Do correlates of HPV vaccine initiation differ between adolescent boys and girls?

Background

Guidelines now recommend that adolescents routinely receive human papillomavirus (HPV) vaccine. Because little is known about uptake among boys, we assessed HPV vaccine initiation in a population-based sample of adolescent boys and girls.

Methods

We analyzed weighted data from 751 parents who reported on an 11- to 17-year-old son or daughter for the 2010 North Carolina Child Health Assessment and Monitoring Program survey. Stratified multivariate logistic regression analyses identified correlates of HPV vaccine initiation separately for boys and girls.

Results

Only 14% of sons had received one or more doses of HPV vaccine compared to 44% of daughters (p < 0.01). For both sons and daughters, vaccine initiation correlated with age and having received meningococcal vaccine. Among sons, initiation of HPV vaccine was lower for those living in high income households (odds ratio [OR] = 0.22, 95% CI, 0.09–0.53) and higher for those whose race was neither white nor black (OR = 3.26, 95% CI, 1.06–10.04). When asked to give the main reason for not vaccinating their child against HPV, parents of unvaccinated sons were more likely than those of daughters to report not getting a provider's recommendation or not being aware that the vaccine was available for their child, but less likely to report concern about safety (p < 0.01). At least 86% of unvaccinated children had missed an opportunity to receive HPV vaccine.

Conclusions

HPV vaccine correlates and concerns varied for parents of boys and girls. To improve very low levels of uptake among boys, providers should recommend HPV vaccine concomitant with other adolescent vaccines.     

The HPV vaccine: are dosing recommendations being followed?

The aims of this study were to determine the percentage of females who after initiating the human papillomavirus (HPV) vaccine series, both completed it and completed it on-time, as well as to examine factors associated with series completion and on-time completion. Using data from the North Carolina Immunization Registry, of 138,823 females analyzed, 55% completed the series, and 28% completed it on-time. Over 83% of those who initiated the vaccine series in 2006 completed it by the final study date, as compared to 32% of those who initiated the vaccine in 2009. On-time dosing rates, however, are declining, and have been hovering at 25% for the last two years of the study. Factors such as African-American race and public funding were significantly associated with lower rates of on-time dosing as well as series completion when compared to White race and private funding, respectively. Among girls and young women who initiate the HPV vaccination series, overall completion rates are low, but if given enough time most of those who begin the series will complete it. Our results suggest that strategies to improve the timely completion of the HPV vaccination series may be needed.     

Providers’ time spent and tools used when discussing the HPV vaccine with parents of adolescents

ObjectivesLittle is known about HPV vaccine communication tools currently used by primary care providers of adolescents, or how such tools impact the quality of HPV vaccine recommendations, which some have defined as using a “presumptive” communication style, continuing to offer vaccines despite resistance, and strongly recommending vaccines at the appropriate ages. We surveyed primary care providers to assess their current use of HPV vaccine communication tools, and how these related to their HPV vaccine recommendation quality.Study DesignCross sectional survey of 183 pediatrics and family medicine primary care providers in the Denver metro area.ResultsResponse rate was 82% (n = 150). Most (59%) providers used a presumptive vaccine recommendation >75% of the time, and 76% reported continuing to offer the HPV vaccine even after parent refusal. However, less than two-thirds of providers “strongly” recommended the vaccine to 11–12 year olds (60% for females, 55% for males, p = 0.02). The HPV vaccine information sheet from the Centers from Disease Control and Prevention was the most frequently used communication tool during clinical visits (64% used at least 75% of the time) and directing parents to preferred websites was the most frequently used between-visit communication tool (21% used >50% of visits). Use of tools was not associated with any measure of HPV vaccine recommendation quality but was associated with longer HPV vaccine discussion times.ConclusionsProviders use only limited types of adolescent HPV vaccine communication tools, and frequently do not use preferred vaccine communication strategies. Better engagement with existing HPV vaccine communication tools, and/or the creation of new tools may be needed to enhance providers’ ability to provide high quality HPV vaccine recommendations.     

