Cobertura da vacinação contra papilomavírus humano no Nordeste do Brasil, 2013-2021: estudo descritivo / Human papillomavirus vaccination coverage in Northeast Brazil, 2013-2021: a descriptive study / Cobertura de vacunación contra el virus del papiloma humano en el Nordeste de Brasil, 2013-2021: un estudio descriptivo

Objetivo: descrever a cobertura da vacina contra papilomavírus humano (HPV) na região Nordeste do Brasil, no período de 2013 a 2021. Métodos: estudo descritivo conduzido com dados obtidos do Programa Nacional de Imunizações, que estabelece a meta de 80% para a vacina contra o HPV para meninas entre 9 e 14 anos e meninos entre 11 e 14 anos. Resultados: as coberturas para as meninas foram de 73,9%, na primeira, e de 54,3% na segunda dose, e para meninos, as coberturas de cada dose foram de 49,7% e 32,6%, respectivamente; excetuando-se Ceará e Paraíba, que alcançaram coberturas acima de 80% na primeira dose para as meninas, nenhum estado alcançou a meta para as duas doses. Conclusões: entre 2013 e 2021, as coberturas da vacina contra HPV estiveram abaixo da meta para ambos os sexos, com exceção de Ceará e Paraíba, que atingiram a meta para a primeira dose no grupo de meninas.

Objective: to describe human papillomavirus (HPV) vaccination coverage in the Northeast region of Brazil, in the period from 2013 to 2021. Methods: this was a descriptive study conducted with data obtained from the National Immunization Program, which sets a goal of 80% coverage of HPV vaccination in girls aged between 9 and 14 years and boys aged between 11 and 14 years. Results: HPV vaccination coverage in girls was 73.9%, regarding the first dose, and 54.3% regarding the second dose, and for boys, the coverage of each dose was 49.7% and 32.6%, respectively; with the exception of the states of Ceará and Paraíba, which reached coverage above 80% regarding the first dose in girls, none of the states reached the goal for both doses. Conclusions: between 2013 and 2021, HPV vaccination coverage was below the target for both sexes, with the exception of the states of Ceará and Paraíba, which reached the goal for the first dose in the girls.

Objetivo: describir las coberturas de la vacuna contra el papilomavirus humano en la Región Nordeste de Brasil y sus estados, de 2013 a 2021. Métodos: se trata de un estudio descriptivo realizado con datos de cobertura vacunal obtenidos del Programa Nacional de Immunizaciones, que establece la meta del 80% para la vacuna. Los datos de población se obtuvieron del Departamento de Informática del Ministerio de Salud. Resultados: la cobertura de vacunación en niñas fue del 73,9% en la primera y del 54,3% en la segunda dosis; en niños la cobertura de cada dosis fue del 49,7% y 32,6%; Ceará y Paraíba alcanzaron una cobertura superior al 80% para la primera dosis en niñas, y ningún estado alcanzó la meta para las dos dosis. Conclusiones: la cobertura de la vacuna está por debajo de la meta para ambos sexos, con excepción de la primera dosis en niñas en Ceará y Paraíba.

RG2-VLP: a Vaccine Designed to Broadly Protect against Anogenital and Skin Human Papillomaviruses Causing Human Cancer.

