Knowledge on Human Papillomavirus Infections, Cancer Biology, Immune Interactions, Vaccination Coverage and Common Treatments: A Comprehensive Review.

Human papillomavirus (HPV) is a circular, double-stranded DNA virus and recognized as the most prevalent sexually transmitted infectious agent worldwide. The HPV life cycle encompasses three primary stages. First, the virus infiltrates the basal cells of the stratified epidermis. Second, there is a low-level expression of viral genes and preservation of the viral genome in the basal layer. Lastly, productive replication of HPV occurs in differentiated cells. An effective immune response, involving various immune cells, including innate immunity, keratinocytes, dendritic cells, and natural killer T cells, is instrumental in clearing HPV infection and thwarting the development of HPV-associated tumors. Vaccines have demonstrated their efficacy in preventing genital warts, high-grade precancerous lesions, and cancers in females. In males, the vaccines can also aid in preventing genital warts, anal precancerous lesions, and cancer. This comprehensive review aims to provide a thorough and detailed exploration of HPV infections, delving into its genetic characteristics, life cycle, pathogenesis, and the role of high-risk and low-risk HPV strains. In addition, this review seeks to elucidate the intricate immune interactions that govern HPV infections, spanning from innate immunity to adaptive immune responses, as well as examining the evasion mechanisms used by the virus. Furthermore, the article discusses the current landscape of HPV vaccines and common treatments, contributing to a holistic understanding of HPV and its associated diseases.

Allelic loss of HLA class I facilitates evasion from immune surveillance in cervical intraepithelial neoplasia.

Loss of heterozygosity (LOH) has been reported to occur in HLA regions in cervical intraepithelial neoplasia (CIN) and cervical cancer. However, the details of how this is related to the progression of CIN have been unclear. In this study, we examined the human papillomavirus (HPV) antigen-presenting capacity of people with CIN and the significance of LOH of HLA class I in the progression of CIN. It was shown that differences in antigen-presenting capacity among each case depended on HLA types, not HPV genotypes. Focusing on the HLA type, there was a positive correlation between antigen-presenting capacity against HPV and the frequency of allelic loss. Furthermore, the lost HLA-B alleles had a higher HPV antigen-presenting capacity than intact alleles. In addition, frequency of LOH of HLA class I was significantly higher in advanced CIN (CIN2-3) than in cervicitis or early-stage CIN (CIN1): around half of CIN2-3 had LOH of any HLA class I. Moreover, the antigen-presenting capacity against E5, which is the HPV proteins that facilitate viral escape from this immune surveillance by suppressing HLA class I expression, had the most significant impact on the LOH in HLA-B. This study suggests that HPV evades immune surveillance mechanisms when host cells lose the capacity for antigen presentation by HLA class I molecules, resulting in long-term infection and progression to advanced lesions.

Development of a human papillomavirus (HPV) multiplex immunoassay to profile HPV antibodies.

Neutralizing antibodies (NAbs) are considered the primary mechanism of vaccine-mediated protection against human papillomaviruses (HPV), the causative agent of cervical cancer. However, the minimum level of NAb needed for protection is currently unknown. The HPV pseudovirion-based neutralization assay (PBNA) is the gold standard method for assessing HPV antibody responses but is time-consuming and labor-intensive. With the development of higher valency HPV vaccines, alternative serological assays with the capacity for multiplexing would improve efficiency and output. Here we describe a multiplex bead-based immunoassay to characterize the antibody responses to the seven oncogenic HPV types (HPV16/18/31/33/45/52/58) contained in the current licensed nonavalent HPV vaccine. This assay can measure antibody isotypes and subclasses (total IgG, IgM, IgA1-2, IgG1-4), and can be adapted to measure other antibody features (e.g., Fc receptors) that contribute to vaccine immunity. When tested with serum samples from unvaccinated and vaccinated individuals, we found high concordance between HPV-specific IgG using this multiplex assay and NAbs measured with PBNA. Overall, this assay is high-throughput, sample-sparing, and time-saving, providing an alternative to existing assays for the measurement and characterization of HPV antibody responses.