Parental predictors of HPV vaccine initiation among low-income Hispanic females aged 11–17 years

PurposeHispanic women experience a disproportionate burden of cervical cancer morbidity and mortality compared to non-Hispanic women. Increasing HPV vaccination among Hispanic adolescents can help alleviate disparities. This study aimed to identify parental psychosocial predictors associated with HPV vaccine initiation and correlates of parental intentions to obtain the vaccine for their Hispanic adolescent daughters aged 11–17 years.MethodsThis study is part of a larger three-arm randomized controlled trial testing the effectiveness of interventions to increase HPV vaccination. Parents of adolescent females were recruited in community clinics where we conducted baseline surveys. We obtained electronic medical records six months after baseline to assess vaccination status. Multilevel logistic regression was used to identify correlates of parental intentions to vaccinate and predictors of HPV vaccine initiation. Analyses with initiation as the outcome also controlled for intervention study arm. The Integrated Behavioral Model guided selection of psychosocial and outcome variables.ResultsOur sample (n = 765) consisted mostly of mothers with less than a high school education born outside of the U.S. Forty-one percent had a household income less than $15,000. Most daughters had public or private insurance. Twenty-one percent initiated the HPV vaccine series. Correlates of intention to vaccinate intention included subjective norms related to daughter’s doctor (AOR = 1.04; 95% CI 1.01–1.07), belief that the vaccine is safe (AOR = 1.38; 95% CI 1.06–1.78), self-efficacy to obtain the vaccine for their daughter (AOR = 2.39; 95% CI 1.52–3.77), and parental concern about vaccine side effects (AOR = 0.73; 95% CI 0.60–0.89). Intentions predicted initiation (AOR = 2.01; 95% CI 1.10–5.26); concern about sexual disinhibition decreased the odds of having a vaccinated daughter at follow-up (AOR = 0.66; 95% CI 0.47–0.92).DiscussionParental intention and concerns about sexual disinhibition predict vaccine initiation. Further research is needed to explore the role of intention as a potential mediator between psychosocial variables and vaccination status.     

Human papillomavirus (HPV), HPV-associated oropharyngeal cancer,and HPV vaccine in the United States—Do we need a broader vaccine policy?

Background

Human papillomavirus (HPV) is a sexually transmitted infection (STI) of global importance; it is the most prevalent STI in the United States, with strains causally linked to oropharyngeal and other cancers. Efforts to prevent HPV have been made to varying degrees by policies implemented by different state governments; however, HPV and associated oropharyngeal cancer continue to show increasing incidence rates in the US.

Design

A narrative review based on search on SciVerse, PubMed/Medline, Google Scholar, and EMBASE databases, as well as literature/documents from the World Health Organization, Centers for Disease Control and Prevention, American Cancer Society, National Conference of State legislatures, and the U.S. Department of Health and Human Services relevant to HPV and HPV vaccine policy in the US.

Results

Vaccination has proved to be a successful policy in the US, and an extant recommendation aimed at preventing HPV and associated cervical and other anogenital cancers is the routine use of HPV vaccines for males and females. However, HPV vaccines are presently not recommended for preventing oropharyngeal cancer, although they have been shown to be highly effective against the HPV strains that are most commonly found in the oropharynx. And while there is a history of successful vaccine mandate in the US with resulting decrease in occurrence of infectious diseases, implementing HPV vaccine mandate has proved to be very unpopular.

Conclusions

With emerging evidence of the efficacy of the use of the HPV vaccine in preventing oral-HPV, more focus should be put on extending HPV vaccine to present oral HPV infection and oropharyngeal cancer. Also, implementing a broader HPV vaccine policy that include mandating HPV vaccines as a school-entry requirement for both sexes may increase vaccine use in the US for the greater good of the public.     

