HPV Vaccination of Boys in Primary Care Practices

PubMed Central

Allison, Mandy A.; Dunne, Eileen F.; Markowitz, Lauri E.; O’Leary, Sean T.; Crane, Lori A.; Hurley, Laura P.; Stokley, Shannon; Babbel, Christine I.; Brtnikova, Michaela; Beaty, Brenda L.; Kempe, Allison

2018-01-01

OBJECTIVE In October 2011, the Advisory Committee on Immunization Practices (ACIP) recommended the quadrivalent human papillomavirus vaccine (HPV4) for the routine immunization schedule for 11- to 12-year-old boys. Before October 2011, HPV4 was permissively recommended for boys. We conducted a study in 2010 to provide data that could guide efforts to implement routine HPV4 immunization in boys. Our objectives were to describe primary care physicians’: 1) knowledge and attitudes about human papillomavirus (HPV)-related disease and HPV4, 2) recommendation and administration practices regarding HPV vaccine in boys compared to girls, 3) perceived barriers to HPV4 administration in boys, and 4) personal and practice characteristics associated with recommending HPV4 to boys. METHODS We conducted a mail and Internet survey in a nationally representative sample of pediatricians and family medicine physicians from July 2010 to September 2010. RESULTS The response rate was 72% (609 of 842). Most physicians thought that the routine use of HPV4 in boys was justified. Although it was permissively recommended, 33% recommended HPV4 to 11- to 12-year-old boys and recommended it more strongly to older male adolescents. The most common barriers to HPV4 administration were related to vaccine financing. Physicians who reported recommending HPV4 for 11- to 12-year-old boys were more likely to be from urban locations, perceive that HPV4 is efficacious, perceive that HPV-related disease is severe, and routinely discuss sexual health with 11- to 12-year-olds. CONCLUSIONS Although most physicians support HPV4 for boys, physician education and evidence-based tools are needed to improve implementation of a vaccination program for males in primary care settings. PMID:24011749

An analysis of the Human Papilloma Virus vaccine debate on MySpace blogs.

PubMed

Keelan, Jennifer; Pavri, Vera; Balakrishnan, Ravin; Wilson, Kumanan

2010-02-10

The roll out of HPV immunization programs across the United States was hindered by controversy. We tracked the debate in the United States through MySpace, then the most popular social networking site, in order to better understand the public's reaction to the vaccine. We searched MySpace for all blog discourse related to HPV immunization. We analyzed each blog according to the overall portrayal of HPV immunization, identified the characteristics of the bloggers, and developed a content analysis to categorize the types of supporting arguments made. 303 blogs met our inclusion criteria. 157 (52%) of the blogs were classified as positive, 129 (43%) as negative, and 17 (6%) were ambivalent toward HPV immunization. Positive blogs generally argued that HPV infection was effective and there were no reasonable alternatives to immunizing. Negative blogs focused on the risks of immunizing and relied heavily on vaccine-critical publications to support their viewpoint. Of the blogs where gender could be identified, 75 (25%) were posted by men and 214 (71%) by women. 60% of blogs posted by men were explicitly critical about HPV immunization versus 36% of women's blogs. Male bloggers also had larger networks of friends. We describe a novel and promising approach to the surveillance of public opinions and attitudes toward immunization. In our analysis, men were far more likely to hold negative views about HPV immunization than women and disseminate negative messages through larger social networks. Blog analysis is a useful tool for Public health officials to profile vaccine criticism and to design appropriate educational information tailored to respond to alternative media/alternative information actively disseminated via social media tools. Public health officials should examine mechanisms by which to leverage this media to better communicate their message through existing networks and to engage in on-going dialogue with the public. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Knowledge, Awareness and Attitude on HPV, HPV Vaccine and Cervical Cancer among the College Students in India

PubMed Central

Rashid, Shazia; Labani, Satyanarayana; Das, Bhudev C.

2016-01-01

Background Infection of specific high risk Human papillomaviruses (HPVs) is known to cause cervical cancer and two prophylactic vaccines have been developed against two major high risk HPV types 16 and 18 for prevention of cervical cancer. Because of societal, religious and ethical issues associated with the vaccination of adolescent girls in India together with lack of awareness about HPV and HPV vaccines, no successful HPV immunization program has been employed in India. Objective To determine knowledge, awareness and attitude of college students on HPV, HPV vaccine and cervical cancer. Method A questionnaire-based survey was conducted in a total of 1580 undergraduate students between the age group 16–26 years comprising 684 girls and 876 boys. Results Out of a total of 1580 students, girls had more knowledge about cervical cancer (82.45%, p<0.001), HPV (45.61%, p<0.001) and HPV vaccines (44%, p<0.001) when compared to those in boys. However, knowledge about the types of HPV and vaccines was poor. Interestingly, students from biology-major had more knowledge and awareness about cervical cancer (81.89%, p<0.001) and HPV (46.58%, <0.001) when compared to non-biology students. Girls from both biology and non-biology group had higher awareness compared to boys. Analysis of odds ratio (ORs) along with 95% CI showed older girls with 1.2 to 3 fold (p<0.05) higher knowledge than boys. All students agreed that girls should get vaccinated against HPV (p<0.001). Conclusion It is suggested that there is a need for educational intervention and awareness campaigns to augment HPV immunization program for control of cervical cancer in India. PMID:27861611

Knowledge, Awareness and Attitude on HPV, HPV Vaccine and Cervical Cancer among the College Students in India.

PubMed

Rashid, Shazia; Labani, Satyanarayana; Das, Bhudev C

2016-01-01

Infection of specific high risk Human papillomaviruses (HPVs) is known to cause cervical cancer and two prophylactic vaccines have been developed against two major high risk HPV types 16 and 18 for prevention of cervical cancer. Because of societal, religious and ethical issues associated with the vaccination of adolescent girls in India together with lack of awareness about HPV and HPV vaccines, no successful HPV immunization program has been employed in India. To determine knowledge, awareness and attitude of college students on HPV, HPV vaccine and cervical cancer. A questionnaire-based survey was conducted in a total of 1580 undergraduate students between the age group 16-26 years comprising 684 girls and 876 boys. Out of a total of 1580 students, girls had more knowledge about cervical cancer (82.45%, p<0.001), HPV (45.61%, p<0.001) and HPV vaccines (44%, p<0.001) when compared to those in boys. However, knowledge about the types of HPV and vaccines was poor. Interestingly, students from biology-major had more knowledge and awareness about cervical cancer (81.89%, p<0.001) and HPV (46.58%, <0.001) when compared to non-biology students. Girls from both biology and non-biology group had higher awareness compared to boys. Analysis of odds ratio (ORs) along with 95% CI showed older girls with 1.2 to 3 fold (p<0.05) higher knowledge than boys. All students agreed that girls should get vaccinated against HPV (p<0.001). It is suggested that there is a need for educational intervention and awareness campaigns to augment HPV immunization program for control of cervical cancer in India.

Costs of delivering human papillomavirus vaccination to schoolgirls in Mwanza Region, Tanzania

PubMed Central

2012-01-01

Background Cervical cancer is the leading cause of female cancer-related deaths in Tanzania. Vaccination against human papillomavirus (HPV) offers a new opportunity to control this disease. This study aimed to estimate the costs of a school-based HPV vaccination project in three districts in Mwanza Region (NCT ID: NCT01173900), Tanzania and to model incremental scaled-up costs of a regional vaccination program. Methods We first conducted a top-down cost analysis of the vaccination project, comparing observed costs of age-based (girls born in 1998) and class-based (class 6) vaccine delivery in a total of 134 primary schools. Based on the observed project costs, we then modeled incremental costs of a scaled-up vaccination program for Mwanza Region from the perspective of the Tanzanian government, assuming that HPV vaccines would be delivered through the Expanded Programme on Immunization (EPI). Results Total economic project costs for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about US$349,400 (including a vaccine price of US$5 per dose). Costs per fully-immunized girl were lower for class-based delivery than for age-based delivery. Incremental economic scaled-up costs for class-based vaccination of 50,290 girls in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose. Excluding vaccine costs, vaccine could be delivered at an incremental economic cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled-up costs, excluding costs of the vaccine and salaries of existing staff were estimated at US$1.73 per dose. Conclusions Project costs of class-based vaccination were found to be below those of age-based vaccination because of more eligible girls being identified and higher vaccine uptake. We estimate that vaccine can be delivered at costs that would make HPV vaccination a very cost-effective intervention. Potentially, integrating HPV vaccine delivery with cost-effective school-based health interventions and a reduction of vaccine price below US$5 per dose would further reduce the costs per fully HPV-immunized girl. PMID:23148516

Costs of delivering human papillomavirus vaccination to schoolgirls in Mwanza Region, Tanzania.

PubMed

Quentin, Wilm; Terris-Prestholt, Fern; Changalucha, John; Soteli, Selephina; Edmunds, W John; Hutubessy, Raymond; Ross, David A; Kapiga, Saidi; Hayes, Richard; Watson-Jones, Deborah

2012-11-13

Cervical cancer is the leading cause of female cancer-related deaths in Tanzania. Vaccination against human papillomavirus (HPV) offers a new opportunity to control this disease. This study aimed to estimate the costs of a school-based HPV vaccination project in three districts in Mwanza Region (NCT ID: NCT01173900), Tanzania and to model incremental scaled-up costs of a regional vaccination program. We first conducted a top-down cost analysis of the vaccination project, comparing observed costs of age-based (girls born in 1998) and class-based (class 6) vaccine delivery in a total of 134 primary schools. Based on the observed project costs, we then modeled incremental costs of a scaled-up vaccination program for Mwanza Region from the perspective of the Tanzanian government, assuming that HPV vaccines would be delivered through the Expanded Programme on Immunization (EPI). Total economic project costs for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about US$349,400 (including a vaccine price of US$5 per dose). Costs per fully-immunized girl were lower for class-based delivery than for age-based delivery. Incremental economic scaled-up costs for class-based vaccination of 50,290 girls in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose. Excluding vaccine costs, vaccine could be delivered at an incremental economic cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled-up costs, excluding costs of the vaccine and salaries of existing staff were estimated at US$1.73 per dose. Project costs of class-based vaccination were found to be below those of age-based vaccination because of more eligible girls being identified and higher vaccine uptake. We estimate that vaccine can be delivered at costs that would make HPV vaccination a very cost-effective intervention. Potentially, integrating HPV vaccine delivery with cost-effective school-based health interventions and a reduction of vaccine price below US$5 per dose would further reduce the costs per fully HPV-immunized girl.

