Lessons learned from nationwide vaccine programs: Comparing human papillomavirus, poliomyelitis vaccine, and swine flu

This assessment compares the human papillomavirus (HPV) nationwide vaccine to the poliomyelitis vaccine and the swine flu vaccine with the purpose of finding parallels and lessons in the controversies faced by the development and use of the vaccines. There are a number of great barriers that are facing the HPV vaccine to date. These controversies lie in dealing with the risk involved in taking the vaccine, how much control the government should have in administering the vaccine, how to communicate the risk to the public, and the cost-effectiveness of the vaccine versus treatment for cervical cancer. The lessons for the HPV vaccine that were learned after comparison and assessment of the controversies were: (1) plan ahead of time on how to inform the public if a risk develops from taking the HPV vaccination and it may be better to provide some information while the event is occurring, always being as truthful as possible, and later dispensing more information once all of the facts are known, (2) the human papillomavirus is not something that will become a pandemic in a short amount of time because the virus takes a long time to develop into cervical cancer, so if a major risk begins to show after continuing to develop and administer the vaccine for an amount of time, it may be better to take it off the market for a while and possibly reconfigure it to help eliminate some of the risks, (3) if side reactions and risks do develop and the government assumes liability for these reactions, the cost-effectiveness can be greatly affected, so it is important to be constantly checking to see if all the monetary and health benefits of the vaccine are outweighing any of the negative costs of the vaccine, and lastly, (4) the public must feel that every aspect of the vaccine, both good and bad, has been thought over and the benefits of taking the vaccine prevail over the negatives and that politics and commercial interests have nothing to do with the production and administration of the vaccine. ^

Long term trends in the evolution of H(3) HA1 human influenza type A

We have studied the HA1 domain of 254 human influenza A(H3N2) virus genes for clues that might help identify characteristics of hemagglutinins (HAs) of circulating strains that are predictive of that strain’s epidemic potential. Our preliminary findings include the following. (i) The most parsimonious tree found requires 1,260 substitutions of which 712 are silent and 548 are replacement substitutions. (ii) The HA1 portion of the HA gene is evolving at a rate of 5.7 nucleotide substitutions/year or 5.7 × 10−3 substitutions/site per year. (iii) The replacement substitutions are distributed randomly across the three positions of the codon when allowance is made for the number of ways each codon can change the encoded amino acid. (iv) The replacement substitutions are not distributed randomly over the branches of the tree, there being 2.2 times more changes per tip branch than for non-tip branches. This result is independent of how the virus was amplified (egg grown or kidney cell grown) prior to sequencing or if sequencing was carried out directly on the original clinical specimen by PCR. (v) These excess changes on the tip branches are probably the result of a bias in the choice of strains to sequence and the detection of deleterious mutations that had not yet been removed by negative selection. (vi) There are six hypervariable codons accumulating replacement substitutions at an average rate that is 7.2 times that of the other varied codons. (vii) The number of variable codons in the trunk branches (the winners of the competitive race against the immune system) is 47 ± 5, significantly fewer than in the twigs (90 ± 7), which in turn is significantly fewer variable codons than in tip branches (175 ± 8). (viii) A minimum of one of every 12 branches has nodes at opposite ends representing viruses that reside on different continents. This is, however, no more than would be expected if one were to randomly reassign the continent of origin of the isolates. (ix) Of 99 codons with at least four mutations, 31 have ratios of non-silent to silent changes with probabilities less than 0.05 of occurring by chance, and 14 of those have probabilities <0.005. These observations strongly support positive Darwinian selection. We suggest that the small number of variable positions along the successful trunk lineage, together with knowledge of the codons that have shown positive selection, may provide clues that permit an improved prediction of which strains will cause epidemics and therefore should be used for vaccine production.

Knowledge and attitudes of Spanish adolescent girls towards human papillomavirus infection: where to intervene to improve vaccination coverage

Background: HPV vaccine coverage is far from ideal in Valencia, Spain, and this could be partially related to the low knowledge about the disease and the vaccine, therefore we assessed these, as well as the attitude towards vaccination in adolescent girls, and tried to identify independently associated factors that could potentially be modified by an intervention in order to increase vaccine coverage. Methods: A cross sectional study was conducted in a random selection of schools of the Spanish region of Valencia. We asked mothers of 1278 girls, who should have been vaccinated in the 2011 campaign, for informed consent. Those that accepted their daughters’ participation, a questionnaire regarding the Knowledge of HPV infection and vaccine was passed to the girls in the school. Results: 833 mothers (65.1%) accepted participation. All their daughters’ responded the questionnaire. Of those, 89.9% had heard about HPV and they associated it to cervical cancer. Only 14% related it to other problems like genital warts. The knowledge score of the girls who had heard about HPV was 6.1/10. Knowledge was unrelated to the number of contacts with the health system (Pediatrician or nurse), and positively correlated with the discussions with classmates about the vaccine. Adolescents Spanish in origin or with an older sister vaccinated, had higher punctuation. 67% of the girls thought that the vaccine prevented cancer, and 22.6% felt that although prevented cancer the vaccine had important safety problems. 6.4% of the girls rejected the vaccine for safety problems or for not considering themselves at risk of infection. 71.5% of the girls had received at least one vaccine dose. Vaccinated girls scored higher knowledge (p = 0.05). Conclusion: Knowledge about HPV infection and vaccine was fair in adolescents of Valencia, and is independent to the number of contacts with the health system, it is however correlated to the conversations about the vaccine with their peers and the vaccination status. An action to improve HPV knowledge through health providers might increase vaccine coverage in the adolescents.

