Assessing university students’ sexual risk behaviors as predictors of human papillomavirus (HPV) vaccine uptake behavior

ObjectivesThere exists a significant gap in vaccine coverage of the human papillomavirus (HPV) among college-aged students. This study assessed sexual risk-taking behavior among university students and analyzed predictors of HPV vaccine initiation and completion in this population.Materials and methodsData (n = 746) were from an anonymous online, cross-sectional survey distributed to university students, between the ages of 19–26 years, at a private Midwestern university. Both chi-square and multivariable logistics regression models estimated the association between sociodemographic characteristics and sexual risk factors (including number of vaginal sexual partners, number of oral sexual partners, initiation of oral sex, and initiation of vaginal sex), with HPV vaccine initiation and completion.ResultsA significant number of participants (40%) had not received a single dose of the HPV vaccine series. Of those who initiated the series, more than half (51%) did not achieve completion. Additionally, a greater number of participants have had multiple (4 or more) oral sexual partners than vaginal sexual partners (25.7% vs. 20.3%). After adjusting for covariates, it was found that sexual risk factors were not significantly associated with HPV vaccine initiation or completion.ConclusionHPV vaccine initiation and completion rates are suboptimal among university students. High levels of sexual-risk taking behaviors associated with HPV infection persist, yet are not significant predictors of HPV vaccine behaviors in this age group. To increase uptake among 18–26-year-old students, future public health interventions should focus on HPV vaccine education and uptake across the entire population, irrespective of sexual risk profile.     

Risk,choice and the ‘girl vaccine’: Unpacking human papillomavirus (HPV) immunisation

The marketing of Gardasil® and Cervarix? vaccines for the prevention of human papillomavirus (HPV) targeted pre-sexual girls and cervical cancer, representing young women as practicing ‘decision autonomy’ in acquiring the ‘facts‘ about HPV and cancer. We challenge this overly simple explanatory model of vaccine choice. Through interviews with vaccine scientists and public health nurses in Canada, we illustrate the clinical, political and practical complexities of introducing a new and controversial vaccine. The omission of provocative sexual themes in the marketing of the vaccine strategically created an object marked for ‘women only’. The public acceptability of the vaccine was promoted by neglecting the clinical and sexual facts of the spread and prevalence of HPV infection and related cancers across genders and sexual orientations. This strategic omission generated a blockbuster vaccine embedded in a discourse of individualised risk and pharmaceutical control centred on female bodies.     

‘It’s really complicated’: How Canadian university women students navigate gendered risk and human papillomavirus (HPV) vaccine decision-making

In this article I examine how a group of female university students in Ontario, Canada navigated the notion of ‘gendered risk’ that underpins the current promotion of human papillomavirus (HPV) vaccine. In 2010, I interviewed 24 female university students from across the province of Ontario focussing on their experiences of making decisions about whether or not to have the HPV vaccine. I found that each student’s vaccine decision – whether it was to forgo vaccination, to wait to make a decision or to vaccinate – involved the consideration of notions of gender, negotiation of sexual health issues and management of the uncertainty of a relatively new vaccine. These considerations created a complex situation and produced a complex decision-making context, one that required the women to reflect on the ways in which they exercised their ethical agency. As a result, the women in my sample practiced identity-based vaccine decision-making that was driven by their developing sense of self as a young woman emerging into adulthood.     

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.     

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9–14 years: Results to month 36 from a randomized trial