Evasion of host immune defenses by human papillomavirus.

PubMed

Westrich, Joseph A; Warren, Cody J; Pyeon, Dohun

2017-03-02

A majority of human papillomavirus (HPV) infections are asymptomatic and self-resolving in the absence of medical interventions. Various innate and adaptive immune responses, as well as physical barriers, have been implicated in controlling early HPV infections. However, if HPV overcomes these host immune defenses and establishes persistence in basal keratinocytes, it becomes very difficult for the host to eliminate the infection. The HPV oncoproteins E5, E6, and E7 are important in regulating host immune responses. These oncoproteins dysregulate gene expression, protein-protein interactions, posttranslational modifications, and cellular trafficking of critical host immune modulators. In addition to the HPV oncoproteins, sequence variation and dinucleotide depletion in papillomavirus genomes has been suggested as an alternative strategy for evasion of host immune defenses. Since anti-HPV host immune responses are also considered to be important for antitumor immunity, immune dysregulation by HPV during virus persistence may contribute to immune suppression essential for HPV-associated cancer progression. Here, we discuss cellular pathways dysregulated by HPV that allow the virus to evade various host immune defenses. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Evasion of Host Immune Defenses by Human Papillomavirus

PubMed Central

Westrich, Joseph A.; Warren, Cody J.; Pyeon, Dohun

2016-01-01

A majority of human papillomavirus (HPV) infections are asymptomatic and self-resolving in the absence of medical interventions. Various innate and adaptive immune responses, as well as physical barriers, have been implicated in controlling early HPV infections. However, if HPV overcomes these host immune defenses and establishes persistence in basal keratinocytes, it becomes very difficult for the host to eliminate the infection. The HPV oncoproteins E5, E6, and E7 are important in regulating host immune responses. These oncoproteins dysregulate gene expression, protein-protein interactions, posttranslational modifications, and cellular trafficking of critical host immune modulators. In addition to the HPV oncoproteins, sequence variation and dinucleotide depletion in papillomavirus genomes has been suggested as an alternative strategy for evasion of host immune defenses. Since anti-HPV host immune responses are also considered to be important for antitumor immunity, immune dysregulation by HPV during virus persistence may contribute to immune suppression essential for HPV-associated cancer progression. Here, we discuss cellular pathways dysregulated by HPV that allow the virus to evade various host immune defenses. PMID:27890631

[Human papillomavirus vaccine. Statement of the Advisory Committee of Immunizations on behalf of the Chilean Infectious Diseases Society. September 2008].

PubMed

Abarca, Katia; Valenzuela, M Teresa; Vergara, Rodrigo; Luchsinger, Vivian; Muñoz, Alma; Jiménez de la J, Jorge; Ripoll, Erna; O'Ryan, Miguel

2008-11-01

This article briefly reviews the epidemiology of human papillomavirus (HPV) infection and associated diseases globally and in Chile, and the scientific information of the licensed HPV vaccines: Gardasil and Cervari. Considering the available information, the Advisory Committee on Immunizations of the Chilean Society of Infectious Diseases recommends vaccination of teenage girls, ideally before initiating sexual activity, i.e., approximately at the age of 12 to 13 years and vaccination of women of any age if they have not started sexual activity. If women are vaccinated after initiating sexual activity, they should be informed of the lower efficacy of immunization if HPV infection has occurred. Education on responsible sexuality and sexually transmitted diseases should be maintained as a priority. Vaccination should be highly considered for inclusion in the National Immunization Program.

Does the success of a school-based HPV vaccine programme depend on teachers' knowledge and religion? -- A survey in a multicultural society.

PubMed

Ling, Woo Yin; Razali, Sharina Mohd; Ren, Chong Kuoh; Omar, Siti Zawiah

2012-01-01

Organized introduction of prophylactic human papillomavirus (HPV) vaccination can reduce the burden of cervical cancer in developing countries. One of the most effective ways is through a national school-based program. Information on teachers is therefore important since this group may have a disproportionate influence in the success of any implementation. To assess teachers' knowledge and perception of HPV, cervical cancer and HPV vaccine prior to commencing a school-based HPV vaccination program in a multiethnic, predominantly Muslim country. Factors associated with acceptability of the vaccine were identified. A bilingual questionnaire was applied to 1,500 secondary school teachers from 20 urban schools in Malaysia. Data collected were analyzed using SPSS version 17. 1,166 questionnaires were returned. From this group, 46.1% had never heard of HPV while 50.9% had never had a pap smear. However, 73.8% have heard of the HPV vaccine with 75% agreeing to have it. 96% considered themselves religious with 79.8% agreeing to have the vaccine. A national school-based HPV immunization program can be implemented effectively in a multiethnic, cultural and religious country despite limited knowledge of HPV-related pathology among teachers. In addition, the perception that religion has a negative influence on such a program is unwarranted.

“Saving lives”: Adapting and adopting Human Papilloma Virus (HPV) vaccination in Austria

PubMed Central

Paul, Katharina T.

2016-01-01

Vaccination against the sexually transmitted Human Papilloma Virus (HPV), a necessary agent for the development of cervical cancer, has triggered much debate. In Austria, HPV policy turned from “lagging behind” in 2008 into “Europe's frontrunner” by 2013. Drawing on qualitative research, the article shows how the vaccine was transformed and made “good enough” over the course of five years. By means of tinkering and shifting storylines, policy officials and experts disassociated the vaccine from gender, vaccine manufacturers, and youth sexuality. Ultimately, the HPV vaccine functioned to strengthen the national immunization program. To this end, preventing an effective problematization of the extant screening program was essential. PMID:26921834

Estimates and determinants of HPV non-vaccination and vaccine refusal in girls 12 to 14 y of age in Canada: Results from the Childhood National Immunization Coverage Survey, 2013

PubMed Central

Gilbert, Nicolas L.; Gilmour, Heather; Dubé, Ève; Wilson, Sarah E.; Laroche, Julie

2016-01-01

ABSTRACT Since the introduction of HPV vaccination programs in Canada in 2007, coverage has been below public health goals in many provinces and territories. This analysis investigated the determinants of HPV non-vaccination and vaccine refusal. Data from the Childhood National Immunization Coverage Survey (CNICS) 2013 were used to estimate the prevalence of HPV non-vaccination and parental vaccine refusal in girls aged 12–14 years, for Canada and the provinces and territories. Multivariate logistic regression was used to examine factors associated with non-vaccination and vaccine refusal, after adjusting for potential confounders. An estimated 27.7% of 12–14 y old girls had not been vaccinated against HPV, and 14.4% of parents reported refusing the vaccine. The magnitude of non-vaccination and vaccine refusal varied by province or territory and also by responding parent's country of birth. In addition, higher education was associated with a higher risk of refusal of the HPV vaccine. Rates of HPV non-vaccination and of refusal of the HPV vaccine differ and are influenced by different variables. These findings warrant further investigation. PMID:26942572

Cellular immune responses to HPV-18, -31, and -53 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinto, Ligia A.; Viscidi, Raphael; Harro, Clayton D.

Human papillomavirus-like particles (HPV VLP) are candidate vaccines that have shown to be efficacious in reducing infection and inducing robust antiviral immunity. Neutralizing antibodies generated by vaccination are largely type-specific, but little is known about the type-specificity of cellular immune responses to VLP vaccination. To determine whether vaccination with HPV-16 L1VLP induces cellular immunity to heterologous HPV types (HPV-18, HPV-31, and HPV-53), we examined proliferative and cytokine responses in vaccine (n = 11) and placebo (n = 5) recipients. Increased proliferative and cytokine responses to heterologous types were observed postvaccination in some individuals. The proportion of women responding to heterologousmore » types postvaccination (36%-55%) was lower than that observed in response to HPV-16 (73%). Response to HPV-16 VLP predicted response to other types. The strongest correlations in response were observed between HPV-16 and HPV-31, consistent with their phylogenetic relatedness. In summary, PBMC from HPV-16 VLP vaccine recipients can respond to L1VLP from heterologous HPV types, suggesting the presence of conserved T cell epitopes.« less

Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles

PubMed Central

Kines, Rhonda C.; Zarnitsyn, Vladimir; Johnson, Teresa R.; Pang, Yuk-Ying S.; Corbett, Kizzmekia S.; Nicewonger, John D.; Gangopadhyay, Anu; Chen, Man; Liu, Jie; Prausnitz, Mark R.; Schiller, John T.; Graham, Barney S.

2015-01-01

Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation. PMID:25785935

Vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles.

PubMed

Kines, Rhonda C; Zarnitsyn, Vladimir; Johnson, Teresa R; Pang, Yuk-Ying S; Corbett, Kizzmekia S; Nicewonger, John D; Gangopadhyay, Anu; Chen, Man; Liu, Jie; Prausnitz, Mark R; Schiller, John T; Graham, Barney S

2015-01-01

Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.

"Saving lives": Adapting and adopting Human Papilloma Virus (HPV) vaccination in Austria.

PubMed

Paul, Katharina T

2016-03-01

Vaccination against the sexually transmitted Human Papilloma Virus (HPV), a necessary agent for the development of cervical cancer, has triggered much debate. In Austria, HPV policy turned from "lagging behind" in 2008 into "Europe's frontrunner" by 2013. Drawing on qualitative research, the article shows how the vaccine was transformed and made "good enough" over the course of five years. By means of tinkering and shifting storylines, policy officials and experts disassociated the vaccine from gender, vaccine manufacturers, and youth sexuality. Ultimately, the HPV vaccine functioned to strengthen the national immunization program. To this end, preventing an effective problematization of the extant screening program was essential. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

hrHPV E5 oncoprotein: immune evasion and related immunotherapies.

