A comprehensive narrative review of challenges and facilitators in the implementation of various HPV vaccination program worldwide.

INTRODUCTION: Cervical cancer has been considered as one of the most common cancers in women (15-44 years) globally, but the advent of the human papilloma virus (HPV) vaccine has raised the anticipation that eradication of cervical carcinoma might be achieved in the near future as several prophylactic cervical carcinoma vaccines have already been currently licensed in various countries. Countries should devise strategies, practices and policies to attain and sustain higher levels of HPV immunization coverage as still 68% countries have introduced HPV vaccine in their national immunization programs even after 17 years following the licensure of the first prophylactic HPV vaccine. METHODOLOGY: A comprehensive literature analysis was conducted using various databases and search engines, to include the most relevant research articles and data available and critically discussed the operational gaps that need to be answered to achieve adequate coverage of HPV vaccination. RESULTS: The present review highlights the existing HPV vaccination strategies, unmet needs and challenges needed to be addressed for proper implementation framework as well as the collaborations required to achieve decent vaccination coverage. Well-coordinated vaccination strategy with focus on adolescent girls and if possible, boys can lead to dramatic impact on disease reduction around the world.

Human papilloma virus vaccines: A comprehensive narrative review.

Cervical cancer is one of the most common cancers in women aged 15-44 years in the world, with more than three-quarters of cases diagnosed at a locally advanced clinical stage with minor prospects of survival. Although only a small percentage of women with Human Papilloma Virus (HPV) develop cervical cancer and most of the HPV infections are cleared subsequently at primary stage itself, but seroconversion not always guarantees that the individual is immune to HPV. The advent of the cervical carcinoma vaccine has raised the expectations that eradication of cervical carcinoma might be possible in the near future as it exhibited remarkably high efficacy against the vaccine-specific types in naive women with no serious vaccine-related adverse events. Few prophylactic HPV vaccines are currently licensed in over 100 countries. It has also been suggested that vaccinating both men and women is more beneficial than vaccinating only females. Vaccination is a cost-effective strategy to reduce the incidence of cervical cancer and mortality compared to no vaccination based on the cost of cancer treatment. Well-coordinated vaccination strategy with focus on adolescent girls and if possible, boys can lead to dramatic impact on disease reduction around the world.

A Comprehensive Review of Treatment Approaches for Cutaneous and Genital Warts.

Cutaneous and genital warts are common in both developed as well as developing countries. Human papillomavirus (HPV), which is a double-stranded DNA virus, is the causative agent of wart infection. Different types of HPV viruses are responsible for the different severity of diseases. Some types are associated with malignancy of the anal region and cervix. HPV is a common sexually transmitted disease in the United States. The incidence is most common in the younger age groups and the elderly population. Our main goal is to describe the different treatment modalities available for warts. Treatment modalities are divided into primary, secondary, and tertiary options. Topical medications, and physical excision of warts via cryotherapy, electrocautery, lasers, or photodynamic therapy are all common forms of treatment. Various clinical trials and randomized control trials have been seen as effective treatment against HPV infection. Higher remission rates are seen irrespective of different treatment options. Warts can be treated but the HPV virus cannot be completely removed. Older age, immunocompromised state, diabetes mellitus, and HIV are the predisposing factors for the disease. There is currently a large variety of medicines in use, all of which can differ significantly in terms of price, side-effect profiles, dosing regimens, length of therapy, and overall effectiveness. The best course of treatment has not yet been identified, and patients are often treated according to their unique needs.

Human papillomavirus vaccination in Africa: An airway perspective.

