Age-Specific Trends of Invasive Cervical Cancer Incidence in British Columbia, Canada, 1971-2017.

This study examined invasive cervical cancer (ICC) incidence trends in British Columbia (BC) by age and stage-at-diagnosis relative to World Health Organization ICC elimination targets (4 per 100,000 persons). Incident ICC cases (1971-2017) were obtained from the BC Cancer Registry. Annual age-standardized incidence rates (ASIRs) per 100,000 persons were generated using the direct method. ASIRs were examined among all ages 15+ years and eight age groups using Joinpoint Regression with the Canadian 2011 standard population. Standardized rate ratios (SRRs) compared stage II-IV (late) versus stage I (early) ASIRs by age (2010-2017). ICC ASIRs did not reach the elimination target. ASIRs declined from 18.88 to 7.08 per 100,000 persons (1971-2017). Stronger declines were observed among ages 45+ years, with the largest decline among ages 70-79 years (AAPC = -3.2%, 95% CI = -3.9% to -2.6%). Among ages 25-69 years, varying levels of attenuation in declining trends and stabilization were observed since the 1980s. SRRs indicated higher rates of late-stage ICC among ages 55+ years (SRR-55-69 years = 1.34, 95% CI = 1.08-1.71). Overall, ICC incidence declined in BC since 1971 but did not reach the elimination target. The pace of decline varied across age groups and increased with age. Continued efforts are needed to progress cervical cancer elimination among all age groups.

Characterization of vaccine confidence among teachers in British Columbia, Canada: A population-based survey.

OBJECTIVES: Teachers are an important occupational group to consider when addressing vaccine confidence and uptake for school-aged children due to their proximate role within school-based immunization programs. The objectives of this study were to characterize and identify sociodemographic factors associated with vaccine confidence and describe teachers' knowledge of and perceived role in the school-based immunization program, with the aim of informing public health policy and identifying opportunities for supporting teachers in their role in school-based immunization programs. METHODS: A cross-sectional survey of elementary and secondary public-school teachers in British Columbia was completed from August to November 2020. Respondents provided sociodemographic information, as well as past vaccination experience, vaccine knowledge, and perceived role in the school-based immunization program. Vaccine confidence was measured using the Vaccine Hesitancy Scale (VHS). Characteristics associated with the VHS sub-scales 'lack of confidence in vaccines' and 'perceived risk of vaccines', were explored using ANOVA. Descriptive analysis was completed for teachers' perceived role in the immunization program. RESULTS: 5,095 surveys were included in this analysis. Overall vaccine confidence was high, with vaccine hesitancy being related to the perceived risk of vaccines rather than a lack of confidence in the effectiveness of vaccines. ANOVA found significant differences for both VHS-sub-scales based on sociodemographic factors, however, the strength of the association was generally small. High general vaccine knowledge and never having delayed or refused a vaccine in the past were associated with higher vaccine confidence. Overall, teachers reported a lack of clarity in their role within the school-based immunization program. CONCLUSIONS: This large population-based observational study of teachers highlights a number of key engagement opportunities between public health and the education sector. Using a validated scale, we found that overall, teachers are highly accepting of vaccines, and well situated as potential partners with public health to address vaccine hesitancy.

Factors associated with intention to receive vaccines for bacterial sexually transmitted infections among young HPV-vaccinated Canadian women.

OBJECTIVE: The aim of this study was to explore the acceptability of bacterial STI vaccines among young HPV-vaccinated Canadian women to inform future vaccine program implementation. METHODS: A 20-item cross-sectional questionnaire was administered from June 2019 to June 2020 to HPV-vaccinated participants of the pan-Canadian QUEST cohort. Multivariable logistic regression models assessed interest in chlamydia, syphilis, and gonorrhea vaccines using a priori variables and factors significant in bivariate analysis. RESULTS: Of the 1092 respondents analyzed, 82% indicated interest in receiving one or more future STI vaccines. Respondents had a median age of 19.6 years (range 16.9-23.4), and 75% of respondents identified as white/European descent. In adjusted analyses, intent to engage in positive health behaviours was associated with vaccine interest for syphilis (OR = 5.76, 95% CI 4.03-8.27), chlamydia (OR = 5.27, 95% CI 3.66-7.63), and gonorrhea (OR = 5.96, 95% CI 4.15-8.60). Willingness to pay for an STI vaccine was also associated with vaccine interest for syphilis (OR = 2.02, 95% CI 1.29-3.19), chlamydia (OR = 2.41, 95% CI 1.50-3.90), and gonorrhea (OR = 2.29, 95% CI 1.44-3.63). Ever having sexual intercourse and identifying as LGBTQ were significantly associated with vaccine interest for all infections, while age and ever being immunosuppressed were not significant in any adjusted models. CONCLUSION: Findings indicate over 80% of participants in a cohort of young HPV-vaccinated Canadian women are interested in receiving future bacterial STI vaccines. Further exploration of STI vaccine acceptability among diverse populations is required to inform future bacterial STI vaccine program implementation.