PubMed

de Freitas, Antonio Carlos; de Oliveira, Talita Helena Araújo; Barros, Marconi Rego; Venuti, Aldo

2017-05-25

The immune response is a key factor in the fight against HPV infection and related cancers, and thus, HPV is able to promote immune evasion through the expression of oncogenes. In particular, the E5 oncogene is responsible for modulation of several immune mechanisms, including antigen presentation and inflammatory pathways. Moreover, E5 was suggested as a promising therapeutic target, since there is still no effective medical therapy for the treatment of HPV-related pre-neoplasia and cancer. Indeed, several studies have shown good prospective for E5 immunotherapy, suggesting that it could be applied for the treatment of pre-cancerous lesions. Thus, insofar as the majority of cervical, oropharyngeal and anal cancers are caused by high-risk HPV (hrHPV), mainly by HPV16, the aim of this review is to discuss the immune pathways interfered by E5 oncoprotein of hrHPV highlighting the various aspects of the potential immunotherapeutic approaches.

Immunological network analysis in HPV associated head and neck squamous cancer and implications for disease prognosis.

PubMed

Chen, Xiaohang; Yan, Bingqing; Lou, Huihuang; Shen, Zhenji; Tong, Fangjia; Zhai, Aixia; Wei, Lanlan; Zhang, Fengmin

2018-04-01

Human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) exhibits a better prognosis than HPV-negative (HPV-) HNSCC. This difference may in part be due to enhanced immune activation in the HPV+ HNSCC tumor microenvironment. To characterize differences in immune activation between HPV+ and HPV- HNSCC tumors, we identified and annotated differentially expressed genes based upon mRNA expression data from The Cancer Genome Atlas (TCGA). Immune network between immune cells and cytokines was constructed by using single sample Gene Set Enrichment Analysis and conditional mutual information. Multivariate Cox regression analysis was used to determine the prognostic value of immune microenvironment characterization. A total of 1673 differentially expressed genes were functionally annotated. We found that genes upregulated in HPV+ HNSCC are enriched in immune-associated processes. And the up-regulated gene sets were validated by Gene Set Enrichment Analysis. The microenvironment of HPV+ HNSCC exhibited greater numbers of infiltrating B and T cells and fewer neutrophils than HPV- HNSCC. These findings were validated by two independent datasets in the Gene Expression Omnibus (GEO) database. Further analyses of T cell subtypes revealed that cytotoxic T cell subtypes predominated in HPV+ HNSCC. In addition, the ratio of M1/M2 macrophages was much higher in HPV+ HNSCC. The infiltration of these immune cells was correlated with differentially expressed cytokine-associated genes. Enhanced infiltration of B cells and CD8+ T cells were identified as independent protective factors, while high neutrophil infiltration was a risk enhancing factor for HPV+ HNSCC patients. A schematic model of immunological network was established for HPV+ HNSCC to summarize our findings. Copyright © 2018 Elsevier Ltd. All rights reserved.

Impact of Coverage-Dependent Marginal Costs on Optimal HPV Vaccination Strategies

PubMed Central

Ryser, Marc D.; McGoff, Kevin; Herzog, David P.; Sivakoff, David J.; Myers, Evan R.

2015-01-01

The effectiveness of vaccinating males against the human papillomavirus (HPV) remains a controversial subject. Many existing studies conclude that increasing female coverage is more effective than diverting resources into male vaccination. Recently, several empirical studies on HPV immunization have been published, providing evidence of the fact that marginal vaccination costs increase with coverage. In this study, we use a stochastic agent-based modeling framework to revisit the male vaccination debate in light of these new findings. Within this framework, we assess the impact of coverage-dependent marginal costs of vaccine distribution on optimal immunization strategies against HPV. Focusing on the two scenarios of ongoing and new vaccination programs, we analyze different resource allocation policies and their effects on overall disease burden. Our results suggest that if the costs associated with vaccinating males are relatively close to those associated with vaccinating females, then coverage-dependent, increasing marginal costs may favor vaccination strategies that entail immunization of both genders. In particular, this study emphasizes the necessity for further empirical research on the nature of coverage-dependent vaccination costs. PMID:25979280

Immunobiology of HPV and HPV vaccines.

PubMed

Stanley, Margaret

2008-05-01

Genital human papillomavirus (HPV) infection with both low- and high-risk types is common, but most infections resolve as a result of a cell-mediated immune response. Failure to induce an effective immune response is related to inefficient activation of innate immunity and ineffective priming of the adaptive immune response; this defective immune response facilitates viral persistence, a key feature of high-risk HPV infection. This milieu becomes operationally HPV antigen tolerant, and the host's defenses become irrevocably compromised. HPV antigen-specific effector cells are poorly recruited to the infected focus and their activity is downregulated; neoplastic HPV containing cervical keratinocytes expressing high levels of E6 and E7 oncoproteins are not killed in this immunosuppressive, tolerant milieu, and progression to high-grade disease and cancer can result. Highly efficacious prophylactic HPV L1 virus-like particle (VLP) vaccines circumvent viral epithelial evasion strategies since they are delivered by intramuscular injection. The stromal dendritic cells of the muscle that encounter the highly immunogenic repeat structure of the VLP then migrate with their cargo to the lymph node, initiating an immune cascade that results in a robust T-cell dependent B-cell response, which generates high levels of L1-specific serum neutralizing antibodies and immune memory.

Mechanisms of virus immune evasion lead to development from chronic inflammation to cancer formation associated with human papillomavirus infection.

PubMed

Senba, Masachika; Mori, Naoki

2012-10-02

Human papillomavirus (HPV) has developed strategies to escape eradication by innate and adaptive immunity. Immune response evasion has been considered an important aspect of HPV persistence, which is the main contributing factor leading to HPV-related cancers. HPV-induced cancers expressing viral oncogenes E6 and E7 are potentially recognized by the immune system. The major histocompatibility complex (MHC) class I molecules are patrolled by natural killer cells and CD8+ cytotoxic T lymphocytes, respectively. This system of recognition is a main target for the strategies of immune evasion deployed by viruses. The viral immune evasion proteins constitute useful tools to block defined stages of the MHC class I presentation pathway, and in this way HPV avoids the host immune response. The long latency period from initial infection to persistence signifies that HPV evolves mechanisms to escape the immune response. It has now been established that there are oncogenic mechanisms by which E7 binds to and degrades tumor suppressor Rb, while E6 binds to and inactivates tumor suppressor p53. Therefore, interaction of p53 and pRb proteins can give rise to an increased immortalization and genomic instability. Overexpression of NF-κB in cervical and penile cancers suggests that NF-κB activation is a key modulator in driving chronic inflammation to cancer. HPV oncogene-mediated suppression of NF-κB activity contributes to HPV escape from the immune system. This review focuses on the diverse mechanisms of the virus immune evasion with HPV that leads to chronic inflammation and cancer.

Integrated analysis of HPV-mediated immune alterations in cervical cancer.

PubMed

Chen, Long; Luan, Shaohong; Xia, Baoguo; Liu, Yansheng; Gao, Yuan; Yu, Hongyan; Mu, Qingling; Zhang, Ping; Zhang, Weina; Zhang, Shengmiao; Wei, Guopeng; Yang, Min; Li, Ke

2018-05-01

Human papillomavirus (HPV) infection is the primary cause of cervical cancer. HPV-mediated immune alterations are known to play crucial roles in determining viral persistence and host cell transformation. We sought to thoroughly understand HPV-directed immune alterations in cervical cancer by exploring publically available datasets. 130 HPV positive and 7 HPV negative cervical cancer cases from The Cancer Genome Atlas were compared for differences in gene expression levels and functional enrichment. Analyses for copy number variation (CNV) and genetic mutation were conducted for differentially expressed immune genes. Kaplan-Meier analysis was performed to assess survival and relapse differences across cases with or without alterations of the identified immune signature genes. Genes up-regulated in HPV positive cervical cancer were enriched for various gene ontology terms of immune processes (P=1.05E-14~1.00E-05). Integrated analysis of the differentially expressed immune genes identified 9 genes that displayed either CNV, genetic mutation and/or gene expression changes in at least 10% of the cases of HPV positive cervical cancer. Genomic amplification may cause elevated levels of these genes in some HPV positive cases. Finally, patients with alterations in at least one of the nine signature genes overall had earlier relapse compared to those without any alterations. The altered expression of either TFRC or MMP13 may indicate poor survival for a subset of cervical cancer patients (P=1.07E-07). We identified a novel immune gene signature for HPV positive cervical cancer that is potentially associated with early relapse of cervical cancer. Copyright © 2018. Published by Elsevier Inc.

Progress toward implementation of human papillomavirus vaccination--the Americas, 2006-2010.

PubMed

2011-10-14

Cervical cancer is a major cause of morbidity and mortality in the Americas, where an estimated 80,574 new cases and 36,058 deaths were reported in 2008, with 85% of this burden occurring in Latin America and the Caribbean. Two oncogenic human papillomavirus (HPV) types (16 and 18) cause approximately 70% of cervical cancers and a substantial proportion of other HPV-related cancers. HPV vaccination provides an opportunity to greatly reduce cervical cancer burden through primary prevention of HPV infection. This report summarizes the progress toward HPV vaccine introduction in the Americas, focusing on countries that have introduced the vaccine in national or regional immunization programs. As of January 2011, four countries in the Americas had introduced HPV vaccine. Overcoming issues related to financing and delivery of HPV vaccine remains a key public health challenge to more widespread implementation of HPV vaccination in the Americas.

Reevaluation of epidemiological data demonstrates that it is consistent with cross-immunity among human papillomavirus types.

PubMed

Durham, David P; Poolman, Eric M; Ibuka, Yoko; Townsend, Jeffrey P; Galvani, Alison P

2012-10-01

The degree of cross-immunity between human papillomavirus (HPV) types is fundamental both to the epidemiological dynamics of HPV and to the impact of HPV vaccination. Epidemiological data on HPV infections has been repeatedly interpreted as inconsistent with cross-immunity. We reevaluate the epidemiological data using a model to determine the odds ratios of multiple to single infections expected in the presence or absence of cross-immunity. We simulate a virtual longitudinal survey to determine the effect cross-immunity has on the prevalence of multiple infections. We calibrate our model to epidemiological data and estimate the extent of type replacement following vaccination against specific HPV types. We find that cross-immunity can produce odds ratios of infection comparable with epidemiological observations. We show that the sample sizes underlying existing surveys have been insufficient to identify even intense cross-immunity. We also find that the removal of HPV type 16, type 18, and types 6 and 11 would increase the prevalence of nontargeted types by 50%, 29%, and 183%, respectively. Cross-immunity between HPV types is consistent with epidemiological data, contrary to previous interpretations. Cross-immunity may cause significant type replacement following vaccination, and therefore should be considered in future vaccine studies and epidemiological models.

