Effectiveness of varying number of doses and timing between doses of quadrivalent HPV vaccine against severe cervical lesions

BackgroundBased on immunogenicity studies, a 2 dose HPV vaccination-schedule was recently recommended for girls younger than 15 years. We aimed to investigate the effectiveness of quadrivalent HPV (qHPV) vaccination against CIN2 or worse (CIN2+), by age at vaccination, number of doses, and to test whether optimal timing of 2 doses of qHPV vaccine can confer the same level of protection as the originally recommended three dose-schedule.MethodsA population-based cohort of all women aged 13–30 years, living in Denmark or Sweden during 2006–2013, was followed for qHPV vaccination status and first occurrence of CIN2+.ResultsThe study cohort comprised 2,253,561 women, of which 33% were vaccinated during follow-up, and 1.7% were diagnosed with CIN2+. Vaccination at ages 13–16 and 17–19 was associated with a reduced risk of CIN2+ after 3 doses (IRR = 0.23, 95% CI 0.11–0.49, and IRR = 0.65, 95% CI 0.41–1.03, respectively), compared to being unvaccinated. After 1 and 2 doses there was a reduced risk, but not statistically significant. Women vaccinated ages 13–16 with 2 doses, where time between first and second dose was 5 months or longer showed no difference in risk compared to 3 doses.ConclusionsWomen vaccinated with 3 doses of qHPV showed a reduced risk of CIN2+ if they were vaccinated before age 20, with a further reduced risk if vaccinated before age 17. Vaccination with 2 doses, with the second dose 5 months or longer after the first dose, did not yield an increased risk of CIN2+, compared to 3 doses.     

Human papillomavirus vaccines effectiveness to prevent genital warts: A population-based study using health system integrated databases, 2009–2017

ObjectivesTo assess the effectiveness of the HPV vaccines in preventing genital warts (GW) in women aged 14–23 years and to estimate the incidence of GW in the whole population aged from 14 to 65.DesignPopulation-based retrospective cohort study using real-world data from the Valencia health system Integrated Databases (VID).Study populationAll subjects aged 14–65 years residing in the Valencia Region during 2009–2017 (n = 4,492,724), including a cohort of 563,240 females aged 14–23 years followed-up for the vaccine effectiveness (VE) estimations.Main outcome measuresIncident cases of GW defined as the first activation of GW-related codes (ICD-9-CM 078.11 or ICD-10-CM A63.0) in hospital, primary and specialized care during the study period. Adjusted VE was estimated as (1-Relative Risk (RR)) × 100 by a negative binomial Bayesian model.ResultsThere were 23,049 cases of GW in the overall population and 2,565 in the females’ cohort 14–23 years old. The incidence rate (IR) (in 100,000 persons-year) was 69.1 (95% CI 68.21–69.99) in the population overall, being higher in men (72.73; 95% CI 71.45–74.04). The IR of GW was 104.08 (95% CI 100.79–108.94) in the cohort of young women. The RR of GW increased with age from 14 to 21 years, reaching a plateau from 21 to 23. The VE of a complete schedule was 74% (95% CrI 68–79) for quadrivalent HPV vaccine (HPV4v). No effectiveness was seen with a full vaccination course with the bivalent HPV vaccine (HPV2v) in girls up to 21 years old. GW IR tends to be higher in unvaccinated cohorts covered by HPV4v vaccine than in unvaccinated cohorts not covered by HPV4v vaccine.ConclusionsA complete HPV4v vaccination schedule was 74% effective in reducing GW in our population. Our results also suggest an indirect protection to unvaccinated and HPV2v vaccinated girls.     

Prevalence of oral human papillomavirus by vaccination status among young adults (18–30 years old)

BackgroundAlthough there is evidence that human papillomavirus (HPV) vaccination may protect against oral HPV infection, no current research has demonstrated this in the general population.MethodsWe used repeated cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2014. Participants 18–30 years who indicated whether they had received the HPV vaccine and provided an adequate oral sample were included (N = 3040). Oral HPV types were grouped by vaccine-type (types 6, 11, 16, 18) and by risk (high or low risk). Chi-square analyses compared oral HPV prevalence by vaccination status.ResultsVaccinated adults had a lower prevalence of vaccine-type oral HPV (types 6, 11, 16, 18) compared to unvaccinated adults. Prevalence of non-vaccine high-risk oral HPV was similar between HPV vaccinated and unvaccinated participants.ConclusionsHPV vaccination appears to provide protection against vaccine-type oral HPV infection among males and females in the general population.     