The family of human papillomaviruses (HPV) includes over 400 genotypes. Genus α genotypes generally infect the anogenital mucosa, and a subset of these HPV are a necessary, but not sufficient, cause of cervical cancer. Of the 13 high-risk (HR) and 11 intermediate-risk (IR) HPV associated with cervical cancer, genotypes 16 and 18 cause 50% and 20% of cases, respectively, whereas HPV16 dominates in other anogenital and oropharyngeal cancers. A plethora of ßHPVs are associated with cutaneous squamous cell carcinoma (CSCC), especially in sun-exposed skin sites of epidermodysplasia verruciformis (EV), AIDS, and immunosuppressed patients. Licensed L1 virus-like particle (VLP) vaccines, such as Gardasil 9, target a subset of αHPV but no ßHPV. To comprehensively target both α- and ßHPVs, we developed a two-component VLP vaccine, RG2-VLP, in which L2 protective epitopes derived from a conserved αHPV epitope (amino acids 17 to 36 of HPV16 L2) and a consensus ßHPV sequence in the same region are displayed within the DE loop of HPV16 and HPV18 L1 VLP, respectively. Unlike vaccination with Gardasil 9, vaccination of wild-type and EV model mice (Tmc6Δ/Δ or Tmc8Δ/Δ) with RG2-VLP induced robust L2-specific antibody titers and protected against ß-type HPV5. RG2-VLP protected rabbits against 17 αHPV, including those not covered by Gardasil 9. HPV16- and HPV18-specific neutralizing antibody responses were similar between RG2-VLP- and Gardasil 9-vaccinated animals. However, only transfer of RG2-VLP antiserum effectively protected naive mice from challenge with all ßHPVs tested. Taken together, these observations suggest RG2-VLP's potential as a broad-spectrum vaccine to prevent αHPV-driven anogenital, oropharyngeal, and ßHPV-associated cutaneous cancers. IMPORTANCE Licensed preventive HPV vaccines are composed of VLPs derived by expression of major capsid protein L1. They confer protection generally restricted to infection by the αHPVs targeted by the up-to-9-valent vaccine, and their associated anogenital cancers and genital warts, but do not target ßHPV that are associated with CSCC in EV and immunocompromised patients. We describe the development of a two-antigen vaccine protective in animal models against known oncogenic αHPVs as well as diverse ßHPVs by incorporation into HPV16 and HPV18 L1 VLP of 20-amino-acid conserved protective epitopes derived from minor capsid protein L2.

Eventos adversos após a vacina papilomavírus humano em adolescentes no estado de Minas Gerais / Eventos adversos después de la vacunación contra el virus del papiloma humano, en adolescentes en el estado de Minas Gerais / Adverse events following human papillomavirus vaccine in adolescents in the state of Minas Gerais

RESUMO Objetivo: investigar as notificações dos eventos adversos pós-vacinação papilomavírus humano no estado de Minas Gerais, de acordo com a localidade de notificação, a causalidade, a gravidade e a evolução dos casos. Métodos: estudo epidemiológico realizado com os dados de 2015-2019, notificados no Sistema de Informação de Vigilância de Eventos Adversos. Os dados foram analisados e apresentados em proporções, segundo as macrorregiões de saúde e os anos do estudo. Resultados: em 2015, foram notificados 26,41% eventos adversos, sendo o ano com maior notificação. Na análise das macrorregiões de saúde, Vale do Jequitinhonha apresentou a menor prevalência de registro (0,43%), e a Centro a maior prevalência de notificação (30,95%). Os eventos adversos locais mais prevalentes foram: dor (56,48%) e edema (38,89%). Já quanto aos eventos sistêmicos, a cefaleia (29,69%) e a gastroenterite (29,69%) tiveram os maiores registros de casos. Os eventos classificados como adversos não graves (59,82%) foram os mais prevalentes, e quanto à causa, 35,94% deles foram atribuídos aos erros de imunização. Conclusão: este estudo reforça que os eventos adversos pós-vacina de HPV foram, em sua maioria, eventos não graves, demonstrando, portanto, a segurança da vacina HPV para o público adolescente, contribuindo para o aumento das taxas de cobertura vacinal.

RESUMEN Objetivo: investigar las notificaciones de eventos adversos de papilomavirus humano en el Estado de Minas Gerais, según la localidad de notificación, la causalidad, la gravedad y la evolución de los casos. Métodos: estudio epidemiológico realizado con datos de 2015-2019, notificados en el Sistema de Información de Vigilancia de Eventos Adversos. Los datos fueron analizados y presentados en proporciones, según las macrorregiones sanitarias y los años del estudio. Resultados: en 2015 se notificaron un 26,41% de eventos adversos, siendo el año con mayor notificación. Al analizar las macrorregiones sanitarias, el Valle de Jequitinhonha tuvo la menor prevalencia de registro, con un 0,43%, y el Centro tuvo la mayor prevalencia de notificación (30,95%). Los efectos adversos locales más frecuentes fueron el dolor (56,48%) y el edema (38,89%). En cuanto a los eventos sistémicos, la cefalea (29,69%) y la gastroenteritis (29,69%) presentaron el mayor número de casos. Los eventos clasificados como adversos no graves (59,82%) fueron los más prevalentes y, en cuanto a la causa, el 35,94% de ellos se atribuyeron a los errores de inmunización. Conclusión: este estudio refuerza que los eventos adversos posteriores a la vacuna contra el VPH fueron en su mayoría eventos no graves, demostrando así la seguridad de la vacuna contra el VPH para el público adolescente y contribuyendo al aumento de las tasas de cobertura de vacunación.