Activation of dendritic cells by human papillomavirus-like particles through TLR4 and NF-B-mediated signalling, moderated by TGF-beta

Human papillomavirus-like particles (HPV-VLP) are a candidate vaccine for prevention of HPV infection, and also are a candidate for an immunogenic delivery system for incorporated antigen. VLP activate in vitro generated dendritic cells (DC) but not Langerhans cells (LC); however, the mechanism of this activation is unknown. We have shown that uptake and activation of DC by VLP involves proteoglycan receptors and can be inhibited by heparin. Heparin has been shown to activate DC by signalling through Toll-like receptor 4 (TLR4) and nuclear factor (NF)-kappaB. The pathway of DC activation by VLP was further investigated in the present study. Exposure to VLP induced costimulatory molecule expression, RelB translocation and IL-10 production by DC but not by LC. The lack of LC activation was reversible when TGF-beta was removed from the LC medium. VLP-induced induction of costimulatory molecule expression, RelB activation and cytokine secretion by DC was blocked by inhibition of NF-kappaB activation, heparin or TLR4 mAb. The data provide evidence that HPV-VLP signal DC through a pathway involving proteoglycan receptors, TLR4 and NF-kappaB, and shed light on the mechanism by which VLP stimulate immunity in the absence of adjuvants in vivo. LC may resist activation in normal epithelium abundant in TGF-beta, but not in situations in which TGF-beta concentrations are reduced.

Genital human papillomavirus: Women's knowledge and attitudes of this sexually transmitted disease

The purpose of this study was to investigate women's knowledge and attitudes regarding genital human papillomavirus (n=100). Using a descriptive design, the Health Education Questionnaire was administered to 100 female patients (Mean Age = 33, SD = 7.17) at a physicians office in South Florida. The results indicated a lack of knowledge regarding genital human papillomavirus with 21 patients (21%) reported having knowledge and 79 (79%) having never heard of this disease. In addition, the group familiar with genital human papillomavirus also possessed a low level of knowledge with only 57% acknowledging an association of genital human papillomavirus and cervical cancer, 52% aware that a pap smear can detect the virus, 42% knowing that antibiotics can not treat the disease and 57% aware that it is not associated with a family history. An association was found between attitudes and health seeking behaviors. Subjects stating that they would take all measures to prevent genital human papillomavirus, were more likely to have a pap smear within the last year (Chi-square (1) = 4.33, p < .05). Higher levels of education and income were associated with increased knowledge regarding genital human papillomavirus when subjects were categorized according to sociodemographic characteristic (Chi-square (1) =9.45, p < .05; Chi-square (1) = 6.75, p < .05). There was no significant correlation between knowledge and ethnicity, marital status or age. Findings indicated the need for improved education and promotion of positive attitudes regarding human papillomaviurs in order to improve health seeking behaviors among women.

Human Papillomavirus (HPV): Making the case for “Immunisation for All”

Human Papillomavirus (HPV) contributes to the most common sexually transmitted infections, with repeated and persistent infection with particular types causing disease in both men and women. Infection with low-risk HPV types can lead to genital warts and benign lesions of the oral cavity, while high-risk types can cause various HPV-related malignancies. The incidence of head and neck cancer has been rising in the past number of decades mostly due to oropharyngeal cancer linked to HPV infection. HPV vaccination has been shown to be effective for cervical and other anogenital HPV-related cancers, and there is significant potential for HPV vaccination to prevent oropharyngeal cancers, given that the HPV types implicated in this disease can be protected against by the HPV vaccine. Few countries have implemented a universal HPV vaccination programme for males and females, with many countries arguing that female only vaccination programmes protect males via herd immunity, and that men-who-have-sex-with-men will be protected via targeted vaccination programmes. We argue these may be limited in their effectiveness. We propose that the most effective, practical, ethical and potentially cost effective solution is universal HPV vaccination that might lead to control of HPV-related diseases in men and women alike.

Knowledge and acceptance of Human Papillomavirus (HPV) and HPV vaccination in adolescent boys worldwide: a systematic review

Aim

To determine HPV and HPV vaccine awareness, knowledge and acceptance in male adolescents worldwide.

Methods

A mixed methods systematic review was conducted. In accordance with PRISMA guidelines, relevant literature was identified through an electronic database search using specified keywords from inception to September 2015. Non-interventional studies presented in English that assessed HPV knowledge and provided data on male adolescents were included. If available, data on HPV and HPV vaccine perceptions, attitudes and/or HPV vaccine acceptance were also extracted. All studies were critically appraised to provide an indication of methodological quality. Results were compiled using a convergent synthesis.

Results

22 papers were included. The majority of studies were cross-sectional and conducted in the US and Europe. Across continents, regardless of a country’s HPV vaccination programme status, boys’ knowledge of HPV and/or HPV vaccination was generally low to moderate and significantly lower than female knowledge or awareness. There was a disagreement in the association of knowledge and vaccine acceptance, with higher knowledge not always being predictive of acceptance.

Conclusions

Comparison and synthesis of research concerning HPV knowledge and attitudes was made difficult due to the lack of universal definition of vaccine acceptance, and no universally accepted tool for its measurement or for the measurement of HPV knowledge. It is imperative that future research utilises consistent measures of HPV knowledge and attitudes to facilitate interpretation and comparison across studies internationally. Prospective longitudinal studies would be more informative providing data on factors that influenced the move from vaccine intention to uptake.

HPV (Human Papillomavirus) Vaccine -- Gardasil®-9: What You Need to Know

This document describes the HPV vaccine. These topics are addressed: why get vaccinated?, HPV vaccine, risks of a vaccine reaction, some people should not get this vaccine, and the National Vaccine Injury Compensation Program.