Early impact of Ontario’s human papillomavirus (HPV) vaccination program on anogenital warts (AGWs): A population-based assessment

IntroductionThis study aimed to evaluate the early population impact of Ontario’s school-based human papillomavirus (HPV) vaccination program, implemented in September 2007 for grade 8 females, by comparing anogenital wart (AGW) health care utilization before and after vaccine program implementation, in program-eligible and program-ineligible cohorts, focusing on 15–26 year olds.MethodsUsing a retrospective longitudinal population-based study design, health administrative data were used to identify incident AGWs and total health service utilization (HSU) for AGWs for Ontario residents 15 years and older between April 1 2004 and March 31 2014. The study period was divided into two eras: the pre-vaccine program era and the vaccine program era. Negative binomial models were generated to analyze trends across time by age group and sex. We adjusted female rates for routine Papanicolaou (Pap) testing to address spillover effects of Pap smear policy changes on AGW diagnosis.ResultsBetween fiscal years 2004 and 2013, AGW incidence decreased 2.6% on average per year in 15–17 year old females, and total HSU for AGWs decreased an average of 4.8% and 2.2% per year in 15–17 and 18–20 year old females. Comparing the vaccine era to the pre-vaccine era, AGW incidence decreased 6.5% in 18–20 year old females, and AGW HSU decreased 13.8%, 11.1%, and 10.0% in 15–17, 18–20, and 21–23 year old females respectively. In contrast, male AGW incidence rates increased an average of 4.1%, 2.8%, and 0.9% per year in 15–17, 21–23, and 24–26 year old males respectively. AGW incidence rates increased 12.2% in 15–17 year old males from the pre-vaccine to vaccine era.ConclusionThe decline in AGW incidence and HSU in program-eligible females suggests the school-based HPV vaccination program has had an early population impact in Ontario. The increasing AGW incidence in males suggests no early evidence of herd effects in males.     

The impact of HPV multi-cohort vaccination: Real-world evidence of faster control of HPV-related morbidity

BackgroundIn 2009, both Norway and Denmark initiated routine quadrivalent human papillomavirus vaccination (qHPV) for 12-year-old girls; however, Denmark also introduced free-of-charge multi-cohort vaccination for older age groups in 2008. We aim to describe trends in genital warts (GWs) incidence rates (IRs) among men and women and qHPV vaccine coverage among women in Norway and Denmark in 2006–2015.MethodsWe linked multiple national health registries in Norway and Denmark via national personal identifiers to access data on GWs incidence and qHPV vaccination among women and men aged 12–35 years residing in Norway and Denmark in 2006–2015. We calculated age-specific and age-standardized GWs IRs, GWs IR trends before (2006–2009) and after (2009–2015) the implementation of qHPV vaccination, and qHPV vaccine coverage among women.ResultsIn Norway and Denmark together, there were more than 200,000 cases of incident GWs and over 710,000 girls got at least one dose of qHPV vaccine during the study period. The total qHPV coverage in Norway and Denmark in 2015 was among women aged 12–35 years 24% and 70%, respectively. GWs IRs in Norway and Denmark decreased annually in 2009–2015 among women by 4.8% (95% confidence interval: 4.3 to 5.3) and 18.0% (95%CI: 17.5 to 18.6), respectively, and among men 1.9% (95%CI: 1.4 to 2.4) and 10.7% (95%CI: 10.3 to 11.2), respectively. In Denmark, GWs IRs decreased rapidly among both sexes and all age groups after qHPV vaccination, while Norway showed only a modest decrease.ConclusionRapid decline in HPV-related morbidity is feasible with high coverage of multi-cohort vaccination. However, the decision to vaccinate a single cohort of 12-years-old girls only will postpone HPV-related disease control by at least a decade. Thus countries planning HPV vaccination programs should also initiate multi-cohort vaccination for faster disease control.     