ABSTRACT Objective: to investigate reports of adverse events following human papillomavirus vaccination in the state of Minas Gerais, according to the location of notification, causality, severity, and evolution of cases. Methods: epidemiological study carried out with data from 2015-2019, reported in the Adverse Event Surveillance Information System. Data were analyzed and presented in proportions, according to health macro-regions and years of study. Results: in 2015, 26.41% of adverse events were reported, being the year with the highest number of notifications. In the analysis of health macro-regions, Vale do Jequitinhonha had the lowest prevalence of registration (0.43%), and the Center had the highest prevalence of notification (30.95%). The most prevalent local adverse events were pain (56.48%) and edema (38.89%). As for systemic events, headache (29.69%) and gastroenteritis (29.69%) had the highest number of cases. Events classified as non-serious adverse events (59.82%) were the most prevalent, and regarding the cause, 35.94% of them were attributed to immunization errors. Conclusion: this study reinforces that adverse events following HPV vaccination were, for the most part, non-serious events, thus demonstrating the safety of the HPV vaccine for the adolescent public, contributing to the increase in vaccine coverage rates.

Increasing global accessibility to high-level treatments for cervical cancers.

Human papillomaviruses (HPV)-related gynecological cancers are a major health care issue, and a leading cause of cancer death in low- and middle-income countries (LMIC). In 2020, the World Health Organization launched a program aimed at cervical cancer elimination, by screening and vaccination strategies. Offering the best possible care to women diagnosed with invasive cancer is a complementary objective. Treatment of cervical cancer as per modern standards is complex and multimodal, mainly relying on surgery, external-beam radiotherapy (+/-chemotherapy) and brachytherapy. In parallel with the pivotal role of multidisciplinary discussion, international societies provide guidance to define the most effective and least toxic anti-cancer strategy, homogenize treatment protocols and provide benchmark quality indicators as a basis for accreditation processes. The challenge is to offer the appropriate diagnostic workup and treatment upfront and to avoid non- evidence-based treatment that consumes resources, impairs quality of life (QoL), and compromises oncological outcome. Various strategies may be applied for improving treatment quality: development of surgical mentorship, companion-training programs and international cooperation. The lack of radiotherapy/brachytherapy facilities is a major concern in LMIC. Reinforcing international support in terms of education, training, research and development and technical cooperation with national projects is required to increase access to minimum requirements but also introduce modern techniques, upgrade radiotherapy/brachytherapy services, and expand access to modern systemic treatments. In countries with robust economies, compliance to standards should also be increased. Integrative cancer care and multidisciplinary approaches are needed to tackle the dual challenge of increasing cure rates while minimizing QoL impairment. Appropriate dimensioning of the resources to avoid harmful treatment delays and access to expert referral centers is also a priority.

WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention, second edition: use of mRNA tests for human papillomavirus ( HPV)

This WHO and HRP guideline is designed to help countries make faster progress, more equitably, on the screening and treatment of cervical cancer. This document includes guidance on an important additional option for cervical screening, the use of mRNA (messenger RNA) HPV testing. This gives countries additional options when considering which type of HPV nucleic acid amplification tests (NAAT) to use in their screening programs. In this present publication, only recommendations for the use of HPV mRNA testing are presented. For other recommendations, please refer to the July 2021 publication of the WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention, second edition.

Design and Immunological Validation of Macaca fascicularis Papillomavirus Type 3 Based Vaccine Candidates in Outbred Mice: Basis for Future Testing of a Therapeutic Papillomavirus Vaccine in NHPs.

