scholarly journals A cluster analysis of serious adverse event reports after human papillomavirus (HPV) vaccination in Danish girls and young women, September 2009 to August 2017

2019 ◽  
Vol 24 (19) ◽  
Author(s):  
Daniel Ward ◽  
Nicklas Myrthue Thorsen ◽  
Morten Frisch ◽  
Palle Valentiner-Branth ◽  
Kåre Mølbak ◽  
...  

Background Suspected adverse events (AE) after human papillomavirus (HPV) vaccines include postural orthostatic tachycardia syndrome (POTS), chronic fatigue syndrome (CFS), complex regional pain syndrome (CRPS) and symptoms including headache and orthostatic intolerance. Aim We aimed to identify phenotypes of AEs after HPV vaccination, defined as patterns of AE terms (signs, symptoms, diagnoses), and to evaluate if identified phenotypes reflected previously suspected symptomatology or heightened public concerns over HPV vaccine safety since 1 January 2015. Methods We conducted a retrospective observational study using latent class cluster analysis of all serious AE reports (n = 963) reported by females residing in Denmark between September 2009 and August 2017. Resulting clusters were characterised according to AE terms associated with POTS, CFS and CRPS before (September 2009–December 2014) and during (January 2015–August 2017) a time of heightened media activity regarding HPV vaccines. Results Four clusters of AE reports were distinguished. The most common symptoms were fatigue, dizziness and headache but their frequency varied among clusters. The majority of reports in one cluster were submitted during a period of heightened media activity, including an anomalous spike in submissions in December 2015; a high proportion of these reports included the symptoms cognitive disorder (78%), abdominal pain (77%), dysuria (60%) and sleep disorder (60%). Conclusions Non-specific symptoms including headache, fatigue and dizziness feature prominently in serious AE reports from females in Denmark. Our analysis identified a cluster of reports, likely media stimulated, with a focus on symptoms of CFS and POTS.

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 856
Author(s):  
Akiyo Hineno ◽  
Shu-Ihi Ikeda

In Japan, a significant number of adolescent females noted unusual symptoms after receiving the human papillomavirus (HPV) vaccination, of which the vast majority of them were initially diagnosed with psychiatric illnesses because of the absence of pathologic radiological images and specific abnormalities in laboratory test results. Later these symptoms were thought to be adverse effects of HPV vaccination. However, a causal link between HPV vaccination and the development of these symptoms has not been demonstrated. Between June 2013 and March 2021, we examined 200 patients who noted various symptoms after HPV vaccination. In total, 87 were diagnosed with HPV vaccination-related symptoms based on our proposed diagnostic criteria. The clinical histories of these 87 patients were analyzed. The age at initial vaccination ranged from 11 to 19 years old (mean ± SD: 13.5 ± 1.5 years old), and the age at the first appearance of symptoms ranged from 12 to 20 years old (mean ± SD: 14.3 ± 1.6 years old). The patients received an initial HPV vaccine injection between May 2010 and May 2013, but the first affected patient developed symptoms in October 2010, and the last affected developed symptoms in October 2015. A cluster of patients with a post-HPV vaccination disorder has not appeared in Japan during the last five years. Our study shows that, in Japan, the period of HPV vaccination considerably overlapped with that of a unique post-HPV vaccination disorder development. This disorder appears as a combination of orthostatic intolerance, chronic regional pain syndrome, and cognitive dysfunction, but its exact pathogenesis remains unclear.


