Efficacy Of Human Papillomavirus Vaccine Research Articles

Duty to Advocate: Human Papillomavirus Vaccination.

Despite the excellent benefit-to-risk ratio for human papillomavirus (HPV) vaccination and recommendations for its routine use from the Advisory Committee on Immunization Practices (ACIP), significant controversy surrounding HPV vaccination continues to exist. In light of this controversy and continued low rates of vaccination among U.S. adolescents, the Pediatric Pharmacy Advocacy Group (PPAG) endorses the safety and efficacy of HPV vaccination and agrees with ACIP recommendations for protection of the U.S. population against the potentially severe consequences of HPV. The PPAG recommends that all eligible individuals undergo vaccination. We further recommend that pediatric pharmacists participate in the education of patients and their families and serve as advocates for HPV vaccination. This document serves as an update to the 2008 PPAG position statement.1.

Human Papillomavirus and Cancer in Men

Although human papillomavirus (HPV) issues have focused primarily on females, it is important to give attention to males because the primary mode of transmission of the virus is through sexual intercourse. There is increasing evidence that HPV is causing serious diseases like penile, anal, head, and neck cancer among males. Studies have also shown that, generally, males have similar rates of HPV infection (0.29 to 0.39 per 1000 person-month) as females. The vaccine against HPV, Gardasil®, has been used in women since 2006. In 2009, the FDA approved Gardasil® for men. Although questions about the efficacy of HPV vaccination in males remain, it is important to understand what males know about HPV and their predisposition towards being vaccinated against the virus.

Development of Human Papillomavirus (HPV) Vaccines: A Review of Literature and Clinical Update

The casual relationship concerning Human papillomaviruses (HPV) and cervical cancer is already established. Therefore, such HPV-associated malignancies might be prevented by prophylactic HPV vaccines. From 2009, two prophylactic HPV L1 Virus-Like Particle vaccines namely, Gardasil®; - quadrivalent (Merck) and Cervarix™ - bivalent (GlaxoSmithKline) are widely commercially available. By Aug 2014, 58 countries had introduced HPV vaccination in their national immunization program; this has led to numerous publications on safety and real world effectiveness. We have also seen long-term immunogenicity and efficacy data emerging. Data on cross-protection has also evolved. In clinical trials, it is observed that vaccinating adolescents results in higher immunological response than young adults hence to achieve best HPV vaccine efficacy it is advisable to immunize before the onset of sexual activity. Recently we have seen development of 2 dose vaccine schedule for adolescent, and emerging evidences even point that single dose of HPV vaccines can result in high efficacy, this observation is currently under consideration but if accepted will greatly impact vaccination coverage. In terms of safety, pregnancy registry did not find any unexpected patterns in fetal or maternal outcomes. This review only focuses on the efficacy and safety data of both Food and Drug Administration approved vaccines from clinical phase I to phase IV.

Comparison of methods using paraffin-embedded tissues and exfoliated cervical cells to evaluate human papillomavirus genotype attribution.

Monitoring the attribution of human papillomavirus (HPV) genotypes to cervical precancerous lesions is essential in assessing the efficacy of HPV vaccines. To resolve the lack of studies comparing the HPV genotyping procedures used to estimate HPV genotype attribution, we undertook a retrospective cross‐sectional study to determine the appropriate genotyping procedures for evaluating the potential efficacy of HPV vaccines. Three procedures, including two different genotyping methods, Clinichip HPV test (C‐Chip) and modified GP5+/6+ PCR coupled to fluorescent bead sorter detection (MGP), using exfoliated cervical cells (C‐Chip and C‐MGP, respectively) or formalin‐fixed paraffin‐embedded tissues (F‐MGP), were compared. The overall agreement in detecting high‐risk HPV was 88.5–92.1% among the three procedures, and genotype‐specific agreement was 83.9–100% for all pairwise comparisons. In cervical intraepithelial neoplasia grade 2/3 specimens, HPV16/18 attribution estimated with the hierarchical attribution method was consistent among the procedures: 52.3% (45/86) for C‐Chip, 54.7% (47/86) for C‐MGP, and 52.3% (45/86) for F‐MGP (P = 0.81). HPV16/18/31/33/45/52/58 hierarchical attribution was 88.4% (76/86) with C‐Chip, 86.0% (74/86) with C‐MGP, and 83.7% (72/86) with F‐MGP (P = 0.49). In cervical intraepithelial neoplasia grade 3 specimens, the corresponding hierarchical attribution was 96.4% (53/55) with C‐Chip, 89.1% (49/55) with C‐MGP, and 94.5% (52/55) with F‐MGP (P = 0.27). Although F‐MGP is theoretically a reliable method for determining HPV genotype attribution, it is acceptable to use C‐Chip or C‐MGP, coupled to the hierarchical attribution formula to correct the bias of multiple infections. These approaches using exfoliated cervical cells are practical for monitoring the efficacy of HPV vaccines.