Decline of HPV infections in Scandinavian cervical screening populations after introduction of HPV vaccination programs

ObjectiveTo monitor the changes in prevalence of human papillomavirus (HPV) infections in women <50 years of age, participating in cervical screening programs of Denmark, Norway, and Sweden, before and after introduction of quadrivalent HPV (qHPV) vaccination.MethodsLiquid-based cytology samples were collected from 6538 women who attended cervical screening in Denmark, Norway, and Sweden in 2006–2008 and from 6332 similarly enrolled women in 2012–2013. Denmark started organized qHPV vaccination in 2008, Norway in 2009, and Sweden in 2012. All HPV testing and genotyping was performed using identical enrollment and analysis methods, by accredited general primer polymerase chain reaction methods with typing using the Luminex system.ResultsOverall HPV positivity declined slightly from 36.5% in 2006–2008 to 34.5% in 2012–2013. The decline was most pronounced among women 18–26 years of age: from 54.4% to 48.1% (P < 0.001). The decline was substantial for vaccine HPV types (HPV6/11/16/18: decline from 22.3% to 16.6%; P < 0.001) and was seen for both low-risk vaccine types (HPV6/11 declined from 5.0% to 2.5%) and high-risk vaccine types (HPV16/18 declined from 18.9% to 14.9%). Among women 27–50 years of age, there was no change between the time periods (22.5% and 21.6%, respectively). The significant decline in the younger age group was different in the 3 countries.ConclusionThis population-based study enrolling >12,000 women participating in cervical screening in the 3 Nordic countries before and after introduction of organized qHPV vaccination demonstrated a marked decline in HPV infection in the younger population in the 2 countries where qHPV vaccination programs started in 2008–2009, suggesting that organized HPV vaccination programs resulted in a decrease of HPV types circulating in the general population.     

HPV vaccine acceptance among adolescent males and their parents in two suburban pediatric practices

PurposeTo measure HPV vaccine acceptance among unvaccinated adolescent males and parents and correlate acceptance with knowledge, awareness, and personal experience.MethodsAdolescent males ages 11–21 years old and their parents completed questionnaires measuring attitudes and knowledge about HPV vaccination and personal experience. Acceptance was defined as wanting the vaccine and conditional acceptance as wanting the vaccine if it would protect against genital warts or cervical cancer.ResultsAdolescent (n = 154) and parent (n = 121) vaccine acceptance was low (16% and 34%, respectively); however, conditional acceptance was higher. While adolescents had similar conditional acceptance for a vaccine against genital warts and cervical cancer, parents reported higher conditional acceptance for protection against genital warts. Independent predictors of acceptance included personal experience and demographic variables.ConclusionsHPV vaccine acceptance among adolescents and parents was low. Conditional acceptance levels highlight the importance of education about a few important benefits of HPV vaccination, which may increase vaccination rates.     

HIV viral suppression results in higher antibody responses in HIV-positive women vaccinated with the quadrivalent human papillomavirus vaccine

ObjectiveTo evaluate the immunogenicity and safety of the quadrivalent HPV (qHPV) vaccine in HIV-positive women over 24 months.DesignBetween November 2008 and December 2012, 372 women aged 15 and older were enrolled from 14 Canadian HIV outpatient clinics in an open label cohort study. The qHPV vaccine (0.5 mL) was administered intramuscularly at months 0, 2 and 6. The primary study endpoint was seroconversion to any of the HPV types targeted by the qHPV vaccine. Antibody levels were measured at 0, 2, 7, 12, 18, and 24 months. Adverse events were recorded throughout.ResultsOf 372 participants enrolled, 310 (83%) received at least one dose of the qHPV vaccine and 277 (74%) received all three doses. Ninety-five percent (293/308) were seronegative for at least one vaccine type at baseline. The median age was 38 years (IQR 32–45, range 15–66), 36% were white, 44% black and 13% were of Indigenous origin. Seventy-two percent of participants had a suppressed HIV viral load (VL < 40 c/ml) at baseline, with a median CD4 count of 510 cells/mm³ (376–695). Month 7 HPV type-specific seroconversion rates were 99.0%, 98.7%, 98.1% and 93.6% for HPV types 6, 11, 16 and 18 respectively in the per-protocol population. Participants with suppressed HIV VL at first vaccine had a 1.74–3.05 fold higher peak antibody response compared to those without (p from 0.006 to <0.0001).ConclusionsThis study is the first to examine the qHPV vaccine in HIV-positive women out to 24 months and the first to include HIV-positive women through to age 66. The qHPV vaccine was well tolerated, and highly immunogenic. As women with suppressed viral load had higher antibody responses, planning HPV vaccination to occur when persons are virologically suppressed would be optimal for maximizing immune response. Findings provide strong evidence that older HIV-positive women can still benefit from HPV vaccination.Clinical trial registration: http://www.isrctn.com/ISRCTN33674451     