INTRODUCTION: Recurrent respiratory papillomatosis (RRP) is a chronic condition caused by Human papillomavirus six (HPV-6) and HPV-11 that involves the respiratory tract. Disease severity ranges from mild (hoarseness), through to severe (stridor, respiratory distress and airway emergencies). Africa has the fastest growing and youngest population of all the continents. It also has the greatest burden of cervical cancer. There is an association with infection of the oncogenic HPV strains and the strains responsible for RRP. It is reasonable to conclude that although RRP may be underestimated in low-to-middle-income countries, it poses a considerable health risk to Africa. The primary aim of this project was to assess the suitability of HPV vaccination coverage on the African continent. METHODS: A prospective study was designed to consist of an online survey. It was distributed to 135 African otolaryngologists. Questions focussed on HPV vaccination programmes; whether they were government directed; and their rollout. Information from countries that had multiple otolaryngologists respond to the survey were compared. Additionally, data review and corroboration were performed. RESULTS: There were 58 (43%) participants from 19 countries. Nine countries reported a national vaccination programme (NVP), five used Cervarix; four used quadrivalent Gardasil. Collateral data revealed 18 of 54 countries had NVP in Africa and 26 countries had completed HPV vaccine pilot or demonstration projects. CONCLUSIONS: HPV vaccination in Africa should be urgently re-evaluated to include the HPV-6 and HPV-11 strains that cause JORRP, which have not been recognised during national vaccination programme planning.

Effectiveness and safety of injectable human papilloma virus vaccine administered as eyedrops.

Mucosal vaccines have the advantages of ease of administration and the induction of strong mucosal immunity and a systemic immune response. Recently, the eye mucosa has been shown to be an effective and safe alternative vaccination route against influenza, Toxoplasma gondii infection, and hemolytic uremic syndrome in mice. In this study, we showed that the commercially available human papilloma virus (HPV) vaccine, Cervarix, induced significant immune reactions in terms of anti-HPV antigen (Ag)-specific immunoglobulin G (IgG) and IgA antibody production following eyedrop (ED) vaccination in mice. The HPV ED vaccines (EDV) provoked no signs of inflammation within 24 h, as indicated by the inflammatory cytokine mRNA levels and infiltration of mononuclear cells in inoculation sites. Moreover, the morphology of the cornea and retina and intraocular pressure of mice did not change after the HPV EDV. The functions of photoreceptor cells, including rod and cone cells, were normal following the HPV EDV inoculation in mice. These results suggest that Cervarix EDV could be a potent, safe, and effective mucosal vaccine against HPV-associated cancers.

Prophylactic Human Papillomavirus Vaccination: From the Origin to the Current State.

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.

Human Papilloma Virus Vaccination.

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

Utility of the Human Papillomavirus Vaccination in Management of HPV-associated Cutaneous Lesions.

Human papillomavirus (HPV)-induced cutaneous disease is a common complaint for patients presenting for dermatology evaluation. Infection by HPV is the major etiologic factor in the development of cutaneous warts, epidermodysplasia verruciformis, and possibly a subset of cutaneous squamous cell carcinoma. Carcinoma of the genitourinary tract, most notably cervical carcinoma, is the most severe manifestation of infection with specific serotypes of HPV. For this reason, the HPV immunization (Gardasil) was developed in 2006 and upgraded in 2018 to a nonavalent formulation that includes serotypes 6, 11, 16, 18, 31, 33, 45, 52, 58. While immunization is highly effective at preventing infection with serotypes included in the formulation, it is less clear if the immunization can aid in managing active HPV infection. This review examines the available literature regarding the role of HPV immunization in managing common warts, genital warts, keratinocyte carcinoma, and epidermodysplasia verruciformis.

Sustained Cross-reactive Antibody Responses After Human Papillomavirus Vaccinations: Up to 12 Years Follow-up in the Finnish Maternity Cohort.

BACKGROUND: Human papillomaviruses (HPV) cause several human cancers. Bivalent (Cervarix) and quadrivalent (qGardasil) HPV vaccines both contain virus-like particles of the major oncogenic HPV types 16 and 18, but also cross-protect against some nonvaccine types. However, data on long-term sustainability of the cross-reactive antibody responses to HPV vaccines are scarce. METHODS: Serum samples donated 7-12 years after immunization at age 16-17 years with bivalent (n = 730) or quadrivalent (n = 337) HPV vaccine were retrieved from the population-based Finnish Maternity Cohort biobank. Serum antibody levels against HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, and 73 were determined using multiplex pseudovirion binding assay. Antibody avidity was assessed using ammonium thiocyanate treatment. RESULTS: Seropositivity for HPV31, 33, 35, 45, 51, 52, 58, 59, 68, and 73 was increasingly common (P ≤ .001; χ 2 test for trend for each of these types) when women had high anti-HPV16 antibody levels. For 8 nonvaccine HPV types seropositivity was more common among recipients of bivalent than quadrivalent vaccine, in particular for HPV31, 35, 45, 51, 52, and 58 (P < .001). Antibody avidity was higher in the quadrivalent vaccine recipients for HPV6, 11, and two of the nonvaccine types, but lower for HPV16 and 18 (P < .001). CONCLUSIONS: Both vaccines elicit cross-reactive antibodies detectable even 12 years after vaccination. Cross-reactive seropositivity is more common in women with high anti-HPV16 antibody response and in the bivalent vaccine recipients.