A Content Analysis of Arabic and English Newspapers before, during, and after the Human Papillomavirus Vaccination Campaign in the United Arab Emirates.

Cervical cancer is the fourth most common cancer among females in the United Arab Emirates (UAE) with an estimated incidence of 7.4 per 100,000 persons per year. In March 2008, the Health Authority of Abu Dhabi launched a free school-based campaign to provide all female Emirati students aged 15-17 years in the emirate of Abu Dhabi with the human papillomavirus vaccine (HPVV). Despite the proven efficacy of the HPVV in clinical trials, there has been limited research exploring the acceptance of this vaccine within a conservative Islamic society. The media plays a key role in changing beliefs and attitudes toward specific public health initiatives, such as vaccination programs. The primary aim of this study was to explore the content and communication style of the UAE newspapers (both Arabic and English) before, during, and after the HPV vaccination program. A systematic literature search was conducted on six national newspapers with the highest circulation figures in the UAE (Arabic: Al Ittihad, Al Khaleej, and Emarat El Youm; English: Khaleej Times, The National, and Gulf News) to retrieve articles related to cervical cancer prevention from January 2000 to May 2013. One bilingual researcher (Arabic-English) utilized content analysis to study the subject matter of communication in each article. A total of 79 newspaper articles (N = 31 Arabic) were included in the study. Content analysis coding revealed five main themes: (i) "HPV Screening or Vaccination Programmes in the UAE" (N = 30); (ii) "Cervical Cancer Statistics in the UAE" (N = 22); (iii) "Aetiology of Cervical Cancer and HPVV Efficacy" (N = 12); (iv) "Cultural Sensitivity and Misconceptions Surrounding HPVV in School-Aged Females" (e.g., promoting promiscuity) (N = 8); and (v) "Cost-Effectiveness, Efficacy, and Safety" (N = 7). The UAE media is playing an important role in raising public awareness about cervical cancer and specific governmental health initiatives such as the HPVV program. Governmental health authorities may want to consider collaborating with the UAE media to develop a communication strategy to reduce the fears and misconceptions surrounding HPVV. Improved parental and adolescent knowledge on the HPVV may lead to increased acceptance and uptake in the UAE society.

Human Papillomavirus Vaccination Requirements in US Schools: Recommendations for Moving Forward

Safe and effective human papillomavirus (HPV) vaccines have been available and recommended for adolescents for a decade in the United States, yet vaccination rates remain suboptimal. School entry requirements have increased uptake of other vaccines for adolescents and made coverage more equitable. However, only 3 jurisdictions require HPV vaccine for school. We summarize the current status of HPV vaccine requirements and discuss the rationales for and against these policies. The rationales for requirements include HPV vaccine efficacy and safety, effectiveness of requirements for increasing vaccine uptake and making it more equitable, and use of requirements as "safety nets" and to achieve herd immunity. The rationales against requirements include low parental acceptance of HPV vaccine, the financial burden on educational systems and health departments, and the possibility for alternatives to increase vaccine uptake. Many challenges to HPV vaccine requirements are addressable, and we conclude with recommendations on how to approach these challenges.