Effectiveness of adenovirus type 5 vectored and inactivated COVID-19 vaccines against symptomatic COVID-19, COVID-19 pneumonia,and severe COVID-19 caused by the B.1.617.2 (Delta) variant: Evidence from an outbreak in Yunnan,China, 2021

BackgroundIn partial response to the coronavirus disease 2019 (COVID-19) pandemic, countries around the world are conducting large-scale vaccination campaigns. Real-world estimates of vaccine effectiveness (VE) against the B.1.617.2 (Delta) variant are still limited. An outbreak in Ruili city of China provided an opportunity to evaluate VE against the Delta variant of two types of COVID-19 vaccines in use in China and globally – inactivated (CoronaVac and BBIBP-CorV) and adenovirus type 5 vectored (Convidecia) vaccines.MethodsWe estimated VE using a retrospective cohort study two months after the Ruili vaccination campaign (median: 63 days). Close contacts of infected people (Chinese nationality, 18 years and above) were included to assess VE against symptomatic Covid-19, COVID-19 pneumonia, and severe COVID-19. We calculated the relative risks (RR) of the outcomes for unvaccinated compared with fully vaccinated individuals. We used logistic regression analyses to estimate adjusted VEs, controlling for gender and age group (18–59 years and 60 years and over).We compared unvaccinated and fully vaccinated individuals on duration of RT-PCR positivity and Ct value.FindingsThere were 686 close contacts eligible for VE estimates. Adjusted VE of ad5-vectored vaccine was 61.5% (95% CI, 9.5–83.6) against symptomatic COVID-19, 67.9% (95%CI: 1.7–89.9) against pneumonia, and 100% (95%CI: 36.6–100) against severe/critical illness. For the two inactivated vaccines, combined VE was 74.6% (95% CI, 36.0–90.0) against symptomatic COVID-19, 76.7% (95% CI: 19.3–93.3) against pneumonia, and 100% (95% CI: 47.6–100) against severe/critical COVID-19. There were no statistically significant differences in VE between two inactivated vaccines for symptomatic COVID-19 and for pneumonia, nor were there statistically significant differences between inactivated and ad5-vectored VE in any of the three outcomes. The median durations of RT-PCR positivity were 17 days for fifteen people vaccinated with an inactivated vaccine, 18 days for forty-four people vaccinated with the Ad5 vectored vaccine, and 26 days for eleven unvaccinated individuals. InterpretationThese results provide reassuring evidence that the three vaccines are effective at preventing Delta-variant COVID-19 in short term following vaccination campaign, and are most effective at preventing more serious illness. The findings of reduced duration of RT-PCR positivity and length of hospital stay associated with full vaccination suggests potential saving of health-care system resources.     