The effect of human papilloma virus vaccination on embryo yield and clinical in vitro fertilisation outcomes: a matched retrospective cohort study.

The effects of HPV vaccination on embryo yield and pregnancy outcomes in IVF cycles with fresh embryo transfer (ET) were investigated. First, embryo yielding rates (EYR) in 2795 cycles with and without HPV vaccination were compared by retrospective cohort study design. EYR of HPV vaccinated and non-vaccinated patients were not significantly different (OR, 1.66; 95% CI, 0.76-3.63). Second, ET outcomes were compared for 155 HPV vaccine + cycles and 465 HPV vaccine - cycles after matching for ages and cycle attempt number. The differences in the number of retrieved oocytes (10.2 ± 6.1, 11.2 ± 6.7; p = .161), mature (MII) oocytes (8.7 ± 5.7, 9.8 ± 6.3; p = .088), two pronuclear zygotes (2PN) (5.4 ± 4.1, 6.1 ± 4.6; p = .110) and fertilisation rates (0.62 ± 0.23, 0.62 ± 0.23; p = .539) were insignificant between the two groups. Moreover, positive (OR, 0.74; 95% CI, 0.47-1.16), clinical (0.60; 0.36-1.01) and the ongoing pregnancy (0.55; 0.30-1.01) rates were lower in the HPV vaccinated group but the difference was not statistically significant.IMPACT STATEMENTWhat is already known on this subject? There are recent case studies that report premature ovarian insufficiency (POI) following a post-vaccination autoimmune response against the HPV vaccine. These studies suggest that the possible trigger for the immune reaction might be the immunogen content of the vaccine. However, the number of clinical studies investigating the effects of the HPV vaccine on reproductive function and in vitro fertilisation outcomes is limited.What do the results of this study add? In contrast to the case reports suggesting impaired reproductive and ovarian functions in HPV vaccinated patients, this study finds that in IVF patients HPV vaccinated and non-vaccinated women have similar EYR, MII, 2PN, oocyte counts, fertilisation rates, positive, clinical and ongoing pregnancy rates.What are the implications of these findings for clinical practice and/or further research? The results suggest the HPV vaccine does not have a negative impact on embryo yielding rates oocyte counts and fertilisation rates, positive, clinical and ongoing pregnancy rates in IVF treatments. Hence, they can be safely used for primary prevention against cervical cancer.

Optimized dose of synthetic analogues of Monophosphoryl lipid A as an effective alternative for formulating recombinant human papillomavirus vaccine.

Adjuvants are a crucial component of recombinant vaccines such as the human papillomavirus (HPV) vaccine. Monophosphoryl lipid A (MPL) extracted from Salmonella Minnesota lipopolysaccharide is used as an adjuvant for the HPV vaccine. Due to the limitations in accessibility and reproducibility of MPL, investigating synthetic analogues of MPL (synMPL) is urgently needed to overcome these limitations. In this study, female BALB/c mice were vaccinated by HPV vaccine formulated with synMPL and aluminum hydroxide gel in which the concentration of synMPL ranged from 0 to 100 µg/dose. Anti-HPV L1 VLP antibody was measured for each group through Indirect ELISA and compared with Cervarix and Gardasil vaccines as approved anti-HPV vaccines. SynMPL showed a concentration-dependent increase up to 50 µg/dose in the immunogenicity of the vaccine. Therefore, synMPL at concentration of 50 µg/dose was selected as optimum concentration. The GMT profiling of synMPL-formulated vaccine (named Papilloguard) and Cervarix was not statistically different (Mann-Whitney test). The Gardasil vaccine showed 10-fold lower GMT for anti-HPV 18 L1 VLP antibody but anti-HPV 16 L1 VLP antibody was similar to Cervarix and Papilloguard. The current findings suggest that the synMPL in combination with aluminum hydroxide could be used as a potential adjuvant candidate for human vaccine.