Enhancement of Tumor Antigen-specific T-cell Responses by Immune Checkpoint Blockade in Human Papillomavirus-related Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is clinically and immunologically distinct from HPV-negative HNSCC. Herein, we investigated the presence of tumor antigens HPV E6/E7 and wild-type p53-specific T-cell responses, and the impact of immune checkpoint blockade in patients with HPV-positive HNSCC. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) from patients with HPV-positive HNSCC were stimulated with HPV E6/E7 or wild-type p53-derived peptide mixture and evaluated using the interferon-γ enzyme-linked immunosorbent spot assay. Flow cytometry was performed to analyze the proportion of T-cell subsets and T cells expressing immune checkpoint molecules. RESULTS: HPV E6/E7-specific T cells were detected in 22 (95.7%) of 23 patients, whereas wild-type p53-specific T cells were detected in 3 (15.0%) of 20 patients. Seven (43.8%) of 16 patients exhibited wild-type p53-specific T-cell responses, as determined using whole proteins instead of peptides. Immune checkpoint blockade enhanced wild-type p53-specific T-cell responses in 9 (45.0%) of 20 patients. Flow cytometric analysis of PBMCs revealed that responders exhibiting enhanced wild-type p53-specific T-cell responses following immune checkpoint blockade had a significantly higher proportion of Ki-67+CD4+ T cells, Ki-67+CD8+ T cells, regulatory T cells, PD-1+CD4+ T cells, and TIM-3+CD4+ T cells than non-responders. CONCLUSION: Our findings indicate that tumor antigen-specific T cells are present in the peripheral blood of patients with HPV-positive HNSCC. Blockade of checkpoint pathways can enhance T-cell responses in certain patients, probably via activated T cells, Tregs, and/or exhausted CD4+ T cells.

Short Communication: Understanding the Barriers to Cervical Cancer Prevention and HPV Vaccination in Saudi Arabia.

Cervical cancer, along with other sexual and reproductive health and rights (SRHR) conditions, poses a significant burden in the Kingdom of Saudi Arabia (KSA). Despite the availability of effective preventive methods such as vaccinations, particularly against the Human Papillomavirus (HPV), awareness about such preventive methods and HPV vaccination remains alarmingly low in the KSA, even with governmental effort and support. While many women are aware of the risks, the uptake of the HPV vaccine remains below 10% (7.6%) at the country level. This highlights the urgent need for Knowledge, Attitude, and Practice (KAP) at the community level to raise awareness, dispel misconceptions, and empower women to embrace vaccinations. Additionally, there is a need to revitalize the cancer registry system to better track and monitor cervical cancer cases. This short communication aims to map these barriers while identifying opportunities for impactful research. Drawing from the scientific literature, government reports, and expert insights, we highlight the challenges surrounding the tackling of HPV. By exploring diverse sources of knowledge, this paper not only highlights current obstacles but also proposes actionable solutions for future interventions.

Prevalence and risk factors for HPV seropositivity and anogenital DNA positivity among men who have sex with men: a repeated cross-sectional study.

OBJECTIVES: This study aimed to assess associations of potential risk factors with human papillomavirus (HPV) seropositivity among men who have sex with men (MSM) and compare these to risk factors for anal and penile (HPV) deoxyribonucleic acid (DNA)-positivity in the same study population. METHODS: Seropositivity and anal and penile HPV DNA-positivity were determined for seven high-risk HPV genotypes for MSM aged 16-24 years participating in Papillomavirus Surveillance among STI clinic Youngsters in the Netherlands (PASSYON) 2009-2021. Logistic regression models were conducted to assess risk factors for seropositivity, anal and penile HPV DNA-positivity. RESULTS: Overall, 1019 MSM were included. HPV-16 and -18 were most common for serology, and anal and penile HPV DNA-positivity. Although no clear similarities were observed for most risk factors for HPV seropositivity and anal or penile DNA positivity, receptive anal intercourse (RAI) was the strongest associated risk factor for both seropositivity ('RAI ever' adjusted odds ratio [aOR] 3.50, 95% confidence interval [CI] 1.56-7.88; 'RAI previous 6 months' aOR 2.17, 95% CI 1.44-3.26) and anal DNA-positivity ('RAI previous 6 months' aOR 1.67, 95% CI 1.09-2.56). CONCLUSIONS: Our study is suggestive of site-specific immune response after HPV infection; RAI might lead to anal HPV infections and consequently to seroconversion. Finally, as the two genotypes that are most oncogenic and preventable by all HPV vaccines were most common, our results underline the importance of gender-neutral vaccination.

