Materiały źródłowe

• #1 Human Papilloma Virus Vaccine – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562186/

  The exact mechanism of action of 9vHPV remains unclear, as HPV only affects humans, which poses challenges for research. However, researchers hypothesize that the vaccine operates by triggering the humoral response. […] The exact mechanism of action of 9vHPV is unknown. Nevertheless, researchers believe that the vaccine works by activating the humoral response. 9vHPV is a noninfectious recombinant vaccine containing purified virus-like particles (VLPs) obtained from the major capsid (L1) protein of HPV serotypes 6, 11, 16, 18, 31, 33, 45, 52, and 58. The L1 proteins are separated using recombinant Saccharomyces cerevisiae and self-assembled into VLPs. Each 0.5 mL dose of the vaccine contains aluminum, sodium chloride, L-histidine, polysorbate, sodium borate, yeast protein less than 7 mcg, and water. The product does not contain preservatives or antibiotics.

• #2 Human Papilloma Virus Vaccine | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/23033

  The exact mechanism of action of 9vHPV remains unclear, as HPV only affects humans, which poses challenges for research. However, researchers hypothesize that the vaccine operates by triggering the humoral response. […] The exact mechanism of action of 9vHPV is unknown. Nevertheless, researchers believe that the vaccine works by activating the humoral response. 9vHPV is a noninfectious recombinant vaccine containing purified virus-like particles (VLPs) obtained from the major capsid (L1) protein of HPV serotypes 6, 11, 16, 18, 31, 33, 45, 52, and 58. The L1 proteins are separated using recombinant Saccharomyces cerevisiae and self-assembled into VLPs. […] A 2016 immunogenicity study reports that the inactive HPV L1 VLPs in the vaccine produce neutralizing antibodies against HPV types, eliciting a strong humoral immune response to protect against the dysplastic lesions caused by HPV. The same study reported that antibody titers for 9vHPV are 10- to 100-fold more significant than those produced by natural infection. Thus, the vaccine’s efficacy is mediated via humoral response mechanisms.

• #3 HPV Vaccine: Mechanism of Action

  https://www.labce.com/spg10262494_preventive_cancer_vaccines_hpv_vaccines___mechanis.aspx?srsltid=AfmBOoq4dSSMs-IBsDdYnn3Nir-sAULcXMMJldu7BsB7j17jnj1NGHRY

  The human papillomavirus (HPV) vaccine targets selective proteins found on the surface of the virus. These protein targets are grown in yeast cells cultured in the laboratory. The mature protein self-assembles to mimic the appearance of the HPV virus. Because the HPV protein does not harbor any HPV genetic materials, the protein is incapable of replication and production, hence HPV vaccines that target the HPV proteins do not cause any HPV infections. […] As for how the HPV vaccine generates immunity, it follows the same logical developmental steps as other types of vaccines: The target delivered by the vaccine is recognized by the host immune system as non-self and dangerous. The target, such as HPV 16, is processed and presented by antigen presentation cells (such as dendritic cells) to naive T helper cells in the lymph nodes. The presentation activates T helper cells, which then interact with B cells. Activated B cells differentiate to become plasma cells that produce antibodies specific to the HPV protein. If and when HPV appears under the radar of the prepared host immune system, the HPV-specific antibodies take immediate action to protect the host from HPV infection.

• #4 Human Papilloma Virus Vaccine – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562186/

  A 2016 immunogenicity study reports that the inactive HPV L1 VLPs in the vaccine produce neutralizing antibodies against HPV types, eliciting a strong humoral immune response to protect against the dysplastic lesions caused by HPV. The same study reported that antibody titers for 9vHPV are 10- to 100-fold more significant than those produced by natural infection. Thus, the vaccine’s efficacy is mediated via humoral response mechanisms.

• #5 Human Papillomavirus (HPV) Vaccine – PAHO/WHO | Pan American Health Organization

  https://www.paho.org/en/human-papillomavirus-hpv-vaccine

  The best way to prevent HPV infection, as well as the complications and the cancers it causes, is to get vaccinated, preferably before having sex for the first time, so that the vaccine ensures protection prior to contact with the virus. […] HPV vaccination provides immunity and is a critical tool for cancer prevention. The serological response after HPV vaccination is much stronger than the response after natural infection, providing people with strong, long-term immune protection against HPV.

• #6 Human Papillomavirus (HPV) Vaccines – NCI

  https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-vaccine-fact-sheet

  The current HPV vaccines are based on virus-like particles (VLPs) that are formed by HPV surface components. VLPs are not infectious because they lack the viruss DNA. However, they closely resemble the natural virus, and antibodies against the VLPs also have activity against the natural virus. The VLPs have been found to be strongly immunogenic, which means that they induce high levels of antibody production by the body. This makes the vaccines highly effective. […] Widespread HPV vaccination has the potential to reduce cervical cancer incidence around the world by as much as 90%. In addition, the vaccines may reduce the need for screening and subsequent medical care, biopsies, and invasive procedures associated with follow-up from abnormal cervical screening, thus helping to reduce health care costs and anxieties related to follow-up procedures. […] Researchers are working to develop therapeutic HPV vaccines, which instead of preventing HPV infection would prevent cancer from developing among women previously infected with HPV. These vaccines work by stimulating the immune system to specifically target and kill infected cells.

