Vaccine Effectiveness Against 12-Month Incident and Persistent Anal Human Papillomavirus Infection Among Gay, Bisexual, and Other Men Who Have Sex With Men.

BACKGROUND: Real-world evidence of human papillomavirus (HPV) vaccine effectiveness (VE) against longitudinal outcomes is lacking among gay, bisexual, and other men who have sex with men (GBM). We compared 12-month incidence and persistence of anal HPV infection between vaccinated and unvaccinated GBM. METHODS: We recruited GBM aged 16-30 years in Montreal, Toronto, and Vancouver, Canada, from 2017 to 2019. Participants were followed over a median of 12 months (interquartile range, 12-13 months). Participants self-reported HPV vaccination and self-collected anal specimens for HPV DNA testing. We calculated prevalence ratios (PR) for 12-month cumulative incidence and persistence with ≥1 quadrivalent vaccine type (HPV 6/11/16/18) between vaccinated (≥1 dose at baseline) and unvaccinated participants using a propensity score-weighted, modified Poisson regression. RESULTS: Among 248 participants, 109 (44.0%) were vaccinated at baseline, of whom 62.6% received 3 doses. PRs for HPV 6/11/16/18 were 0.56 (95% confidence interval [CI], .24-1.31) for cumulative incidence and 0.53 (95% CI, .25-1.14) for persistence. PRs were 0.23 (95% CI, .05-1.03) and 0.08 (95% CI, .01-.59) for incidence and persistence, respectively, among participants who received their first dose at age ≤23 years and 0.15 (95% CI, .03-.68) and 0.12 (95% CI, .03-.54) among participants who were sexually active for ≤5 years before vaccination. CONCLUSIONS: Findings support national recommendations for HPV vaccination at younger ages or soon after sexual debut.

Temporal Trends in the Incidence of Anogenital Warts: Impact of Human Papillomavirus Vaccination.

BACKGROUND: Studies in countries with high human papillomavirus (HPV) vaccination coverage have demonstrated marked reductions in anogenital wart (AGW) incidence. Our goal was to assess the impact of HPV vaccination in a population with suboptimal coverage by comparing AGW incidence trends in the years before and after vaccine introduction. METHODS: We conducted a retrospective analysis of AGW incidence trends using an ecologic study design among 11- through 39-year-olds enrolled at Kaiser Permanente Northwest. We defined incidence as the proportion of persons who had a new AGW diagnosis for each calendar year in the prevaccine periods (2000 through 2006 for female individuals, 2000 through 2010 for male individuals) and the postvaccine periods (2007 through 2016 for female individuals, 2011 through 2016 for male individuals). We also described cumulative HPV vaccination coverage. RESULTS: The average annual AGW incidence rates in the prevaccine periods were 27.8 per 10,000 in female individuals and 26.9 per 10,000 in male individuals. In the postvaccine periods, AGW incidence rates decreased by 31% (P < 0.001) in female individuals and 10% (P = 0.006) in male individuals; the largest reductions were observed in 15- to 19-year-old female individuals (67%, P < 0.001) and male individuals (45%, P < 0.001). Three dose HPV coverage rates were less than 50% in all age groups and both sexes. CONCLUSIONS: In a population of young adults with moderate HPV vaccination coverage, we observed declines in AGW incidence among both female and male year after the introduction of HPV vaccination. The largest incidence reductions were observed in 15- to 19-year-olds who were most likely to have been vaccinated.

Public-private knowledge transfer and access to medicines: a systematic review and qualitative study of perceptions and roles of scientists involved in HPV vaccine research.

BACKGROUND: Public research organizations and their interactions with industry partners play a crucial role for public health and access to medicines. The development and commercialization of the Human Papillomavirus (HPV) vaccines illustrate how licensing practices of public research organizations can contribute to high prices of the resulting product and affect accessibility to vulnerable populations. Efforts by the international community to improve access to medicines have recognised this issue and promote the public health-sensitive management of research conducted by public research organizations. This paper explores: how medical knowledge is exchanged between public and private actors; what role inventor scientists play in this process; and how they view the implementation of public health-sensitive knowledge exchange strategies. METHODS: We conducted a systematic qualitative literature review on medical knowledge exchange and qualitative interviews with a purposive sample of public sector scientists working on HPV vaccines. We explored the strategies by which knowledge is exchanged across institutional boundaries, how these strategies are negotiated, and the views of scientists regarding public health-sensitive knowledge exchange. RESULTS: We included 13 studies in the systematic review and conducted seven semi-structured interviews with high-ranking scientists. The main avenues of public-private medical knowledge exchange were publications, formal transfer of patented knowledge, problem-specific exchanges such as service agreements, informal exchanges and collaborative research. Scientists played a crucial role in these processes but appeared to be sceptical of public health-sensitive knowledge exchange strategies, as these were believed to deter corporate interest in the development of new medicines and thus risk the translation of the scientists' research. CONCLUSION: Medical scientists at public research institutions play a key role in the exchange of knowledge they generate and are concerned about the accessibility of medicines resulting from their research. Their scepticism towards implementing public health-sensitive knowledge management strategies appears to be based on a biased understanding of the costs and risks involved in drug development and a perceived lack of alternatives to private engagement. Scientists could be encouraged to exchange knowledge in a public health-sensitive manner through not-for-profit drug development mechanisms, education on industry engagement, and stronger institutional and legal backing.