Immunological Response against Breast Lineage Cells Transfected with Human Papillomavirus (HPV).

Breast cancer is the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. Despite the detection of HPV in breast carcinomas, the virus's activity against this type of cancer remains controversial. HPV infection promotes remodeling of the host's immune response, resulting in an immunosuppressive profile. This study assessed the individual role of HPV oncogenes in the cell line MDA-MB-231 transfected with the E5, E6, and E7 oncogenes and co-cultured with peripheral blood mononuclear cells. Immunophenotyping was conducted to evaluate immune system modulation. There was an increase in CD4+ T cell numbers when compared with non-transfected and transfected MDA-MB-231, especially in the Treg profile. Pro-inflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17, were impaired by transfected cells, and a decrease in the cytolytic activity of the CD8+ and CD56+ lymphocytes was observed in the presence of HPV oncogenes, mainly with E6 and E7. The E6 and E7 oncogenes decrease monocyte expression, activating the expected M1 profile. In the monocytes found, a pro-inflammatory role was observed according to the cytokines released in the supernatant. In conclusion, the MDA-MB-231 cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes.

High-risk HPV oncoproteins E6 and E7 and their interplay with the innate immune response: Uncovering mechanisms of immune evasion and therapeutic prospects.

Human papillomaviruses (HPVs) are double-stranded DNA (dsDNA) tumor viruses causally associated with 5% of human cancers, comprising both anogenital and upper aerodigestive tract carcinomas. Despite the availability of prophylactic vaccines, HPVs continue to pose a significant global health challenge, primarily due to inadequate vaccine access and coverage. These viruses can establish persistent infections by evading both the intrinsic defenses of infected tissues and the extrinsic defenses provided by professional innate immune cells. Crucial for their evasion strategies is their unique intraepithelial life cycle, which effectively shields them from host detection. Thus, strategies aimed at reactivating the innate immune response within infected or transformed epithelial cells, particularly through the production of type I interferons (IFNs) and lymphocyte-recruiting chemokines, are considered viable solutions to counteract the adverse effects of persistent infections by these oncogenic viruses. This review focuses on the complex interplay between the high-risk HPV oncoproteins E6 and E7 and the innate immune response in epithelial cells and HPV-associated cancers. In particular, it details the molecular mechanisms by which E6 and E7 modulate the innate immune response, highlighting significant progress in our comprehension of these processes. It also examines forward-looking strategies that exploit the innate immune system to ameliorate existing anticancer therapies, thereby providing crucial insights into future therapeutic developments.

The HPV viral regulatory mechanism of TLRs and the related treatments for HPV-associated cancers.

Infection with human papillomavirus (HPV) typically leads to cervical cancer, skin related cancers and many other tumors. HPV is mainly responsible for evading immune tumor monitoring in HPV related cancers. Toll like receptors (TLRs) are particular pattern recognition molecules. When the body is facing immune danger, it can lead to innate and direct adaptive immunity. TLR plays an important role in initiating antiviral immune responses. HPV can affect the expression level of TLR and interfere with TLR related signaling pathways, resulting in sustained viral infection and even carcinogenesis. This paper introduces the HPV virus and HPV related cancers. We discussed the present comprehension of TLR, its expression and signaling, as well as its role in HPV infection. We also provided a detailed introduction to immunotherapy methods for HPV related diseases based on TLR agonists. This will provide insights into methods that support the therapeutic method of HPV related conditions with TLR agonists.

