverage among women age 18–26 years remains low. Opportunities to vaccinate are missed. Healthcare providers can play an important role in educating young women about HPV and encouraging vaccination. Successful public health and educational interventions will need to address physician attitudes and practice patterns and other factors that influence vaccination behaviors.     

Impact of medical education on knowledge and attitudes regarding the human papilloma virus and vaccination: Comparison before and 6 years after the introduction of the vaccines

Aim

The lifetime risk for acquiring a human papilloma virus (HPV) infection is 80% for sexually active people. High-risk HPVs are causally related to almost every case of cervical cancer, and to a subgroup of vaginal, vulvar, anal, penile and oral/oropharyngeal cancer. Low-risk HPVs are related to cutaneous, anogenital, and oral warts.Two prophylactic vaccines were launched in 2007: they were included in the national vaccination program in Belgium (2009) and in the Netherlands (2010). The objectives of the present study were to determine and compare knowledge and attitudes regarding HPV and vaccination among a study population in 2006 and in 2012.

Materials and methods

Shortly before the introduction, and three years after the inclusion, 715 (2006) and 678 participants (2012) were questioned. Participants were categorised as into non-medics, medics, or paramedics.

Results

In general, knowledge about HPV has increased over time (p < 0.01).Well-known facts are the relationship of HPV with cervical cancer (>94% in 2006; >96% in 2012), and that an HPV infection might be asymptomatic (>95% in 2006; >99% in 2012).In 2012, versus in 2006, paramedics and non-medics (both p < 0.01), were more likely to vaccinate all female teenagers. Medics were less likely to support this (p = 0.001). More respondents agreed to vaccinate their daughters (p < 0.01), as well as their sons (p < 0.01).In 2012, when compared with 2006, less non-medics and medics (both p < 0.01) and more paramedics (p = 0.001) would accept a free catch-up vaccination. Arguments against catch-up vaccination reflected the belief not being at risk and doubts about the vaccines’ safety.

Conclusion

The facts that vaccination programs are regarded as being important, and that knowledge on HPV increased, do not automatically result in an increase in participation in HPV vaccination programs. To increase participation, information must be provided with arguments that cannot be misinterpreted.