RéSUMé: OBJECTIF: Cette étude visait à explorer l'acceptabilité des vaccins contre les ITS bactériennes chez les jeunes Canadiennes vaccinées contre le VPH pour éclairer la mise en œuvre de futurs programmes de vaccination. MéTHODE: Un questionnaire transversal de 20 questions a été administré entre juin 2019 et juin 2020 aux participantes de la cohorte QUEST pancanadienne ayant été vaccinées contre le VPH. Des modèles de régression logistique multivariée ont permis d'analyser l'intérêt pour les vaccins contre la chlamydia, la syphilis et la gonorrhée à l'aide de variables a priori et des facteurs significatifs dans l'analyse bivariée. RéSULTATS: Sur les 1 092 répondantes analysées, 82 % ont manifesté l'intérêt de recevoir un ou plusieurs futurs vaccins contre les ITS. L'âge médian des répondantes était de 19,6 ans (intervalle 16,9­23,4), et 75 % s'identifiaient comme étant blanches/d'ascendance européenne. Dans les analyses ajustées, l'intention de s'adonner à des comportements de santé positifs était associée à l'intérêt pour les vaccins contre la syphilis (RC = 5,76, IC de 95 % 4,03­8,27), la chlamydia (RC = 5,27, IC de 95 % 3,66­7,63) et la gonorrhée (RC = 5,96, IC de 95 % 4,15­8,60). La volonté de payer pour un vaccin contre les ITS était aussi associée à l'intérêt pour les vaccins contre la syphilis (RC = 2,02, IC de 95 % 1,29­3,19), la chlamydia (RC = 2,41, IC de 95 % 1,50­3,90) et la gonorrhée (RC = 2,29, IC de 95 % 1,44­3,63). Le fait d'avoir déjà eu des rapports sexuels et le fait de s'identifier comme une personne LGBTQ présentaient une corrélation significative avec l'intérêt pour les vaccins contre toutes les infections, mais l'âge et le fait d'avoir déjà subi un traitement immunodépresseur n'étaient des facteurs significatifs dans aucun des modèles ajustés. CONCLUSION: Selon nos constatations, plus de 80 % des participantes d'une cohorte de jeunes Canadiennes vaccinées contre les VPH sont intéressées à recevoir de futurs vaccins contre les ITS bactériennes. Une exploration plus poussée de l'acceptabilité des vaccins contre les ITS dans des populations à forte mixité est nécessaire pour éclairer la mise en œuvre de futurs programmes de vaccination contre les ITS bactériennes.

Treatment of UTIs in Infants <2 Months: A Living Systematic Review.

CONTEXT: Urinary tract infections (UTIs) are the most common bacterial infections in infants <2 months of age. However, there are no clear guidelines on the appropriate duration of antibiotics in this age group. OBJECTIVE: In this living systematic review, we compared different durations of parenteral antibiotics (≤3 vs >3 days) in neonates and young infants (<2 months) with UTIs. The secondary objective was to compare different durations of total antibiotic courses (≤10 vs >10 days). DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Literatura Latino-Americana e do Caribe em Ciências da Saúde, Google Scholar, and gray literature, up to March 2, 2021. STUDY SELECTION: Citations were screened in triplicate by using a crowdsourcing methodology, to identify randomized controlled trials and observational studies. DATA EXTRACTION: Data were extracted by 2 crowd members and verified by an expert investigator. Outcomes were pooled via random-effects models. RESULTS: A total of 10 334 citations were screened, and 12 eligible studies were identified. A total of 59 of 3480 (1.7% [95% confidence interval (CI): 1.3% to 2.2%]) infants had a UTI recurrence within 30 days after short parenteral treatment (≤3 days), and 47 of 1971 (2.4% [95% CI: 1.8% to 3.2%]) after longer courses. The pooled adjusted odds ratio for UTI recurrence with a short versus long duration of parenteral antibiotics was 1.02 (95% CI: 0.64 to 1.61; P = .95; n = 5451). A total of 5 studies assessed the risk of recurrence on the basis of the total duration of antibiotics (≤10 vs >10 days) with no significant differences (pooled odds ratio: 1.29 [95% CI: 0.45 to 3.66; P = .63; n = 491). CONCLUSIONS: On the basis of retrospective studies and Grading of Recommendations, Assessment, Development, and Evaluation level low evidence, short and long duration of parenteral antibiotics were associated with a similar risk of UTI recurrence in infants <2 months.