The potential use of therapeutics and prophylactic mRNA vaccines in human papillomavirus (HPV).

Cervical cancer (CC) and other malignant malignancies are acknowledged to be primarily caused by persistent human papillomavirus (HPV) infection. Historically, vaccinations against viruses that produce neutralizing antibodies unique to the virus have been an affordable way to manage viral diseases. CC risk is decreased, but not eliminated, by HPV vaccinations. Since vaccinations have been made available globally, almost 90% of HPV infections have been successfully avoided. On the lesions and diseases that are already present, however, no discernible treatment benefit has been shown. As a result, therapeutic vaccines that elicit immune responses mediated by cells are necessary for the treatment of established infections and cancers. mRNA vaccines possess remarkable potential in combating viral diseases and malignancy as a result of their superior industrial production, safety, and efficacy. Furthermore, considering the expeditiousness of production, the mRNA vaccine exhibits promise as a therapeutic approach targeting HPV. Given that the HPV-encoded early proteins, including oncoproteins E6 and E7, are consistently present in HPV-related cancers and pre-cancerous lesions and have crucial functions in the progression and persistence of HPV-related diseases, they serve as ideal targets for therapeutic HPV vaccines. The action mechanism of HPV and HPV-related cancer mRNA vaccines, their recent advancements in clinical trials, and the potential for their therapeutic applications are highlighted in this study, which also offers a quick summary of the present state of mRNA vaccines. Lastly, we highlight a few difficulties with mRNA HPV vaccination clinical practice and provide our thoughts on further advancements in this quickly changing sector. It is expected that mRNA vaccines will soon be produced quickly for clinical HPV prevention and treatment.

Exploring Indonesian Primary Schoolgirls' Experiences of School-based HPV Vaccination, Knowledge of HPV Risks and Prevention, and Preferences for Cervical Cancer Education.

OBJECTIVE: In 2016, Indonesia introduced its Human Papillomavirus (HPV) vaccination demonstration program for girls in grades 5 and 6 of primary school, to reduce cervical cancer (CC) burden in selected provinces and test the viability of nationwide vaccination. This study explored schoolgirls' experience of school-based HPV vaccination, their knowledge of HPV and HPV vaccination, and their preferences for cervical cancer (CC) education. METHODS: An online survey was conducted with schoolgirls who experienced HPV vaccination between 2019 and 2021 through the demonstration program. Using purposive sampling, respondents were recruited through partnerships with primary public health centres and primary schools in Jakarta and Yogyakarta. Data analysis was conducted using Chi-square test, Independent-samples t-test, and one-way ANOVA. RESULTS: One hundred and forty primary schoolgirls with a mean age of 12.2 years (SD = 0.70) completed the survey. Schools and mothers were identified as key actors in socialising children about important health information and as girls' preferred sources of information. The average summed score for girls' knowledge of HPV, the HPV vaccine, and CC after being vaccinated was 5.07 out of 10 (SD 0.23). Significant differences in the mean knowledge scores among participants with different preferences regarding CC education in school were observed. CONCLUSION: While schoolgirls' experiences of HPV vaccination were largely positive, their knowledge of critical health information regarding HPV vaccination and CC prevention needs improving. Thus, it is necessary to provide parents, and school-based educators with culturally appropriate strategies and comprehensive evidence-based information about HPV vaccination and CC prevention more effectively to children.

Cervical cytology and HPV distribution in Cape Verde: A snapshot of a country taken during its first HPV nation-wide vaccination campaign.