Ill-informed consent? A content analysis of physical risk disclosure in school-based HPV vaccine programs.

PubMed

Steenbeek, Audrey; Macdonald, Noni; Downie, Jocelyn; Appleton, Mary; Baylis, Françoise

2012-01-01

This study examines the accuracy, completeness, and consistency of human papilloma virus (HPV) vaccine related physical risks disclosed in documents available to parents, legal guardians, and girls in Canadian jurisdictions with school-based HPV vaccine programs. We conducted an online search for program related HPV vaccine risk/benefit documents for all 13 Canadian jurisdictions between July 2008 and May 2009 including follow-up by e-mail and telephone requests for relevant documents from the respective Ministries or Departments of Health. The physical risks listed in the documents were compared across jurisdictions and against documents prepared by the vaccine manufacturer (Merck Frosst Canada), the National Advisory Committee on Immunization (NACI), the Society of Obstetricians and Gynecologists of Canada (SOGC), and a 2007 article in Maclean's Magazine. No jurisdiction provided the same list of vaccine related physical risks as any other jurisdiction. Major discrepancies were identified. Inaccurate, incomplete, and inconsistent information can threaten the validity of consent/authorization and potentially undermine trust in the vaccine program and the vaccine itself. Efforts are needed to improve the quality, clarity, and standardization of the content of written documents used in school-based HPV vaccine programs across Canada. © 2011 Wiley Periodicals, Inc.

The role of TLRs in cervical cancer with HPV infection: a review

PubMed Central

Yang, Xiao; Cheng, Yanxiang; Li, Chunsheng

2017-01-01

The main cause of cervical cancer is persistent infection with high-risk human papilloma virus (HR-HPV), but not all human papilloma virus (HPV) infections lead to cervical cancer. The key factors that determine the outcome of HPV infection remain poorly understood, and how the host immune system protects against HPV infection is unclear. Toll-like receptors (TLRs) are a group of pattern recognition receptors present in the cytoplasm and cell membrane, and can specifically recognize pathogen-associated molecular patterns. As the key molecules of innate and acquired immunity, TLRs not only play important roles in the immune defense against infectious diseases, but also are involved in the occurrence and development of a variety of malignant tumors. In cervical cancer caused by HR-HPV infection, TLRs have been found to regulate the local immune microenvironment. The role of TLRs in HR-HPV infection and HPV-induced cervical cancer and its relationship with HPV vaccine are reviewed in this article. PMID:29263932

History repeats itself in Japan: Failure to learn from rubella epidemic leads to failure to provide the HPV vaccine.

PubMed

Tanaka, Yusuke; Ueda, Yutaka; Yoshino, Kiyoshi; Kimura, Tadashi

2017-08-03

Eradication of vaccine-preventable diseases is one of the most important goals of public health interventions. Herd immunity can be established by national vaccination programs. However, once the national vaccination program stops for any reason, unprotected group will be generated depending on an unfortunate year of birth. Currently, there are 2 major concerns regarding vaccine cohort gaps in Japan: one is for the rubella vaccine, the other for the human papillomavirus (HPV) vaccine.

A case study using the United Republic of Tanzania: costing nationwide HPV vaccine delivery using the WHO Cervical Cancer Prevention and Control Costing Tool.

PubMed

Hutubessy, Raymond; Levin, Ann; Wang, Susan; Morgan, Winthrop; Ally, Mariam; John, Theopista; Broutet, Nathalie

2012-11-13

The purpose, methods, data sources and assumptions behind the World Health Organization (WHO) Cervical Cancer Prevention and Control Costing (C4P) tool that was developed to assist low- and middle-income countries (LMICs) with planning and costing their nationwide human papillomavirus (HPV) vaccination program are presented. Tanzania is presented as a case study where the WHO C4P tool was used to cost and plan the roll-out of HPV vaccines nationwide as part of the national comprehensive cervical cancer prevention and control strategy. The WHO C4P tool focuses on estimating the incremental costs to the health system of vaccinating adolescent girls through school-, health facility- and/or outreach-based strategies. No costs to the user (school girls, parents or caregivers) are included. Both financial (or costs to the Ministry of Health) and economic costs are estimated. The cost components for service delivery include training, vaccination (health personnel time and transport, stationery for tally sheets and vaccination cards, and so on), social mobilization/IEC (information, education and communication), supervision, and monitoring and evaluation (M&E). The costs of all the resources used for HPV vaccination are totaled and shown with and without the estimated cost of the vaccine. The total cost is also divided by the number of doses administered and number of fully immunized girls (FIGs) to estimate the cost per dose and cost per FIG. Over five years (2011 to 2015), the cost of establishing an HPV vaccine program that delivers three doses of vaccine to girls at schools via phased national introduction (three regions in year 1, ten regions in year 2 and all 26 regions in years 3 to 5) in Tanzania is estimated to be US$9.2 million (excluding vaccine costs) and US$31.5 million (with vaccine) assuming a vaccine price of US$5 (GAVI 2011, formerly the Global Alliance for Vaccines and Immunizations). This is equivalent to a financial cost of US$5.77 per FIG, excluding the vaccine cost. The most important costs of service delivery are social mobilization/IEC and service delivery operational costs. When countries expand their immunization schedules with new vaccines such as the HPV vaccine, they face initial costs to fund critical pre-introduction activities, as well as incremental system costs to deliver the vaccines on an ongoing basis. In anticipation, governments need to plan ahead for non-vaccine costs so they will be financed adequately. Existing human resources need to be re-allocated or new staff need to be recruited for the program to be implemented successfully in a sustainable and long-term manner.Reaching a target group not routinely served by national immunization programs previously with three doses of vaccine requires new delivery strategies, more transport of vaccines and health workers and more intensive IEC activities leading to new delivery costs for the immunization program that are greater than the costs incurred when a new infant vaccine is added to the existing infant immunization schedule. The WHO C4P tool is intended to help LMICs to plan ahead and estimate the programmatic and operational costs of HPV vaccination.

A case study using the United Republic of Tanzania: costing nationwide HPV vaccine delivery using the WHO Cervical Cancer Prevention and Control Costing Tool

PubMed Central

2012-01-01

Background The purpose, methods, data sources and assumptions behind the World Health Organization (WHO) Cervical Cancer Prevention and Control Costing (C4P) tool that was developed to assist low- and middle-income countries (LMICs) with planning and costing their nationwide human papillomavirus (HPV) vaccination program are presented. Tanzania is presented as a case study where the WHO C4P tool was used to cost and plan the roll-out of HPV vaccines nationwide as part of the national comprehensive cervical cancer prevention and control strategy. Methods The WHO C4P tool focuses on estimating the incremental costs to the health system of vaccinating adolescent girls through school-, health facility- and/or outreach-based strategies. No costs to the user (school girls, parents or caregivers) are included. Both financial (or costs to the Ministry of Health) and economic costs are estimated. The cost components for service delivery include training, vaccination (health personnel time and transport, stationery for tally sheets and vaccination cards, and so on), social mobilization/IEC (information, education and communication), supervision, and monitoring and evaluation (M&E). The costs of all the resources used for HPV vaccination are totaled and shown with and without the estimated cost of the vaccine. The total cost is also divided by the number of doses administered and number of fully immunized girls (FIGs) to estimate the cost per dose and cost per FIG. Results Over five years (2011 to 2015), the cost of establishing an HPV vaccine program that delivers three doses of vaccine to girls at schools via phased national introduction (three regions in year 1, ten regions in year 2 and all 26 regions in years 3 to 5) in Tanzania is estimated to be US$9.2 million (excluding vaccine costs) and US$31.5 million (with vaccine) assuming a vaccine price of US$5 (GAVI 2011, formerly the Global Alliance for Vaccines and Immunizations). This is equivalent to a financial cost of US$5.77 per FIG, excluding the vaccine cost. The most important costs of service delivery are social mobilization/IEC and service delivery operational costs. Conclusions When countries expand their immunization schedules with new vaccines such as the HPV vaccine, they face initial costs to fund critical pre-introduction activities, as well as incremental system costs to deliver the vaccines on an ongoing basis. In anticipation, governments need to plan ahead for non-vaccine costs so they will be financed adequately. Existing human resources need to be re-allocated or new staff need to be recruited for the program to be implemented successfully in a sustainable and long-term manner. Reaching a target group not routinely served by national immunization programs previously with three doses of vaccine requires new delivery strategies, more transport of vaccines and health workers and more intensive IEC activities leading to new delivery costs for the immunization program that are greater than the costs incurred when a new infant vaccine is added to the existing infant immunization schedule. The WHO C4P tool is intended to help LMICs to plan ahead and estimate the programmatic and operational costs of HPV vaccination. PMID:23146319

Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors.