Persistent human papillomavirus (HPV) infections are causative for cervical neoplasia and carcinomas. Despite the availability of prophylactic vaccines, morbidity and mortality induced by HPV are still too high. Thus, an efficient therapy, such as a therapeutic vaccine, is urgently required. Herein, we describe the development and validation of Macaca fascicularis papillomavirus type 3 (MfPV3) antigens delivered via nucleic-acid and adenoviral vectors in outbred mouse models. Ten artificially fused polypeptides comprising early viral regulatory proteins were designed and optionally linked to the T cell adjuvant MHC-II-associated invariant chain. Transfected HEK293 cells and A549 cells transduced with recombinant adenoviruses expressing the same panel of artificial antigens proved proper and comparable expression, respectively. Immunization of outbred CD1 and OF1 mice led to CD8+ and CD4+ T cell responses against MfPV3 antigens after DNA- and adenoviral vector delivery. Moreover, in vivo cytotoxicity of vaccine-induced CD8+ T cells was demonstrated in BALB/c mice by quantifying specific killing of transferred peptide-pulsed syngeneic target cells. The use of the invariant chain as T cell adjuvant enhanced the T cell responses regarding cytotoxicity and in vitro analysis suggested an accelerated turnover of the antigens as causative. Notably, the fusion-polypeptide elicited the same level of T-cell responses as administration of the antigens individually, suggesting no loss of immunogenicity by fusing multiple proteins in one vaccine construct. These data support further development of the vaccine candidates in a follow up efficacy study in persistently infected Macaca fascicularis monkeys to assess their potential to eliminate pre-malignant papillomavirus infections, eventually instructing the design of an analogous therapeutic HPV vaccine.

Design of a multi-epitope protein vaccine against herpes simplex virus, human papillomavirus and Chlamydia trachomatis as the main causes of sexually transmitted diseases.

Sexually transmitted diseases (STDs) have a profound effect on reproductivity and sexual health worldwide. According to world health organization (WHO) 375 million new case of STD, including chlamydia trachomatis (chlamydia), Neisseria gonorrhoeae, HSV, HPV has been reported in 2016. More than 30 diverse pathogenesis have identified to be transmitted through sexual intercourse. Of these, viral infections (hepatitis B, herpes simplex virus (HSV or herpes), HIV, and human papillomavirus (HPV) are incurable. However, symptoms caused by the incurable viral infections can be alleviated through treatment. Antimicrobial resistance (AMR) of sexually transmitted infections (STIs) to antibiotics has increased recent years, in this regard, vaccination is proposed as an important strategy for prevention or treatment of STDs. Vaccine against HPV 16 and 18 suggests a new approach for controlling STDs but until now, there is no prophylactic or therapeutic vaccine have been approved for HSV-2 and Chlamydia trachomatis (CT); in this reason, developing an efficient vaccine is inevitable. Recently, different combinatorial forms of subunit vaccines against two or three type of bacteria have been designed. In this study, to design a combinatorial vaccine against HSV, CT, and HPV, the E7 and L2 from HPV, glycoprotein D from HSV-2 and ompA from CT were selected as final antigens. Afterward, the immunodominant helper T lymphocytes (HTLs) and cytolytic T lymphocytes (CTLs) epitopes were chosen from aforesaid antigens. P30 (tetanus toxoid epitope) as universal T-helper were also added to the vaccine. Moreover, flagellin D1/D0 as TLR5 agonist and the RS09 as a TLR4 ligand were incorporated to N and C-terminals of peptide vaccine, respectively. Finally, all selected parts were fused together by appropriate linkers to enhance vaccine efficiency. The physicochemical, structural, and immunological properties of the designed vaccine protein were assessed. To achieve the best 3D model of the protein vaccine, modeling, refinement, and validation of modeled structures were also done. Docking evaluation demonstrated suitable interaction between the vaccine and TLR5. Moreover, molecular dynamics (MD) studies showed an appropriate and stable structure of protein and TLR5. Based on immunoinformatic analysis, our vaccine candidate could potentially incite humoral and cellular immunities, which are critical for protection against HPV, HSV-2, and chlamydia trachomatis. It should be noted that, experimental studies are needed to confirm the efficacy of the designed vaccine.