High-risk HPV prevalence among women undergoing cervical cancer screening: Findings a decade after HPV vaccine implementation in British Columbia, Canada.

BACKGROUND: British Columbia (BC) introduced a publicly funded, school-based human papillomavirus (HPV) immunization program in 2008 with the quadrivalent vaccine. In 2010/2011, a baseline evaluation of HPV prevalence was conducted among women undergoing cervical cancer screening. After 10 years of publicly funded HPV vaccination, HPV-type prevalence was re-evaluated. METHODS: From August 2017 to March 2018, 1107 physicians were invited to return cytobrushes used during routine Pap screening to the Cervical Cancer Screening Laboratory for HPV testing. Only age or year of birth was collected. Specimens were screened for high-risk HPV (hrHPV) and positive samples were genotyped. HPV type prevalence was compared for females 15-22 yrs (those eligible for the school-based vaccination) and 23+ yrs (ineligible for school-based vaccination) for the 2010/2011 and the 2017/2018 data. RESULTS: There were 3309 valid samples received for testing; of these, 3107 were included in the analysis. The overall hrHPV prevalence was 12.2% (95% CI 11.3-13.3) in 2010/11, and 12.0% (95% CI 10.9-13.2) in 2017/18. For the 15-22 age group, the prevalence for any hrHPV was 26.8% (95% CI 23.1-30.8) in 2010/11 and 25.4% (95% CI 15.3-37.9) in 2017/18. For those aged 15-22, HPV16 prevalence in 2010/11 was 8.8% (95% CI 6.5-11.5) and in 2017/18 was 6.3% (95% CI 1.8-15.5), with corresponding figures for HPV18 3.7% (95% CI 2.3-5.7) and 0% (95% CI 0.0-5.7), respectively. For all hrHPV types, there were no statistically significant differences between the 2010/11 and 2017/18 periods. CONCLUSIONS: This study illustrates the prevalence of hrHPV in BC over time in women undergoing cervical cancer screening, where an indication of a decline in HPV16/18 is seen in vaccine eligible women.

Priorities for sexually transmitted infection vaccine research and development: Results from a survey of global leaders and representatives.

OBJECTIVE: To determine the sexually transmitted infection (STI) vaccine research priorities of global leaders in STI vaccine research, development, and service provision. METHODS: Global representatives attending the STI Vaccines: Opportunities for Research, Development, and Implementation symposium preceding the STI & HIV World Congress in 2019 were invited to complete an electronic survey. We asked participants to rank items by importance/priority for STI vaccine development for the following areas of focus: specific STIs (gonorrhea, chlamydia, syphilis, herpes, and trichomoniasis), broad research domains (basic science, funding, communication, program planning, and vaccine hesitancy), and specific research activities related to these domains. We calculated weighted value scores based on the ranking (e.g., first, second, third) and the total number of responses in order to produce a ranked list of the priorities. RESULTS: A total of 46 out of 97 (44%) symposium attendees responded to the survey. Gonorrhea was identified as the STI that should be prioritized for vaccine development, followed by syphilis with weighted value scores of 3.82 and 3.37, respectively, out of a maximum of five. Basic science (and vaccine development) was the domain ranked with the highest priority with a weighted value score of 4.78 out of six. Research activities related to basic science and vaccine development (including pre-clinical and clinical trials, and surveillance measures) and increased funding opportunities were the most highly ranked activities in the "STI vaccine development" and "research domains and activities" categories. CONCLUSION: Global leaders in attendance at the STI Vaccines symposium prioritized continued scientific work in vaccine development and program planning. Gonorrhea was identified as the highest priority infection, followed by syphilis.