• #7 HPV Vaccine Introduction to Drop Cervical Cancer Rates

  https://www.delveinsight.com/blog/impact-of-hpv-vaccine-on-cervical-cancer

  Currently, the HPV vaccine is based on virus-like particles (VLPs) that form on the surface of HPV components. What makes virus-like particles (VLPs) non-infectious is the lack of the virus’s DNA. Nonetheless, they resemble the natural virus very closely, and antibodies against the VLPs also have activity against the natural virus. Through many studies and clinical trials, it is found that VLPs are strongly immunogenic, so they are able to induce very high levels of antibody production in the body. […] […] The VLPs have been found to be strongly immunogenic, which means that they induce high levels of antibody production by the body. This makes these vaccines highly effective. All the HPV vaccines have been observed to have higher efficacy (even closer to 100%) for prevention from HPV infection. The initial trials that were conducted included women aged between 15 to age 26 years, which resulted in a three-dose HPV vaccine schedule. […]

• #7 HPV Vaccine Introduction to Drop Cervical Cancer Rates

  https://www.delveinsight.com/blog/impact-of-hpv-vaccine-on-cervical-cancer

  HPV vaccine Mechanism of Action And Efficacy […] The HPV vaccine consists of individual viral-like proteins that copy (imitate) different types of HPV. These viruses are not live viruses, but they can still produce an immune response (antibodies) when administered into the body. Like other immunization processes, these HPV vaccines also generate antibodies in the body that would bind to the antigen of the virus, if the body gets infected in the future. HPV vaccination has been working exceptionally well in recent years. It is observed that the HPV vaccine immune response has the potential to protect against 90% of HPV-attributable cancers. […] […] Most notably, HPV vaccination has been the cause of a reduction in the number of precancer of the cervix (part of the uterus) cases in young women. The protection from this vaccine lasts for around 10 years and sometimes even more. When the people receiving HPV vaccines were followed up for at least 12 years of complete dosage, their protection remained substantially high with no evidence of decreasing over time. […]

• #8 Chapter 11: Human Papillomavirus | Pink Book | CDC

  https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-11-human-papillomavirus.html?utm_source=chatgpt.com

  HPV infection occurs at the basal epithelium. Although incidence of infection is high, most infections resolve spontaneously within a year or two. A small proportion of infected persons become persistently infected; persistent infection is the most important risk factor for the development of cervical cancer. […] High-risk or oncogenic HPV types act as carcinogens in the development of cervical cancer and other anogenital cancers. High-risk types (including types 16, 18, and others) can cause low-grade cervical cell abnormalities, high-grade cervical cell abnormalities that are precursors to cancer, and anogenital cancers. High-risk HPV types are detected in 99% of cervical precancers. Type 16 is the cause of approximately 50% of cervical cancers worldwide, and types 16 and 18 together account for about 66% of cervical cancers. An additional five high-risk types, 31, 33, 45, 52, and 58, are responsible for another 15% of cervical cancers and 11% of all HPV-associated cancers. Infection with a high-risk HPV type is considered necessary for the development of cervical cancer but, by itself, is not sufficient to cause cancer. The vast majority of women with HPV infection, even those with high-risk HPV types, do not develop cancer.

• #9 Chapter 11: Human Papillomavirus | Pink Book | CDC

  https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-11-human-papillomavirus.html?utm_source=chatgpt.com

  The pathogenesis of other types of HPV-related cancers may follow a similar course, although less is known about their respective precursor lesions: anal HSIL has been identified as a precursor to anal cancer, vulvar HSIL has been identified as a precursor to vulvar cancer, and vaginal HSIL has been identified as a precursor to vaginal cancer.

• #10 Human papillomavirus (HPV) | The Australian Immunisation Handbook

  https://immunisationhandbook.health.gov.au/contents/vaccine-preventable-diseases/human-papillomavirus-hpv

  HPV requires a breach in the epithelial surface to enter the basal epithelial cells and cause infection. However, infectious virions are only produced in the terminally differentiated layer of the epithelium. […] HPV types 16, 18, 31, 33, 35, 45, 52 and 58 are high risk because they can cause cancer. The most oncogenic HPV type is HPV-16. This is the most frequent cause of HPV-related cancers. […] HPV vaccine protection is believed to be predominantly antibody mediated. Even low levels of antibodies can stop HPV entering the basal epithelial cells. HPV can only access the basal cell at sites of microtrauma, where there is a breach in the epithelium, and circulating HPV antibodies from sera are present at these sites.

• #11 Non-sexual HPV transmission and role of vaccination for a better future (Review)

  https://www.spandidos-publications.com/10.3892/etm.2020.9316

  Human papilloma viruses (HPVs) belong to the Papillomaviridae family and are epitheliotropic infecting squamous epithelia (skin and mucosae). HPV is estimated to be the cause of 99% of cervical cancers, 90% of anal cancer, 65% vaginal cancers, 50% vulvar cancers, and 45-90% oropharyngeal cancers. The microabrasions of epithelia permit the HPV particles to penetrate the basal layer of cells (the early phase probably promotes HPV-related disease). The virus can remain latent or inactive for months or years (the mechanism may be immunological). Hormones are presumed to participate in the carcinogenic mechanism; thus, the malignancy prospect in the case of new or recurrent HPV infections in menopausal women is uncertain. The HPV-related disease is divided into malignant and benign tumors. The virus invades its host through the anogenital and/or oropharyngeal mucosae. The effects range from warts (low-risk types) to intraepithelial dysplastic lesions, which can advance to invasive carcinoma (high-risk types). The process of cancer development from HPV infection takes ~5-10 years minimum and 20-25 years on average.