PubMed

Wood, Oliver; Woo, Jeongmin; Seumois, Gregory; Savelyeva, Natalia; McCann, Katy J; Singh, Divya; Jones, Terry; Peel, Lailah; Breen, Michael S; Ward, Matthew; Garrido Martin, Eva; Sanchez-Elsner, Tilman; Thomas, Gareth; Vijayanand, Pandurangan; Woelk, Christopher H; King, Emma; Ottensmeier, Christian

2016-08-30

Human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than it's HPV negative (HPV(-)) counterpart. This may be due to the higher numbers of tumor-infiltrating lymphocytes (TILs) in HPV positive (HPV(+)) tumors. RNA-Sequencing (RNA-Seq) was used to evaluate whether the differences in clinical behaviour simply reflect a numerical difference in TILs or whether there is a fundamental behavioural difference between TILs in these two settings. Thirty-nine HNSCC tumors were scored for TIL density by immunohistochemistry. After the removal of 16 TILlow tumors, RNA-Seq analysis was performed on 23 TILhigh/med tumors (HPV(+) n=10 and HPV(-) n=13). Using EdgeR, differentially expressed genes (DEG) were identified. Immune subset analysis was performed using Functional Analysis of Individual RNA-Seq/ Microarray Expression (FAIME) and immune gene RNA transcript count analysis. In total, 1,634 DEGs were identified, with a dominant immune signature observed in HPV(+) tumors. After normalizing the expression profiles to account for differences in B- and T-cell number, 437 significantly DEGs remained. A B-cell associated signature distinguished HPV(+) from HPV(-) tumors, and included the DEGs CD200, GGA2, ADAM28, STAG3, SPIB, VCAM1, BCL2 and ICOSLG; the immune signal relative to T-cells was qualitatively similar between TILs of both tumor cohorts. Our findings were validated and confirmed in two independent cohorts using TCGA data and tumor-infiltrating B-cells from additional HPV(+) HNSCC patients. A B-cell associated signal segregated tumors relative to HPV status. Our data suggests that the role of B-cells in the adaptive immune response to HPV(+) HNSCC requires re-assessment.

Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors

PubMed Central

Savelyeva, Natalia; McCann, Katy J.; Singh, Divya; Jones, Terry; Peel, Lailah; Breen, Michael S.; Ward, Matthew; Martin, Eva Garrido

2016-01-01

Human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than it's HPV negative (HPV(−)) counterpart. This may be due to the higher numbers of tumor-infiltrating lymphocytes (TILs) in HPV positive (HPV(+)) tumors. RNA-Sequencing (RNA-Seq) was used to evaluate whether the differences in clinical behaviour simply reflect a numerical difference in TILs or whether there is a fundamental behavioural difference between TILs in these two settings. Thirty-nine HNSCC tumors were scored for TIL density by immunohistochemistry. After the removal of 16 TILlow tumors, RNA-Seq analysis was performed on 23 TILhigh/med tumors (HPV(+) n=10 and HPV(−) n=13). Using EdgeR, differentially expressed genes (DEG) were identified. Immune subset analysis was performed using Functional Analysis of Individual RNA-Seq/ Microarray Expression (FAIME) and immune gene RNA transcript count analysis. In total, 1,634 DEGs were identified, with a dominant immune signature observed in HPV(+) tumors. After normalizing the expression profiles to account for differences in B- and T-cell number, 437 significantly DEGs remained. A B-cell associated signature distinguished HPV(+) from HPV(−) tumors, and included the DEGs CD200, GGA2, ADAM28, STAG3, SPIB, VCAM1, BCL2 and ICOSLG; the immune signal relative to T-cells was qualitatively similar between TILs of both tumor cohorts. Our findings were validated and confirmed in two independent cohorts using TCGA data and tumor-infiltrating B-cells from additional HPV(+) HNSCC patients. A B-cell associated signal segregated tumors relative to HPV status. Our data suggests that the role of B-cells in the adaptive immune response to HPV(+) HNSCC requires re-assessment. PMID:27462861

Cost-effectiveness analysis of different types of human papillomavirus vaccination combined with a cervical cancer screening program in mainland China.

PubMed

Mo, Xiuting; Gai Tobe, Ruoyan; Wang, Lijie; Liu, Xianchen; Wu, Bin; Luo, Huiwen; Nagata, Chie; Mori, Rintaro; Nakayama, Takeo

2017-07-18

China has a high prevalence of human papillomavirus (HPV) and a consequently high burden of disease with respect to cervical cancer. The HPV vaccine has proved to be effective in preventing cervical cancer and is now a part of routine immunization programs worldwide. It has also proved to be cost effective. This study aimed to assess the cost-effectiveness of 2-, 4-, and 9-valent HPV vaccines (hereafter, HPV2, 4 or 9) combined with current screening strategies in China. A Markov model was developed for a cohort of 100,000 HPV-free girls to simulate the natural history to HPV infection. Three recommended screening methods (1. liquid-based cytology test + HPV DNA test; 2. pap smear cytology test + HPV DNA test; 3. visual inspection with acetic acid) and three types of HPV vaccination program (HPV2/4/9) were incorporated into 15 intervention options, and the incremental cost-effectiveness ratio (ICER) was calculated to determine the dominant strategies. Costs, transition probabilities and utilities were obtained from a review of the literature and national databases. One-way sensitivity analyses and threshold analyses were performed for key variables in different vaccination scenarios. HPV9 combined with screening showed the highest health impact in terms of reducing HPV-related diseases and increasing the number of quality-adjusted life years (QALYs). Under the current thresholds of willingness to pay (WTP, 3 times the per capita GDP or USD$ 23,880), HPV4/9 proved highly cost effective, while HPV2 combined with screening cost more and was less cost effective. Only when screening coverage increased to 60% ~ 70% did the HPV2 and screening combination strategy become economically feasible. The combination of the HPV4/9 vaccine with current screening strategies for adolescent girls was highly cost-effective and had a significant impact on reducing the HPV infection-related disease burden in Mainland China.

Immune responses in macaques to a prototype recombinant adenovirus live oral human papillomavirus 16 vaccine.

PubMed

Berg, Michael G; Adams, Robert J; Gambhira, Ratish; Siracusa, Mark C; Scott, Alan L; Roden, Richard B S; Ketner, Gary

2014-09-01

Immunization with human papillomavirus (HPV) L1 virus-like particles (VLPs) prevents infection with HPV. However, the expense and logistical demands of current VLP vaccines will limit their widespread use in resource-limited settings, where most HPV-induced cervical cancer occurs. Live oral adenovirus vaccines have properties that are well-suited for use in such settings. We have described a live recombinant adenovirus vaccine prototype that produces abundant HPV16 L1 protein from the adenovirus major late transcriptional unit and directs the assembly of HPV16 VLPs in tissue culture. Recombinant-derived VLPs potently elicit neutralizing antibodies in mice. Here, we characterize the immune response to the recombinant after dual oral and intranasal immunization of pigtail macaques, in which the virus replicates as it would in immunized humans. The immunization of macaques induced vigorous humoral responses to adenovirus capsid and nonstructural proteins, although, surprisingly, not against HPV L1. In contrast, immunization elicited strong T-cell responses to HPV VLPs as well as adenovirus virions. T-cell responses arose immediately after the primary immunization and were boosted by a second immunization with recombinant virus. T-cell immunity contributes to protection against a wide variety of pathogens, including many viruses. The induction of a strong cellular response by the recombinant indicates that live adenovirus recombinants have potential as vaccines for those agents. These studies encourage and will inform the continued development of viable recombinant adenovirus vaccines. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Durable immunity to oncogenic human papillomaviruses elicited by adjuvanted recombinant Adeno-associated virus-like particle immunogen displaying L2 17–36 epitopes

PubMed Central

Jagu, Subhashini; Karanam, Balusubramanyam; Wang, Joshua W.; Zayed, Hatem; Weghofer, Margit; Brendle, Sarah A.; Balogh, Karla K.; Tossi, Kerstin Pino; Roden, Richard B.S.; Christensen, Neil D.

2016-01-01

Vaccination with the minor capsid protein L2, notably the 17–36 neutralizing epitope, induces broadly protective antibodies, although the neutralizing titers attained in serum are substantially lower than for the licensed L1 VLP vaccines. Here we examine the impact of other less reactogenic adjuvants upon the induction of durable neutralizing serum antibody responses and protective immunity after vaccination with HPV16 and HPV31 L2 amino acids 17–36 inserted at positions 587 and 453 of VP3, respectively, for surface display on Adeno-Associated Virus 2-like particles [AAVLP (HPV16/31L2)]. Mice were vaccinated three times subcutaneously with AAVLP (HPV16/31L2) at two week intervals at several doses either alone or formulated with alum, alum and MPL, RIBI adjuvant or Cervarix. The use of adjuvant with AAVLP (HPV16/31L2) was necessary in mice for the induction of L2-specific neutralizing antibody and protection against vaginal challenge with HPV16. While use of alum was sufficient to elicit durable protection (>3 months after the final immunization), antibody titers were increased by addition of MPL and RIBI adjuvants. To determine the breadth of immunity, rabbits were immunized three times with AAVLP (HPV16/31L2) either alone, formulated with alum ± MPL, or RIBI adjuvants, and after serum collection, the animals were concurrently challenged with HPV16/31/35/39/45/58/59 quasivirions or cottontail rabbit papillomavirus (CRPV) at 6 or 12 months post-immunization. Strong protection against all HPV types was observed at both 6 and 12 months post-immunization, including robust protection in rabbits receiving the vaccine without adjuvant. In summary, vaccination with AAVLP presenting HPV L2 17–36 epitopes at two sites on their surface induced cross-neutralizing serum antibody, immunity against HPV16 in the genital tract, and long-term protection against skin challenge with the 7 most common oncogenic HPV types when using a clinically relevant adjuvant. PMID:26382603

CDC Activities for Improving Implementation of Human Papillomavirus Vaccination, Cervical Cancer Screening, and Surveillance Worldwide.

PubMed

Senkomago, Virginia; Duran, Denise; Loharikar, Anagha; Hyde, Terri B; Markowitz, Lauri E; Unger, Elizabeth R; Saraiya, Mona

2017-12-01

Cervical cancer incidence and mortality rates are high, particularly in developing countries. Most cervical cancers can be prevented by human papillomavirus (HPV) vaccination, screening, and timely treatment. The US Centers for Disease Control and Prevention (CDC) provides global technical assistance for implementation and evaluation of HPV vaccination pilot projects and programs and laboratory-related HPV activities to assess HPV vaccines. CDC collaborates with global partners to develop global cervical cancer screening recommendations and manuals, implement screening, create standardized evaluation tools, and provide expertise to monitor outcomes. CDC also trains epidemiologists in cancer prevention through its Field Epidemiology Training Program and is working to improve cancer surveillance by supporting efforts of the World Health Organization in developing cancer registry hubs and assisting countries in estimating costs for developing population-based cancer registries. These activities contribute to the Global Health Security Agenda action packages to improve immunization, surveillance, and the public health workforce globally.