This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or 3D of 4vHPV] in 1075 healthy girls aged 9–14 years. Girls were randomized (1:1:1) to receive 2D of AS04-HPV-16/18 at months (M) 0, 6 (N = 359), 2D of 4vHPV at M0, 6 (N = 358) or 3D of 4vHPV at M0, 2, 6 (N = 358). 351, 339 and 346 girls, respectively, returned for the concluding visit at M36. Superiority was demonstrated at M7 and M12; comparison of the immune response to both vaccine antigens was made between 2D of AS04-HPV-16/18 and 2D or 3D of 4vHPV at subsequent time points in the according-to-protocol immunogenicity cohort (ATP-I; N = 958 at M36) and the total vaccinated cohort (TVC: N = 1036 at M36). HPV-16/18-specific T-cell- and B-cell-mediated immune responses and safety were also investigated. At M36, anti-HPV-16/18 ELISA responses in the 2D AS04-HPV-16/18 group remained superior to those of the 2D and 3D 4vHPV groups. In the M36 TVC, geometric mean titers were 2.78-fold (HPV-16) and 6.84-fold (HPV-18) higher for 2D of AS04-HPV-16/18 vs. 2D of 4vHPV and 2.3-fold (HPV-16) and 4.14-fold (HPV-18) higher vs. 3D of 4vHPV. Results were confirmed by vaccine pseudovirion-based neutralisation assay. Numbers of circulating CD4⁺ T cells and B cells appeared similar across groups. Safety was in line with the known safety profiles of both vaccines. In conclusion, superior HPV-16/18 antibody responses were elicited by 2D of the AS04-HPV-16/18 compared with 2D or 3D of the 4vHPV vaccine in girls aged 9–14 years.Clinical Trial Registration: NCT0146235.     

Benefit-risk assessment of COVID-19 vaccine,mRNA (Comirnaty) for age 16–29 years

Since authorization of the Pfizer-BioNTech COVID-19 Vaccine, mRNA (Comirnaty), real-world evidence has indicated the vaccines are effective in preventing COVID-19 cases and related hospitalizations and deaths. However, increased cases of myocarditis/pericarditis have been reported in the United States associated with vaccination, particularly in adolescents and young adults. FDA conducted a benefit-risk assessment to determine whether the benefits of vaccination outweigh the risks among various age (16–17, 18–24, 25–29) and sex (M/F) subgroups being considered for approved use of the vaccine. We conducted a simulation study with sensitivity analysis of the benefits and risks of the vaccine across possible pandemic scenarios. The model results show benefits outweigh the risks for all scenarios including the high-risk subgroup, males 16–17 years old. Our worst-case scenario used sex and age subgroup-specific incidences for COVID-19 cases (47–98 per million per day) and hospitalizations (1–4 per million per day) which are the US COVID-19 incidences as of July 10, 2021, vaccine efficacy of 70% against COVID-19 cases and 80% against hospitalization, and unlikely, pessimistic, non-zero vaccine-attributable myocarditis death rate. For males 16–17 years old, the model predicts prevented COVID cases, hospitalizations, ICUs, and deaths of 13577, 127, 41, and 1, respectively; while the predicted ranges for excess myocarditis/pericarditis cases, hospitalizations, and deaths attributable to the vaccine are [98–196], [98–196], and 0, respectively, for the worst-case scenario. Considering the different clinical implications of hospitalization due to COVID-19 infection versus vaccine-attributable myocarditis/pericarditis cases, we determine the benefits still outweigh the risks even for this high-risk subgroup. Our results demonstrate that the benefits of the vaccine outweigh its risks for all age and sex subgroups we analyze in this study. Uncertainties exist in this assessment as both benefits and risks of vaccination may change with the continuing evolution of the pandemic.     

Binding antibody levels to vaccine (HPV6/11/16/18) and non-vaccine (HPV31/33/45/52/58) HPV antigens up to 7 years following immunization with either Cervarix® or Gardasil® vaccine

Human Papillomavirus (HPV) bivalent (Cervarix®) and quadrivalent (Gardasil®) vaccines demonstrate robust efficacy against vaccine types and cross-protection against related non-vaccine types. Here we evaluate the breadth, magnitude and durability of the vaccine-induced antibody response against vaccine (HPV6/11/16/18) and non-vaccine (HPV31/33/45/52/58) type antigens up to 7 years following vaccination of 12‐15 year old girls in a three dose schedule and contrast these data with the levels of antibody typically seen in natural infection. Vaccine-type antibody levels waned over the 7-year follow up period but remained at least an order of magnitude above the typical antibody levels elicited by natural infection. Seropositivity to non-vaccine types remained high 7 years after initial vaccination, but antibody levels approached those typically generated following natural infection. Empirical data on the breadth, magnitude, specificity and durability of the immune response elicited by the HPV vaccines contribute to improving the evidence base supporting this important public health intervention.     