Cervical cancer ranks as the third most common female cancer in Cape Verde and is the leading cause of cancer-related deaths among women in the country. While Human Papillomavirus (HPV) vaccination, which started in 2021, is anticipated to significantly reduce disease incidence, cervical screening remains crucial for non-vaccinated women. We retrospectively reviewed gynecologic cytology exams and HPV tests performed in Cape Verde between 2017 and April 2023 and processed at IMP Diagnostics. For this study, we considered 13035 women with cytology examinations performed and, 2013 of these, also with an HPV molecular test. Cytology diagnostics comprised 83 % NILM cases; 12 % ASC-US; 2.7 % LSIL; 1.2 % ASC-H; 0.5 % HSIL and 0.1 % SCC. In 505 (25.1 %) high-risk HPV infection was detected. Prevalence of HPV infection varied with age, peaking at young ages - ≤24 years old (55.5 %) and 25-35-year-old women (31.5 %) - and the lowest after 66 years old (9.7 %). Herein we present a comprehensive study regarding Cape Verde's cervical cytology and HPV distribution, aiming to provide a snapshot of the country's cervical cytology results and HPV distribution in recent years. Moreover, these data may contribute to establish a baseline to assess, in the future, the vaccination impact in the country.

Comprehensive analysis of a novel subtype of immune microenvironment-derived HPV-infected colorectal cancer.

BACKGROUND: The current study proposed a novel subtype, Human papillomavirus (HPV)-infected colorectal cancer (CRC), to understand the impact of HPV on CRC. METHODS: We assessed the prevalence and clinical implications of HPV in CRC by integrating a single cohort in Guangdong Provincial People's Hospital and public datasets. Differential gene, pathway enrichment, and immune infiltration analysis were conducted to explore the patterns in HPV-infected CRC. Quantitative polymerase chain reaction, cell proliferation, scratch, and flow cytometry assays were employed to validate the impact of HPV on CRC. RESULTS: The study revealed a high prevalence of HPV infection in CRC, with infection rates ranging from 10% to 31%. There was also a significant increase in tumor proliferation in HPV-infected CRC. The study showed increased immune cell infiltration, including T cells, γδ T cells, cytotoxic cells, and plasmacytoid dendritic cells in HPV-infected CRC (P < 0.05). Furthermore, our findings confirmed that HPV infection promoted M1 polarization. Our results demonstrated that low ISM2 expression was associated with a less advanced clinical stage (P < 0.001) and better survival outcomes (P = 0.039). Low ISM2 expression correlated with a strong tumor immune response, potentially contributing to the improved survival observed in HPV-infected CRC. CONCLUSIONS: These findings provided a novel subtype of HPV-infected CRC. The subtype with a better prognosis showed a "hot" tumor immune microenvironment that may be responsive to immunotherapy.

Primary prevention of HPV-related diseases from the patients' perspective in Poland.

OBJECTIVES: This study aimed to assess the knowledge of human papillomavirus (HPV) and attitudes toward HPV vaccination (HPVv) among female patients in Poland, investigating the impact of sociodemographic factors on these aspects. The study also explored awareness of state-funded bivalent vaccination and gauged willingness to vaccinate children, especially in the aspect of the newly introduced nonavalent vaccine. MATERIAL AND METHODS: An 11-question questionnaire was administered to newly referred patients at a dysplasia consultation center in Kraków University Hospital between February and December 2022. Statistical analysis using IBM SPSS Statistics 25 evaluated sociodemographic characteristics, HPV knowledge, attitudes toward HPVv and correlations among responses. RESULTS: By December 2022, 187 completed forms were received, primarily from women aged 30-40 years, residing in large cities, and with higher education qualifications. While most were aware of HPV's association with cancer and abnormal cytology, over 40% were unaware of its asymptomatic nature. Higher education is correlated with better HPV awareness. Participants generally showed positive attitudes toward HPVv for themselves and their children, yet only a small fraction had received the vaccine. Education significantly influenced HPV knowledge, with higher education levels linked to better awareness and willingness to vaccinate children. Awareness of HPV is positively correlated with knowledge test performance and vaccination attitudes. CONCLUSION: The study revealed a lack of awareness regarding government co-financing for the bivalent vaccine. Campaigns endorsing reimbursed vaccination were found to be inadequate, highlighting the need for corrective measures to enhance awareness and improve vaccination rates, particularly for individuals outside the age range between 12 and 13 years relying on self-financing or sporadic government initiatives.

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.