Optimization and validation of ELISA immunoassay for the evaluation of in-vitro relative potency of a four-component human papillomavirus vaccine products

A sandwich-type ELISA was optimized and validated to determine the in-vitro relative potency of the four-component prophylactic Human papillomavirus (HPV) vaccine. The vaccine contains the non-infectious virus like particles (VLP) corresponding to HPV Types 6, 11, 16 and 18. A modification of the desorption step required to release the VLPs from the aluminum adjuvant was carried out. Samples were incubated with citrate buffer for two hours at 37 °C instead of overnight incubation at room temperature. Assay validation was then carried out according to ICH guidelines. The assay was linear over a concentration range of 0.30–2000.00 ng/mL for the four HPV types. The assay was accurate and precise with a LOD of 0.092, 0.081, 0.086 and 0.068 ng/mL for type 6, 11, 16 and 18 respectively. Results were also statistically compared to those obtained using the reported ELISA assay and no significant difference was noted. In contrary to the reported ELISA protocol, this optimized immunoassay was superior with respect to analysis time, without affecting the accuracy and precision (RSD < 5%). This assay has proven to be useful for evaluating the efficacy of the quadrivalent HPV vaccine and is applicable for quality control and batch release purposes.

Characterization of serum antibodies from women immunized with Gardasil: A study of HPV-18 infection of primary human keratinocytes

The prevalent human papillomaviruses (HPVs) infect human epithelial tissues. Infections by the mucosotropic HPV genotypes cause hyperproliferative ano-genital lesions. Persistent infections by high-risk (HR) HPVs such as HPV-16, HPV-18 and related types can progress to high grade intraepithelial neoplasias and cancers. Prophylactic HPV vaccines are based on DNA-free virus-like particles (VLPs) composed of the major capsid protein L1 of HPV-16, -18, -6 and -11 (Gardasil) or HPV-16 and -18 (Cervarix). Sera from vaccinated animals effectively prevent HPV pseudovirions to infect cell lines and mouse cervical epithelia. Both vaccines have proven to be highly protective in people. HPV pseudovirions are assembled in HEK293TT cells from matched L1 and L2 capsid proteins to encapsidate a reporter gene. Pseudovirions and genuine virions have structural differences and they infect cell lines or primary human keratinocytes (PHKs) with different efficiencies. In this study, we show that sera and isolated IgG from women immunized with Gardasil prevent authentic HPV-18 virions from infecting PHKs, whereas non-immune sera and purified IgG thereof are uniformly ineffective. Using early passage PHKs, neutralization is achieved only if immune sera are added within 2–4h of infection. We attribute the timing effect to a conformational change in HPV virions, thought to occur upon initial binding to heparan sulfate proteoglycans (HSPG) on the cell surface. This interpretation is consistent with the inability of immune IgG bound to or taken up by PHKs to neutralize the virus. Interestingly, the window of neutralization increases to 12–16h in slow growing, late passage PHKs, suggestive of altered cell surface molecules. In vivo, this window might be further lengthened by the time required to activate the normally quiescent basal cells to become susceptible to infection. Our observations help explain the high efficacy of HPV vaccines.

Analytical performance evaluation of Anyplex II HPV28 and Euroarray HPV for genotyping of cervical samples

Analytically accurate human papillomavirus (HPV) genotyping methods are required to assess the impact of HPV vaccination. The aim of this study was to evaluate the analytical performance of Anyplex II HPV28 (Seegene, Korea) and Euroarray HPV (Euroimmun, Germany) genotyping kits, for conducting a future HPV vaccine efficacy monitoring study in Luxembourg. A total number of 150 cervical swabs were collected from women with mean age 31.4 years. Agreements for detecting any HPV between Aptima/Anyplex (88.0%) and Aptima/Euroarray (90.7%) were similar. Agreement of Anyplex/EuroArray with Aptima was higher for Genotypes 16, 18 or 45 than for the other 11 HPVs. The average number of HPV genotypes detected per sample was similar with 2.6 and 2.5, for Anyplex and EuroArray, respectively. In conclusion, Anyplex and Euroarray showed high agreement in general and in particular for detecting genotypes contained in HPV vaccines.

Current global status & impact of human papillomavirus vaccination: Implications for India.