BMJ ◽  
2020 ◽  
pp. m2930 ◽  
Author(s):  
Anders Hviid ◽  
Nicklas M Thorsen ◽  
Palle Valentiner-Branth ◽  
Morten Frisch ◽  
Kåre Mølbak

Abstract Objective To evaluate the association between quadrivalent human papillomavirus vaccination and syndromes with autonomic dysfunction, such as chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome. Design Population-based self-controlled case series. Setting Information on human papillomavirus vaccinations and selected syndromes with autonomic dysfunction (chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome) identified using ICD-10 (international classification of diseases, revision 10) diagnostic codes from Danish nationwide registers. Participants 869 patients with autonomic dysfunction syndromes from a cohort of 1 375 737 Danish born female participants aged 10 to 44 years during 2007-16. Main outcome measures Self-controlled case series rate ratios (95% confidence intervals) of the composite outcome of chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome, adjusted for age and season, comparing female participants vaccinated and unvaccinated with the quadrivalent human papillomavirus vaccine. Chronic fatigue syndrome, complex regional pain syndrome, and postural orthostatic tachycardia syndrome were also considered separately in secondary analyses. Results During 10 581 902 person years of follow-up, 869 female participants with syndromes of autonomic dysfunction (136 with chronic fatigue syndrome, 535 with complex regional pain syndrome, and 198 with postural orthostatic tachycardia syndrome) were identified. Quadrivalent human papillomavirus vaccination did not statistically significantly increase the rate of a composite outcome of all syndromes with autonomic dysfunction in a 365 day risk period following vaccination (rate ratio 0.99, 95% confidence interval 0.74 to 1.32) or the rate of any individual syndrome in the risk period (chronic fatigue syndrome (0.38, 0.13 to 1.09), complex regional pain syndrome (1.31, 0.91 to 1.90), or postural orthostatic tachycardia syndrome (0.86, 0.48 to 1.54)). Conclusions When vaccination is introduced, adverse events could occur in close temporal relation to the vaccine purely by chance. These results do not support a causal association between quadrivalent human papillomavirus vaccination and chronic fatigue syndrome, complex regional pain syndrome, or postural orthostatic tachycardia syndrome, either individually or as a composite outcome. An increased risk of up to 32% cannot be formally excluded, but the statistical power of the study suggests that a larger increase in the rate of any syndrome associated with vaccination is unlikely.


2019 ◽  
Vol 29 (8) ◽  
pp. 1317-1326 ◽  
Author(s):  
Raúl Murillo ◽  
Camila Ordóñez- Reyes

Cervical cancer incidence and mortality have decreased in high-income countries, but low- and middle-income countries continue to bear a significant burden from the disease. Human papillomavirus (HPV) vaccines are a promising alternative for disease control; however, their introduction is slow in settings with greater need. We conducted a review of HPV vaccine efficacy and effectiveness reported in clinical trials and population-based studies. Efficacy of HPV vaccines is close to 100% when using a three-dose schedule in HPV-negative young women (<25 years old) for protection against persistent infection and HPV vaccine-type associated pre-cancerous lesions. Furthermore, sustained protection for up to 12 years of follow-up has been demonstrated; cross-protection against non-vaccine types is particularly observed for the bivalent vaccine, and preliminary data regarding impact on invasive cancer have emerged. Given its lower efficacy, catch-up vaccination beyond 19 years of age and proposals for vaccinating adult women deserve careful evaluation in accurately designed studies and economic analyses. Despite positive results regarding immunogenicity and post-hoc analysis for cervical intra-epithelial neoplasia in clinical trials, population-based data for prime and booster two-dose schedules are not available. Evaluation of vaccine safety from surveillance systems in immunization programs that have already distributed more than 270 million doses found no association of HPV vaccination with serious side effects. The introduction of HPV vaccination in national immunization programs remains the main challenge in tackling the burden of cervical cancer (up to 2018, only 89 countries have introduced vaccination worldwide, and most of these are high-income countries). Access models and technical capacity require further development to help low- and middle-income countries to increase the pace of vaccine delivery. Alternative approaches such as one-dose schedules and vaccination at younger ages may help reduce the programmatic and economic challenges to adolescent vaccination.


2020 ◽  
Vol 189 (4) ◽  
pp. 277-285 ◽  
Author(s):  
Reimar Wernich Thomsen ◽  
Buket Öztürk ◽  
Lars Pedersen ◽  
Sia Kromann Nicolaisen ◽  
Irene Petersen ◽  
...  