Human Papillomavirus Vaccines: An Updated Review.

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.

A cross-sectional study of the relationship between reported human papillomavirus vaccine exposure and the incidence of reported asthma in the United States.

OBJECTIVES: Asthma is a chronic disorder that affects persons of all ages impacting the quality of their lives. This cross-sectional hypothesis-testing study evaluated the relationship between human papillomavirus vaccine and the risk of an incident asthma diagnosis in a defined temporal period post-vaccination. METHODS: The 2015-2016 National Health and Nutrition Examination Survey data were examined for a group of 60,934,237 weighted persons between 9 and 26 years old in Statistical Analysis Software. RESULTS: Reported incident asthma significantly clustered in the year of reported human papillomavirus vaccination. When the data were separated by gender, the effects observed remained significant for males but not females. CONCLUSION: The results suggest that human papillomavirus vaccination resulted in an excess of 261,475 asthma cases with an estimated direct excess lifetime cost of such persons being US$42 billion. However, it is unclear what part of the vaccine and/or vaccine medium may have increased an individual's susceptibility to an asthma episode, whether the asthma diagnosis represented one asthma episode or if it is chronic, and how much therapeutic support was needed (if any) and for how long, which would impact cost. Despite the negative findings in this study, routine vaccination is an important public health tool, and the results observed need to be viewed in this context.

Bivalent Vaccine Effectiveness Against Type-Specific HPV Positivity: Evidence for Cross-Protection Against Oncogenic Types Among Dutch STI Clinic Visitors.

Background: Observational postmarketing studies are important to assess vaccine effectiveness (VE). We estimated VE from the bivalent human papillomavirus (HPV) vaccine against HPV positivity of vaccine and nonvaccine types in a high-risk population. Methods: We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional survey in Dutch sexually transmitted infection clinics. Vaginal swabs were analyzed using a polymerase chain reaction-based assay (SPF10-LiPA25) able to detect the 12 high-risk HPV (hrHPV) types 16/18/31/33/35/39/45/51/52/56/58/59. We compared hrHPV positivity between self-reported vaccinated (≥1 dose) and unvaccinated women, and estimated VE by a logistic mixed model. Results: We included 1087 women of which 53% were hrHPV positive and 60% reported to be vaccinated. The adjusted pooled VE against HPV-16/18 was 89.9% (81.7%-94.4%). Moreover, we calculated significant VE against nonvaccine types HPV-45 (91%), HPV-35 (57%), HPV-31 (50%), and HPV-52 (37%). Among women who were offered vaccination 5/6 years ago, we estimated similar VE against HPV-16/18 (92%) and all hrHPV types (35%) compared to women who were offered vaccination <5 years ago (83% and 33%, respectively). Conclusion: We demonstrated high VE of the bivalent vaccine against HPV-16/18 and cross-protection against HPV-45/35/31/52. Protection against HPV-16/18 was sustained up to 6 years postvaccination.

Elimination of Cancer Health Disparities through the Acceleration of HPV Vaccines and Vaccinations: A Simplified Version of the President's Cancer Panel Report on HPV Vaccinations.