Too Late to Vaccinate? The Incremental Benefits and Cost-effectiveness of a Delayed Catch-up Program Using the 4-Valent Human Papillomavirus Vaccine in Norway

PubMed Central

Burger, Emily A.; Sy, Stephen; Nygård, Mari; Kristiansen, Ivar S.; Kim, Jane J.

2015-01-01

Background Human papillomavirus (HPV) vaccines are ideally administered before HPV exposure; therefore, catch-up programs for girls past adolescence have not been readily funded. We evaluated the benefits and cost-effectiveness of a delayed, 1-year female catch-up vaccination program in Norway. Methods We calibrated a dynamic HPV transmission model to Norwegian data and projected the costs and benefits associated with 8 HPV-related conditions while varying the upper vaccination age limit to 20, 22, 24, or 26 years. We explored the impact of vaccine protection in women with prior vaccine-targeted HPV infections, vaccine cost, coverage, and natural- and vaccine-induced immunity. Results The incremental benefits and cost-effectiveness decreased as the upper age limit for catch-up increased. Assuming a vaccine cost of $150/dose, vaccination up to age 20 years remained below Norway's willingness-to-pay threshold (approximately $83 000/quality-adjusted life year gained); extension to age 22 years was cost-effective at a lower cost per dose ($50–$75). At high levels of vaccine protection in women with prior HPV exposure, vaccinating up to age 26 years was cost-effective. Results were stable with lower coverage. Conclusions HPV vaccination catch-up programs, 5 years after routine implementation, may be warranted; however, even at low vaccine cost per dose, the cost-effectiveness of vaccinating beyond age 22 years remains uncertain. PMID:25057044

HPV-specific immunotherapy: key role for immunomodulators.

PubMed

Van de Wall, Stephanie; Nijman, Hans W; Daemen, Toos

2014-02-01

Cervical cancer is the second most common malignancy among women worldwide. The prime causal factor of the disease is a persistent infection with human papillomavirus (HPV) with individuals failing to mount a sufficient immune response against the virus. Despite the current success of HPV16- and 18-specific prophylactic vaccination, established HPV infections and associated neoplasia require therapeutic vaccines with the induction of cellular immunity. The sustained expression of early proteins E6 and E7 from major oncogenic HPV genotypes in cervical lesions are ideal targets for the design of immunotherapeutic strategies. These strategies, particularly subunit vaccines, may require additional help from immunomodulators to enhance HPV-specific cellular responses. This review discusses recent studies, published since 2008, relating to immunotherapeutic strategies against HPV that include immunomodulators. These immunomodulators fall within the category of toll-like receptor adjuvants for innate immune activation, adjuvants directly contributing to adaptive immunity, such as cytokines and costimulatory molecules, and those that target tumor-induced immunosuppressive mechanisms. Using a combination of these strategies with delivery-based approaches may be most beneficial for the success of therapeutic vaccines against HPV-induced neoplasia in the clinic.

Suppression of Langerhans cell activation is conserved amongst human papillomavirus α and β genotypes, but not a µ genotype.

PubMed

Da Silva, Diane M; Movius, Carly A; Raff, Adam B; Brand, Heike E; Skeate, Joseph G; Wong, Michael K; Kast, W Martin

2014-03-01

Human papillomavirus (HPV) has evolved mechanisms that allow it to evade the human immune system. Studies have shown HPV-mediated suppression of activation of Langerhans cells (LC) is a key mechanism through which HPV16 evades initial immune surveillance. However, it has not been established whether high- and low-risk mucosal and cutaneous HPV genotypes share a common mechanism of immune suppression. Here, we demonstrate that LC exposed to capsids of HPV types 18, 31, 45, 11, (alpha-papillomaviruses) and HPV5 (beta-papillomavirus) similarly suppress LC activation, including lack of costimulatory molecule expression, lack of cytokine and chemokine secretion, lack of migration, and deregulated cellular signaling. In contrast, HPV1 (mu-papillomavirus) induced costimulatory molecule and cytokine upregulation, but LC migration and cellular signaling was suppressed. These results suggest that alpha and beta HPV genotypes, and partially a mu genotype, share a conserved mechanism of immune escape that enables these viruses to remain undetected in the absence of other inflammatory events. Copyright © 2014 Elsevier Inc. All rights reserved.

[Immune response in cervical cancer. Strategies for the development of therapeutic vaccines].

PubMed

Mora-García, María Lourdes; Monroy-García, Alberto

2015-01-01

High-risk human papillomaviruses (HR-HPV), as HPV-16, evade immune recognition through the inactivation of cells of the innate immune response. HPV-16 E6 and E7 genes down-regulate type I interferon response. They do not produce viremia or cell death; therefore, they do not cause inflammation or damage signal that alerts the immune system. Virus-like particles (VLPs), consisting of structural proteins (L1 and L2) of the main HR-HPV types that infect the genitourinary tract, are the most effective prophylactic vaccines against HR-HPV infection. While for the high grade neoplastic lesions, therapeutic vaccines based on viral vectors, peptides, DNA or complete HR-HPV E6 and E7 proteins as antigens, have had limited effectiveness. Chimeric virus-like particles (cVLPs) that carry immunogenic peptides derived from E6 and E7 viral proteins, capable to induce activation of specific cytotoxic T lymphocytes, emerge as an important alternative to provide prophylactic and therapeutic activity against HR-HPV infection and cervical cancer.

Health Disparities in the Immunoprevention of Human Papillomavirus Infection and Associated Malignancies

PubMed Central

Bakir, Amira H.; Skarzynski, Martin

2015-01-01

Human papillomavirus (HPV) causes roughly 1.6% of the plus 1.6 million cases of cancer that are diagnosed in the United States each year. Despite the proven safety and efficacy of available vaccines, HPV remains the most common sexually transmitted infection. Underlying the high prevalence of HPV infection is the poor adherence to the Centers for Disease Control recommendation to vaccinate all 11- to 12-year-old males and females. In fact, only about 38 and 14% of eligible females and males, respectively, receive the complete, three-dose immunization. The many factors associated with missed HPV vaccination opportunities – including race, age, family income, and patient education – contribute to widespread disparities in vaccine completion and related health outcomes. Beyond patient circumstance, however, research indicates that the rigor and consistency of recommendation by primary care providers also plays a significant role in uptake of HPV immunization. Health disparities data are of vital importance to HPV vaccination campaigns because they can provide insight into how to address current problems and allocate limited resources where they are most needed. Furthermore, even modest gains in populations with low vaccination rates may yield great benefits because HPV immunization has been shown to provide herd immunity, indirect protection for non-immunized individuals achieved by limiting the spread of an infectious agent through a population. However, the impact of current HPV vaccination campaigns is hindered by stagnant immunization rates, which remain far below target levels despite a slow overall increase. Furthermore, gains in immunization are not equally distributed across gender, age, demographic, and socioeconomic divisions within the recommended group of vaccine recipients. To achieve the greatest impact, public health campaigns should focus on improving immunization coverage where it is weakest. They should also explore more subtle but potentially significant determinants of HPV vaccine initiation and completion, such as the attitudes of parents and healthcare providers and factors that exacerbate HPV-related health outcomes, including smoking and human immunodeficiency virus-mediated immunosuppression. Optimizing the efficacy of vaccination campaigns will require a health disparities approach that both identifies and remedies the underlying causes of population differences in HPV vaccination. PMID:26734596

Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression1

PubMed Central

Woodham, Andrew W.; Raff, Adam B.; Raff, Laura M.; Da Silva, Diane M.; Yan, Lisa; Skeate, Joseph G.; Wong, Michael K.; Lin, Yvonne G.; Kast, W. Martin

2014-01-01

High-risk human papillomaviruses (HPV) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cellsin a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the antigen presenting cells of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. Here, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by siRNA downregulation of A2t, significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein. PMID:24719459

Human papillomavirus 16 (HPV16) and HPV52 E6-specific immunity in HIV-infected adults on combination antiretroviral therapy.

PubMed

Leng, C Y; Low, H C; Chua, L L; Chong, M L; Sulaiman, H; Azwa, I; Roberts, J M; Kamarulzaman, A; Rajasuriar, R; Woo, Y L

2017-05-01

Human papillomavirus (HPV)-associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) T-cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution. Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/μL) and oIR (CD4 T-cell count > 500 cells/μL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells. HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses. HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%). © 2016 British HIV Association.

Mapping HPV Vaccination and Cervical Cancer Screening Practice in the Pacific Region-Strengthening National and Regional Cervical Cancer Prevention

PubMed Central

Obel, J; McKenzie, J; Buenconsejo-Lum, LE; Durand, AM; Ekeroma, A; Souares, Y; Hoy, D; Baravilala, W; Garland, SM; Kjaer, SK; Roth, A

2015-01-01

Objective To provide background information for strengthening cervical cancer prevention in the Pacific by mapping current human papillomavirus (HPV) vaccination and cervical cancer screening practices, as well as intent and barriers to the introduction and maintenance of national HPV vaccination programmes in the region. Materials and Methods A cross-sectional questionnaire-based survey among ministry of health officials from 21 Pacific Island countries and territories (n=21). Results Cervical cancer prevention was rated as highly important, but implementation of prevention programs were insufficient, with only two of 21 countries and territories having achieved coverage of cervical cancer screening above 40%. Ten of 21 countries and territories had included HPV vaccination in their immunization schedule, but only two countries reported coverage of HPV vaccination above 60% among the targeted population. Key barriers to the introduction and continuation of HPV vaccination were reported to be: (i) Lack of sustainable financing for HPV vaccine programs; (ii) Lack of visible government endorsement; (iii) Critical public perception of the value and safety of the HPV vaccine; and (iv) Lack of clear guidelines and policies for HPV vaccination. Conclusion Current practices to prevent cervical cancer in the Pacific Region do not match the high burden of disease from cervical cancer. A regional approach, including reducing vaccine prices by bulk purchase of vaccine, technical support for implementation of prevention programs, operational research and advocacy could strengthen political momentum for cervical cancer prevention and avoid risking the lives of many women in the Pacific. PMID:25921158

[Preparation and activity detection of chicken egg yolk IgY antibody against human papillomavirus 16 type L1 main capsid protein].