Host defence and persistent human papillomavirus infection.

The ability to establish long term persistent infection is a feature of human papillomaviruses. The available evidence is that this ability is a consequence of a complex local immune milieu whereby innate immune receptors and signalling pathway cascades are inhibited by HPV early proteins resulting in failure of dendritic cell maturation, antigen processing and presentation and activation of cytotoxic antigen specific T cell responses. The development of cutaneous and mucosal infection models with the mouse papillomavirus MmuPV1 and the access to multiple gene deficient strains is providing the frame work to dissect the mechanisms underlying these complex host virus interactions.

Precisely Shaped Self-Adjuvanting Peptide Vaccines with Enhanced Immune Responses for HPV-Associated Cancer Therapy.

Peptide vaccines exhibit great potential in cancer therapy via eliciting antigen-specific host immune response and long-term immune memory to defend cancer cells. However, the low induced immune response of many developing vaccines implies the imperatives for understanding the favorable structural features of efficient cancer vaccines. Herein, we report on the two groups of self-adjuvanting peptide vaccines with distinct morphology and investigate the relationship between the morphology of peptide vaccines and the induced immune response. Two nanofibril peptide vaccines were created via co-assembly of a pentapeptide with a central 4-aminoproline residue, with its derivative functionalized with antigen epitopes derived from human papillomavirus E7 proteins, whereas utilization of a pentapeptide with a natural proline residue led to the formation of two nanoparticle peptide vaccines. The immunological results of dendritic cell (DCs) maturation and antigen presentation induced by the peptide assemblies implied the self-adjuvanting property of the resulting peptide vaccines. In particular, cellular uptake studies revealed the enhanced internalization and elongated retention of the nanofibril peptide vaccines in DCs, leading to their advanced performance in DC maturation, accumulation at lymph nodes, infiltration of cytotoxic T lymphocytes into tumor tissues, and eventually lysis of in vivo tumor cells, compared to the nanoparticle counterparts. The antitumor immune response caused by the nanofibril peptide vaccines was further augmented when simultaneously administrated with anti-PD-1 checkpoint blockades, suggesting the opportunity of the combinatorial immunotherapy by utilizing the nanofibril peptide vaccines. Our findings strongly demonstrate a robust relationship between the immune response of peptide vaccines and their morphology, thereby elucidating the critical role of morphological control in the design of efficient peptide vaccines and providing the guidance for the design of efficient peptide vaccines in the future.

Episome partitioning and symmetric cell divisions: Quantifying the role of random events in the persistence of HPV infections.

Human Papillomaviruses (HPV) are one of the most prevalent sexually transmitted infections (STI) and the most oncogenic viruses known to humans. The vast majority of HPV infections clear in less than 3 years, but the underlying mechanisms, especially the involvement of the immune response, are still poorly known. Building on earlier work stressing the importance of randomness in the type of cell divisions in the clearance of HPV infection, we develop a stochastic mathematical model of HPV dynamics that combines the previous aspect with an explicit description of the intracellular level. We show that the random partitioning of virus episomes upon stem cell division and the occurrence of symmetric divisions dramatically affect viral persistence. These results call for more detailed within-host studies to better understand the relative importance of stochasticity and immunity in HPV infection clearance.

Human Papillomavirus Vaccines.

Human papillomavirus (HPV) vaccines are among the most effective vaccines available, the first to prevent infection by a mucosatropic sexually transmitted infectious agent and to do so without specific induction of mucosal immunity. Currently available prophylactic HPV vaccines are based on virus-like particles that self-assemble spontaneously from the L1 major capsid protein. The first HPV vaccine was licensed in 2006. All vaccines target HPV-16 and HPV-18, types which cause the majority of HPV-attributable cancers. As of 2020, HPV vaccines had been introduced into national immunization programs in more than 100 countries. Vaccination polices have evolved; most programs target vaccination of young adolescent girls, with an increasing number also including boys. The efficacy and safety found in prelicensure trials have been confirmed by data from national immunization programs. The dramatic impact and effectiveness observed has stimulated interest in ambitious disease reduction goals.