"I can be the Judge of What's Serious": A Qualitative Pilot Study of Parents' Responses to Messaging About Side Effects of the HPV Vaccine.

OBJECTIVE: Parents' concerns about vaccine safety and side effects likely contribute to low rates of human papillomavirus (HPV) vaccination among adolescents. To facilitate parent-provider discussions about the HPV vaccine, we developed and tested the content of a clinical decision support application for implementation in pediatric clinical settings. This study sought to elicit perspectives of parents and providers on the best way to communicate information on vaccine side effects. METHODS: To understand the acceptability of the application's content, we conducted focus groups with parents (n = 11) and providers (n = 9) at three primary care clinics. Focus groups transcriptions were analyzed using iterations of deductive and inductive coding, with independent coding by two trained reviewers to improve inter-rater reliability. RESULTS: Surprisingly, when parents reviewed screen shots of HPV vaccine safety and side effect messages, parents took exception to the expression "no evidence of serious side effects". Parents wanted side effects listed explicitly so they could decide for themselves which side effects were "serious". Parents also felt that the HPV vaccine did have serious side effects, and the wording undermined their trust in the vaccine messaging overall. Providers accepted the phrasing of side effects and did not express concerns that parents would object to the messaging. CONCLUSIONS: Further research is needed to confirm parents' concerns with the phrasing "no serious side effects" for the HPV vaccine and to assess the impact on HPV vaccination deferral or delay.

Dimensions of Misinformation About the HPV Vaccine on Instagram: Content and Network Analysis of Social Media Characteristics.

BACKGROUND: The human papillomavirus (HPV) vaccine is a major advancement in cancer prevention and this primary prevention tool has the potential to reduce and eliminate HPV-associated cancers; however, the safety and efficacy of vaccines in general and the HPV vaccine specifically have come under attack, particularly through the spread of misinformation on social media. The popular social media platform Instagram represents a significant source of exposure to health (mis)information; 1 in 3 US adults use Instagram. OBJECTIVE: The objective of this analysis was to characterize pro- and anti-HPV vaccine networks on Instagram, and to describe misinformation within the anti-HPV vaccine network. METHODS: From April 2018 to December 2018, we collected publicly available English-language Instagram posts containing hashtags #HPV, #HPVVaccine, or #Gardasil using Netlytic software (n=16,607). We randomly selected 10% of the sample and content analyzed relevant posts (n=580) for text, image, and social media features as well as holistic attributes (eg, sentiments, personal stories). Among antivaccine posts, we organized elements of misinformation within four broad dimensions: 1) misinformation theoretical domains, 2) vaccine debate topics, 3) evidence base, and 4) health beliefs. We conducted univariate, bivariate, and network analyses on the subsample of posts to quantify the role and position of individual posts in the network. RESULTS: Compared to provaccine posts (324/580, 55.9%), antivaccine posts (256/580, 44.1%) were more likely to originate from individuals (64.1% antivaccine vs 25.0% provaccine; P<.001) and include personal narratives (37.1% vs 25.6%; P=.003). In the antivaccine network, core misinformation characteristics included mentioning #Gardasil, purporting to reveal a lie (ie, concealment), conspiracy theories, unsubstantiated claims, and risk of vaccine injury. Information/resource posts clustered around misinformation domains including falsification, nanopublications, and vaccine-preventable disease, whereas personal narrative posts clustered around different domains of misinformation, including concealment, injury, and conspiracy theories. The most liked post (6634 likes) in our full subsample was a positive personal narrative post, created by a non-health individual; the most liked post (5604 likes) in our antivaccine subsample was an informational post created by a health individual. CONCLUSIONS: Identifying characteristics of misinformation related to HPV vaccine on social media will inform targeted interventions (eg, network opinion leaders) and help sow corrective information and stories tailored to different falsehoods.