Intentions of public school teachers in British Columbia, Canada to receive a COVID-19 vaccine.

BACKGROUND: To control the COVID-19 pandemic high vaccine acceptability and uptake will be needed. Teachers represent a priority population to minimize social disruption and ensure continuity in education, which is vital for the well-being and healthy development of youth during the pandemic. The objective of this analysis was to measure public school teachers' intentions to receive a COVID-19 vaccine in British Columbia (BC), Canada. METHODS: A population-wide cross-sectional online survey from August to November 2020 asked all BC public school teachers with an available email address how likely they were to receive a COVID-19 vaccine. Two multivariable logistic regression models explored separately sociodemographic and vaccine hesitancy predictors for intention to receive a COVID-19 vaccine. RESULTS: A total of 5,076 teachers participated. The majority, 89.7%, reported they were likely or very likely to accept a COVID-19 vaccine. In multivariable regression, sociodemographic predictors of intention to be vaccinated included being male, having an educational background in science or engineering, and using reliable information sources on vaccination such as public health and health care providers. Teachers who reported lower levels of vaccine hesitancy, higher general vaccine knowledge, and belief that COVID-19 was a serious illness were more likely to intend to receive a COVID-19 vaccine. CONCLUSION: A high proportion of public-school teachers in BC intend to receive a COVID-19 vaccine. Continued monitoring of vaccine intentions will be important to inform public health vaccine implementation.

Non-inferior antibody levels for HPV16/18 after extended two-dose schedules compared with a six-month interval: findings of a systematic review and meta-analysis.

Protection after human papillomavirus (HPV) vaccination can be maximized by optimizing vaccination schedules. We systematically reviewed immunogenicity and effectiveness of HPV vaccines administered 6 months apart compared with longer intervals. Seroconversion to vaccine-type HPV was non-inferior for 12- compared with 6-month intervals, but inconclusive for comparison of 36-96 months with 6 months. A 12-month interval showed non-inferior (margin 0.5) vaccine-type HPV antibody responses compared with a 6-month interval. Compared to 6 months, an interval of 36-96 months resulted in non-inferior antibody responses for HPV6 and high-risk types HPV16 and 18, but did not lead to a non-inferior antibody response for HPV11 (GMR 0.63, 95% CI:0.41-0.97). Data on the effectiveness of extended two-dose schedules were limited. Our findings indicate that HPV immunization programs could adopt a 12-month interval instead of 6 months for increased flexibility without compromising immunogenicity. Further evaluation to confirm the immunogenicity and effectiveness of intervals beyond 12 months is warranted.

Declining rates of cervical intraepithelial neoplasia in British Columbia, Canada: An ecological analysis on the effects of the school-based human papillomavirus vaccination program.

Since 2008, girls in British Columbia (BC), Canada, have been offered HPV vaccination through a school-based, publicly funded immunization program. The oldest birth cohort eligible for the vaccination program was born in 1994 and uptake is on average 63%. To evaluate the impact of the HPV vaccine in BC, ecological trends in cervical intraepithelial neoplasia (CIN) rates were assessed in young women before and after the implementation of the HPV vaccination program. Information on all Pap smears and histopathological abnormalities, in calendar years 2004-2017 in women 16-28 years of age in BC were obtained from the population-based BC Cancer Cervix Screening Program database. Rates of CIN 2 and 3 were calculated as the number of cases divided by the number of cytology specimens for that period. Rate ratios (RR) were calculated by negative binomial piecewise regression. Age-centered incidence rates of CIN 2 and 3 in BC declined significantly among women 16-23 years of age after HPV vaccine introduction compared to before vaccine introduction. The overall reduction postvaccination for CIN2 and 3 in women 16-23 years was respectively 62% (95% CI 54-68%) and 65% (95% CI 58-71%). Age-specific rates for CIN2 significantly declined for those 18-22 years of age and for those 19, 20 and 23 years of age for CIN3. Among women 24-28 years of age no decline in CIN2 and 3 rate over time was observed. The observed reduction in CIN 2 and 3 rates since the introduction of the school-based HPV vaccine program might illustrate the population impact of the BC provincial school-based HPV vaccination program.

Association between human papillomavirus vaccine status and sexually transmitted infection outcomes among females aged 18-35 with a history of sexual activity in the United States: A population survey-based cross-sectional analysis.