Barriers towards HPV Vaccinations for Boys and Young Men: A Narrative Review.

BACKGROUND: HPV vaccination of both girls and boys can protect against infection and eliminate the risk for HPV-associated cancer. Due to a common misconception that the virus only poses risks to women, vaccine coverage is suboptimal among men in many countries. It is urgent to identify barriers to vaccination of boys and men. METHODS: We conducted a narrative review of publications examining attitudes and beliefs regarding HPV vaccination for boys and young men. The electronic databases searched were PubMed, PsychInfo and Scopus (December 2020; last update July 2021). A total of 103 original articles were included in the final analysis. RESULTS: The central barriers against vaccination of boys and men are: (1) lack of knowledge, (2) vaccine hesitancy in general, (3) lack of recommendation from and/or discussions with healthcare providers, (4) cost and logistics, and (5) the idea that HPV vaccination may promote promiscuity. Men who have sex with men and families belonging to ethnic minorities express a need for information tailored to their situation. CONCLUSIONS: Boys should be included in national immunization programs and men should also be offered catch-up vaccinations. Future studies should focus on addressing vaccine hesitancy and developing interventions to promote pan-gender HPV vaccination.

The Effect of Prophylactic HPV Vaccines on Oral and Oropharyngeal HPV Infection-A Systematic Review.

Human papillomavirus (HPV) imposes an increased risk of developing cervical, anal and oropharyngeal cancer. In the Western world, HPV infection is currently the major cause of oropharyngeal cancer. The effectiveness of HPV vaccines for oral or oropharyngeal HPV infection is yet to be determined. This study conducted a systematic literature search in Pubmed and Embase. Studies investigating the impact of HPV vaccines on oral or oropharyngeal HPV infection were enrolled. This review reports the relative prevention percentage (RPP), including a risk of bias assessment as well as a quality assessment study. Nine studies were included (48,777 participants): five cross-sectional studies; one randomized community trial study (RCT); one longitudinal cohort study; and two case-control studies. A significant mean RPP of 83.9% (66.6-97.8%) was calculated from the cross-sectional studies, 82.4% in the included RCT and 83% in the longitudinal cohort study. Further, two case-control studies that measured antibody response in participants immunized with HPV vaccines were included. Respectively, 100% and 93.2% of participants developed HPV-16 Immunoglobulin G (IgG) antibodies in oral fluids post-vaccination. Analysis of the studies identified a significant decrease in vaccine-type oral or oropharyngeal HPV infections in study participants immunized with HPV vaccines across study designs and heterogenous populations. Further, a significant percentage of participants developed IgG antibodies in oral fluid post-vaccination.

Human Papillomavirus: Screening, Testing, and Prevention.

With more than 200 types identified, human papillomavirus (HPV) commonly causes infections of the skin and mucosa. HPV infection is the most common sexually transmitted infection in the United States. Although most HPV infections are transient and subclinical, some lead to clinical manifestations ranging from benign papillomas or warts to intraepithelial lesions. In some patients, persistent infection with high-risk mucosal types, especially HPV-16 and HPV-18, causes anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancers. Most HPV-related cancers are believed to be caused by sexual spread of the virus. A history of multiple sex partners; initiation of sexual activity at an early age; not using barrier protection; other sexually transmitted infections, including HIV; an immunocompromised state; alcohol use; and smoking have been identified as risk factors for persistent HPV infections. Screening for HPV infection is effective in identifying precancerous lesions and allows for interventions that can prevent the development of cancer. Use of condoms and dental dams may decrease spread of the virus. Vaccination is the primary method of prevention. The nonavalent HPV vaccine is effective in preventing the development of high-grade precancerous cervical lesions in noninfected patients. Vaccination is ideally administered at 11 or 12 years of age, irrespective of the patient's sex. In general, a two-dose series is recommended if administered before 15 years of age; however, individuals who are immunocompromised require three doses.

Significant decline of HPV 6 infection and genital warts despite low HPV vaccination coverage in young women in Germany: a long-term prospective, cohort data analysis.