Trends and predictors of HPV vaccination among U.S. College women and men

BackgroundHPV vaccination was recommended by the Advisory Committee on Immunization Practices for young adult females in 2006 and males in 2011 to prevent HPV-related cancers and genital warts. As this prevention mechanism continues to disseminate, it is necessary to monitor the uptake of this vaccine. College students represent an important population for HPV vaccination efforts and surveillance due to increased risk for HPV infection and representing a priority population for catch-up HPV vaccination. The purpose of this study was to assess the trends in HPV vaccination among U.S. college females and males from 2009 to 2013, and to examine whether predictors for HPV vaccination differ between males and females.MethodsThe National College Health Assessment-II (Fall 2009–2013) was used to assess trends in HPV vaccination using hierarchical logistic regression across genders and demographics. Data from 2013 were used to assess demographic variables associated with HPV vaccination for males and females, respectively. The analysis was conducted in 2015.ResultsFemales had nearly double the rates of HPV vaccination compared to males over time. All demographic sub-groups had significant increases in vaccine rates over time, with select male sub-groups having more accelerated increases (e.g., gay). Young age (18–21 vs. 22–26 years) was a significant predictor for HPV vaccination among males and females, while race/ethnicity was a predictor of vaccination among females only.ConclusionsThese findings identified specific demographic sub-groups that need continued support for HPV vaccination. Campus health centers may be rational settings to facilitate clinical opportunities for HPV vaccination among unvaccinated college students.     

Four-year persistence of type-specific immunity after quadrivalent human papillomavirus vaccination in HIV-infected children: Effect of a fourth dose of vaccine

ObjectiveAlthough HIV-infected children are recommended to receive quadrivalent human papillomavirus vaccine (QHPV) there is limited information on their response to QHPV. This study in HIV-infected children, evaluated the magnitude and duration of immune responses to QHPV. This report describes type-specific serum antibody responses over a 4-to-5 year period after either 3 or 4 doses of QHPV.Design/methodsHIV-infected children, ages 7-to-11 years, received 3 doses of QHPV (n = 96) or placebo (n = 30). At 72 weeks QHPV recipients received a fourth dose (n = 84), while placebo recipients began the 3-dose QHPV schedule (n = 27). HPV serotype-specific antibody was determined, by competitive Luminex immunoassay (cLIA) and IgG Luminex immunoassay, at 2, 3.5, and 4-to-5 years after the last dose of QHPV in each treatment arm.ResultsAt 4-to-5 years after the last dose of QHPV, antibody titers were significantly higher in 4-dose than in 3-dose group. However, the proportion of vaccinees with a seroresponse in the cLIA assay was not different between the two groups (86–93% for HPV types 6, 11, and 16, and 64% for HPV type 18). These results were very similar to the seroresponse rate in these HIV-infected children at 1 month after completing vaccination.ConclusionsChildren with well-controlled HIV infection who receive 3 doses of the QHPV vaccine maintain seropositivity and antibody levels that are generally similar to children of the same age who are not HIV-infected. Antibody titer correlated strongly with low log HIV RNA, low CD8%, and high CD4%. Additionally, a fourth dose of vaccine in HIV-infected children produces a marked rise in antibody characteristic of an anamnestic response and persistence of high antibody levels.Study identification: IMPAACT P1085 (V501-021). CLINICALTRIALS.GOV identifier: NCT01206556.     

Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination

BackgroundThe recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women.MethodsParticipants received at age 10–18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women.ResultsThe dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination.ConclusionOur study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination.     

A single dose of quadrivalent human papillomavirus (HPV) vaccine is immunogenic and reduces HPV detection rates in young women in Mongolia,six years after vaccination