Physicians’ decision processes about the HPV vaccine: A qualitative study

BackgroundThe contemporary crisis of trust in vaccines has severely impaired acceptance of the HPV vaccine, especially in France, where its uptake culminated at 23.7% in 2018 (complete course at age 16). Physicians’ recommendations strongly influence its acceptance/refusal. Our study sought to understand the decision processes leading physicians to recommend this vaccine (or not).MethodsQualitative interviews of French physicians (general practitioners, gynecologists, and pediatricians). We first randomly selected doctors in a national register of medical professionals and then resorted to snowballing to build a convenience sample. We coded the interviews in a thematic analysis built both inductively and deductively from our research questions and data.ResultsTwo thirds of the participants (19/28) were favorable to HPV vaccination, some (4) opposed it, while the others were hesitant about recommending it. In explaining their opinions, most participants mentioned that they trusted the stakeholders within the vaccination system: the less trust they had, the more critical they were of the vaccine and the more importance they attributed to patients’ opinions. We identified three different ways they interacted with patients on this topic: informing and convincing; adapting to patients’ opinions; refusing compromise about vaccination. Crossing these various themes, we found 5 types of physicians: dissidents (mistrustful of the healthcare system and HPV vaccine), hesitant (finding it difficult to make up their minds about this vaccination), laissez-faire (letting patients decide by themselves, but very favorable to HPV vaccination), educator (very favorable), and uncompromising vaccinators (refusing debate). Pediatricians were overrepresented among the latter two types.ConclusionsPhysicians’ judgment was influenced by their trust in the stakeholders involved in designing and implementing the HPV vaccination strategy. In this sense, doctors did not differ substantially from laypeople. They were, nonetheless, strongly influenced by their professional style and ethos.     

Do the media provide transparent health information? A cross-cultural comparison of public information about the HPV vaccine

The media is a powerful tool for informing the public about health treatments. In particular, the Internet has gained importance as a widely valued source for health information for parents and adolescents. Nonetheless, traditional sources, such as newspapers, continue to report on health innovations. But do websites and newspaper reports provide balanced information? We performed a systematic media analysis to evaluate and compare media coverage of the human papillomavirus (HPV) vaccine on websites and in newspapers in Germany and Spain. We assessed to what extent the media provide complete (pros and cons), transparent (absolute instead of relative numbers), and correct information about the epidemiology and etiology of cervical cancer as well as the effectiveness and costs of the HPV vaccine. As a basis for comparison, a facts box containing current scientific evidence about cervical cancer and the HPV vaccine was developed. The media analysis included 61 websites and 141 newspaper articles in Germany, and 41 websites and 293 newspaper articles in Spain. Results show that 57% of German websites and 43% of German newspaper reports communicated correct estimates of epidemiological data, whereas in Spain 39% of the websites and 20% of the newspaper did so. While two thirds of Spanish websites explicitly mentioned causes of cervical cancer as well as spontaneous recovery, German websites communicated etiological information less frequently. Findings reveal that correct estimates about the vaccine's effectiveness were mentioned in 10% of German websites and 6% of German newspaper reports; none of the Spanish newspaper reports and 2% of Spanish websites reported effectiveness correctly. Only German websites (13%) explicitly referred to scientific uncertainty regarding the vaccine's evaluation. We conclude that the media lack balanced reporting on the dimensions completeness, transparency, and correctness. We propose standards for more balanced reporting on websites and in newspapers.     

How much will it hurt? HPV vaccine side effects and influence on completion of the three-dose regimen

We examined the prevalence of reported pain following human papillomavirus (HPV) vaccination and whether it differed from that for other adolescent vaccines or affected completion of the HPV vaccine regimen. In 2008, we conducted cross-sectional surveys with parents of adolescent girls aged 11–20 living in areas of North Carolina with elevated cervical cancer rates who had received at least one dose of HPV vaccine. Pain from HPV vaccination, while commonly reported by parents, was less frequent compared to other adolescent vaccines and did not appear to affect vaccine regimen completion. These findings may be important to increase HPV vaccination coverage.     

Early smallpox vaccine manufacturing in the United States: Introduction of the “animal vaccine” in 1870, establishment of “vaccine farms”, and the beginnings of the vaccine industry