BACKGROUND: The introduction of human papillomavirus (HPV) vaccination has resulted in a remarkable decline of genital warts in women and men, but in Germany historical rates of vaccination are relatively low. We report long-term surveillance data on changes in HPV 6 and HPV 11 infection and the prevalence of genital warts in young women in the Wolfsburg HPV epidemiological study (WOLVES). METHODS: Women born in 1983/84, 1988/89, and 1993/94 participated in four cohorts between 2009/10 and 2014/15. Quadrivalent vaccination coverage and prevalence of HPV 6/11 infection and genital warts are reported for participants aged 19-22 years and 24-27 years at the time of sample collection. Statistical analyses were done to compare similarly aged participants using 2 × 2 contingency tables (Röhmel-Mansmann unconditional exact test; two-side alpha of 0.05). RESULTS: A total of 2456 women were recruited. Between 2010 and 2015, there was a statistically significant decrease in the prevalence of HPV 6 infection among women aged 24-27 years (2.1% versus 0.0%; P < 0.0001) and women aged 19-22 years (2.0% versus 0.0%; P = 0.0056). There was no significant decline in HPV 11 infection. In total, 52 of 2341 participants were diagnosed with genital warts. There was a statistically significant drop in the risk of developing genital warts in women aged 24-27 years between 2010 and 2015 (4.7% versus 1.7%, respectively; P = 0.0018). The overall risk of developing genital warts in women aged 19-27 years decreased from 3.1% in 2010 to 1.2% in 2015 (P = 0.0022). CONCLUSIONS: An increase in vaccination coverage was associated with a decreased prevalence of genital warts in young women. A protective effect greater than herd immunity alone was seen despite low vaccination rates. Quadrivalent vaccine had a protective effect on genital HPV 6 infection and an almost fully protective effect on the development of genital warts in the youngest population.

A nationwide birth year-by-year analysis of effectiveness of HPV vaccine in Japan.

In Japan, the age-adjusted incidence of cervical cancer has been increasing constantly and rapidly among younger women. We set out to accurately confirm the effectiveness of the HPV vaccine in Japan. Data were collected for women born in the fiscal year (FY) 1990 to 1997, who became eligible for their 20-y-old cervical cancer screening between the FY 2010 to 2017. The adjusted incidence of cervical intraepithelial neoplasia (CIN)1+ in women born in FY 1990 to 1993, that is those who reached the national vaccination target age prior to the introduction of publicly subsidized HPV vaccinations, referred here after as "the pre-introduction generation", was 1.42% (242/17 040). The incidence in the "vaccination generation" (women born in FY 1994 to 1997, that is those who were heavily vaccinated as a group when they were of the nationally targeted age of 13-16) was 1.66% (135/8020). There was no significant difference between these incidence rates. However, our FY birth year-by-year analysis revealed that the incidence of CIN1+ was obviously lower than that predicted based on just the trend for CIN1+ seen in the pre-introduction generation. Our analysis revealed that the incidence of CIN3+ was obviously lower in the vaccination generation than in the pre-introduction generation (P = .0008). The incidence of CIN was already tending to increase in both the pre-introduction and vaccination generations. The changes in CIN incidence by individual birth FY must be examined to accurately determine the actual effects of the HPV vaccine for reducing mild cervical lesions.

Mixed Bacteriophage MS2-L2 VLPs Elicit Long-Lasting Protective Antibodies against HPV Pseudovirus 51.