BackgroundEmerging observational evidence suggests a single-dose of human papillomavirus (HPV) vaccine may be protective against vaccine-targeted HPV infection and associated cervical dysplasia. We aimed to demonstrate whether a single dose of quadrivalent HPV (4vHPV) vaccine was immunogenic and reduced HPV detection rates in young women in Mongolia. We also assessed knowledge and attitudes regarding HPV and the HPV vaccine.MethodsA retrospective paired cohort study was undertaken to evaluate the effect of a single dose of 4vHPV, given at age 11–17 years in 2012, on HPV detection rates, when compared with unvaccinated women. Real time PCR was performed on self-administered vaginal swabs for HPV detection. An immunological analysis detecting neutralising antibodies (NAb) to high-risk HPV (HRHPV) genotypes 16 and 18 was performed on sera from a subset of 58 participants. Questionnaires evaluated knowledge, attitudes and self-swab acceptability.FindingsA total of 475 women (mean age 20.4 years ± 1.6) were recruited; 118 vaccinated and 357 unvaccinated women. The prevalence of vaccine-targeted HRHPV16 and 18 was reduced by 92% (95%CI 44–99%) in the vaccinated (1·1%) compared with the unvaccinated (15.4%) group. The percentage of non-vaccine HPV genotypes was similar between vaccinated (26.5%) and unvaccinated (26.7%) groups. Approximately 90% and 58% of vaccinated women remained seropositive after six years for HRHPV16 and 18, respectively, with neutralising antibody levels 5- and 2-fold higher than unvaccinated women (p < 0.001).InterpretationOne dose of 4vHPV vaccine reduces vaccine-targeted HPV genotypes, six years following vaccination, with high levels of HR genotype seropositivity among young Mongolian women.     

Human papillomavirus prevalence and risk factors among Australian women 9–12 years after vaccine program introduction

BackgroundIn Australia, high and widespread uptake of the quadrivalent human papillomavirus (HPV) vaccine has led to substantial population-level reductions in the prevalence of quadrivalent vaccine targeted HPV genotypes 6/11/16/18 in women aged ≤ 35 years. We assessed risk factors for HPV detection among 18–35 year old women, 9–12 years after vaccine program introduction.MethodsWomen attending health services between 2015 and 2018 provided a self-collected vaginal specimen for HPV genotyping (Roche Linear Array) and completed a questionnaire. HPV vaccination status was validated against the National Register. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated for factors associated with HPV detection.ResultsAmong 1564 women (median age 24 years; IQR 21–27 years), Register-confirmed ≥ 1-dose vaccine coverage was highest at 69.3% and 68.1% among women aged 18–21 and 22–24 years respectively, decreasing to 42.9% among those aged 30–35 years. Overall prevalence of quadrivalent vaccine-targeted HPV types was very low (2.0%; 95% CI: 1.4–2.8%) and influenced only by vaccination status (5.5% among unvaccinated compared with 0.7% among vaccinated women; aOR = 0.13 (95% CI: 0.05–0.30)). Prevalence of remaining HPV types, at 40.4% (95% CI: 38.0–42.9%), was influenced by established risk factors for HPV infection; younger age-group (p-trend < 0.001), more recent (p < 0.001) and lifetime sexual partners (p-trend < 0.001), but not vaccination status. Prevalence of HPV31/33/45, which shared risk factors with that of non-vaccine targeted HPV types, was also lower among vaccinated (4%) compared with unvaccinated (7%) women (aOR = 0.51; 95% CI: 0.29–0.89), indicative of cross-protection.ConclusionVaccination has changed the epidemiology of HPV infection in Australian women, having markedly reduced the prevalence of vaccine-targeted types, including amongst women with known risk factors for infection. Vaccinated women appear to be benefiting from modest cross-protection against types 31/33/45 afforded by the quadrivalent HPV vaccine. These results reinforce the importance of HPV vaccination.     

Introduction of a National HPV vaccination program into Bhutan

BackgroundCervical cancer is the most common cancer in Bhutanese women. To help prevent the disease, the Ministry of Health (MoH) developed a national human papillomavirus (HPV) vaccine program.MethodsMoH considerations included disease incidence, the limited reach of cervical screening, poor outcomes associated with late diagnosis of the disease, and Bhutan's ability to conduct the program. For national introduction, it was decided to implement routine immunization for 12 year-old girls with the quadrivalent HPV6/11/16/18 (QHPV) vaccine and a one-time catch-up campaign for 13–18 year-old girls in the first year of the program (2010). Health workers would administer the vaccine in schools, with out-of-school girls to receive the vaccine at health facilities. From 2011, HPV vaccination would enter into the routine immunization schedule using health-center delivery.ResultsDuring the initial campaign in 2010, over 130,000 doses of QHPV were administered and QHPV 3-dose vaccination coverage was estimated to be around 99% among 12 year-olds and 89% among 13–18 year-olds. QHPV vaccine was well tolerated and no severe adverse events were reported. In the three following years, QHPV vaccine was administered routinely to 12 year-olds primarily through health centers instead of schools, during which time the population-level 3-dose coverage decreased to 67–69%, an estimate which was confirmed by individual-level survey data in 2012 (73%). In 2014, when HPV delivery was switched back to schools, 3-dose coverage rose again above 90%.DiscussionThe rapid implementation and high coverage of the national HPV vaccine program in Bhutan were largely attributable to the strength of political commitment, primary healthcare and support from the education system. School-based delivery appeared clearly superior to health centers in achieving high-coverage among 12 year-olds.ConclusionsBhutan's lessons for other low/middle-income countries include the superiority of school-based vaccination and the feasibility of a broad catch-up campaign in the first year.     