Going beyond the individual: how state-level characteristics relate to HPV vaccine rates in the United States.

BACKGROUND: The human papillomavirus (HPV) vaccine is an underutilized cancer control practice in the United States. Although individual contextual factors are known to impact HPV vaccine coverage rates, the impact of macro-level elements are still unclear. The aim of this analysis was to use HPV vaccination rates to explore the underuse of an evidence-based cancer control intervention and explore broader-level correlates influencing completion rates. METHODS: A comprehensive database was developed using individual-level date from the National Immunization Survey (NIS)-Teen (2016) and state-level data collected from publically available sources to analyze HPV vaccine completion. Multi-level logistic models were fit to identify significant correlates. Level-1 (individual) and level-2 (state) correlates were fitted to a random intercept model. Deviance and AIC assessed model fit and sampling weights were applied. RESULTS: The analysis included 20,495 adolescents from 50 U.S. states and the District of Columbia. Teen age, gender, race/ethnicity, and maternal education were significant individual predictors of HPV completion rates. Significant state-level predictors included sex education policy, religiosity, and HPV vaccine mandate. States with the lowest HPV coverage rates were found to be conservative and highly religious. Little variation in vaccine exemptions and enacted sex and abstinence education polices were observed between states with high and low HPV vaccine coverage suggesting various contextual and situational factors impact HPV vaccine completion rates. CONCLUSIONS: Given that gender, religiosity, political ideology, and education policies are predictors of HPV vaccine completion, the interaction and underlying mechanism of these factors can be used to address the underutilization of the HPV vaccine.

Human papillomavirus vaccination for boys.

QUESTION: In Canada, generally provincial human papillomavirus (HPV) vaccination programs exist for only the female population. What should I recommend when parents and teenage boys ask about male HPV vaccination? ANSWER: The quadrivalent HPV vaccine is effective and will reduce the incidence of disease in boys and girls. The quadrivalent HPV vaccination is approved and recommended for both boys and girls in Canada. Public funding for male vaccination is available in Prince Edward Island and Alberta. The remaining provinces and territories will need to consider cost-effectiveness analyses before expanding their female-only vaccination programs to include the male population.

Modeling the impact of screening policy and screening compliance on incidence and mortality of cervical cancer in the post-HPV vaccination era.

BACKGROUND: In Norway, pap smear screening target women aged 25-69 years on a triennial basis. The introduction of human papillomavirus (HPV) mass immunization in 2009 raises questions regarding the cost-saving future changes to current screening strategies. METHODS: We calibrated a dynamic HPV transmission model to Norwegian data and assessed the impact of changing screening 20 or 30 years after vaccine introduction, assuming 60 or 90% vaccination coverage. Screening compliance among vaccinated women was assumed at 80 or 50%. Strategies considered: (i) 5-yearly screening of women of 25-69 years, (ii) 3-yearly screening of women of 30-69 years and (iii) 3-yearly screening of women of 25-59 years. RESULTS: Greatest health gains were accomplished by ensuring a high vaccine uptake. In 2060, cervical cancer incidence was reduced by an estimated 36-57% compared with that of no vaccination. Stopping screening at the age of 60 years, excluding opportunistic screening, increased cervical cancer incidence by 3% (2060) compared with maintaining the current screening strategy, resulting in 1.0-2.4% extra cancers (2010-2060). The 5-yearly screening strategy elevated cervical cancer incidence by 30% resulting in 4.7-11.3% additional cancers. CONCLUSION: High vaccine uptake in the years to come is of primary concern. Screening of young women <30 years remains important, even under the conditions of high vaccine coverage.

Monitoring of human papillomavirus vaccination.

Persistent infection with oncogenic human papillomavirus (HPV) is a necessary causal factor in the development of cervical cancer. Moreover, HPV, predominately type 16 and to a lesser degree type 18, is linked causally to varying proportions of other anogenital cancers (vulva, vagina, penis, anus) as well as cancers elsewhere in the body (oropharynx, larynx, conjunctiva). HPV types 6 and 11 cause most of genital warts and recurrent respiratory papillomatosis. Effective prophylactic vaccines have been developed. In this review, we address briefly the immunological aspects of HPV infection and the results of HPV vaccination trials. Internationally standardized monitoring and evaluation of prophylactic HPV vaccination programmes will be essential for arriving at the most cost-effective strategies for cancer control.

Human papillomavirus vaccination rates and state mandates for tetanus-containing vaccines.