This review addresses the effectiveness and safety of human papillomavirus (HPV) vaccines, the current status of its introduction in the National Immunization Programmes (NIPs) and its relevance to India, which contributes a fifth of the global burden of cervical cancer. The vast literature on efficacy, acceptability and safety of HPV vaccination and its impact after population level introduction was reviewed and discussed. The efficacy of HPV vaccines in preventing high-grade precancerous lesions caused by vaccine-targeted HPV infections was 90 per cent or higher in HPV naïve women in randomized clinical trials. Two doses at 6 or 12 months apart are recommended for 9-14 yr old girls and three doses over six months to one year period for those aged above 15 yr. More than 80 countries or territories have introduced HPV vaccination in their NIPs, of which 33 are low- and middle-income countries (LMICs); in addition, 25 LMICs have introduced pilot programmes before a phased national expansion. Significant reductions in the frequency of HPV 16 and 18 infections, genital warts and cervical premalignant lesions in vaccinated cohorts and herd immunity in general populations have been reported from countries that introduced vaccination in NIPs as early as 2007. More than 280 million doses of HPV vaccines have been administered worldwide with the excellent safety profile with no serious adverse events linked to it. The high burden of cervical cancer and the high efficacy and safety of HPV vaccination justify its introduction in the Indian NIP at the earliest possibility to substantially reduce the cervical cancer burden in future.

HPV Knowledge, HPV Vaccination Intention, and Barriers on HPV Vaccination in Male Undergraduate Students of Health Department and Non-health Department

The aim of this study was to identify the level of Human papillomavirus (HPV) knowledge, intention of HPV vaccination, and barriers on HPV vaccination among male undergraduate students of Health department and Non-health department. Methods: A total of 149 male undergraduate students responded to self-administered questionnaires about their HPV knowledge, HPV vaccination intention, and their barriers on HPV vaccination. ANOVA, t-test and x2 test (Fisher``s exact test) were used for data analysis. Results: Mean score of HPV knowledge was 3.39±3.05, and there was significant difference between Health department (4.15±3.08) and Non-health department (2.58±2.82) in HPV knowledge (t=3.241, p=.001). There was no significant difference in HPV vaccination acceptance between the two groups. The barriers on HPV vaccination were ‘lack of information about HPV vaccine efficacy’ and ‘lack of information about HPV vaccination time and strategy’, and there were significant differences in barriers on HPV vaccination between the two groups. Conclusion: The knowledge on HPV was low, and HPV vaccination was hindered due to lack of information about HPV vaccine despite their intention to obtain HPV vaccine. HPV education to promote HPV vaccination should be targeted among male students.

Effect of Quadrivalent Human Papillomavirus Vaccination on Oral Squamous Cell Papillomas.

Cutaneous verruca vulgaris lesions (warts) and oral squamous cell papillomas are common lesions caused by human papillomavirus (HPV). Multiple reports have described cases of wart resolution following quadrivalent HPV vaccination. We report the case of a patient with chronic oral papillomas with resolution after quadrivalent HPV vaccination and perform a review of the literature. An immunocompetent man in his 60s presented with chronic verrucous papules on the lips, tongue, and buccal mucosa refractory to multiple excisions. Biopsy showed squamous cell papilloma, and DNA sequencing revealed HPV-32. He received the quadrivalent HPV vaccine resulting in clearance of all lesions after 3 months. We found 8 reported cases of disseminated, recurrent warts with resolution after quadrivalent HPV vaccination. Improvement was seen within 4 weeks of vaccination, and resolution after 3 to 8 months. We report the case of recurrent oral papillomas caused by HPV-32 with complete resolution after quadrivalent HPV vaccination and reviewed reports of resolution of recalcitrant and disseminated warts after vaccination. Production of cross-protective immunoglobulins and cytotoxic T cells is a possible mechanism. There remains a critical need for randomized clinical trials to assess efficacy of quadrivalent HPV vaccination for treatment of oral squamous papillomas and cutaneous verruca vulgaris.

Abstract B29: Improving the efficacy of dendritic cell-based human papillomavirus vaccines in mice using a natural lignin-carbohydrate complex and/or synthetic lignin-like polyphenol polymers