Three prophylactic vaccines are approved to protect against HPV infections. These vaccines are highly immunogenic. The most recent HPV vaccine, Gardasil-9, protects against HPV types associated with ~90% of cervical cancer (worldwide). Thus, ~10% of HPV-associated cancers are not protected by Gardasil-9. Although this is not a large percentage overall, the HPV types associated with 10% of cervical cancer not protected by the current vaccine are significantly important, especially in HIV/AIDS patients who are infected with multiple HPV types. To broaden the spectrum of protection against HPV infections, we developed mixed MS2-L2 VLPs (MS2-31L2/16L2 VLPs and MS2-consL2 (69-86) VLPs) in a previous study. Immunization with the VLPs neutralized/protected mice against infection with eleven high-risk HPV types associated with ~95% of cervical cancer and against one low-risk HPV type associated with ~36% of genital warts & up to 32% of recurrent respiratory papillomatosis. Here, we report that the mixed MS2-L2 VLPs can protect mice from three additional HPV types: HPV51, which is associated with ~0.8% of cervical cancer; HPV6, which is associated with up to 60% of genital warts; HPV5, which is associated with skin cancers in patients with epidermodysplasia verruciformis (EV). Overall, mixed MS2-L2 VLPs can protect against twelve HPV types associated with ~95.8% of cervical cancers and against two HPV types associated with ~90% of genital warts and >90% recurrent respiratory papillomatosis. Additionally, the VLPs protect against one of two HPV types associated with ~90% of HPV-associated skin cancers in patients with EV. More importantly, we observed that mixed MS2-L2 VLPs elicit protective antibodies that last over 9 months. Furthermore, a spray-freeze-dried formulation of the VLPs is stable, immunogenic, and protective at room temperature and 37 °C.

Human Papilloma Virus Vaccination.

Human papilloma virus (HPV) is the most common sexually transmitted infection worldwide causing a variety of benign and malignant conditions. A significant portion of the global population is infected with HPV, with the virus attributed to causing up to 5% of cancers worldwide. Bivalent, quadrivalent, and nine-valent vaccinations exist to aid in the prevention of these diseases and have been proven to be effective at preventing both benign and malignant disease. While vaccination is readily accessible in more developed countries, barriers exist to worldwide distribution and acceptance of vaccination. Vaccination and screening of HPV infection when used in combination are proven and predicted to decrease HPV related pathology. Improvements in vaccination formulations, for treatment as well as prevention, are actively being sought from a variety of mechanisms. Despite these advancements, and the data supporting their efficacy, there has been substantial delay in obtaining adequate vaccination coverage. In reviewing these challenges and looking forward to new vaccine development-especially within the current pandemic-it is clear from the challenges of HPV we require methods to more effectively encourage vaccination, ways to dispel vaccination myths as they occur, and implement better processes for vaccine distribution globally.

The Synthesis of Main Capsid Protein of Anogenital Type HPV6 L1 in Plant Expression System on the Basis of Tomato Fruits.

The anogenital type HPV6 L1 major capsid protein was synthesized in a plant expression system on the basis of tomato fruits. The content of HPV6 L1 reached 380 µg per 1 mg of total soluble protein of raw fruit mass, which was represented as a single band with a molecular mass of 56 kDa on the SDS electrophoregram. When orally administrated to mice, the vaccine material from the tomato fruit transgenic for HPV6 L1 induced highly effective antibody immune response with a high titer. The cross-reactivity during the interaction of the antibody to the HPV6 L1 protein from peripheral blood serum of mice vaccinated with HPV6 L1 with the antigenic proteins HPV16 L1, HPV18 L1, HPV31 L1, and HPV45 L1 was found. This is promising for creating a vaccine with a broad reactivity against dangerous anogenital papillomatoses and cervical cancer.

Success of community approach to HPV vaccination in school-based and non-school-based settings in Haiti.

OBJECTIVES: To assess the success of a human papillomavirus (HPV) vaccination program among adolescent girls aged 9-14 years in Haiti and to understand predictors of completion of a two-dose HPV vaccination series. METHODS: Data collection was conducted during HPV vaccination campaigns in Port-au-Prince between August 2016 and April 2017. Descriptive statistics and logistic regression models were used to examine characteristics associated with vaccination series completion of school based and non-school based vaccination delivery modalities. RESULTS: Of the 2,445 adolescent girls who participated in the awareness program, 1,994 participants (1,307 in non-school program, 687 in school program) received the first dose of the vaccine; 1,199 (92%) in the non-school program and 673 (98%) in the school program also received the second dose. Menarche (OR: 1.87; 95% CI, 1.11-3.14), if the participant was a prior patient at the GHESKIO clinics (OR: 2.17; 95% CI, 1.32-3.58), and participating in the school-based program (OR: 4.17; 95% CI, 2.14-8.12) were significantly associated with vaccination completion. CONCLUSIONS: Vaccination in school- and non-school-based settings was successful, suggesting that a nationwide HPV vaccination campaign using either approach would be successful using either approach.