Abstract Human papillomavirus (HPV) vaccination has been associated with subsequent diffuse symptoms in girls, reducing public confidence in the vaccine. We examined whether girls have nonspecific outcomes of HPV vaccination, using triangulation from cohort, self-controlled case series (SCCS), and population time trend analyses carried out in Denmark between 2000 and 2014. The study population consisted of 314,017 HPV-vaccinated girls and 314,017 age-matched HPV-unvaccinated girls (cohort analyses); 11,817 girls with hospital records (SCCS analyses); and 1,465,049 girls and boys (population time trend analyses). The main outcome measures were hospital records of pain, fatigue, or circulatory symptoms. The cohort study revealed no increased risk among HPV vaccine-exposed girls, with incidence rate ratios close to 1.0 for abdominal pain, nonspecific pain, headache, hypotension/syncope, tachycardia (including postural orthostatic tachycardia syndrome), and malaise/fatigue (including chronic fatigue syndrome). In the SCCS analyses, we observed no association between HPV vaccination and subsequent symptoms. In time trend analyses, we observed a steady increase in these hospital records in both girls and (HPV-unvaccinated) boys, with no relationship to the 2009 introduction of HPV vaccine to Denmark’s vaccination program. This study, which had nationwide coverage, showed no evidence of a causal link between HPV vaccination and diffuse autonomic symptoms leading to hospital contact.


Sexual Health ◽  
2010 ◽  
Vol 7 (3) ◽  
pp. 383 ◽  
Author(s):  
Margaret E. Heffernan ◽  
Suzanne M. Garland ◽  
Mark A. Kane

Background: Worldwide, prophylactic vaccines against two major human cancers are now commercially available: hepatitis B virus (HBV) vaccines (first licensed in 1982) against primary hepatocellular carcinoma and human papillomavirus (HPV) vaccines (first licensed 2006) against cervical cancer. Initial implementation strategies for HBV vaccination were not successful in preventing disease in the community: it took 15 years for significant global reduction in the burden of this disease. Methods: We compare and contrast HBV vaccine experiences to challenges for successful global HPV vaccination strategies, and make recommendations accordingly. Results: Lessons from HBV immunisation for successful outcomes with HPV immunisation showed that several factors need to be met: (i) the engagement of key stakeholders in all aspects of planning and delivery of HPV vaccine strategies; (ii) understanding the specific characteristics of targeted population groups; (iii) global cooperation and support with WHO recommendations; (iv) Government supported mass immunization programs and cooperation between public and private entities; (v) affordable HPV vaccines for some regions; (vi) culturally appropriate and diverse public education programs in targeted health promotion strategies; (vii) pro-active health providers and parents in encouraging adolescents to undertake HPV vaccination; and (vii) eventual immunisation of infants. Conclusions: The key to success will be affordable, readily deliverable HPV vaccines to young girls as universal campaigns.


2021 ◽  
Vol 3 ◽  
Author(s):  
David B. Buller ◽  
Sherry Pagoto ◽  
Kimberly Henry ◽  
Julia Berteletti ◽  
Barbara J. Walkosz ◽  
...  