Abstract Immunization with dendritic cell (DC)-based vaccines is a promising vaccination strategy to provide an effective personalized immunotherapy against cancer and other diseases. However, the results of clinical cancer immunotherapy trials carried out using DC-based vaccines to date have shown only modest clinical outcomes. We have previously demonstrated that a polyphenylpropenoid-polysaccharide complex (PPC), a lignin-carbohydrate complex derived from the cones of Pinus sylvestris, induces in vitro the differentiation and maturation of human mononuclear cell-derived DCs (Bradley et al., Int Immunopharmacol 2003;3) and murine bone marrow-derived DCs (BMDCs) (An et al., Anticancer Res 2010;30). Furthermore, oral administration of PPC enhanced a DC vaccine-induced melanoma antigen-specific CD8+ T-cell response (Burrows et al., BMC Complement Altern Med 2009;9) and the proliferative phase of a primary T cell response (Bradley et al., BMC Complement Altern Med 2014;14). In the present study, using a human papillomavirus (HPV)-induced mouse tumor model, we investigated whether ex vivo treatment of BMDCs with the synthetic lignin-like polyphenol polymers poly-caffeic acid (pCA) and poly-coumaric acid (pCoA), as well as PPC, improves the efficacy of DC-based vaccines. Polymerization of the phenylpropenoic acids caffeic acid (CA) and poly-coumaric acid (CoA) was performed by horseradish peroxidase/hydrogen peroxide-mediated enzymatic reactions. BMDCs were prepared by culturing murine bone marrow cells in the presence of GM-CSF for 8-10 days. These BMDCs were pulsed with synthetic tumor antigen peptides HPV16 E743-62 or HPV16 E743-77 that contain both a cytotoxic T lymphocyte (CTL) and a helper T cell epitope. Peptide-pulsed DCs were treated further ex vivo with synthetic polyphenol polymers or PPC and then injected twice into C57BL/6 mice. In addition, splenocytes obtained from immunized mice were restimulated with HPV16 E749-57 peptide (E7 CTL epitope) for 5 days. Tumor antigen-specific CD8+ T cell responses were assessed by HPV16 E749-57/H-2Db pentamer staining. We observed that immunization with PPC-treated HPV16 E743-77 peptide-loaded BMDCs significantly enhanced the induction of pentamer-positive CD8 positive cells in splenocytes (2- to 3-fold increase). Moreover, ex vivo restimulation with E7 CTL epitope peptide dramatically increased the number of pentamer-positive CD8 positive cells in splenocytes obtained from mice immunized with PPC-treated, peptide-loaded DCs (6- to 7-fold increase) when compared to splenocytes from mice immunized with PPC-nontreated, peptide-loaded DCs. Experiments using pCA and pCoA are in progress. We conclude that 1) ex vivo treatment with the natural PPC complex significantly potentiates the in vivo efficacy of DC-based HPV vaccines and 2) tumor antigen-specific CD8+ T cells are significantly expanded ex vivo by restimulating splenocytes from mice primed in vivo with PPC-treated, peptide-loaded BMDCs. In addition, our preliminary studies show that PPC, pCA and pCoA significantly increase the expression levels of CD8α, XCR1 and/or CLEC9A on murine BMDCs that have been demonstrated to be essential for the induction of CTL responses. Our approaches will provide innovative strategies for the design of more effective DC-based vaccines and adaptive T-cell therapies for the treatment of patients with cancer and other immune disorders. Citation Format: Soichi Haraguchi, Tina Pastoor, William Guy Bradley, Akiko Tanaka. Improving the efficacy of dendritic cell-based human papillomavirus vaccines in mice using a natural lignin-carbohydrate complex and/or synthetic lignin-like polyphenol polymers. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B29.

Immunogenicity and safety of Gardasil among mid-adult aged men (27–45 years)—The MAM Study

BackgroundThe quadrivalent (types 6/11/16/18) human papillomavirus (HPV) vaccine, Gardasil, has demonstrated efficacy against persistent HPV infection and associated anogenital disease in males. The goal of this Phase II trial was to establish the immunogenicity and safety of Gardasil among mid-adult men ages 27–45 years. MethodsOne hundred and fifty men from Tampa, FL, US, and Cuernavaca, Mexico who met eligibility criteria (male, 27–45 years old, completed four years of follow-up in the HPV Infection in Men (HIM) natural history study) were enrolled. Subjects completed four visits over seven months, with Gardasil administered at Day 1 and Months 2 and 6. Sera were collected at Day 1 (pre-vaccination) and Month 7 (one month post-dose three). Anti-HPV6, 11, 16, and 18 IgG levels were determined by competitive Luminex immunoassay. Findings100% of men seroconverted to each of the four HPV vaccine components, and the vaccine was generally well-tolerated. Antibody responses to vaccine did not differ by age group or sexual orientation, regardless of HPV type, and were significantly higher at Month 7 among men who entered the trial seropositive for HPV 6 or 11. InterpretationThe immune response to HPV vaccination in men ages 27–45 was comparable to that observed in younger men, in whom clinical efficacy was demonstrated. Further trials to assess the efficacy of HPV vaccines to prevent persistent HPV infections in mid-adult men are needed. FundingMerck & Co. Inc. was the main sponsor of this trial (IISP39256) and provided the study product.