Sexual Network Patterns and Their Association With Genital and Anal Human Papillomavirus Infection in Adolescent and Young Men

PurposeThis study aimed to determine individual- and partner-level factors associated with human papillomavirus (HPV) infection in vaccinated and unvaccinated men.MethodsA total of 747 men, aged 13–26 years, completed a survey of sexual behaviors and were tested for genital and perianal/anal HPV (36 types). Sexual network variables included recent and lifetime concurrency (being in more than one sexual relationship at the same time) and recent sex partner discordance (by race, ethnicity, age, and number of sexual partners). We determined individual-level and sexual network variables associated with ≥1 HPV type and HPV16/18, stratified by vaccination status, using separate multivariable logistic regression models.ResultsParticipants' mean age was 21.2 years; 64% were positive for ≥1 HPV type and 21% for HPV16/18. Factors associated with ≥1 HPV type in unvaccinated men included recruitment site and lifetime concurrency. Factors associated with ≥1 HPV type among vaccinated men included recruitment site, Chlamydia history, main male partner, number of lifetime female partners, and no condom use with female partner. Factors associated with HPV16/18 in unvaccinated men included race and partner concurrency. Factors associated with HPV16/18 in vaccinated men included ethnicity, main male partner, and recent concurrency.ConclusionsSexual network variables associated with HPV infection were different based on vaccination status and HPV type, suggesting risk factors for HPV infection may change as the proportion of vaccinated men increases. In addition, participant report of concurrency and not knowing whether one had practiced concurrency were consistent risk factors; clinicians should consider including concurrency in the sexual history to determine the risk of HPV.     

Short-term safety of COVID-19 mRNA vaccines with respect to all-cause mortality in the older population in Norway

BackgroundThere have been concerns about COVID-19 vaccination safety among frail older individuals. We investigated the relationship between COVID-19 mRNA vaccination and mortality among individuals aged ≥ 70 years and whether mortality varies across four groups of health services used.MethodsIn this nationwide cohort study, we included 688,152 individuals aged ≥ 70 years at the start of the Norwegian vaccination campaign (December 27, 2020). We collected individual-level data from the Norwegian Emergency Preparedness Register for COVID-19. Vaccinated and unvaccinated individuals were matched (1:1 ratio) on the date of vaccination based on sociodemographic and clinical characteristics. The main outcome was all-cause mortality during 21 days after first dose of COVID-19 mRNA vaccination. Kaplan-Meier survival functions were estimated for the vaccinated and unvaccinated groups. We used Cox proportional-hazards regression to estimate hazard ratios (HRs) of death between vaccinated and unvaccinated individuals, with associated 95% confidence intervals (CIs), overall and by use of health services (none, home-based, short- and long-term nursing homes) and age group.ResultsBetween December 27, 2020, and March 31, 2021, 420,771 older individuals (61.1%) were vaccinated against COVID-19. The Kaplan-Meier estimates based on the matched study sample showed a small absolute risk difference in all-cause mortality between vaccinated and unvaccinated individuals, with a lower mortality in the vaccinated group (overall HR 0.28 [95% CI: 0.24–0.31]). Similar results were obtained in analyses stratified by use of health services and age group.ConclusionWe found no evidence of increased short-term mortality among vaccinated individuals in the older population after matching on sociodemographic and clinical characteristics affecting vaccination and mortality.     