Understanding the public health value and defining preferred product characteristics for therapeutic human papillomavirus (HPV) vaccines: World Health Organization consultations,October 2021—March 2022

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in >62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness.     

Innate and adaptive cellular immunity in flavivirus-naïve human recipients of a live-attenuated dengue serotype 3 vaccine produced in Vero cells (VDV3)

VDV3, a clonal derivative of the Mahidol live-attenuated dengue 3 vaccine was prepared in Vero cells. Despite satisfactory preclinical evaluation, VDV3 was reactogenic in humans. We explored whether immunological mechanisms contributed to this outcome by monitoring innate and adaptive cellular immune responses for 28 days after vaccination. While no variations were seen in serum IL12 or TNFalpha levels, a high IFNgamma secretion was detected from Day 8, concomitant to IFNalpha, followed by IL10. Specific Th1 and CD8 responses were detected on Day 28, with high IFNgamma/TNFalpha ratios. Vaccinees exhibited very homogeneous class I HLA profiles, and a new HLA B60-restricted CD8 epitope was identified in NS3. We propose that, among other factors, adaptive immunity may have contributed to reactogenicity, even after this primary vaccination. In addition, the unexpected discordance observed between preclinical results and clinical outcome in humans led us to reconsider some of our preclinical acceptance criteria. Lessons learned from these results will help us to pursue the development of safe and immunogenic vaccines.     

HPV triage testing or repeat Pap smear for the management of atypical squamous cells (ASCUS) on Pap smear: is there evidence of process utility?

A two-stage standard gamble was used to evaluate women's preferences for alternative managements of atypical squamous cells of undermined significance (ASCUS) on Pap smear (repeat Pap smear compared with immediate HPV test), and to test for the evidence of process utility. Women's utilities for the health state scenarios were clustered towards the upper end of the 0-1 scale with considerable variability in women's preferences. There was evidence of process utility, with immediate human papillomavirus (HPV) testing strategies having lower valuations than repeat Pap smear, where the clinical outcome was the same. Mean (95% CI) utilities for HPV testing (negative test) followed by resolution were 0.9967 (0.9957-0.9978) compared with repeat Pap smear followed by resolution: 0.9972 (0.9964-0.9980). Mean (95% CI) utilities for immediate HPV testing (positive test), followed by colposcopy, biopsy and treatment were 0.9354 (0.8544-1.0) compared with repeat Pap smear followed by colposcopy, biopsy and treatment: 0.9656 (0.9081-1.0). Our results add to the existing evidence that the impact of healthcare interventions on well-being is not limited to the effect of the intervention on the health outcomes expected from the intervention; process of care can have quality of life implications for the individual. A modelled application of trial-based data will allow characterisation of the true population costs, benefits, risks and harms of alternative triage strategies and subsequent policy implications thereof.     

Tocopherol metabolites 2, 5, 7, 8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman (α-CEHC) and 2, 7, 8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC) in human serum after a single dose of natural vitamin E

Summary Backgroundα- and γ-Tocopherol are vitamin E compounds in human blood and tissues. α-CEHC (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman) and γ-CEHC (2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman) have been identified as water-soluble metabolites which are excreted with the urine in humans. Aim of the study To assess over-time changes of serum levels of α- and γ-CEHC in humans after a single dose of vitamin E from a natural source. Methods Twenty-one healthy subjects ingested a single dose of vitamin E (306 mg of RRR-α-tocopherol and 1.77 mg of γ-tocopherol). Blood was collected before (baseline) and 2, 6, 12, 24, 35, 50, and 74 h after ingestion. Serum was separated and levels of α- and γ-tocopherol and α- and γ-CEHC were determined by HPLC. Results After vitamin E ingestion, a statistically significant increase was observed for α-tocopherol and α-CEHC. Maximum serum levels for both compounds were measured 12 h after application (33.3 ± 11.1 μmol α-toco-pherol /L and 42.4 ± 18.3 nmol α-CEHC /L); baseline values were reached again after 72 h. While γ-tocopherol levels decreased during the study period, an increase in the metabolite γ-CEHC was observed. The optical isomer formed in the metabolism of RRR-α-tocopherol was assigned as S-α-CEHC. Conclusionsα-CEHC levels increase after administration of a single dose of natural vitamin E in humans. The appearance of the metabolite in blood parallels that of the parent compound. The γ-tocopherol analog appears to be metabolized more efficiently than α-tocopherol. Received: 14 November 2001, Accepted: 5 April 2002     

Does accounting for gene‐environment (G×E) interaction increase the power to detect the effect of a gene in a multifactorial disease?