BACKGROUND: Current human papillomavirus (HPV) vaccine coverage in the United States (in 2019, 66-70%), remains below the Healthy People 2020 coverage goal of 80%. HPV vaccine misinformation, including parental concerns of sexual risk-compensation influence vaccine uptake. We examined the association between HPV vaccination and sexually transmitted infection (STI) outcomes. METHODS: Of the 20,146 participants from 2013 to 2014 and 2015-2016 cycles of the National Health and Nutrition Examination Survey, 1050 females aged 18-35 with a history of sexual activity had complete case data. Roa-Scott Chi-squared and F-tests assessed survey-weighted socio-demographic differences between vaccinated and unvaccinated participants. Weighted logistic regression assessed crude and adjusted associations between self-reported HPV vaccination (none vs. ≥ 1dose) and lab-confirmed STIs (trichomonas and chlamydia) and vaccine-type HPV (6/11/16/18). As a sensitivity analysis, we conducted weighted-propensity score (PS) models and inverse probability weighting by vaccination status. PS and logistic regression were estimated through survey-weighted logistic regression on variables including race, education, income, marital status, US citizenship, cycle year and age. RESULTS: Overall, 325 (31.8%) females with a history of sexual activity were HPV vaccinated, of which 22 (6.1%) received the vaccine at the routine-recommended ages of 11-12, 65.7% were vaccinated after their self-reported sexual debut, 3.8% had a lab-confirmed STI and 3.5% had vaccine-type HPV. There was no association between HPV vaccination and any STIs (adjusted odds ratio [aOR] 0.67, 95%CI:0.38-1.20), and vaccinated participants had 61% reduced odds of vaccine-type HPV (vs. unvaccinated; aOR 0.39, 95%CI:0.19-0.83). Results from the PS sensitivity analysis were similar to the main findings. CONCLUSION: Among females who reported a history of sexual activity, HPV vaccination status was protective against vaccine-type HPV and not associated with lab-based STI outcomes. Although findings may be susceptible to reporting bias, results indicating low vaccine uptake at routine-recommended ages requires additional efforts promoting HPV vaccination before sexual-debut.

Impacts of Human Papillomavirus Immunization Programs on Rates of Anogenital Warts in British Columbia, Canada, 2000 to 2017.

BACKGROUND: In 2008, British Columbia (BC) implemented a school-based quadrivalent human papillomavirus (HPV-4) immunization program for girls born in 1994 or later. In 2015, an expanded clinic-based program included men who report sex with men (MSM) born in 1989 or later. To evaluate the impacts of HPV-4 programs on anogenital warts (AGWs), diagnosis rates were measured among women who report sex with men (WSM), men who report sex with women (MSW), and MSM. METHODS: Diagnoses of AGW were ascertained from 16 sexually transmitted infection clinics. Rates were calculated as new AGW diagnoses over person-years (py) at risk and stratified by age group, calendar period, and birth cohort. Adjusted relative rates (aRR) were estimated using multivariable Poisson regression. RESULTS: There were 204,832 clinic visits by 85,158 individuals: 28,366 (33%) WSM, 35,688 (42%) MSW, and 14,534 (17%) MSM. After adjusting for age and period, AGW rates in the 1994-1996 birth cohort decreased by 56% overall (1.21 vs. 2.72 cases/100 py; aRR, 0.44; 95% confidence interval [CI], 0.34-0.59), 65% among WSM (0.97 vs. 2.77 cases/100 py; aRR, 0.35; 95% CI, 0.22-0.57), 58% among MSW (1.60 vs. 3.78 cases/100 py; aRR, 0.42; 95% CI, 0.28-0.65), and 41% among MSM (1.14 vs. 1.19 cases/100 py; aRR, 0.59; 95% CI, 0.38-0.91) versus the 1991-1993 birth cohort. CONCLUSIONS: The HPV-4 programs had significant impacts on lowering AGW rates in BC. The greatest decrease was among WSM eligible for the school-based program, followed by birth cohorts of men who likely have sex with HPV-4 eligible women. The smallest decrease among MSM may reflect the later introduction of the clinic-based program.

Factors associated with interest in bacterial sexually transmitted infection vaccines at two large sexually transmitted infection clinics in British Columbia, Canada.