• #12 Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis

  https://www.mdpi.com/2076-0817/12/12/1380

  The involvement of HPV in cancer induction and progression can take many years for conversion into a carcinoma with the help of different tumor-stimulating steps, such as E6/E7 proteins that interact with cellular proteins. […] HPV can be transmitted through sexual or nonsexual interactions. However, sexual transmission is the most common cause of HPV infection, especially the genital type. […] HPV can enter the body through skin abrasions/warts, epidermal injuries, and mucous membranes. […] For effective infection, these viruses attack actively dividing basal-layer cells, which act as stem cells. […] After initial binding of HPV to a primary receptor such as heparin sulphate proteoglycans (HSPGs), there is a conformational change facilitated by cyclophilin B that occurs at the N-terminus of the L2 region, a viral capsid protein present on the virion surface, resulting in L2 cleavage by proprotein convertase (PC), furin, and/or PC5/6, followed by N-terminus L2 epitope exposure and binding with a secondary receptor present on the target cell plasma membrane.

• #13 Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis

  https://www.mdpi.com/2076-0817/12/12/1380

  HPV enters target cells via endocytosis in a manner similar to micropinocytosis. […] Ultimately, the viral genome is transferred to the nucleus via the tubulin-mediated pathway through nuclear pores or fragmented nuclear membranes in the mitosis process, which then associates with promyelocytic leukemia (PML) nuclear bodies to form a nuclear infection and initiates viral transcription. […] HPV DNA replication is initiated by E1 and E2 proteins, which are expressed in the middle epithelial cell layer. […] The E6 protein is required for the maintenance of the episomal genome, and the E7 protein is responsible for the activation of the G1 to S-phase checkpoint and potentially controls transcriptional alterations in infected cells. […] HPV uses a variety of immune evasion mechanisms to suppress immune responses and promote cancer progression.

• #14 HPV Infections—Classification, Pathogenesis, and Potential New Therapies

  https://www.mdpi.com/1422-0067/25/14/7616

  To date, more than 400 types of human papillomavirus (HPV) have been identified. […] This paper presents the systematics of HPV and the differences in HPV structure between different genetic types, lineages, and sublineages, based on the literature and GenBank data. We also present the pathogenesis of diseases caused by HPV, with a special focus on the role played by E6, E7, and other viral proteins in the development of benign and cancerous lesions. […] Early viral proteins such as E5, E6, and E7 play the most important role in the pathogenesis of neoplastic lesions arising from HPV infections. […] The E6 protein (150–160 amino acids, about 18 kDal) is a major oncoprotein. It inhibits apoptosis and differentiation. It affects cell shape, polarity, mobility, and signaling. […] E7 binds to the retinoblastoma tumor suppressor protein pRb and to smaller proteins such as p107 and p130, inhibiting their action and, in the case of oncogenic HPV, leading to accelerated degradation.

• #15 HPV Infections—Classification, Pathogenesis, and Potential New Therapies

  https://www.mdpi.com/1422-0067/25/14/7616

  E6 and E7 may also interact with other metabolic pathways involved in cell differentiation and proliferation. An important role in cell immortalization is played by the activation of telomerase by E6 and, to a lesser extent, E7 proteins produced by oncogenic HPV. […] In most cases of HPV infection, the DNA remains in an episomal form, unintegrated into the host DNA, allowing the virus to replicate efficiently. […] The integration of the HPV genome into the cellular genome has been demonstrated to play a crucial role in the development of cancer. […] The effectiveness of treatment may be enhanced by the inclusion of methods which are based on the stimulation of the immune system in the fight against infection.

• #16 Human papillomavirus infection – Wikipedia

  https://en.wikipedia.org/wiki/Human_papillomavirus_infection

  HPV vaccines can prevent the most common types of infection. […] To be most effective, inoculation should occur before the onset of sexual activity, and are therefore recommended between the ages of 9-13 years. […] HPV is believed to cause cancer by integrating its genome into nuclear DNA. […] Some of the early genes expressed by HPV, such as E6 and E7, act as oncogenes that promote tumor growth and malignant transformation. […] E6 produces a protein (also called E6) that simultaneously binds to two host cell proteins called p53 and E6-Associated Protein (E6-AP). […] The degradation of p53, induced by E6, promotes unregulated cell division, cell growth and cell survival, all characteristics of cancer. […] The two primary oncoproteins of high-risk HPV types are E6 and E7. […] The E6/E7 proteins inactivate two tumor suppressor proteins, p53 (inactivated by E6) and pRb (inactivated by E7). […] The viral oncogenes E6 and E7 are thought to modify the cell cycle so as to retain the differentiating host keratinocyte in a state that is favourable to the amplification of viral genome replication and consequent late gene expression.