PubMed

Yang, Jun; Zhang, Ming-juan; Qiang, Lei; Su, Bao-shan; Wang, Yi-li; Si, Lü-sheng

2008-03-01

To prepare highly specific chicken egg yolk IgY antibody against human papillomavirus 16 type L1 main capsid protein (HPV16L1) for detection of HPV16L1. Purified HPV16L1 protein was used to immunize the hens, from which the eggs were collected since one week after the first immunization. The egg yolk was separated and the IgY antibody purified by PEG-6000 method. The bioactivity of the antibody was tested using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was performed to detect the HPV16L1 in the CHO cells transfected with the recombinant pcDNA-EGFP-HPV16L1 plasmid (containing EGFP-HPV16L1 fusion gene) for assessing the specific affinity of IgY to HPV16L1. After 3 immunizations of the hens, the titer of the purified IgY antibody against HPV16L1 from the egg yolk reached 1:10240. The IgY bound specifically to the EGFP-HPV16L1 protein expressed in the transfected CHO cells. High titer IgY can be prepared by immunization of the hens with HPV16L1 protein, and the prepared IgY can be used for HPV16L1 detection at the cellular level.

TGFβ Receptor 1: An Immune Susceptibility Gene in HPV-Associated Cancer

PubMed Central

Levovitz, Chaya; Chen, Dan; Ivansson, Emma; Gyllensten, Ulf; Finnigan, John P.; Alshawish, Sara; Zhang, Weijia; Schadt, Eric E.; Posner, Marshal R.; Genden, Eric M.; Boffetta, Paolo; Sikora, Andrew G.

2015-01-01

Only a minority of those exposed to human papillomavirus (HPV) develop HPV-related cervical and oropharyngeal cancer. Because host immunity affects infection and progression to cancer, we tested the hypothesis that genetic variation in immune-related genes is a determinant of susceptibility to oropharyngeal cancer and other HPV-associated cancers by performing a multitier integrative computational analysis with oropharyngeal cancer data from a head and neck cancer genome-wide association study (GWAS). Independent analyses, including single-gene, gene-interconnectivity, protein–protein interaction, gene expression, and pathway analysis, identified immune genes and pathways significantly associated with oropharyngeal cancer. TGFβR1, which intersected all tiers of analysis and thus selected for validation, replicated significantly in the head and neck cancer GWAS limited to HPV-seropositive cases and an independent cervical cancer GWAS. The TGFβR1 containing p38–MAPK pathway was significantly associated with oropharyngeal cancer and cervical cancer, and TGFβR1 was overexpressed in oropharyngeal cancer, cervical cancer, and HPV+ head and neck cancer tumors. These concordant analyses implicate TGFβR1 signaling as a process dysregulated across HPV-related cancers. This study demonstrates that genetic variation in immune-related genes is associated with susceptibility to oropharyngeal cancer and implicates TGFβR1/TGFβ signaling in the development of both oropharyngeal cancer and cervical cancer. Better understanding of the immunogenetic basis of susceptibility to HPV-associated cancers may provide insight into host/virus interactions and immune processes dysregulated in the minority of HPV-exposed individuals who progress to cancer. PMID:25273091

Cellular immunogenicity of human papillomavirus vaccines Cervarix and Gardasil in adults with HIV infection

PubMed Central

Zurek Munk-Madsen, Maria; Toft, Lars; Kube, Tina; Richter, Rolf; Ostergaard, Lars; Søgaard, Ole S.; Tolstrup, Martin; Kaufmann, Andreas M.

2018-01-01

ABSTRACT Human papillomavirus (HPV) infection is a frequent cause of malignant and non-malignant disease, in particular among persons with HIV. HPV serotype-specific anti L1 antibodies protect against HPV infection but little is known about prophylactic HPV vaccine-induced cell-mediated immunity against HPV in high-risk individuals. We recently showed that both HPV vaccines (Gardasil® and Cervarix®) induce solid, serological immune responses in HIV-infected persons. This study aimed to characterize HPV-specific CD4 T cells in HIV-infected HPV-vaccine recipients, T cell responses being critical for B cell activation and antibody-isotype switching. Thirty HIV-infected patients on long-term antiretroviral treatment (ART) received 3 doses of either Cervarix (n = 15) or Gardasil (n = 15) vaccine at month 0, 1.5 and 6. Cryopreserved peripheral blood mononuclear cells (PBMC) from baseline, 7 and 12 months were subjected to 24-hour stimulation with specific pools of HPV L1-peptides (HPV6, 11, 16, 18, 31 and 45) and HPV E6/E7-peptide pools (HPV6/11 and HPV16/18). Fluorescence-activated cell sorting with intracellular staining (IC-FACS) against CD4, CD154, IL-2, and IFNγ was performed. Frequencies (%) of HPV-antigen specific CD4+ T cells (CD154+/IL-2+ or CD154+/ IFNγ+) were determined. Both HPV-vaccines significantly and comparably enhanced cell-mediated vaccine L1 antigen-specific immunity in HIV-positive adults receiving ART therapy at month 7 and 12 after first vaccine dose. This suggests that the vaccines induce CD4 T cellular memory despite HIV-induced immune compromisation. PMID:29172992

Cellular immunogenicity of human papillomavirus vaccines Cervarix and Gardasil in adults with HIV infection.

PubMed

Zurek Munk-Madsen, Maria; Toft, Lars; Kube, Tina; Richter, Rolf; Ostergaard, Lars; Søgaard, Ole S; Tolstrup, Martin; Kaufmann, Andreas M

2018-04-03

Human papillomavirus (HPV) infection is a frequent cause of malignant and non-malignant disease, in particular among persons with HIV. HPV serotype-specific anti L1 antibodies protect against HPV infection but little is known about prophylactic HPV vaccine-induced cell-mediated immunity against HPV in high-risk individuals. We recently showed that both HPV vaccines (Gardasil® and Cervarix®) induce solid, serological immune responses in HIV-infected persons. This study aimed to characterize HPV-specific CD4 T cells in HIV-infected HPV-vaccine recipients, T cell responses being critical for B cell activation and antibody-isotype switching. Thirty HIV-infected patients on long-term antiretroviral treatment (ART) received 3 doses of either Cervarix (n = 15) or Gardasil (n = 15) vaccine at month 0, 1.5 and 6. Cryopreserved peripheral blood mononuclear cells (PBMC) from baseline, 7 and 12 months were subjected to 24-hour stimulation with specific pools of HPV L1-peptides (HPV6, 11, 16, 18, 31 and 45) and HPV E6/E7-peptide pools (HPV6/11 and HPV16/18). Fluorescence-activated cell sorting with intracellular staining (IC-FACS) against CD4, CD154, IL-2, and IFNγ was performed. Frequencies (%) of HPV-antigen specific CD4+ T cells (CD154 + /IL-2 + or CD154 + / IFNγ + ) were determined. Both HPV-vaccines significantly and comparably enhanced cell-mediated vaccine L1 antigen-specific immunity in HIV-positive adults receiving ART therapy at month 7 and 12 after first vaccine dose. This suggests that the vaccines induce CD4 T cellular memory despite HIV-induced immune compromisation.

Comparative humoral and cellular immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18–45 years: Follow-up through Month 48 in a Phase III randomized study

PubMed Central

Einstein, Mark H; Levin, Myron J; Chatterjee, Archana; Chakhtoura, Nahida; Takacs, Peter; Catteau, Grégory; Dessy, Francis J; Moris, Philippe; Lin, Lan; Struyf, Frank; Dubin, Gary

2014-01-01

We previously reported higher anti-HPV-16 and -18 immune responses induced by HPV-16/18 vaccine compared with HPV-6/11/16/18 vaccine at Month 7 (one month after completion of full vaccination series) in women aged 18–45 y in an observer-blind study NCT00423046; the differences of immune response magnitudes were maintained up to Month 24. Here we report follow-up data through Month 48. At Month 48, in according-to-protocol cohort for immunogenicity (seronegative and DNA-negative for HPV type analyzed at baseline), geometric mean titers of serum neutralizing antibodies were 2.0- to 5.2-fold higher (HPV-16) and 8.6- to 12.8-fold higher (HPV-18) in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. The majority of women in both vaccine groups remained seropositive for HPV-16. The same trend was observed for HPV-18 in HPV-16/18 vaccine group; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably, particularly in the older age groups. In the total vaccinated cohort (regardless of baseline serological and HPV-DNA status), anti-HPV-16 and -18 neutralizing antibody levels induced by HPV-16/18 vaccine were higher than those induced by HPV-6/11/16/18 vaccine. CD4+ T-cell response for HPV-16 and HPV-18 was higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Memory B-cell responses appeared similar between vaccine groups. Both vaccines were generally well tolerated. Overall, the higher immune response observed with the HPV-16/18 vaccine was maintained up to Month 48. A head-to-head study incorporating clinical endpoints would be required to confirm whether the observed differences in immune response between the vaccines influence the duration of protection they provided. PMID:25483700

Comparative humoral and cellular immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: follow-up through Month 48 in a Phase III randomized study.

PubMed

Einstein, Mark H; Levin, Myron J; Chatterjee, Archana; Chakhtoura, Nahida; Takacs, Peter; Catteau, Grégory; Dessy, Francis J; Moris, Philippe; Lin, Lan; Struyf, Frank; Dubin, Gary

2014-01-01

We previously reported higher anti-HPV-16 and -18 immune responses induced by HPV-16/18 vaccine compared with HPV-6/11/16/18 vaccine at Month 7 (one month after completion of full vaccination series) in women aged 18-45 y in an observer-blind study NCT00423046; the differences of immune response magnitudes were maintained up to Month 24. Here we report follow-up data through Month 48. At Month 48, in according-to-protocol cohort for immunogenicity (seronegative and DNA-negative for HPV type analyzed at baseline), geometric mean titers of serum neutralizing antibodies were 2.0- to 5.2-fold higher (HPV-16) and 8.6- to 12.8-fold higher (HPV-18) in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. The majority of women in both vaccine groups remained seropositive for HPV-16. The same trend was observed for HPV-18 in HPV-16/18 vaccine group; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably, particularly in the older age groups. In the total vaccinated cohort (regardless of baseline serological and HPV-DNA status), anti-HPV-16 and -18 neutralizing antibody levels induced by HPV-16/18 vaccine were higher than those induced by HPV-6/11/16/18 vaccine. CD4+ T-cell response for HPV-16 and HPV-18 was higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Memory B-cell responses appeared similar between vaccine groups. Both vaccines were generally well tolerated. Overall, the higher immune response observed with the HPV-16/18 vaccine was maintained up to Month 48. A head-to-head study incorporating clinical endpoints would be required to confirm whether the observed differences in immune response between the vaccines influence the duration of protection they provided.