Introduction: Parents acquire information about human papillomavirus (HPV) vaccines online and encounter vaccine-critical content, especially on social media, which may depress vaccine uptake. Secondary analysis in a randomized trial of a Facebook-delivered adolescent health campaign targeting mothers with posts on HPV vaccination was undertaken with the aims of (a) determining whether the pre–post-change occurred in self-reports of the mothers on HPV vaccination of their adolescent daughters; (b) describing the comments and reactions to vaccine posts; (c) exploring the relationship of campaign engagement of the mothers assessed by their comments and reactions to posts to change in the self-reports of the mothers of HPV vaccination.Materials and Methods: Mothers of daughters aged 14–17 were recruited from 34 states of the US (n = 869). A social media campaign was delivered in two Facebook private groups that differed in that 16% of posts in one were focused on indoor tanning (IT) and 16% in the other, on prescription drug misuse, assigned by randomization. In both groups, posts promoted HPV vaccination (n = 38 posts; no randomization) and vaccination for other disease (e.g., influenza, n = 49). HPV and other vaccination posts covered the need for a vaccine, the number of adolescents vaccinated, how vaccines are decreasing the infection rates, and stories of positive benefits of being vaccinated or harms from not vaccinating. Guided by social cognitive theory and diffusion of innovations theory, posts were intended to increase knowledge, perceived risk, response efficacy (i.e., a relative advantage over not vaccinated daughters), and norms for vaccination. Some vaccination posts linked to stories to capitalize on identification effects in narratives, as explained in transportation theory. All mothers received the posts on vaccination (i.e., there was no randomization). Mothers completed surveys at baseline and 12- and 18-month follow-up to assess HPV vaccine uptake by self-report measures. Reactions (such as sad, angry) and comments to each HPV-related post were counted and coded.Results: Initiation of HPV vaccination (1 dose) was reported by 63.4% of mothers at baseline, 71.3% at 12-month posttest (pre/post p &lt; 0.001), and 73.3% at 18-month posttest (pre/post p &lt; 0.001). Completion of HPV vaccination (two or three doses) was conveyed by 50.2% of mothers at baseline, 62.5% at 12-month posttest (pre/post p &lt; 0.001), and 65.9% at 18-month posttest (pre/post p &lt; 0.001). For posts on HPV vaccines, 8.1% of mothers reacted (n = 162 total), and 68.4% of posts received a reaction (63.2% like; 13.2% love, 7.9% sad). In addition, 7.6% of mothers commented (n = 122; 51 unfavorable, 68 favorable, 1 neutral), and 50.0% of these posts received a comment. There were no differences in pre–post change in vaccine status by the count of reactions or comments to HPV vaccine posts (Ps &gt; 0.05). Baseline vaccination was associated with the valence of comments to HPV vaccine posts (7.2% of mothers whose daughters had completed the HPV series at baseline made a favorable comment but 7.6% of mothers whose daughters were unvaccinated made an unfavorable comment).Conclusion: Effective strategies are needed in social media to promote HPV vaccines and counter misinformation about and resistance to them. Mothers whose daughters complete the HPV vaccine course might be recruited as influencers on HPV vaccines, as they may be predisposed to talk favorably about the vaccine. Comments from mothers who have not been vaccinated should be monitored to ensure that they do not spread vaccine-critical misinformation. Study limitations included lack of randomization and control group, relatively small number of messages on HPV vaccines, long measurement intervals, inability to measure views of vaccination posts, reduced generalizability related to ethnicity and social media use, and use of self-reported vaccine status.Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT02835807.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Zhao ◽  
Xiaoli Xin ◽  
Huiwen Deng ◽  
Junjie Xu ◽  
Wenjia Weng ◽  
...  

Objectives: To investigate the acceptability of human papillomavirus (HPV) vaccination among men who have sex with men (MSM) and its associated factors.Methods: We searched studies written in English in PubMed, EMBASE, and Web of Science with no geographical or time restrictions. We evaluated the quality of the included literature. We calculated the pooled acceptability and performed meta-analysis of selected studies, including factors associated with the acceptability among MSM, using Review Manager (v5.3).Results: The acceptability among the 15 studies (n = 8,658) was 50% (95% CI: 0.27–0.72). The meta-analysis of seven articles (n = 4,200) indicated that having a college or higher degree (OR = 1.62, 95% CI: 1.35–1.95), disclosure of sexual orientation to healthcare professionals (HCPs; OR = 2.38, 95% CI: 1.47–3.86), vaccination with at least one dose for hepatitis A or B (OR = 2.10, 95% CI: 1.42–3.10), awareness of HPV (OR = 1.85, 95% CI: 1.21–2.83), knowledge of HPV (SMD = 0.28, 95% CI: 0.16–0.39), perceived susceptibility to HPV infection (SMD = 0.31, 95% CI: 0.11–0.50), and perceived severity of HPV-related disease (SMD = 0.40, 95% CI: 0.28–0.51) can promote acceptance of HPV vaccines. Meanwhile, people who have had unprotected anal sex or have more sex partners tend to have low acceptance of HPV vaccines.Conclusions: HPV education should be actively promoted according to the factors that influence the acceptability of HPV vaccines among the MSM population. HPV education should be especially aimed at people with low academic qualifications and people with risky sexual behaviors, and should emphasize the aspects of susceptibility to and severity of HPV-related disease. More intervention trials should be conducted to increase the credibility of the results.