English

The interaction between human papilloma virus (HPV) and human immunodeficiency virus (HIV), both sexually transmitted infections appears to be related to the alteration in cell-mediated immunity in HIV infected persons. Linkage studies of HIV/AIDs and cancer registries have indicated a 2 to 22 fold increase in cervical cancer in HIV positive women compared to HIV negative women. Data on the prevalence of HPV types in invasive cervical carcinoma (ICC) suggest that the proportion of infection with types HPV16/18 (responsible for over 70% of all cervical cancers) is similar in HIV negative and HIV positive women. The biological interaction between HIV and HPV needs further elucidation, although there is some evidence that the presence of HPV infection may be associated with increased HIV transmission. Adolescents perinatally infected by HIV are known to have higher rates of HPV infection and also have been shown to seroconvert in response to HPV vaccination with the quadrivalent vaccine, albeit to lower titers than HIV negative individuals. Anal cancer incidence is greatly increased in HIV positive individuals, particularly in HIV positive men who have sex with men. Screening for anal cancer precursors is feasible and effective; however, the impact on reduction of anal cancer remains to be demonstrated. There are ongoing studies on the safety, immunogenicity, and efficacy of current HPV vaccines in HIV positive individuals and mature data are awaited. &nbsp; Key words: human immunodeficiency virus (HIV), human papilloma virus (HPV), cervicovaginal cancer.

The impact of HPV vaccination on future cervical screening: a simulation study of two birth cohorts in Denmark

ObjectivesTo explore the interplay between primary and secondary prevention of cervical cancer by estimating future screening outcomes in women offered human papillomavirus (HPV) vaccination when they were sexually naïve.DesignEstimation of...

Vaccines against human papillomavirus in low and middle income countries: a review of safety, immunogenicity and efficacy.

Currently, there is limited data on the immunogenicity and efficacy of human papillomavirus vaccines in Low and Middle income countries (LMIC). The review aims to summarize the current status from published HPV vaccine safety, immunogenicity and efficacy studies in low and middle income countries (LMIC). Electronic databases (PubMed/MEDLINE and HINARI) were searched for peer reviewed English language articles on HPV vaccination in LMIC that have so far been published from 1st January 2006 up to 30th January 2015. Eligible studies were included if they had used the bivalent (bHPV) or quadrivalent HPV (qHPV) vaccines in a LMIC and investigated safety, immunogenicity and/or efficacy. The main findings were extracted and summarized. A total of fourteen HPV vaccine studies assessing safety, Immunogenicity and efficacy of the bivalent or quadrivalent vaccines in LMIC were included. There are only ten published clinical trials where a LMIC has participated. There was no published study so far that assessed efficacy of the HPV vaccines in Sub-Saharan Africa. From these studies, vaccine induced immune response was comparable to that from results of HICs for all age groups. Studies assessing HPV vaccine efficacy of the bivalent or quadrivalent vaccine within LMIC were largely missing. Only three studies were found where a LMIC was part of a multi center clinical trial. In all the studies, there were no vaccine related serious adverse events. The findings from the only study that investigated less than three doses of the bivalent HPV-16/18 vaccine suggest that even with less than three doses, antibody levels were still comparable with older women where efficacy has been proven. The few studies from LMIC in this review had comparable safety, Immunogenicity and efficacy profiles like in HIC. Overall, the LMIC of Africa where immune compromising/modulating situations are prevalent, there is need for long term immunogenicity as well as surveillance studies for long term clinical effectiveness after two and three dose regimens.

Understanding Public Perceptions of the HPV Vaccination Based on Online Comments to Canadian News Articles.