Despite tremendous efforts, few genes involved in the susceptibility for complex disorders have been identified. One explanation is that these disorders are a result of an interaction between genes and environment, and under such conditions, it may be difficult to measure the true genetic effect without accounting for the interaction. Umbach and Weinberg ([2000] Am. J. Hum. Genet. 66:251-261) proposed an association test which looks at the joint effects of genotype and environment, using case-parent trios. In this study, we explore under which conditions accounting for GxE interaction enhances one's ability to detect the role of genetic factors in complex diseases. Using asymptotic power calculations, we investigate the power to detect the gene effect over varying exposure frequencies and different scenarios of GxE interaction. We show that for a given sample size, interaction scenario, and allele frequency, the actual gain in power while accounting for the interaction depends on the magnitude of the exposure frequency: the largest gains are seen for relatively low exposure frequencies. Moreover, a loss of power can be observed when the exposure is frequent and/or the exposure effect is strong. If we consider a gene with a disease allele frequency of 0.2, with no effect in the absence of exposure, an exposure with a 10-fold increase risk and a GxE relative risk of 2, then when the exposure frequency is 0.1, accounting for GxE interaction increases the power to detect the gene effect in 200 trios by 10%; alternatively, when the exposure frequency is 0.9, it decreases the power by 15%.     

Immunogenicity and safety of two novel human papillomavirus 4- and 9-valent vaccines in Chinese women aged 20–45 years: A randomized,blinded, controlled with Gardasil (type 6/11/16/18), phase III non-inferiority clinical trial

BackgroundHuman papillomavirus (HPV) infections were the main cause of anogenital cancers and warts. HPV 6/11/16/18 vaccines provide protection against the high-risk types of HPV responsible for 70% of cervical cancers and 90% of genital warts. This randomized, blinded, non-inferiority phase III trial was to determine whether immunogenicity and tolerability would be non-inferior among women after receiving two novel 4- and 9-valent HPV vaccines (4vHPV, HPV 6/11/16/18; 9vHPV, HPV 6/11/16/18/31/33/45/52/58) compared with those receiving Gardasil 4 (4-valent).Methods1680 females between 20 and 45 years were randomized in a 2:1:1 ratio to 20–26, 27–35, or 36–45 y groups. Subjects then equally assigned to receive 4vHPV, 9vHPV or Gardasil 4 (control) vaccine at months 0, 2, and 6. End points included non-inferiority of HPV-6/11/16/18 antibodies for 4vHPV versus control, and 9vHPV versus control and safety. The immunogenicity non-inferiority was pre-defined as the lower bound of 95% confidence interval (CI) of seroconversion rate (SCR) difference > ?10% and the lower bound of 95% CI of geometric mean antibody titer (GMT) ratio > 0.5.ResultsAmong the three vaccine groups, more than 99% of the participants seroconverted to all 4 HPV types. The pre-specified statistical non-inferiority criterion for the immunogenicity hypothesis was met: all the lower bounds of 95% CIs on SCR differences exceeded ?10% for each vaccine HPV type and the corresponding lower bounds of 95% CIs for GMT ratios > 0.5. Across vaccination groups, the most common vaccination reaction were injection-site adverse events (AEs), including pain, swelling, and redness. General and serious AEs were similar in the three groups. There were no deaths.ConclusionsThis study demonstrated that the novel 4- and 9-valent HPV vaccination was highly immunogenic and generally well tolerated, both of which were non-inferior to Gardasil 4 in immunogenicity and safety.