2004 ◽  
Vol 14 (5) ◽  
pp. 751-761 ◽  
Author(s):  
W. A. A. Tjalma ◽  
M. Arbyn ◽  
J. Paavonen ◽  
T. R. Van Waes ◽  
J. J. Bogers

Persistent infection with one of the oncogenic human papillomavirus (HPV) types is a necessity for the development of cervical cancer. By HPV vaccination, cervical cancer could become a very rare disease. Two types of HPV vaccines can be distinguished: (i) therapeutic vaccines which induce cellular immunity targeted against epithelial cells infected with HPV and (ii) prophylactic vaccines inducing virus-neutralizing antibodies protecting against new but not against established infections. At present, several vaccines have been developed and tested in clinical trials. The vaccines are generally well tolerated and highly immunogenic. The current clinical data indicate that prophylactic vaccines are very effective against new persistent infections and the development of cervical intraepithelial lesions. The protection is type specific. However, the follow-up of the vaccination trials is still short. The effect of HPV vaccines on future cancer incidence will only be known after decades of follow-up. This article will address the status of recently terminated phase II and currently running phase III trials with prophylactic HPV vaccines.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
C. (Linda) M. C. van Campen ◽  
Peter C. Rowe ◽  
Frans C. Visser

Abstract Background Orthostatic intolerance (OI) is a frequent finding in individuals with myalgic encephalomyelitis /chronic fatigue syndrome (ME/CFS). Published studies have proposed that deconditioning is an important pathophysiological mechanism in various forms of OI, including postural orthostatic tachycardia syndrome (POTS), however conflicting opinions exist. Deconditioning can be classified objectively using the predicted peak oxygen consumption (VO2) values from cardiopulmonary exercise testing (CPET). Therefore, if deconditioning is an important contributor to OI symptomatology, one would expect a relation between the degree of reduction in peak VO2during CPET and the degree of reduction in CBF during head-up tilt testing (HUT). Methods and results In 22 healthy controls and 199 ME/CFS patients were included. Deconditioning was classified by the CPET response as follows: %peak VO2 ≥ 85% = no deconditioning, %peak VO2 65–85% = mild deconditioning, and %peak VO2 < 65% = severe deconditioning. HC had higher oxygen consumption at the ventilatory threshold and at peak exercise as compared to ME/CFS patients (p ranging between 0.001 and < 0.0001). Although ME/CFS patients had significantly greater CBF reduction than HC (p < 0.0001), there were no differences in CBF reduction among ME/CFS patients with no, mild, or severe deconditioning. We classified the hemodynamic response to HUT into three categories: those with a normal heart rate and blood pressure response, postural orthostatic tachycardia syndrome, or orthostatic hypotension. No difference in the degree of CBF reduction was shown in those three groups. Conclusion This study shows that in ME/CFS patients orthostatic intolerance is not caused by deconditioning as defined on cardiopulmonary exercise testing. An abnormal high decline in cerebral blood flow during orthostatic stress was present in all ME/CFS patients regardless of their %peak VO2 results on cardiopulmonary exercise testing.


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