BackgroundGiven the variation in human papillomavirus (HPV) vaccine coverage across Canada, and debate regarding delivery of HPV vaccines in Catholic schools, we studied online comments on Canadian news websites to understand public perceptions of HPV and HPV vaccine.MethodsWe searched English- and French-language Canadian news websites for 2012 articles that contained the terms “HPV” or “human papillomavirus.” Articles about HPV vaccinations that contained at least one comment were included. Two researchers independently coded comments, analyzing them for emerging themes.ResultsWe identified 3073 comments from 1198 individuals in response to 71 news articles; 630 (52.6%) individuals expressed positive sentiments about HPV vaccination (2.5 comments/individual), 404 (33.7%) were negative (3.0 comments/individual), 34 (2.8%) were mixed (1.5 comments/individual) and 130 (10.8%) were neutral (1.6 comments/individual). Vaccine-supportive commenters believed the vaccine is safe and effective. Common themes in negative comments included concerns regarding HPV vaccine safety and efficacy, distrust of pharmaceutical companies and government, and belief that school-age children are too young for HPV vaccine. Many comments focused on whether the Catholic Church has the right to inform health policy for students, and discussion often evolved into debates regarding HPV and sexual behaviour. We noted that many individuals doubted the credibility of vaccine safety information.ConclusionThe majority of commenters do not appear to be against HPV vaccination, but public health messaging that focuses on both the vaccine’s safety profile, and its use as a means to prevent cancer rather than sexually transmitted HPV infection may facilitate its acceptance.

Design of a large outcome trial for a multivalent human papillomavirus L1 virus-like particle vaccine

BackgroundThe 9-valent human papillomavirus (HPV) (9vHPV) vaccine targets the four HPV types (6/11/16/18) covered by the licensed quadrivalent HPV (qHPV) vaccine and five additional types (31/33/45/52/58). A large outcome trial of 9vHPV vaccine was conducted. MethodsAn active control (qHPV vaccine) was used because a placebo is not ethically acceptable. Since qHPV vaccine is (and 9vHPV vaccine was anticipated to be) highly efficacious against HPV 6/11/16/18, low incidence of HPV 6/11/16/18-associated disease was expected. Consequently, an efficacy comparison of 9vHPV versus qHPV vaccine for HPV 6/11/16/18 would have been prohibitively large in size. Moreover, no minimum antibody level predicting protection against infection or disease is defined for HPV vaccination. As an alternative approach, the two vaccines were compared using immunogenicity bridging for HPV 6/11/16/18 and clinical efficacy for HPV 31/33/45/52/58. ResultsThe two co-primary objectives were to demonstrate: (1) non-inferior anti-HPV 6/11/16/18 antibody response; and (2) superior efficacy in HPV 31/33/45/52/58-related clinical outcome, for 9vHPV vaccine versus qHPV vaccine. For HPV 6/11/16/18, supportive analyses included a non-inferiority assessment of the percent risk reduction (compared to historical placebo) for 9vHPV versus qHPV vaccine. ConclusionsA Phase III study of 9vHPV vaccine was successfully implemented. Experience from this study design may be applicable when developing a multivalent vaccine covering the same serotypes as an existing vaccine plus additional serotypes and there is no immune correlate of protection. Also, this study established that efficacy of a new HPV vaccine may be demonstrated using immunogenicity endpoints, which may open new options in HPV vaccine development.

Quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (Gardasil®): a guide to its use in the EU

The quadrivalent human papillomavirus (HPV) [types 6, 11, 16, 18] recombinant vaccine (Gardasil®) is approved in the EU for use from the age of 9 years for the prevention of premalignant anogenital lesions and cervical and anal cancers, and genital warts caused by the vaccine HPV types. In clinical trials, quadrivalent HPV vaccine provided high-level protection against infection or disease caused by the vaccine HPV types in females aged 15–45 years who are negative for the vaccine types. Quadrivalent HPV vaccine also provided high-level protection against genital warts, anogenital precancerous lesions and persistent infection caused by the vaccine HPV types in males aged 16–26 years who are negative for the vaccine types in clinical trials. In addition, bridging studies show robust immune responses in young girls and boys aged from 9 years, allowing extrapolation of the efficacy results seen in clinical trials and approval of quadrivalent HPV vaccine for use from the age of 9 years. The prophylactic efficacy of HPV vaccination was also shown in real-world settings. Quadrivalent HPV vaccine is generally well tolerated. Thus, quadrivalent HPV vaccine offers an effective means, in combination with screening programmes, to substantially reduce the burden of cervical cancer. In addition, it is effective in reducing the burden of HPV-related anogenital disease, including anal cancers and genital warts, in females and males.