OBJECTIVE: To explore sexually transmitted infection (STI) clinic client attitudes and preferences towards STI vaccines and STI vaccine programming in an urban clinic setting. METHODS: A 31-item questionnaire was administered during check-in by clinic clerical staff at two STI clinics in Vancouver, Canada. Demographic characteristics and preferences were summarised descriptively. Multivariable logistic regression models to assess factors associated with STI vaccine interest (reported as ORs) were constructed using a priori clinically relevant variables and factors significant at p≤0.05 in bivariate analysis. RESULTS: 293 surveys were included in analysis. 71.3% of respondents identified as male, 80.5% had college level education or higher and 52.9% identified as white/of European descent. The median age was 33. 86.5% of respondents reported they would be interested in receiving an STI vaccine, with a primary motivator to protect oneself. Bivariate analysis indicated several factors associated with vaccine interest, with differences for each infection. After adjusting for other variables, willingness to pay for an STI vaccine (OR=3.83, 95% CI 1.29 to 11.38, p=0.02) remained a significant factor for syphilis vaccine interest and intent to engage in future positive health behaviours remained a significant factor for chlamydia (OR=5.94, 95% CI 1.56 to 22.60, p=0.01) and gonorrhoea (OR=5.13, 95% CI 1.45 to 18.07, p=0.01) vaccine interest. CONCLUSION: Respondents expressed a strong willingness to receive STI vaccines. These valuable findings will inform for eventual STI vaccine programme planning and implementation.

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.

Cervical Intraepithelial Neoplasia Rates in British Columbia Women: A Population-Level Data Linkage Evaluation of the School-Based HPV Immunization Program.

BACKGROUND: To understand real-world human papillomavirus (HPV) vaccine impact, continuous evaluation using population-based data is critical. We evaluated the early impact of the school-based HPV immunization program on cervical dysplasia in women in British Columbia, Canada. METHODS: Data linkage was performed using records from provincial cervical screening and immunization registries. Precancerous outcomes were compared between unvaccinated and HPV-vaccinated women born 1994-2005. Incidence rate, relative rate (RR), and vaccine effectiveness (VE), using unadjusted and adjusted Poisson regression of cytology (HSIL) and histopathology (CIN2, CIN3, and CIN2+) outcomes, were compared across vaccination status groups. RESULTS: Women who received a complete series of vaccine on schedule between age 9 and 14 years had an adjusted RR = 0.42 (95% confidence interval [CI], 0.31-0.57) for CIN2+ over 7 years of follow-up compared to unvaccinated women, resulting in a VE of 57.9% (95% CI, 43.2%-69.0%). Adjusted RR for HSIL was 0.53 (95% CI, .43-.64), resulting in a VE of 47.1% (95% CI, 35.6%-56.7%). CONCLUSION: Women vaccinated against HPV have a lower incidence of cervical dysplasia compared to unvaccinated women. Immunization between 9 and 14 years of age should be encouraged. Continued program evaluation is important for measuring long-term population impact.

Immunogenicity of 2 and 3 Doses of the Quadrivalent Human Papillomavirus Vaccine up to 120 Months Postvaccination: Follow-up of a Randomized Clinical Trial.

BACKGROUND: Several countries have implemented a 2-dose (2D) human papillomavirus (HPV) vaccination schedule for adolescents based on immunobridging studies. We compared immunogenicity of 2D vs 3-dose (3D) schedules of the quadrivalent vaccine (4vHPV) up to 10 years after the first dose. METHODS: Girls aged 9-13 years were randomized to receive 2D or 3D and were compared with women aged 16-26 receiving 3D at day 1 and months 7, 24, and 120 after the first dose. Antibody levels for HPV6/11/16/18 were evaluated using the competitive Luminex immunoassay (cLIA) and total immunoglobulin G assay. Geometric mean titers (GMTs) and seropositivity rates were compared between the different groups at different time points. Noninferiority of GMT ratios was defined as the lower bound of the 2-sided 95% confidence interval (CI) being greater than 0.5. Kinetics of antibody titers over time among study groups were examined. RESULTS: At 120 months, data from 35 2D girls, 38 3D girls, and 30 3D women were used for analyses. cLIA seropositivity rates were above 95% for all HPV vaccine types and all schedules, except HPV18, with the lowest seropositivity observed among 3D women (60.0%; 95% CI, 40.6%-77.3%). GMT ratios (cLIA) for both 2D and 3D girls were noninferior to 3 doses in women for HPV6/11/16/18. Trends were comparable between assays. CONCLUSIONS: GMTs for HPV6/11/16/18 after 2D or 3D of 4vHPV in girls were noninferior to 3D in adult women up to 120 months postvaccination. This study demonstrates long-term immunogenicity of the 2D HPV vaccine schedule.