For the first 80–90 years after Jenner’s discovery of vaccination in 1796, the main strategy used to disseminate and maintain the smallpox vaccine was arm-to-arm vaccination, also known as Jennerian or humanized vaccination. A major advance occurred after 1860 with the development of what was known as “animal vaccine”, which referred to growing vaccine material from serial propagation in calves before use in humans. The use of “animal vaccine” had several advantages over arm-to-arm vaccination: it would not transmit syphilis or other human diseases, it ensured a supply of vaccine even in the absence of the spontaneous occurrence of cases of cowpox or horsepox, and it allowed the production of large amounts of vaccine. The “animal vaccine” concept was introduced in the United States in 1870 by Henry Austin Martin. Very rapidly a number of “vaccine farms” were established in the U.S. and produced large quantities of “animal vaccine”. These “vaccine farms” were mostly established by medical doctors who saw an opportunity to respond to an increasing demand of smallpox vaccine from individuals and from health authorities, and to make a profit. The “vaccine farms” evolved from producing only smallpox “animal vaccine” to manufacturing several other biologics, including diphtheria- and other antitoxins. Two major incidents of tetanus contamination happened in 1901, which led to the promulgation of the Biologics Control Act of 1902. The US Secretary of the Treasury issued licenses to produce and sell biologicals, mainly vaccines and antitoxins. Through several mergers and acquisitions, the initial biologics licensees eventually evolved into some of the current major American industrial vaccine companies. An important aspect that was never clarified was the source of the vaccine stocks used to manufacture the smallpox “animal vaccines”. Most likely, different smallpox vaccine stocks were repeatedly introduced from Europe, resulting in polyclonal vaccines that are now recognized as “variants” more appropriately than “strains”. Further, clonal analysis of modern “animal vaccines” indicate that they are probably derived from complex recombinational events between different strains of vaccinia and horsepox. Modern sequencing technologies are now been used by us to study old smallpox vaccine specimens in an effort to better understand the origin and evolution of the vaccines that were used to eradicate the smallpox.     

Impact of BRICS’ investment in vaccine development on the global vaccine market

Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector’s price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS’ accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes.     

Comparison of the immune responses to the CIA06-adjuvanted human papillomavirus L1 VLP vaccine with those against the licensed HPV vaccine Cervarix™ in mice

CIA05 is a toll-like receptor (TLR) 4 agonist derived from an Escherichia coli lipopolysaccharide (LPS) mutant and has been shown to have potential as a vaccine adjuvant. In this study, we investigated the immunopotentiating activity of the adjuvant system CIA06, which is comprised of CIA05 and aluminum hydroxide (alum), when used with the human papillomavirus (HPV) L1 virus-like particles (VLPs) vaccine. BALB/c mice were immunized intramuscularly three times at 2-week intervals with HPV16 L1 VLPs alone or in the presence of various combinations of CIA05 and alum, and the immune responses were assessed. We found that the combination of CIA05 and alum at a ratio of 1:50 (designated CIA06B) yielded the highest immune response in terms of serum anti-HPV L1 VLP IgG antibody titers, splenocyte interferon (IFN)-γ secretion, and antigen-specific memory B cell responses. The immunogenicity of the CIA06B-adjuvanted HPV16/18 L1 VLP vaccine was compared with that of the currently licensed HPV vaccine Cervarix™. The CIA06B-adjuvanted vaccine was similar to Cervarix™ with regard to eliciting serum antigen-specific IgG antibodies and virus-neutralizing antibodies but more effective at inducing splenic cytokine production and memory B cells. We also observed that the antigen-specific IgG antibody titers, splenic IFN-γ secretion and memory B cells induced by the CIA06B-adjuvanted HPV vaccine remained high up to 24 weeks post-immunization. Based on these data, we concluded that CIA06B may have potential as an adjuvant in a potent prophylactic vaccine against HPV infection.     

US medical students’ willingness to offer the HPV vaccine by vaccination status

We surveyed third-year medical students to assess whether personal vaccination status was associated with willingness to recommend the human papillomavirus vaccine to patients. A total of 231 students completed an anonymous survey evaluating their knowledge, attitudes, and personal vaccine history. Of 122 female students, 81 (66.4%) reported initiating the vaccine, as did 16 of 109 males (14.7%). Females and students ⩽25 years old were more likely to be vaccinated. Knowledge did not vary by vaccination status, but anticipated behaviors did. Vaccinated students reported greater willingness to vaccinate adolescents before 15–16 years of age (92.1% vs. 78.6%, p = 0.008) and discuss vaccination at any type of medical visit (100% vs. 89.7%, p < 0.001). Our findings suggest that prior experiences with the HPV vaccine may influence a provider’s future actions. Thus, interventions that increase awareness of this relationship as well as vaccination rates among health care students may be beneficial.     

Effectiveness of inactivated influenza vaccine in children by vaccine dose, 2013–18

ObjectivesWe assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses.MethodsVE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed.ResultsIn the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 [95% CI, 0.505–0.621], 0.550 [95% CI, 0.516–0.586]), 0.549 [95% CI, 0.517–0.583], and 1.014 [95% CI, 0.907–1.135], for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1–12 years, especially among those aged 1–5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A.ConclusionsBoth one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.     