• #17 Human Papillomavirus (HPV) Vaccines – NCI

  https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-vaccine-fact-sheet

  HPV vaccines protect against infection with human papillomaviruses (HPV). HPV is a group of more than 200 related viruses, of which more than 40 are spread through direct sexual contact. Among these, two HPV types cause genital warts, and about a dozen HPV types can cause certain types of cancercervical, anal, oropharyngeal, penile, vulvar, and vaginal. […] Clinical trials have shown that HPV vaccines are highly effective in preventing cervical infection with the types of HPV they target when given before first exposure to the virusthat is, before individuals begin to engage in sexual activity. HPV vaccines have also been found to reduce infections in other tissues that HPV infects, including the anus and oral region. […] Like other immunizations that guard against viral infection, HPV vaccines stimulate the body to produce antibodies that, in future encounters with HPV, bind to the virus and prevent it from infecting cells.

• #18 HPV pathogenesis, various types of vaccines, safety concern, prophylactic and therapeutic applications to control cervical cancer, and future perspective

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10208188/

  The main effect on developing nations would be a decrease in the actual number of CC cases and the overall cost. […] In response to an HPV vaccine, the body produces antibodies that attach to the virus and stop it from infecting cells in subsequent contacts with the virus. […] The basis for the current HPV vaccines is the formation of virus-like particles (VLPs) from HPV surface elements. […] VLPs are not contagious since the virus’s DNA is missing from them. […] According to research, the VLPs are strongly immunogenic to produce substantial antibodies, effective and safe to control CC. […] The primary mechanism of vaccine-induced protection is the induction of antibodies. […] In the event of HPV contact, the vaccination attaches to the HPV viruses and stops to infect further epithelial tissues.

• #19 HPV pathogenesis, various types of vaccines, safety concern, prophylactic and therapeutic applications to control cervical cancer, and future perspective

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10208188/

  The amount of antibody generated during natural infection is typically not enough to stop a reinfection. […] Therefore, a perfect HPV vaccination should boost the immune system’s defenses and protect against all high-risk HPV types as well as those forms that are probably or maybe carcinogenic. […] The HPV vaccines available today are based on VLPs, which lack viral DNA and are made from recombinant HPV capsid proteins. […] By inducing high and long-lasting antibodies titers that bind to the native virion and destroy the virus, HPV vaccinations can prevent HPV infection and render people immunized to subsequent viral challenges. […] The two vaccines designed to prevent CC are composed of empty VLPs generated by expression systems for recombinant capsid antigen L1. […] VLPs do not contain viral DNA and these are non-infectious.

• #20 Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis

  https://www.mdpi.com/2076-0817/12/12/1380

  In this review, we emphasize HPV infection and its role in cancer progression, molecular and immunopathogenesis, host immune response, immune evasion by HPV, vaccination, and preventive schemes battling HPV infection and HPV-related cancers. […] HPV can use the evasion process to escape the immune response. Therefore, HPV can multiply in host cells during viral replication without causing cytolysis, which neither stimulates the inflammatory process nor presents viral antigenic representatives. […] In host cells, type-I IFNs levels are reduced by the E6 and E7 proteins of HPV16 and generate an immune tolerance stage in the absence of costimulatory factors through inflammatory cytokines. […] These immune escape phenomena may contribute to the existence and stability of HPV infection, which further addresses cancer progression.

• #21 HPV pathogenesis, various types of vaccines, safety concern, prophylactic and therapeutic applications to control cervical cancer, and future perspective

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10208188/

  Many nations have approved the use of three preventative vaccines. […] These three vaccinations demonstrate safety and efficacy in randomized studies and post marketing surveillance preventing 70%90% of HPV-related malignancies. […] The HPV6 and HPV11 vaccines are nonavalent and quadrivalent to provide protection against anogenital warts. […] The first dose of the HPV vaccines was administered to about 118 million women globally. […] These vaccines are substantially efficient and effective to prevent HPV infections and neoplastic illnesses. […] As these are preventive in nature, these have limited therapeutic benefits and no effect on treating pre-existing infections. […] Additionally, it appears that the impact of vaccination may not lower the incidence of cancer due to the lengthy period of time needed for the development of pre-cancerous lesions.

• #22 Human Papillomavirus (HPV) Vaccine – Medical Clinical Policy Bulletins | Aetna

  https://www.aetna.com/cpb/medical/data/700_799/0726.html

  Gardasil 9 offers protection against 7 oncogenic (cancer-causing) HPV types (16, 18, 31, 33, 45, 52 and 58) and two HPV types that cause most genital warts (6 and 11) (Immunication Action Coalition, 2019). […] The FDA approved Gardasil 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) vaccine for the prevention of certain diseases caused by nine types of Human Papillomavirus (HPV) (FDA, 2014). […] Gardasil 9 has the potential to prevent approximately 90 percent of cervical, vulvar, vaginal and anal cancers. […] The effectiveness of Gardasil 9 in females and males ages 9 through 15 was determined in studies that measured antibody responses to the vaccine in approximately 1,200 males and 2,800 females in this age group (FDA, 2014). […] The ACIP (2015) has recommended Gardasil 9, in addition to Gardasil, for routine vaccination of females aged 11 or 12 years and females through age 26 years who have not been vaccinated previously or who have not completed the 3-dose series.

• #23 New Research Shows the HPV Cancer Vaccine Saves Lives | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/news/new-research-shows-hpv-cancer-vaccine-saves-lives

  Getting vaccinated against HPV in childhood can prevent cancer later in life. […] The human papillomavirus (HPV) vaccine protects against not only HPV but also certain types of cancer. […] Having a vaccine that protects people from getting any cancer is a life-saving medical breakthrough; the HPV vaccine protects against many cancers those of the cervix, anus, throat, penis, vagina, and more. […] According to the Centers for Disease Control and Prevention, getting vaccinated could prevent an estimated 92 percent of cancers attributed to HPV. […] The HPV vaccine stops cancers before they start. […] A 2019 Lancet study of 66 million young people worldwide found that the vaccine reduced pre-cancerous cervical lesions in young women by more than 50 percent. […] HPV is the most common sexually transmitted infection in the United States.

• #24 HPV pathogenesis, various types of vaccines, safety concern, prophylactic and therapeutic applications to control cervical cancer, and future perspective

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10208188/

  Recent clinical studies with L1 VLP-based vaccines have primarily revolved around the prevention of cancer associated with the female genital tract, including CC. […] L1 VLP vaccines may also prevent additional HPV-associated cancers. […] Although prophylactic vaccines against high-risk HPV types have been highly effective. […] Conversely, E6 and E7 proteins are very promising target proteins for therapeutic vaccines, as these are the only viral proteins constitutively expressed in CC cells and are required to maintain the disease phenotype.

• #25 Therapeutic Use of Human Papillomavirus Vaccines in Cervical Lesions

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0034-83762020000400239

  Human papillomavirus (HPV) has been associated with the development of precancerous lesions of the cervix and cervical cancer (CC). Prophylactic HPV vaccination induces the development of a specific memory immune response that facilitates HPV elimination once the natural infection occurs. […] Unlike prophylactic vaccines, whose main mechanism of action is mediated by antibodies that neutralize viral particles, therapeutic vaccines can induce a cytotoxic immune response targeted against HPV-infected cells. […] HPV E6 and E7 oncoproteins are essential for the establishment and maintenance of the neoplasm, and given their constitutive expression once the cell is infected, they represent ideal targets for the development of therapeutic vaccines against HPV-infected cells and already established lesions.

• #26 Therapeutic Use of Human Papillomavirus Vaccines in Cervical Lesions

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0034-83762020000400239

  Therefore, an ideal therapeutic vaccine should target E1, E6, or E7 proteins to induce a cytotoxic T-cell response, whose effector function is to eliminate infected or transformed cells. […] Most therapeutic vaccines are intended to generate an immune response against HPV-infected cells, through antigen presentation of E6 and E7 oncoprotein by antigen-presenting cells (APCs) to T lymphocytes that in turn mount a response mediated by both helper T lymphocytes and cytotoxic T lymphocytes. […] At present, there are several therapeutic vaccines that are under development and being tested in preclinical and clinical trials. […] It is important to emphasize that to assess the efficacy and safety of therapeutic vaccines, it is essential to demonstrate both their immunogenicity and safety through clinical trials.

• #27 Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis

  https://www.mdpi.com/2076-0817/12/12/1380

  Currently, six HPV vaccines are available: three bivalent (cervarix, cecolin, and walrinvax) that are effective against HPV-16 and 18; two quadrivalent (gardasil and cervavax) that are effective against four strains (HPV-16, 18, 6, and 11); and one nonavalent (gardasil 9) that is effective against the maximum number of strains (HPV-16, 18, 6, 11, 31, 33, 45, 52, and 58). […] These vaccines are based on virus-like particles (VLPs) that self-assemble in the L1 capsid protein when expressed by recombinant DNA vectors and provide immunogens for prophylactic vaccines.

• #28 Differences in HPV-specific antibody Fc-effector functions following Gardasil® and Cervarix® vaccination | npj Vaccines

  https://www.nature.com/articles/s41541-023-00628-8

  Gardasil (Merck) and Cervarix (GlaxoSmithKline) both provide protection against infection with Human Papillomavirus 16 (HPV16) and Human Papillomavirus 18 (HPV18), that account for around 70% of cervical cancers. […] However, beyond the transmission-blocking activity of neutralizing antibodies against HPV, no clear correlate of protection has been defined that may explain persistent control and clearance elicited by HPV vaccines. […] Thus, here, we used systems serology to comprehensively profile Gardasil- and Cervarix- induced antibody subclass, isotype, Fc-receptor binding, and Fc-effector functions against the HPV16 and HPV18 major capsid protein (L1). […] However, Cervarix elicited higher IgG3 and antibody-dependent complement activating responses, and an overall more coordinated response between HPV16 and 18 compared to Gardasil, potentially related to the distinct adjuvants delivered with the vaccines.

• #29 Differences in HPV-specific antibody Fc-effector functions following Gardasil® and Cervarix® vaccination | npj Vaccines

  https://www.nature.com/articles/s41541-023-00628-8

  Thus, these data point to robust Fc-effector functions induced by both Gardasil and Cervarix, albeit with enhanced coordination observed with Cervarix, potentially underlying immunological correlates of post-infection control of HPV. […] Beyond the sterilizing protection afforded by HPV vaccines, they have also been linked to protection against neoplastic progression. […] Moreover, data from clinical trials have shown that although Gardasil is effective at preventing progression to CIN2+ by HPV genotypes included in the vaccine, Cervarix offers superior protection against CIN2+, even against phylogenetically related non-vaccine genotype infections. […] Thus, here we profiled the HPV-specific humoral responses elicited by Gardasil and Cervarix in a cohort of 24 Women over 13 months. […] Both vaccines induced robust humoral immune responses, with similar isotype/subclass, Fc-receptor binding profiles, and Fc-effector functions.

• #30 Differences in HPV-specific antibody Fc-effector functions following Gardasil® and Cervarix® vaccination | npj Vaccines

  https://www.nature.com/articles/s41541-023-00628-8

  However, Cervarix induced higher IgG3 titers and complement-fixing antibodies compared to Gardasil. […] Moreover, Cervarix induced a highly coordinated functional humoral immune response toward HPV18 and HPV16 L1, whereas Gardasil induced a highly variegated functional humoral immune response to the 2 HPV genotypes. […] Collectively, these data highlight the robust evolution of functional humoral immune responses, with key immunologic differences across HPV vaccine platforms and formulations that may contribute to differential outcomes following HPV infection. […] Cervarix induced higher HPV16 and HPV18 L1 antibodies able to activate NK cell degranulation (CD107a) and chemokine MIP1b secretion at later timepoints. […] Both vaccines also induced antibody-dependent complement deposition (ADCD), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent neutrophil phagocytosis (ADNP), with a trend towards superior complement deposition at later timepoints in Cervarix immunized individuals compared to those induced by Gardasil.

• #31

  https://link.springer.com/article/10.1007/s10238-024-01470-5

  Replication-defective viral vector vaccines have several advantages over conventional subunit vaccines, including potent antibody responses, cellular responses critical for eliminating pathogen-infected cells, and the induction of highly immunogenic and durable immune responses without adjuvants. […] In recent years, the development of therapeutic HPV vaccines utilizing viral vectors for the treatment of premalignant lesions or tumors caused by HPV infection has experienced rapid growth, with numerous research pipelines currently underway. […] In terms of preclinical research, we present the various models used to assess vaccine efficacy, highlighting their respective advantages and disadvantages. […] Further, we present current research status of therapeutic vaccines using HPV viral vectors, especially the indications, initial efficacy, combination drugs, etc.

• #32

  https://link.springer.com/article/10.1007/s10238-024-01470-5

  This paper provides an in-depth understanding of the evolving landscape of HPV vaccine technology, highlighting the vectors employed, the diseases they aim to target, the antigens chosen for optimal immune response, the metrics used to evaluate their effectiveness, and the significant strides made in clinical evaluations. […] HPV prophylactic vaccines exhibit excellent immunogenicity and prevent the development of HPV-related precancerous lesions and tumors. […] In May 2024, the WHO issued a document clarifying that HPV therapeutic vaccine is an important means to eliminate tumors associated with HPV infection. […] The HPV therapeutic vaccines are universally used to treat cancers and precancerous lesions. […] Therapeutic vaccines are capable of elevating the levels of systemic cytotoxic CD8+T cells and facilitating an increase in CD8+cell counts within tumor tissue.

• #33 Human papillomavirus (HPV) vaccine market shaping roadmap

  https://www.gavi.org/news-resources/knowledge-products/human-papillomavirus-hpv-vaccine-market-shaping-roadmap

  HPV9 vaccines are not currently available as part of Gavi’s vaccine product menu. This will remain the case in the short term, but might change once a competitive, sustainable supplier base and market develops. […] Vaccine microarray patches (MAPs) are clusters of microscopic projections that are applied to the skin to painlessly deliver a vaccine. The technology has the potential to significantly simplify vaccination administration and logistics, especially for vaccines like HPV that are delivered outside of traditional routine immunisation settings. […] A number of manufacturers are developing HPV vaccines that protect against more types of HPV than HPV9 vaccines. These are currently being investigated in preclinical and clinical trials. The public health benefit of these higher valency HPV vaccines is not yet understood and may be marginal.

• #34 How a single HPV vaccine dose can prevent cervical cancer | PATH

  https://www.path.org/our-impact/articles/how-a-single-hpv-vaccine-dose-can-prevent-cervical-cancer/

  HPV vaccine is a subunit vaccine, which is a class of vaccines that uses a piece of the virus to generate an immune response. Researchers used an HPV protein called L1, an important region for the immune systems interaction with the virus. When the vaccines teach the immune system to recognize L1, were able to fight the real virus in the future. […] Protection from just one dose of a subunit vaccine was unprecedented. To understand what set HPV vaccines apart, researchers took a close look at the immune response. […] In HPV vaccines, the L1 protein is delivered using a virus-like particle (VLP) mechanism, which retains the proteins original shape. In its native shape, the protein behaves in a specific way: hundreds of these L1 VLPs (360, to be exact) link up to form a kind of super-sphere, with the L1 targets fanning outward around the perimeter, inviting swarms of B cells (a type of immune cell) to bind them through their cell surface antibodies.

• #35 How a single HPV vaccine dose can prevent cervical cancer | PATH

  https://www.path.org/our-impact/articles/how-a-single-hpv-vaccine-dose-can-prevent-cervical-cancer/

  This simultaneous response to multiple L1 proteins (as opposed to one or two L1 proteins) results in potent B cell activation signals, and these strong signals stimulate the development of long-lasting plasma cells (LLPCs). LLPCs continuously churn out large numbers of antibodies into the blood for round-the-clock extracellular surveillance duty, humming along as a consistent backdrop of our immune ecosystem. […] Critically, LLPCs dont depend on additional vaccine doses or virus exposures to continue production. True to their name, these cells provide long-lasting protection. […] Evidence of this type of immune response has borne out in clinical observation: after an approximately one-year decline following a single dose of HPV vaccine, the antibody level stabilizes at a steady plateau and is sufficient to provide solid long-term protection from infection. […] While monitoring will continue, given what we know about this type of immune response, the levels are unlikely to dramatically change in subsequent years, and are expected to maintain protection against the HPV infections that are at highest risk of becoming cervical cancer.

• #36 Vaccine candidate designed to treat cancer caused by HPV : Revista Pesquisa Fapesp

  https://revistapesquisa.fapesp.br/en/vaccine-candidate-designed-to-treat-cancer-caused-by-hpv/

  A vaccine that can treat certain types of viral cancer, rather than solely preventing the underlying viral infection, could be on its way to the market. […] Researchers from the University of Pennsylvania and the University of So Paulo (USP), Brazil, reported encouraging results from animal tests of a candidate vaccine designed to combat tumors caused by chronic HPV infection. […] The vaccine works by stimulating the immune system to eliminate already diseased cells, rather than preventing HPV infection like other vaccines currently available in most countries. […] In all formulations, the RNA molecule contained instructions for making two proteins: E7 from HPV, which remains exposed on the surface of tumor cells infected by the virus, and glycoprotein D, which is contained in the outer layer of the herpes virus.

• #37 Vaccine candidate designed to treat cancer caused by HPV : Revista Pesquisa Fapesp

  https://revistapesquisa.fapesp.br/en/vaccine-candidate-designed-to-treat-cancer-caused-by-hpv/

  Analyses showed that these RNA-based formulations activate CD8 T lymphocytes, which recognize HPV-infected tumor cells and destroy them by perforating their membranes. […] Even against advanced-stage disease, the RNA-based vaccine candidates performed remarkably well with just a single injection, allowing 60% of the animals to become and remain completely cancer-free for an extended period of time. […] All RNA-based formulations yielded significantly superior results compared to two other vaccine technologies the researchers evaluated: one using a DNA molecule coding for E7 and glycoprotein D, and another where a hybrid molecule purified from the two proteins was directly administered to the animals. […] Developing an effective therapeutic vaccine against tumors caused by HPV would be groundbreaking for the treatment of genital organ cancers, especially advanced-stage cervical cancer, a field that has seen little progress in the past 20 years.

• #38 Human Papillomavirus (HPV) Vaccination | Doctor

  https://patient.info/doctor/human-papillomavirus-hpv-vaccination

  In males, HPV infection can progress to cause anal, penile, oropharyngeal, and oral cavity cancers as well as anogenital warts. The high-risk HPV types 16 and 18 are strongly implicated in anal/genital cancers (penis, vagina and vulva, anus) although the incidence of these cancers in the general population is low. […] More than 80% of anal cancers are caused by high-risk HPV types and the incidence of anal cancer in MSM is increasing. […] HPV vaccines are highly effective at preventing the infection of susceptible people with the HPV types covered by the vaccine. In clinical trials, both vaccines are over 99% effective at preventing pre-cancerous lesions associated with HPV types 16 or 18 in young women. Studies suggest that protection is maintained for at least ten years. Based on the immune responses, it is expected that protection will be extended further; long-term follow-up studies are in place. Current evidence suggests that HPV immunisation in males generates comparable immunogenicity to that seen in females.

• #39 HPV vaccine: an overview of immune response, clinical protection, and new approaches for the future | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-8-105

  A rapid, potent, and sustained immunologic response to the administration of a quadrivalent vaccine (targeting HPV 6, 11, 16, and 18) and after a bivalent vaccine (targeting HPV 16 and 18) has been reported so far. […] Another question that we are faced with is: does the intensity of such a humoral immune response correlate with long-term protection? […] Although a direct correlation between antibody levels and protection may seem intuitively obvious, it is still unclear whether differing antibody titers indicate better disease protection or longer duration of immune protection. […] The mechanisms of long-term immune-protection by means of memory B-cells have been, once again, elucidated for the hepatitis B virus vaccine, whose evoked-immunity appears similar to that of the HPV vaccination.

• #40 HPV vaccine: an overview of immune response, clinical protection, and new approaches for the future | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-8-105

  Indeed, memory B cells play an important role in effective immunization and in the memory-mechanism that produces antibodies in response to further antigenic challenges. […] WHO explicitly stated that the induction of the immune memory „should be assessed by means of evaluating immune responses to additional doses of vaccine administered at planned intervals following completion of the primary series.” […] The current vaccines are able to elicit an immunological response against the two most common oncogenic types found in cervical cancer, HPV-16 and HPV-18, but not against all high-risk mucosal HPVs. […] It is obvious that a multivalent vaccine against a multitude of HPVs will have a major impact on public health, and efforts to develop a nine-type L1 VLP combination vaccine are ongoing.