The immune response to a two-dose schedule of quadrivalent HPV vaccine in 9-13 year-old girls: Is it influenced by age, menarche status or body mass index?

HPV vaccines are highly immunogenic. A two-dose schedule for 9-14 year-old is recommended. However, no data exist regarding the impact of age, menarche status and body mass index (BMI) on the immune response to a two-dose schedule. In this post-hoc analysis, we present antibody titers to HPV6/11/16/18 in 9-13 year-old girls participating in a randomized clinical trial and assigned to receive two doses of quadrivalent HPV vaccine at 6 months interval (NCT00501137). Antibody titers were measured at month 7 and 24 of the study by using a competitive Luminex immunoassay (cLIA).Both, at Month 7 and 24 the GMTs for four HPV genotypes were similar across the age bands, and did not vary significantly by menarche status. Overweight and obese girls had lower GMTs. More than 99% of girls remained seropositive for HPV 6/11/16 and 89% for HPV18 at month 24. Comprehensive data in overweight and obese vaccines are warranted.

Effect of the bivalent HPV vaccine on viral load of vaccine and non-vaccine HPV types in incident clearing and persistent infections in young Dutch females.

BACKGROUND: HPV vaccination with the bivalent vaccine is efficacious against HPV16 and 18 infections and cross-protection against non-vaccine HPV types has been demonstrated. Here, we assessed (cross-) protective effects of the bivalent HPV16/18 vaccine on incident and persistent infections and viral load (VL) of fifteen HPV types in an observational cohort study monitoring HPV vaccine effects. METHODS: Vaginal samples were obtained annually. Type-specific VL assays were developed for HPV6,11,31 33,35,39,45,51,52,56,58,59 and 66 and used in addition to existing HPV16 and 18 assays. Rate differences of incident clearing and persistent infections were correlated with differences in VL and vaccination status. RESULTS: HPV16/18 vaccination resulted in significantly lower incidence of HPV16/18 infections and significantly lower VL in breakthrough HPV16 (p<0.01) and 18 infections (p<0.01). The effects of vaccination on non-vaccine type VL were ambiguous. Incidence and/or persistence rates of HPV31, 33, 35 and 45 were reduced in the vaccinated group. However, no significant type specific VL effects were found against HPV31, 33, 45, 52 in the vaccinated group. For HPV 6, 59 and 66 no significant reductions in numbers of incident and persistent infections were found, however borderline) VL reductions following vaccination were observed for HPV6 (p = 0.01), 59 (p = 0.10) and 66 (p = 0.03), suggesting a minor effect of the vaccine on the VL level of these HPV types. Overall, vaccination resulted in infections with slightly lower VL, irrespective of HPV type. CONCLUSIONS: In conclusion, vaccination with the bivalent HPV16/18 vaccine results in significantly reduced numbers of HPV16 and 18 incidence rates and reduced VL in breakthrough infections. Significant reductions in incident and/or persistent HPV31, 33, 35 and 45 infections were found, but no significant effect was observed on the VL for infections with these types. For the other non-vaccine HPV types no reduction in incident and/or persistent infections were found, but overall the VL tended to be somewhat lower in vaccinated women.

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.

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.

Effect of human papillomavirus vaccination on sexual behaviour among young females.

Question At the time of implementation of human papillomavirus (HPV) vaccine immunization programs, concerns were raised by parents, clinicians, and public health professionals about HPV vaccination possibly leading to riskier sexual health choices among young females. If HPV vaccination influences sexual behaviour among vaccinated females, this might influence the effect of HPV vaccination programs. What is known about the effects of the HPV vaccination program on sexual behaviour among young females?Answer Human papillomavirus vaccination has not been associated with increased sexual risk behaviour among young females. However, currently available studies have some important limitations, and future studies should focus on a longitudinal design that includes a prevaccination baseline measurement, adjustment for possible confounders, and measurement of both clinical indicators and behavioural outcomes.