Sequential administration of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine–naïve adults 60–64 years of age

Background

Unlike free pneumococcal polysaccharide vaccines (PPSVs), pneumococcal conjugate vaccines (PCVs) induce a T–cell–dependent immune response. The study assessed potential influence of initial 13-valent PCV (PCV13) or 23-valent PPSV (PPSV23) on subsequent vaccine administrations.

Methods

We conducted a randomized, modified double-blind study in 720 pneumococcal vaccine–naïve adults 60–64 years of age. Subjects received either PCV13 at year 0 and PCV13 at year 1; PCV13 at year 0 and PPSV23 at year 1; or PPSV23 at year 0 and PCV13 at year 1. Antipneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after each vaccination.

Results

OPA titers following PPSV23 given 1 year after PCV13 (PCV13/PPSV23) (a) were noninferior for the 12 common serotypes and significantly higher for 6 of 12 common serotypes than those following only an initial PPSV23; and (b) were significantly higher for 11 of 12 common serotypes compared with PPSV23 followed by PCV13 (PPSV23/PCV13). In addition, PPSV23 followed 1 year later by PCV13 (PPSV23/PCV13) elicited significantly lower OPA titers than after only an initial dose of PCV13 for all 13 serotypes. Responses after a second vaccination with either PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for 9 of 13 and 8 of 12 common serotypes compared with the initial PCV13 dose.

Conclusion

In pneumococcal vaccine–naïve adults 60–64 years of age, an initial PCV13 augmented the antipneumococcal response to subsequent administration of PPSV23 for many of the serotypes in common to both vaccines. In contrast, an initial PPSV23 resulted in a diminished response to subsequent administration of PCV13 for all serotypes. With a relatively short 1-year interval between doses, responses after a second vaccination with PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for a majority of serotypes compared with the initial PCV13 dose, probably reflecting the need for a longer interval between vaccine administrations.ClinicalTrials.gov Identifier: NCT00574548.     

Cost–effectiveness of the prophylactic HPV vaccine: An application to the Netherlands taking non-cervical cancers and cross-protection into account

Despite an effective screening programme, 600–700 women are still diagnosed with cervical cancer in the Netherlands each year. In 2009 a prophylactic vaccine against HPV-type 16 and 18 was implemented in the national immunisation programme to decrease the incidence of cervical cancer. There is evidence that infections with several oncogenic HPV types other than the vaccine types 16 and 18 are also prevented by vaccination, also known as cross-protection. Besides cervical cancer, HPV can also cause cancers at other sites such as the oropharynx, vulva, vagina and the anus/anal area. In this study we estimated the maximum health and economic benefits of vaccinating 12-year old girls against infection with HPV, taking cross-protection and non-cervical cancers into account. In the base-case, we found an incremental cost ratio (ICER) of €5815 per quality adjusted life year (QALY). Robustness of this result was examined in sensitivity analysis. The ICER proved to be most sensitive to vaccine price, discounting rates, costs of cervical cancer and to variation in the disutility of cervical cancer.     

Optimization of human papillomavirus (HPV) type 16 E7-expressing lactobacillus-based vaccine for induction of mucosal E7-specific IFNγ-producing cells

Therapeutic HPV vaccine is an agent to induce E7-specific Th1 immune responses to treat cervical neoplasia (CIN2-3). Our previous clinical trial has demonstrated that oral administration of HPV16 E7-expressing Lactobacillus casei (L. casei), GLBL101c, resulted in the regression of HPV16-related CIN3. Here we examined optimization of the E7-expressing L. casei for induction of the mucosal immune responses to E7. Various doses of HPV16 E7 molecule were displayed on the L. casei. Immunization with E7-bound L. casei showed the induction of E7-specific mucosal IFNγ-producing cells was dependent on displayed E7-doses but saturated beyond 0.3 μg/10⁸ cells. A new agent, L. casei with endogenous expression of E7 (IGMKK16E7), showed the optimal amount of displayed-E7. Immunization with IGMKK16E7 demonstrated 4-fold higher induction of E7-specific mucosal IFNγ-producing cells when compared with the former one. Our new system provided the optimal E7-expressing L. casei for displayed-E7 amount and induction of mucosal Th1 immune response.