The human papillomavirus (HPV) is a major public health concern affecting both females and males. HPV is associated with cervical, anal, head and neck cancers. About 99% of all cervical cancers are related to HPV. HPV vaccines, Gardasil, Cervarix, and Gardasil 9 are used in the primary prevention of HPV related cancers. Gardasil and Gardasil 9 are available for use in both females and males ages 9 to 26, while Cervarix is available for females ages 9 to 25. Gardasil 9 was approved by the FDA for prevention against additional HPV types. Despite the availability of this preventative measure against cervical cancer, the rate of HPV vaccination in the United States remains lower than that of other industrialized nations. The purpose of this study is to elucidate mechanisms to help increase the HPV vaccination rate by using education as a tool; by simplifying the president report so that lay person can understand the information presented in the report. Through the quantitative examination of the data from the states with the lowest and highest vaccination rates, using SPSS statistical analysis; we analyzed several factors involved with the low uptake of the vaccines. The results collected show that socioeconomic status, misconceptions about HPV, and misconceptions about the safety of the vaccines were identified as possible obstacles to the effective uptake of HPV vaccinations. The proposals made by the President's Cancer Panel to accelerate the uptake of vaccines include, increasing coverage of the vaccines through government-sponsored programs, and the Affordable Care Act; increasing accessibility to vaccines through pharmacies, schools, and clinics; and disseminating more information on HPV to healthcare providers, parents, caregivers, and patients. Allowing greater accessibility to the vaccines for all populations regardless of income, education, and eliminating misconceptions of the vaccines would play a significant role in eliminating cancer.

Sustained Immunogenicity of 2-dose Human Papillomavirus 16/18 AS04-adjuvanted Vaccine Schedules in Girls Aged 9-14 Years: A Randomized Trial.

Background: We previously reported the noninferiority 1 month after the last dose of 2-dose human papillomavirus 16/18 AS04-adjuvanted (AS04-HPV-16/18) vaccine schedules at months 0 and 6 (2D_M0,6) and months 0 and 12 (2D_M0,12) in girls aged 9-14 years compared with a 3-dose schedule at months 0, 1, and 6 (3D_M0,1,6) in women aged 15-25 years. Here, we report the results at study end (month 36 [M36]). Methods: Girls were randomized 1:1 and received 2 vaccine doses either 6 months (2D_M0,6) or 12 months apart (2D_M0,12); women received 3 doses at months 0, 1, and 6 (3D_M0,1,6). Endpoints included noninferiority of HPV-16/18 antibodies for 2D_M0,6 versus 3D_M0,1,6; 2D_M0,12 versus 3D_M0,1,6; and 2D_M0,12 versus 2D_M0,6; and assessment of neutralizing antibodies, T cells, B cells, and safety. Results: At M36, the 2D_M0,6 and 2D_M0,12 schedules remained noninferior to the 3D_M0,1,6 schedule in terms of seroconversion rates and 3D/2D geometric mean titers for anti-HPV-16 and anti-HPV-18. All schedules elicited sustained immune responses up to M36. Conclusions: Both 2-dose schedules in young girls remained noninferior to the 3-dose schedule in women up to study conclusion at M36. The AS04-HPV-16/18 vaccine administered as a 2-dose schedule was immunogenic and well tolerated in young girls.

HPV vaccines - A review of the first decade.

Pre-adolescent girls (9-15years) have the option of receiving a two dose HPV vaccine series at either a six month or one year interval to provide protection from HPV 16, the most prevalent type associated with cervical cancers, as well as several other less prevalent types. This series of vaccinations is highly likely to protect her from HPV infection until she enters the routine screening program, whether that be primary HPV testing or a combination of HPV testing and cytology. The two dose program has been recommended by the World Health Organization (WHO) since 2015. For women 15years and older, the three dose vaccine schedule is still recommended. The past ten years of Gardasil use has provided evidence of reduced HPV 16/18 infections in countries where there has been high coverage. Gardasil9 has replaced Gardasil. Gardasil9 has the same rapid anti-HPV 18 and HPV45 titer loss as Gardasil did. Cervarix remains equivalent to Gardasil9 in the prevention of HPV infections and precancers of any HPV type; Cervarix also has demonstrated sustained high antibody titers for at least 10years. One dose of Cervarix provides protection against HPV 16/18 infection with robust antibody titers well above natural infection titers. This may offer the easiest and most cost effective vaccination program over time, especially in low and lower middle income countries. Cervical cancer screening must continue to control cancer incidence over the upcoming decades. Future studies of prophylactic HPV vaccines, as defined by the WHO, must demonstrate protection against six month type specific persistent infections, not actual cervical cancer precursor disease endpoints, such as cervical intraepithelial neoplasia grade 3 (CIN 3) or adenocarcinoma in situ (AIS). This simplifies and makes less expensive future comparative studies between existing and new generic vaccines.