HPV vaccination coverage and willingness to be vaccinated among 18–30 year-old students in Italy

ObjectivesIn Italy, free HPV vaccination has been offered to 12 years-old girls since 2007, while for males only since 2015. The aims of our study were: to measure HPV vaccination coverage among young women; to assess willingness to receive HPV vaccination among unvaccinated males and females; to evaluate the association of coverage and attitudes with knowledge regarding HPV and with sexual behavior.MethodsA cross-sectional survey was conducted in an Italian region among 18–30 year-old students attending medical and healthcare professions schools. Participants completed a self-administered questionnaire exploring knowledge, attitudes and behaviors related to HPV infections, sexually transmitted diseases and their prevention. Information on vaccination status was also verified for each student through the immunization records provided by the participants during the occupational medical visit.Results517 students were enrolled, with a 97% response rate. Of female participants, 40.5% had received at least one dose of HPV vaccine, while among unvaccinated participants, 60.5% stated their willingness to be vaccinated. A negative attitude towards HPV vaccination was associated with an older age, whereas a correct knowledge that both sexes are at risk of HPV infection, and the knowledge that vaccine protects against cervical cancer were confirmed to be associated to a willingness to receive HPV vaccination.ConclusionsOur results showed low HPV vaccination coverage among young women and high reported willingness to receive vaccination among both sexes. More active education on the link between HPV and all related cancers could be beneficial to help prevent significant burden of the HPV-related diseases.     

Safety and immunogenicity of a 9-valent HPV vaccine in females 12–26 years of age who previously received the quadrivalent HPV vaccine

ObjectivesTo assess the safety and immunogenicity of the investigational 9-valent (6/11/16/18/31/33/45/52/58) HPV (9vHPV) vaccine in prior recipients of a 3-dose regimen of quadrivalent (6/11/16/18) HPV (qHPV) vaccine.MethodsV503-006 was a randomized, double-blinded, safety/tolerability and immunogenicity study of the 9vHPV vaccine in females 12–26 years of age who were previously vaccinated with qHPV vaccine. Subjects were randomized in a 2:1 ratio to receive 3 doses of 9vHPV vaccine (n = 618) or saline placebo (n = 306) at day 1, month 2, and month 6. Systemic, injection-site and serious adverse experiences (AEs) were monitored. Serum samples were collected at day 1, month 2, and month 7. Anti-HPV 6/11/16/18/31/33/45/52/58 titers were measured using the 9-valent HPV competitive Luminex Immunoassay (cLIA).ResultsThe frequency of injection-site AEs (days 1–5 following any vaccination) was higher in the 9vHPV vaccine group than in the placebo group (91.1% and 43.9%, respectively). The frequencies of vaccine-related systemic AEs (days 1–15 following any vaccination) were generally comparable between the 2 groups (30.6% in the 9vHPV vaccine group, and 25.9% in the placebo group). One vaccine-related serious AE was reported in each of the 9vHPV vaccine and placebo groups. Few subjects (9vHPV = 0.5%; placebo = 0%) discontinued due to an AE. At 4 weeks post-dose 3, over 98% of subjects in the 9vHPV vaccine group were seropositive for HPV types 31/33/45/52/58, with marked elevations in cLIA geometric mean titers (GMTs) to these HPV types. Anti-HPV 31/33/45/52/58 GMTs were lower than in subjects administered 9vHPV vaccine who had not previously received qHPV vaccine (based on cross-study analyses); the clinical significance of this difference is unknown.ConclusionsAdministration of a 3-dose regimen of 9vHPV vaccine to adolescent girls and young women 12–26 years of age who are prior qHPV vaccine recipients is highly immunogenic with respect to HPV types 31/33/45/52/58 and generally well tolerated.     

Effectiveness of herpes zoster vaccination in an older United Kingdom population

BackgroundVaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71–79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed.MethodsIn a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013–31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN.ResultsAmong 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60–68%) against incident zoster and 81% (95%CI = 61–91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31–58%) versus 64% (95%CI = 60–68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65–74%) in the first year after vaccination to 45% (95%CI = 29–57%) by the third year.ConclusionThis first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK.