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Human papillomavirus (HPV) vaccines, which were introduced in many countries in the past decade, have shown promising results in decreasing HPV infection and related diseases, such as warts and precancerous lesions. In this review, we present the updated information about current HPV vaccines, focusing on vaccine coverage and efficacy. In addition, pan-gender vaccination and current clinical trials are also discussed. Currently, more efforts should be put into increasing the vaccine’s coverage, especially in low- and middle-income countries. Provision of education on HPV and vaccination is one of the most important methods to achieve this. Vaccines that target HPV types not included in current vaccines are the next stage in vaccine development. In the future, all HPV-related cancers, such as head and neck cancer, and anal cancer, should be tracked and evaluated, especially in countries that have introduced pan-gender vaccination programs. Therapeutic vaccines, in combination with other cancer treatments, should continue to be investigated.

Prophylactic human papillomavirus (HPV) vaccination programs constitute major public health initiatives worldwide. We assessed the global effect of quadrivalent HPV (4vHPV) vaccination on HPV infection and disease. PubMed and Embase were systematically searched for peer-reviewed articles from January 2007 through February 2016 to identify observational studies reporting the impact or effectiveness of 4vHPV vaccination on infection, anogenital warts, and cervical cancer or precancerous lesions. Over the last decade, the impact of HPV vaccination in real-world settings has become increasingly evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. Maximal reductions of approximately 90% for HPV 6/11/16/18 infection, approximately 90% for genital warts, approximately 45% for low-grade cytological cervical abnormalities, and approximately 85% for high-grade histologically proven cervical abnormalities have been reported. The full public health potential of HPV vaccination is not yet realized. HPV-related disease remains a significant source of morbidity and mortality in developing and developed nations, underscoring the need for HPV vaccination programs with high population coverage.

Currently, the best method for preventing Human Papilloma Virus (HPV) infection is vaccination. The present systematic review aims to review the latest findings on the factors affecting the efficacy of Gardasil 4, Cervarix, and Gardasil-9 vaccines on reducing pregenital lesions and reducing high-risk genotypes of cervical cancer in females aged 9–45 years and to examine the distribution of studies conducted in this regard in regions. In this study only the names of the vaccines were used and the vaccines were examined only according to the name. The name of WHO is only used to imply the distribution and access to health services in the world and not in terms of the vaccine approval in different organizations. A search for each vaccine was performed using PubMed, Scopus, and Web of Science. Five hundred and forty, 257, and 191 unique studies were obtained from the aforementioned databases for Gardasil 4, Cervarix, and Gardasil 9 vaccines, respectively. After applying the inclusion and exclusion criteria, 17 studies on Gardasil 4, seven studies on Cervarix, and two studies on Gardasil 9 were reviewed. This study indicated that within various regions of the WHO, comprehensive effectiveness studies have not been conducted, and specifically within the Eastern Mediterranean Region (EMR) and South-East Asia Region (SEAR), no effectiveness studies have been recorded. Consequently, these regions necessitate the execution of effectiveness studies. Therefore, it is advisable to undertake investigations regarding the effectiveness of papillomavirus vaccination in the EMR and SEAR regions as delineated by the WHO. Moreover, it was demonstrated that in diverse nations, an array of factors such as age, gender, prevalent genotypes within the population, culture, the age at sexual activity initiation, the healthcare infrastructure, and timely screening can significantly impact the effectiveness of the vaccine. Furthermore, in nations with suboptimal vaccination coverage, a robust healthcare system coupled with the implementation of specialized testing and prompt follow-up can substantially aid in cancer prevention. The outcomes of this investigation confirm the administration of at least one dose of the vaccination. It reveals that in the absence of vaccination, a stringent healthcare system may contribute to the reduction of cervical cancer incidence. Additionally, in these nations, enhancements in healthcare systems, screening protocols, and public awareness play a crucial role in augmenting vaccination effectiveness. Collectively, a lower age at the time of vaccination (9–15 years), reduced sexual exposure prior to vaccination, vaccination prior to the onset of precancerous lesions, and adherence to the recommended vaccination schedule are associated with heightened vaccine effectiveness. Furthermore, the effectiveness of the vaccination dose is age-dependent, as one dose can be effective for individuals aged 15 years or younger. Various factors, including age, sex, common genotypes in population, culture, age at sexual initiation, healthcare system, and screening at recommended time, can play a significant role in vaccine effectiveness. Additionally, it is suggested that in the developing countries, a single dose vaccination program is sufficient for children aged 15 years or younger. Also in these countries, improving the care system, screening system, and awareness play a significant role in enhancing the effectiveness of vaccination. It is also recommended that studies on the effectiveness of the papilloma vaccination in the EMR and SEAR regions covered by the WHO to be conducted. According to the inclusion criteria, all countries were included in the study; thus, the effects of the individual’s genotype, which depends on the geographical region, can affect the vaccine effectiveness. Individuals aged 9–45 who can receive the vaccine according to the guidelines, were included in the study. Age is one of the factors affecting the vaccine effectiveness. Also, according to the policies of healthcare organizations, including the Ministries of Health of countries, various health services are provided in different geographical regions. Therefore, females's access to the vaccine occurs at different ages, and the effectiveness of the vaccine decreases by increasing the age at which the vaccine is received. Countries with poor healthcare system have less access to the vaccine, which can affect the effectiveness of the vaccine and herd immunity.

We performed a long-term head-to-head comparison of seroresponses of the 2 human papillomavirus (HPV) vaccines. For most vaccine recipients, HPV-16/18 antibody levels remain stable 7–12 years postvaccination and above natural infection levels. The median antibody levels were higher among Cervarix recipients. Abstract Background Most cervical cancers are caused by vaccine-preventable infections with human papillomaviruses (HPV). The HPV prophylactic vaccines Gardasil and Cervarix have been widely used for >10 years and are reported to induce high antibody levels. A head-to-head comparison of the antibody responses induced by the 2 vaccines has been performed only up to 5 years. Methods Among 3300 Finnish females aged 16–17 years who got 1 of the 2 HPV vaccines in phase 3 licensure trials, virtually all consented to registry-based long-term follow-up. Linkage with the Finnish Maternity Cohort found that they donated >2500 serum samples up to 12 years later. Sera of 337 (38.6%) Gardasil and 730 (30.3%) Cervarix vaccine recipients were retrieved from the Finnish Maternity Cohort biobank and type-specific anti-HPV antibody levels were determined using in-house multiplexed heparin-HPV pseudovirion Luminex assay. Results Anti-HPV-16 and anti-HPV-18 antibody levels remained stable and above natural infection-related antibody levels for up to 12 years for most vaccine recipients. The median antibody levels were higher among Cervarix recipients 7–12 years post vaccination (P < .0001). Conclusions The stability of vaccine-induced antibody levels is in accordance with the high long-term protection reported previously. The differences in antibody levels induced by the 2 vaccines imply that continued follow-up to identify possible breakthrough cases and estimation of the minimal protective levels of serum antibodies is a research priority.

► The analyses of human papilloma virus/virus-like particle vaccine phase III efficacy trials in young women are largely completed. ► High efficacy was observed for incident infection and disease by vaccine types. ► Other clinical trials demonstrated protection against genital warts and anal dysplasia in men. ► Immunobridging studies have extended vaccine recommendations to adolescents. End of study analyses of the phase III trials of prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines in young women are now largely completed. Two distinct vaccines were evaluated, Gardasil® (Merck & Co., Whitehouse Station, NJ USA) a quadrivalent vaccine containing VLPs of types 6, 11, 16 and 18 and Cervarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types 16 and 18. Both vaccines exhibited excellent safety and immunogenicity profiles. The vaccines also demonstrated remarkably high and similar efficacy against the vaccine-targeted types for a range of cervical endpoints from persistent infection to cervical intraepithelial neoplasia grade 3 (CIN3) in women naïve to the corresponding type at the time of vaccination. However, protection from incident infection or disease from non-vaccine types was restricted, and the vaccines had no effect on prevalent infection or disease. Gardasil® also demonstrated strong protection against genital warts and vulvar/vaginal neoplasia associated with the vaccine types. In other trials, Gardasil® protected mid-adult women from incident infection and CIN caused by the vaccine types and protected men for incident infection, genital warts and anal intraepithelial neoplasia by the vaccine types. Cervarix® protected against vaccine-targeted anal infections in women in an end of study evaluation. For practical reasons, efficacy studies have not been conducted in the primary target populations of current vaccination programs, adolescent girls and boys. However, immunogenicity bridging studies demonstrating excellent safety and strong immune responses in adolescence, coupled with the documentation of durable antibody responses and protection in young adults, leads to an optimistic projection of the effectiveness of the vaccines in adolescent vaccination programs. Taken together, the excellent clinical trial results strongly support the potential of the vaccines as high value public health interventions and justify their widespread implementation to prevent anogenital HPV infections and their associated neoplasia. This article forms part of a special supplement entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012.

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

Background Recurrent respiratory papillomatosis (RRP) is a rare, benign disease of the aerodigestive tract, especially the larynx, caused by infection with the human papillomavirus (HPV) types 6 or 11. Current management focuses on surgical debulking with microdebrider of papillomatous lesions with or without concurrent adjuvant therapy, e.g. Cidofovir®. This retrospective study evaluates the results of patients treated at a department of the university clinic between 1990 and 2012 and compares the results of the conventional treatment with a new treatment approach using adjuvant vaccination with Gardasil®. Methods A retrospective Kaplan Maier analysis of n  = 24 patients diagnosed and treated with RPR was performed. The records were reviewed for gender, age at the time of first manifestation of disease and time to recurrence. Results Only n  = 2 (15.4%) of the n  = 13 vaccinated patients developed a recurrence of the disease after a mean time of 54.9 months (SD: 9.5 months). All patients who were not vaccinated ( n  = 11; 100%) developed a relapse after a mean time of 12.3 months (SD: 9.72 months). Conclusion We propose that adjuvant HPV vaccination with Gardasil® might have a preventive effect in RRP by occluding new papilloma formation.

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.

Objectives Recurrent respiratory papillomatosis (RRP) is a rare disease, but one with severe morbidity and occasional mortality. The aetiological agent is human papillomavirus (HPV), and HPV types 6 and 11 account for over 90% of all cases. In the active phase of the disease, patients require multiple hospital admissions for surgical removal or ablation of these benign tumors, which are likely to obstruct the airways if left unchecked. Long‐term sequelae include scarring of the vocal cords, change in voice timbre, or even muteness if a tracheostomy is required. The aim of this study was to determine if adjuvant vaccination with the quadrivalent HPV L1 vaccine (Gardasil™) would decrease numbers of surgical treatments post‐vaccination. Methods A prospective pilot study following a cohort of 12 RRP patients, all of whom gave fully informed consent to participate. All patients had their papillomas typed and if they were found to have types 6 or 11, were vaccinated at the time of first surgical treatment in the hospital, according to the manufacturer's protocols. Patients were followed up closely with 3 or 6 month follow‐up visits. Standard surgical treatments were given and were not affected by whether they participated in the study. Results We found a >7‐fold decrease in the incidence rates of papillomatosis requiring surgical intervention from the pre‐vaccination period (47.44/1000 patient‐months) compared to the post‐vaccination period (6.71/1000 patient‐months). Discussion Surgical treatments for RRP are robust markers for papillomata which require treatment because of the dangers of obstruction of the airway. Despite the small size of this cohort (due to the rarity of this disease), the data suggests that adjuvant use of quadrivalent HPV L1 vaccine imparts significant benefit to this group of patients. A large multi‐center randomized placebo controlled trial is required to definitively establish whether this hypothesis is true and can become the new standard of therapy. Level of Evidence 3b

Background Human Papillomavirus (HPV) is a prevalent STI (Sexually Transmitted Infection) that is estimated almost all sexually active Patients at some stage of their life will be infected by the virus. Although most HPV infections resolve spontaneously, some can result in health complications, such as genital warts and several types of cancer. This study analyzed the variety of HPV genotypes in females and males among the infected population. Methods Samples were obtained from the oral, vaginal, and genital sites of study participants and the samples underwent DNA extraction and subsequently amplified using Real-Time PCR. The recognition of high-risk (HR) and low-risk (LR) HPV genotypes was carried out using the HPV REALQUALITY RQ-Multi diagnostic kit and demographic information was analyzed alongside statistical virological data. Results Out of 936 samples, 324 cases (34.6%) were found to be positive for HPV, while 612 cases (65.4%) were negative. Of our participants, 70 samples of males (27.5%) and 254 samples of females (37.3%) were HPV-positive. Common genotypes included 16, 6, 11, and 18, while genotypes 59, 56, 31, 45, and 52 were also detected. Conclusion According to the findings of this study, a significant prevalence of HPV infection was seen in males and females, and the incidence of high-risk genotypes was more diverse in males. While the vaccine was effective in preventing some types of HPV, such as 16, 18, 6, and 11, there seems to be an increase in infections caused by other genotypes, and precautions should be taken to prevent future health problems.