HPV vaccination of immunocompromised hosts

Human papillomavirus (HPV) is the most common sexually transmitted infection. About 90% of HPV infections are transient, resolving without any need for intervention. Most of HPV infections are low-risk non-oncogenic. However, persistent infection with high-risk oncogenic HPV types is the cause of cervical as well as various other anogenital and oropharyngeal cancers. HPV infection on either cutaneous or mucosal surfaces activates both innate and adaptive antiviral immune cells including Langerhans and keratinocyte cells, natural killer cells, B and T cells. These cellular responses alongside their corresponding cytokine profiles have been associated with clearance of HPV infection and regression of HPV associated disease although the actual immune mechanisms involved are not well understood. Current HPV vaccines are based on self -assembled virus-like particles (VLP) from the major viral capsid protein and target the high-risk HPV types as well as two low-risk types responsible for genital warts. The vaccines generate antibody protection against new infections with no effect on already established infections and HPV-associated diseases. Certainly, despite the high effectiveness of current prophylactic HPV vaccines, therapeutic HPV vaccines are needed for treatment of already established HPV infections and disease. Although there have been great efforts in development of therapeutic vaccines, none is yet to be licensed due to low efficacy and safety concerns. There is therefore a need to understand both natural and vaccine-induced immunity, for development of effective and safe therapeutic HPV vaccines. Additionally, a better understanding of the immunogenicity of HPV vaccines, which are among the best subunit vaccines developed to date, may identify immune pathways that could be targeted for development of similarly effective vaccines for other diseases. This review summarises available literature on immune responses to both HPV infection and vaccination, with an aim of improving overall understanding on this subject. This may provide insights for better targeting of both therapeutic and prophylactic vaccines, not only for HPV but also other antigen targets.

HPV vaccines in Brazil and the world

In this paper, we review the published evidence about the long-term efficacy of the available human papillomavirus (HPV) vaccines and their safety profile. Two prophylactic HPV vaccines – bivalent (bHPV) and quadrivalent (qHPV) – are now available, and vaccination programs are being widely implemented, primarily targeting adolescent girls. Efficacy has been widely demonstrated for both vaccines. Since the risk of HPV exposure potentially persists throughout a woman’s sexual life, vaccine duration of protection is critical to overall effectiveness. Interpreting the results of long-term efficacy studies for the two HPV vaccines can be puzzling, due to the heterogeneity of studies, different methods used in the assessment of immunogenicity, histopathological and virological end points, and statistical power issues. Moreover, an immunologic correlate of protection has not yet been established, and it is unknown whether higher antibody levels will really result in a longer duration of protection. Disease prevention remains the most important measure of long-term duration of vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4 years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8 years. The vaccine continues to be immunogenic and well tolerated up to 9 years following vaccination. All randomized controlled clinical trials of the bHPV and the qHPV vaccines provide evidence of an excellent safety profile. The most common complaint reported is pain in the injection site, which is self-limiting and spontaneously resolved. The incidence of systemic adverse events (AEs), serious AEs, and discontinuations due to a serious AE reported in clinical studies are similar between the two vaccines and their control groups. In particular, no increased risk of autoimmune disease has been shown among HPV-vaccinated subjects in long-term observation studies. As these are crucial topics in HPV vaccination, it is important to establish systems for continued monitoring of vaccine immunogenicity, efficacy, and safety over time.

This article takes a critical look at the pros and cons of human papillomavirus (HPV) vaccines. There is enough evidence to suggest that the prophylactic vaccines are efficacious in preventing various benign and malignant conditions (including cervical cancers) caused by HPV. Even though the vaccine is costly, hypothetical analysis has shown that HPV vaccination will be cost effective in the long run. Therapeutic HPV vaccines used to treat established disease are still undergoing evaluation in clinical studies, and results seem to be encouraging. Although several countries have started mandatory vaccination programs with the prophylactic HPV vaccines, conservatives have voiced concerns regarding the moral impact of such vaccination programs.

The incidence and mortality of cervical cancer in young women of reproductive ages have recently increased, which is a serious issue worldwide. This chapter will focus on the prevention of cervical cancer with HPV testing and vaccination. It is recognized that strategies for preventing cervical cancer consist of two major steps: preventing infection of oncogenic human papillomavirus (HPV)-16 and HPV-18 by HPV vaccination and secondary prevention by screening using HPV testing and/or cytology. Current cervical cancer screening strategies using cytology combined with HPV testing have been successfully introduced, with shifting from cytology alone to cytology plus HPV cotesting and now to a new paradigm in which HPV testing alone may become a primary screening tool. HPV vaccination is a “primary prevention” tool, and both the bivalent and quadrivalent HPV vaccines have excellent safety and efficacy profiles. Recently, a 9-valent vaccine, targeted against HPV-6, HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58, has been developed, which may possibly protect against over 80% of invasive cervical cancers. Further evidence on the 9-valent HPV vaccine should be accumulated worldwide, and its application is expected as a new strategy. Finally, the WHO recognizes the prevention of cervical cancer and other HPV-related diseases as global public health problems and strongly recommends the HPV vaccination programs. Both HPV vaccination and cancer screening tests are indispensable for cervical cancer prevention. The complete eradication of this malignant disease in the world will be realized in the near future by the further development and widespread application of these two strategies.

ObjectiveTo investigate the effect of a web-based educational intervention on changing female college students’ willingness and uptake of human papillomavirus (HPV) vaccines, and factors associated with HPV vaccination acceptance in Western and Northern China.MethodsA web-based cluster randomized controlled trial was conducted in Western and Northern China from February to May 2020. A total of 967 female freshmen were recruited from two universities through convenience sampling, stratified sampling (liberal arts or sciences), and cluster sampling. Eligible students were randomized into intervention and control group with a 1:1 allocation ratio. The intervention group received seven days of web-based health education regarding HPV and HPV vaccines, whereas the control group received non-HPV-related materials. All students were asked to complete a post-intervention questionnaire to measure their awareness, uptake, and willingness to receive HPV vaccination at 7-day and one-month intervals. The chi-square test and Student’s t-test were employed to examine the differences between the intervention and control groups for categorical and continuous data. Logistic regressions were used to analyze factors associated with vaccination intentions.ResultsNine hundred forty-six female freshmen aged 18.99 ± 0.63 years were enrolled in the study, with 532 in the intervention group and 414 in the control group. Prior to the intervention, 63.8%, 66.3%, and 60.8% of students had heard of HPV, HPV-related diseases, and HPV vaccines, respectively. Only 2.2% of students reported being vaccinated, but 33.0% were willing to be vaccinated against HPV. After seven days of education, students in the intervention group exhibited higher awareness (p < 0.001) and knowledge scores (5.13 ± 1.23 vs. 3.10 ± 1.99, p < 0.001) than those in the control group. Similarly, in the intervention groups, willingness to be vaccinated against HPV was significantly higher than in the control groups (p < 0.001). The high cost (57.7%) and concerns about adverse events (56.0%) were the main reasons female college students did not accept HPV vaccines. School location in urban areas, parents’ higher education backgrounds, history of HPV vaccination counseling, history of sexual behavior, and having heard of HPV vaccines were associated with a higher willingness to be vaccinated.ConclusionFemale college students’ HPV vaccination uptake is insufficient, and they have minimal detailed knowledge about HPV and its vaccines. Web-based health education on HPV vaccines is an easy, feasible, and effective way to improve the awareness and acceptance of HPV vaccination among female college students, but it has limited effect on HPV vaccination uptake.

The casual relationship concerning Human papillomaviruses (HPV) and cervical cancer is already established. Therefore, such HPV-associated malignancies might be prevented by prophylactic HPV vaccines. From 2009, two prophylactic HPV L1 Virus-Like Particle vaccines namely, Gardasil®; - quadrivalent (Merck) and Cervarix™ - bivalent (GlaxoSmithKline) are widely commercially available. By Aug 2014, 58 countries had introduced HPV vaccination in their national immunization program; this has led to numerous publications on safety and real world effectiveness. We have also seen long-term immunogenicity and efficacy data emerging. Data on cross-protection has also evolved. In clinical trials, it is observed that vaccinating adolescents results in higher immunological response than young adults hence to achieve best HPV vaccine efficacy it is advisable to immunize before the onset of sexual activity. Recently we have seen development of 2 dose vaccine schedule for adolescent, and emerging evidences even point that single dose of HPV vaccines can result in high efficacy, this observation is currently under consideration but if accepted will greatly impact vaccination coverage. In terms of safety, pregnancy registry did not find any unexpected patterns in fetal or maternal outcomes. This review only focuses on the efficacy and safety data of both Food and Drug Administration approved vaccines from clinical phase I to phase IV.

Men who have sex with men (MSM) are at risk of genital warts and anal cancer due to human papillomavirus (HPV) infection. This study explores MSMs' perceptions of HPV and HPV vaccination prior to the introduction of this programme. Focus groups and one-to-one interviews with self-identified MSM were conducted between November 2014 and March 2015 in Brighton, UK. Participants were recruited from community-based lesbian-gay-bisexual-transgender (LGBT) venues and organizations. Discussions were recorded, transcribed verbatim, and analysed using framework analysis. Thirty-three men took part (median age 25years, IQR: 21-27), most of whom (n=25) did not know about HPV, anal cancer (31), or HPV vaccination (26). While genital warts and anal cancer were perceived as severe, men did not perceive themselves at risk of HPV. All MSM would accept the HPV vaccine if offered by a health care professional. The challenges of accessing sexual health services or openly discussing same-sex experiences with health care professionals were perceived as barriers to accessing HPV vaccination. Two participants were concerned that selective HPV vaccination could increase stigma and prejudice against MSM, comparable to the AIDS epidemic. Ten MSM were unsure about the effectiveness of HPV vaccination for sexually active men and were in favour of vaccinating all adolescent boys at school. Most MSM have poor knowledge about HPV and associated anal cancer. Despite the lack of concern about HPV, most MSM expressed willingness to receive HPV vaccination. There is a need for health education about the risks of HPV and HPV-related diseases so that MSM can appraise the benefits of being vaccinated. Concerns about HPV vaccine effectiveness in sexually active men and possible stigmatization need to be addressed to optimize HPV vaccine acceptability. Statement of contribution What is already known on this subject? Men who have sex with men (MSM) have poor knowledge about HPV and HPV-related diseases. Perceived risk of HPV and attitudes towards HPV vaccination are associated with HPV vaccine acceptability amongst MSM in the United States. There is a gap between acceptability and uptake of HPV vaccination amongst MSM. What does this study add? Due to concerns about compromised effectiveness of the HPV vaccine in sexually active men, most MSM would recommend vaccination of all adolescent boys. Restricted access to sexual health services and the inability to discuss same-sex experiences were perceived as barriers to HPV vaccination. While the HPV vaccine is acceptable amongst MSM, the motivation to be vaccinated and complete the three-dose series might be low.

Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide. Early prevention with HPV vaccination is a safe and effective method against this disease. HPV vaccines provided more protection against several oncogenic HPV strains. Three prophylactic HPV vaccines have been approved to target high-risk HPV types and protect against HPV-related disorders. These existing vaccines are based on the recombinant DNA technology and purified L1 protein that is assembled to form HPV empty shells. The prophylactic vaccines are highly immunogenic and can induce production of specific neutralizing antibodies. However, therapeutic vaccines are different from these prophylactic vaccines. They induced cell-mediated immunity against transformed cells, instead of neutralizing antibodies. The second generation of prophylactic HPV vaccines, made from alternative viral components using cost-effective production strategies, is undergoing clinical evaluation. The purpose of this review is to provide a complete and up-to-date review of the types of HPV vaccines and the efficiency of each of them for readers.

Currently, there is limited data on the immunogenicity and efficacy of human papillomavirus vaccines in Low and Middle income countries (LMIC). The review aims to summarize the current status from published HPV vaccine safety, immunogenicity and efficacy studies in low and middle income countries (LMIC). Electronic databases (PubMed/MEDLINE and HINARI) were searched for peer reviewed English language articles on HPV vaccination in LMIC that have so far been published from 1st January 2006 up to 30th January 2015. Eligible studies were included if they had used the bivalent (bHPV) or quadrivalent HPV (qHPV) vaccines in a LMIC and investigated safety, immunogenicity and/or efficacy. The main findings were extracted and summarized. A total of fourteen HPV vaccine studies assessing safety, Immunogenicity and efficacy of the bivalent or quadrivalent vaccines in LMIC were included. There are only ten published clinical trials where a LMIC has participated. There was no published study so far that assessed efficacy of the HPV vaccines in Sub-Saharan Africa. From these studies, vaccine induced immune response was comparable to that from results of HICs for all age groups. Studies assessing HPV vaccine efficacy of the bivalent or quadrivalent vaccine within LMIC were largely missing. Only three studies were found where a LMIC was part of a multi center clinical trial. In all the studies, there were no vaccine related serious adverse events. The findings from the only study that investigated less than three doses of the bivalent HPV-16/18 vaccine suggest that even with less than three doses, antibody levels were still comparable with older women where efficacy has been proven. The few studies from LMIC in this review had comparable safety, Immunogenicity and efficacy profiles like in HIC. Overall, the LMIC of Africa where immune compromising/modulating situations are prevalent, there is need for long term immunogenicity as well as surveillance studies for long term clinical effectiveness after two and three dose regimens.

Human papillomavirus vaccination and risk of autoimmune diseases: A large cohort study of over 2million young girls in France.

We conducted a meta-analysis to assess the efficacy of prophylactic human papillomavirus (HPV) vaccines against cervical cancer precursors and HPV persistent infection among Asian populations. Randomized controlled clinical trials conducted in Asian countries were identified from three electronic databases (PubMed, EMBASE and the Cochrane Library). Publication retrieval was performed on September 1, 2022 and only those written in English were included. The data were analyzed with Cochrane Review Manager (version 5.3) and Stata/SE (15.1). Effect sizes were presented as risk ratios (RRs) and 95% confidence intervals (CIs). Ten articles were considered in the meta-analysis, without significant heterogeneity among them. The fixed-effect RRs and 95% CIs for cervical intraepithelial neoplasia grade 1 (CIN1+) and CIN2+ were 0.10 (0.05-0.21) and 0.11 (0.04-0.27), respectively. Positive effect of HPV vaccination on 6- and 12-month persistent infection were observed, with the respective pooled RRs of 0.05 (95% CI: 0.03-0.09) and 0.09 (95% CI: 0.05-0.15). HPV vaccination has a positive effect on the incidence of cytological abnormalities associated with HPV 16/18 (RR, 0.13; 95% CI (0.09-0.20)). Positive effects of HPV vaccination were also observed for HPV 16- and 18-specific immunogenicity (RR, 235.02; 95% CI (82.77-667.31) and RR, 98.24; 95% CI (50.36-191.67), respectively). Females receiving an initial vaccination showed significant decreased incidences of cervical intraepithelial neoplasia, HPV persistent infection and cytological abnormalities and a significantly higher antibody positive conversion rate compared with non-vaccination counterparts. Prophylactic HPV vaccines are highly efficacious in preventing cervical cancer in Asian females. The government should accelerate the processes of vaccine introduction and vaccination implementation by prioritizing them in public health policies, which should be helpful to enhance Asian females' awareness of receiving HPV vaccination volitionally.

Introduction: Nigeria recently introduced the human papillomavirus (HPV) vaccine into its National Programme of Immunization (NPI). The uptake of this vaccine was fraught with several challenges, such as misinformation, vaccine hesitancy and belief barriers. Healthcare provider recommendations are known to improve the uptake of HPV vaccine. This study assessed the pattern and predictors of HPV vaccine recommendations among healthcare providers in Ebonyi State. Methods: This was a facility-based cross-sectional study conducted from July to August 2024 among healthcare providers in Ebonyi State. The respondents were selected using a multistage sampling technique. An interviewer-administered structured questionnaire programmed into Open Data Kit was used to collect data. Descriptive, bivariate, and multivariate analyses were done using IBM Statistical Product and Service Solutions (SPSS) version 26. The level of significance was set at 5%. Results: A total of 935 healthcare providers participated in the survey. The mean age of the respondents was 36.6±9.5 years. The prevalence of frequent recommendations of HPV vaccination was 37.3% (95% CI: 34.1 – 40.6). Among those who had never recommended the vaccine (33.7%), the most frequent reasons included lack of information (35.9%) and the perception that vaccine recommendation was not their duty (31.1%). The independent predictors of HPV vaccine recommendation by healthcare providers included age (aOR=0.50; 95% CI: 0.28 – 0.90), education [(West African Examination Council O’ level; aOR = 0.06; 95% CI: 0.01–0.22) and (Ordinary National Diploma/Higher National Diploma; aOR = 0.31; 95% CI: 0.14–0.71)], actual knowledge (aOR=12.38; 95% CI: 7.28 – 21.10), self-reported knowledge (aOR=2.94; 95% CI: 1.74 – 4.96) and attitude to HPV vaccination (aOR=15.62; 95% CI: 7.76 – 31.44). Conclusions: Only one third of the healthcare providers frequently recommended the HPV vaccine. Age, educational status, knowledge of HPV vaccination, and attitude of healthcare providers to HPV vaccination were associated with HPV vaccine recommendation by healthcare providers. Reorienting healthcare providers through regular training sessions on the national HPV vaccination guidelines, while designing targeted health education programmes to address identified knowledge gaps among healthcare providers, is recommended.

Gay, bisexual, and other men who have sex with men (MSM) and transgender women, particularly those who are living with HIV, are disproportionately affected by human papillomavirus (HPV). For this narrative review of HPV health outcomes and vaccination for gay, bisexual, and other MSM and transgender women in the United States, we highlighted 71 publications regarding 1) burden of HPV infections and related diseases; 2) HPV vaccine efficacy; 3) HPV vaccination recommendations; 4) HPV vaccination coverage; 5) real-world vaccine effectiveness and health impacts; and 6) HPV vaccination acceptability. Vaccination is effective at reducing HPV infections among MSM; in the United States, routine HPV vaccination is recommended for all adolescents at age 11–12 years and for all persons through age 26 years. Efforts are ongoing to increase vaccination coverage and monitor health impacts of vaccination. Increasing vaccination coverage before sexual exposure to HPV is expected to reduce the burden of HPV-related disease.

Immunization is the most successful method in preventing and controlling infectious diseases, which has helped saving millions of lives worldwide. The discovery of the human papillomavirus (HPV) infection being associated with a variety of benign conditions and cancers has driven the development of prophylactic HPV vaccines. Currently, four HPV vaccines are available on the pharmaceutical market: Cervarix, Gardasil, Gardasil-9, and the recently developed Cecolin. Multiple studies have proven the HPV vaccines’ safety and efficacy in preventing HPV-related diseases. Since 2006, when the first HPV vaccine was approved, more than 100 World Health Organization member countries reported the implementation of HPV immunization. However, HPV vaccination dread, concerns about its safety, and associated adverse outcomes have a significant impact on the HPV vaccine implementation campaigns all over the world. Many developed countries have successfully implemented HPV immunization and achieved tremendous progress in preventing HPV-related conditions. However, there are still many countries worldwide which have not created, or have not yet implemented, HPV vaccination campaigns, or have failed due to deficient realization plans associated with establishing successful HPV vaccination programs. Lack of proper HPV information campaigns, negative media reflection, and numerous myths and fake information have led to HPV vaccine rejection in many states. Thus, context-specific health educational interventions on HPV vaccination safety, effectiveness, and benefits are important to increase the vaccines’ acceptance for efficacious prevention of HPV-associated conditions.