• #41 SciELO Brazil – HPV vaccines: a controversial issue? HPV vaccines: a controversial issue?

  https://www.scielo.br/j/bjmbr/a/cKZtv56rsmQrffKx59S3yjd/

  Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. […] The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. […] We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. […] However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. […] We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination.

• #42 SciELO Brazil – HPV vaccines: a controversial issue? HPV vaccines: a controversial issue?

  https://www.scielo.br/j/bjmbr/a/cKZtv56rsmQrffKx59S3yjd/

  It is important to emphasize that the HPV vaccines are not a therapeutic treatment for any HPV-associated disease that might exist at the time of vaccination, nor will it invariably protect against diseases that are caused by types of HPV not targeted by the vaccines. […] Despite the efforts by public health agencies in the United States, the coverage of HPV vaccination remains low. […] However, much of the published scientific data regarding the safety of HPV vaccines could be influenced by conflicts of interest such as receiving advisory board fees and grant support with commercial interests from the competitive HPV vaccine market. […] One systematic review that involved a total of 29,540 individuals showed that the most frequently reported adverse event related to the HPV vaccines was pain and swelling at the injection site followed by fatigue, fever, gastrointestinal symptoms and headaches.

• #43 SciELO Brazil – HPV vaccines: a controversial issue? HPV vaccines: a controversial issue?

  https://www.scielo.br/j/bjmbr/a/cKZtv56rsmQrffKx59S3yjd/

  For HPV vaccines, the body of evidence suggests that their potential to elicit life-threatening side effects is very low with autoimmune responses being the greatest concern. […] For this reason, it is important to stress the need to maintain routine surveillance for lower genital tract diseases especially in women, even if there is widespread use of the HPV vaccine.

• #44 HPV Vaccine: Age, Schedule, Importance & Side Effects

  https://my.clevelandclinic.org/health/treatments/21613-hpv-vaccine

  The HPV vaccine protects against certain cancers caused by human papillomavirus (HPV) infection. […] The HPV vaccine is a series of shots that can protect you from an HPV (human papillomavirus) infection. […] But some HPV infections dont go away. Some progress to cancer. For example, most cervical cancer and cancers affecting your genitals are associated with an HPV infection. […] The HPV vaccine prevents HPV infections that can progress to cancer or genital warts. […] The HPV vaccine can protect you from strains you havent encountered before. These include high-risk types and low-risk types. High-risk HPV strains can progress to cancer. […] The vaccine contains a simulation of the virus not the actual live virus. The vaccine stimulates your immune system to produce antibodies that fight HPV. If youre exposed to the actual virus, these antibodies prevent it from causing an infection.

• #45 5 Reasons Boys and Young Men Need the HPV Vaccine, Too | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/news/5-reasons-boys-and-young-men-need-hpv-vaccine-too

  Vaccination protects men from HPV-related cancers in the short and long term. […] The HPV vaccine went through years of rigorous safety testing before it was approved in 2006 to prevent cervical cancer in women and in 2009 to prevent HPV-related cancers in males. […] The benefits of vaccinating against HPV far outweigh any potential risk of side effects. […] HPV-related cancers are usually able to be treated successfully. But preventing a cancer is far better than treating it, which makes the HPV vaccine a valuable weapon against cancer.

• #46 Patient education: Human papillomavirus (HPV) vaccine (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/human-papillomavirus-hpv-vaccine-beyond-the-basics

  HPV vaccination in females is very effective in preventing HPV infections and cervical pre-cancers and cancers caused by HPV types targeted by the vaccine. HPV vaccination in females reduces the risk of genital warts and of transmitting the warts to their sexual partners. HPV vaccination in males reduces the risk of developing genital warts and penile HPV infection, which decreases the risk of HPV transmission to sexual partners. HPV vaccination also reduces the risk of anal cancer in both males and females. HPV vaccination prevents oral HPV infection, which is associated with oropharyngeal (mouth and throat) cancer. It is expected that the vaccine can reduce the risk of this cancer as well, and the vaccine is US Food and Drug Administration (FDA) approved for this indication.

• #47 Non-sexual HPV transmission and role of vaccination for a better future (Review)

  https://www.spandidos-publications.com/10.3892/etm.2020.9316

  The route of HPV transmission is primarily through skin-to-skin or skin-to-mucosa contact. Sexual transmission is the most documented, but there have been studies suggesting non-sexual ways. Self-inoculation is described in studies as a potential HPV transmission route. Vertical transmission from mother to newborn is another HPV transmittal route. Several studies have emphasized the possibility of infection through the amniotic fluid, or the placenta, or via contact with maternal genital mucosa during natural birth. […] In Australia, in 2014, there were no new genital warts cases in females under 21 years, due to the vaccine implementation. There has been a decrease in genital warts in age-matched heterosexual men also, ~82%, suggesting herd protection. The early effects after the HPV vaccine program in Australia are: Decrease in the incidence of high-grade cervical abnormalities (associated with type 16 and 18), but no significant decrease in low-grade cervical abnormalities. Recent data suggest a real and measurable effect of Gardasil vaccination on non-targeted HPV types. Another benefit of vaccination could occur in people already infected with targeted types of HPV. There is little information on this topic, but the possibility that the antibodies could break the cycle of reinfection exists, thus reducing the residence time of infection, and also reducing the risk of transmission.

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