OBJECTIVE: We sought to examine nationally the association between school mandates for adolescent tetanus-containing vaccines (Td and/or Tdap) and adolescent female human papillomavirus (HPV) vaccination. METHODS: Each state was categorized by whether a school mandate for adolescent Td and/or Tdap vaccines was enacted. Mean HPV vaccine series initiation levels among adolescent females were compared between each mandate category. RESULTS: Mean HPV vaccine series initiation levels were significantly lower in states without Td/Tdap vaccine mandates than in those with mandates (42.9% vs. 47.3%; p=0.004). CONCLUSIONS: School mandates for adolescent Td/Tdap vaccination may have a carry-over effect on HPV vaccination.

Guidance for future HTA applications to vaccines: the HPV lesson.

The HTA is a multidisciplinary approach which is increasingly applied worldwide in order to support decision-makers in the introduction of health technologies. The application of HTA to vaccines is quite recent and linked to the increasing number of vaccines available or in development, especially to those intended to non pediatric immunization. In this article a description of the HTA approach used in the evaluation of the bivalent HPV vaccine in Italy is provided; moreover the reasons for keeping HTA process "alive" and identifying new or pending Public Health issues are discussed. In fact, the project raised questions and challenges about the standardization and sharing of HTA methods in Italy. Recently the need of updating the results is starting to be seen as urgent due to the evolution of scientific knowledge, the availability of the first results after technology introduction and the observed differences in vaccination strategies among Italian regions. Moreover in these last two years after the completion of the HTA project a number of new issues have risen in the Italian context as immunization rates, regional vaccination strategies, processes for vaccine selection and health economic issues.

Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1)-infected men are at increased risk for anal cancer. Human papillomavirus (HPV) vaccination may prevent anal cancer caused by vaccine types. METHODS: AIDS Malignancy Consortium Protocol 052 is a single-arm, open-label, multicenter clinical trial to assess the safety and immunogenicity of the quadrivalent HPV (types 6, 11, 16, and 18) vaccine in HIV-1-infected men. Men with high-grade anal intraepithelial neoplasia or anal cancer by history or by screening cytology or histology were excluded. Men received 0.5 mL intramuscularly at entry, week 8, and week 24. The primary end points were seroconversion to vaccine types at week 28, in men who were seronegative and without anal infection with the relevant HPV type at entry, and grade 3 or higher adverse events related to vaccination. RESULTS: There were no grade 3 or greater adverse events attributable to vaccination among the 109 men who received at least 1 vaccine dose. Seroconversion was observed for all 4 types: type 6 (59 [98%] of 60), type 11 (67 [99%] of 68), type 16 (62 [100%] of 62), and type 18 (74 [95%] of 78). No adverse effects on CD4 counts and plasma HIV-1 RNA levels were observed. CONCLUSIONS: The quadrivalent HPV vaccine appears safe and highly immunogenic in HIV-1-infected men. Efficacy studies in HIV-1-infected men are warranted. Clinical trials registration. NCT 00513526.

WHO Expert Committee on biological standardization.

This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international recommendations for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the attention of the Committee and provides information on the status and development of reference materials for various antibodies, antigens, blood products and related substances, cytokines, growth factors, and endocrinological substances. The second part of the report, of particular relevance to manufacturers and national regulatory authorities, contains WHO recommendations and guidelines on human papillomavirus vaccines; meningococcal A conjugate vaccines; and stability evaluation of vaccines. Also included are a list of recommendations, guidelines and other documents for biological substances used in medicine, and of international standards and reference reagent for biological substances.

HPV vaccination's second act: promotion, competition, and compulsion.

Developments regarding human papillomavirus (HPV) vaccines will transform HPV vaccination in the United States while simultaneously raising several new policy and ethical concerns. Policymakers, vaccine manufacturers, and the public health community must now respond to the presence of competing vaccines that are similar but distinct, particularly with respect to genital wart prevention and the benefits of vaccinating males. This work arises in the shadow of the contentious introduction of the HPV vaccine Gardasil (Merck & Co, Inc, Whitehouse Station, NJ) in 2006, particularly the opposition to efforts in many states to require the vaccine for school attendance. I review the current status of HPV vaccine policy in the United States and examine issues of public health ethics and policy central to ongoing and future HPV vaccination programs.

Executive summary--performance monitoring for cervical cancer screening programs in Canada.

The purpose of this report is to define a core set of performance indicators for organized cervical cancer screening programs in Canada. The goals for establishing a pan-Canadian set of performance indicators are to promote high quality screening through monitoring and evaluation. Over time, with regular monitoring and reporting of these indicators, an evidence base will grow which will permit the setting of pan-Canadian targets.