Fewer Doses of HPV Vaccine Result in Immune Response Similar to Three-Dose Regimen

MedlinePlus

... Releases NCI News Note Fewer doses of HPV vaccine result in immune response similar to three-dose ... that two doses of a human papillomavirus (HPV) vaccine, trademarked as Cervarix, resulted in similar serum antibody ...

Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression.

PubMed

Woodham, Andrew W; Raff, Adam B; Raff, Laura M; Da Silva, Diane M; Yan, Lisa; Skeate, Joseph G; Wong, Michael K; Lin, Yvonne G; Kast, W Martin

2014-05-15

High-risk human papillomaviruses (HPVs) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cells in a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the APC of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. In this study, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by small interfering RNA downregulation of A2t significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC class II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein.

High-risk oncogenic HPV genotype infection associates with increased immune activation and T cell exhaustion in ART-suppressed HIV-1-infected women

PubMed Central

Papasavvas, Emmanouil; Surrey, Lea F.; Glencross, Deborah K.; Azzoni, Livio; Joseph, Jocelin; Omar, Tanvier; Feldman, Michael D.; Williamson, Anna-Lise; Siminya, Maureen; Swarts, Avril; Yin, Xiangfan; Liu, Qin; Firnhaber, Cynthia; Montaner, Luis J.

2016-01-01

ABSTRACT Persistence of human papillomavirus (HPV) and cervical disease in the context of HIV co-infection can be influenced by introduction of antiretroviral therapy (ART) and sustained immune activation despite ART. We conducted a cross-sectional study in order to evaluate immune activation/exhaustion in ART-suppressed HIV+ women with or without high-risk (HR) HPV-related cervical intraepithelial neoplasia (CIN). 55 South African women were recruited in three groups: HR (-) (n = 16) and HR (+) (n = 15) HPV with negative cervical histopathology, and HR (+) HPV with CIN grade 1/2/3 (n = 24). Sampling included endocervical brushing (HPV DNA genotyping), Pap smear (cytology), colposcopic punch biopsy (histopathology, histochemical evaluation of immune cells), and peripheral blood (clinical assessment, flow cytometry-based immune subset characterization). Statistics were done using R2.5.1. Irrespective of the presence of CIN, HR (+) HPV women had higher circulating levels of T cells expressing markers of activation/exhaustion (CD38, PD1, CTLA-4, BTLA, CD160), Tregs, and myeloid subsets expressing corresponding ligands (PDL1, PDL2, CD86, CD40, HVEM) than HR (-) HPV women. A decrease in circulating NK cells was associated with CIN grade. CD4+ T cell count associated negatively with T cell exhaustion and expression of negative regulators on myeloid cells. Women with CIN when compared to HR (-) HPV women, had higher cervical cell density in stroma and epithelium for CD4+, CD68+, and CD11c+ cells, and only in stroma for CD8+ cells. We conclude that in ART-suppressed HIV-infected women with HPV co-infection the levels of T and myeloid cell activation/exhaustion are associated with the presence of HR HPV genotypes. PMID:27467943

Acquired immune response to oncogenic human papillomavirus associated with prophylactic cervical cancer vaccines.

PubMed

Einstein, Mark H

2008-04-01

Human papillomavirus (HPV) is a common infection among women and a necessary cause of cervical cancer. Oncogenic HPV types infecting the anogenital tract have the potential to induce natural immunity, but at present we do not clearly understand the natural history of infection in humans and the mechanisms by which the virus can evade the host immune response. Natural acquired immune responses against HPV may be involved in the clearance of infection, but persistent infection with oncogenic virus types leads to the development of precancerous lesions and cancer. B cell responses are important for viral neutralization, but antibody responses in patients with cervical cancer are poor. Prophylactic vaccines targeting oncogenic virus types associated with cervical cancer have the potential to prevent up to 80% of cervical cancers by targeting HPV types 16 and 18. Clinical data show that prophylactic vaccines are effective in inducing antibody responses and in preventing persistent infection with HPV, as well as the subsequent development of high-grade cervical intraepithelial neoplasia. This article reviews the known data regarding natural immune responses to HPV and those developed by prophylactic vaccination.

Impact of Louisiana's HPV Vaccine Awareness Policy on HPV Vaccination among 13- to 17-Year-Old Females

ERIC Educational Resources Information Center

Pierre-Victor, Dudith; Trepka, Mary Jo; Page, Timothy F.; Li, Tan; Stephens, Dionne P.; Madhivanan, Purnima

2017-01-01

The Advisory Committee on Immunization Practices recommends routine human papillomavirus (HPV) immunization for 11- to 12-year-old adolescents. In 2008, Louisiana required the school boards to distribute HPV vaccine information to parents or guardian of students in Grades 6 to 12. This article investigates the impact of this policy on HPV…

Purification and immunogenicity study of human papillomavirus 58 virus-like particles expressed in Pichia pastoris.

PubMed

Jiang, Zijun; Tong, Guangjie; Cai, Beibei; Xu, Yihan; Lou, Jueren

2011-12-01

Two human papillomavirus (HPV) prophylactic vaccines are currently available in the market: Gardasil and Cervarix. These two vaccines work against tumor high-risk subtypes HPV 16 and HPV 18. However, they do not include other high-risk subtypes such as HPV 58. Epidemiological research in China shows that HPV 58 is a prevalent high-risk subtype, second only to HPV 16 and HPV 18. Thus, for cervical cancer prevention in China, developing a vaccine against HPV 58 is necessary. In this study, HPV 58 virus-like particles (VLPs) were expressed in the Pichia pastoris, and subsequently purified through pretreatment and a three-step purification process consisting of strong cation exchange chromatography, size-exclusion chromatography, and hydroxyapatite chromatography. The highly purified HPV 58 VLPs were confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, electron microscopy, dynamic laser scattering, and ultracentrifugation. The purified VLPs were used to immunize mice to test their ability to induce humoral immunity. Enzyme-linked immunosorbent assays were performed on the sera of the immunized mice and significantly high anti-HPV 58 VLP antibody titers were observed. The immunogenicity study demonstrates that the purified HPV 58 VLPs are HPV vaccine candidates. Copyright © 2011 Elsevier Inc. All rights reserved.

Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

PubMed

Verma, Meghna; Erwin, Samantha; Abedi, Vida; Hontecillas, Raquel; Hoops, Stefan; Leber, Andrew; Bassaganya-Riera, Josep; Ciupe, Stanca M

2017-01-01

Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

Immunostimulatory Activity of the Cytokine-Based Biologic, IRX-2, on Human Papillomavirus-Exposed Langerhans Cells

PubMed Central

Da Silva, Diane M.; Woodham, Andrew W.; Naylor, Paul H.; Egan, James E.; Berinstein, Neil L.

2016-01-01

Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8+ T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers. PMID:26653678

Immunostimulatory Activity of the Cytokine-Based Biologic, IRX-2, on Human Papillomavirus-Exposed Langerhans Cells.

PubMed

Da Silva, Diane M; Woodham, Andrew W; Naylor, Paul H; Egan, James E; Berinstein, Neil L; Kast, W Martin

2016-05-01

Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8(+) T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers.

School Entry Requirements and Coverage of Nontargeted Adolescent Vaccines

PubMed Central

Reiter, Paul L.; Truong, Young K.; Rimer, Barbara K.; Brewer, Noel T.

2016-01-01

BACKGROUND: Low human papillomavirus (HPV) vaccination coverage is an urgent public health problem requiring action. To identify policy remedies to suboptimal HPV vaccination, we assessed the relationship between states’ school entry requirements and adolescent vaccination. METHODS: We gathered data on states’ school entry requirements for adolescent vaccination (tetanus, diphtheria, and pertussis [Tdap] booster; meningococcal; and HPV) from 2007 to 2012 from Immunization Action Coalition. The National Immunization Survey–Teen provided medical record–verified vaccination data for 99 921 adolescents. We calculated coverage (among 13- to 17-year-olds) for individual vaccinations and concomitant vaccination. HPV vaccination outcomes were among female adolescents. Analyses used weighted longitudinal multivariable models. RESULTS: States with requirements for Tdap booster and meningococcal vaccination had 22 and 24 percentage point increases in coverage for these vaccines, respectively, compared with other states (both P < .05). States with HPV vaccination requirements had <1 percentage point increase in coverage for this vaccine (P < .05). Tdap booster and meningococcal vaccination requirements, respectively, were associated with 8 and 4 percentage point spillover increases for HPV vaccination coverage (both P < .05) and with increases for concomitant vaccination (all P < .05). CONCLUSIONS: Ensuring all states have meningococcal vaccination requirements could improve the nation’s HPV vaccination coverage, given that many states already require Tdap booster but not meningococcal vaccination for school entry. Vaccination programs and clinicians should capitalize on changes in adolescent vaccination, including concomitant vaccination, that may arise after states adopt vaccination requirements. Additional studies are needed on the effects of HPV vaccination requirements and opt-out provisions. PMID:27940689

School Entry Requirements and Coverage of Nontargeted Adolescent Vaccines.

PubMed

Moss, Jennifer L; Reiter, Paul L; Truong, Young K; Rimer, Barbara K; Brewer, Noel T

2016-12-01

Low human papillomavirus (HPV) vaccination coverage is an urgent public health problem requiring action. To identify policy remedies to suboptimal HPV vaccination, we assessed the relationship between states' school entry requirements and adolescent vaccination. We gathered data on states' school entry requirements for adolescent vaccination (tetanus, diphtheria, and pertussis [Tdap] booster; meningococcal; and HPV) from 2007 to 2012 from Immunization Action Coalition. The National Immunization Survey-Teen provided medical record-verified vaccination data for 99 921 adolescents. We calculated coverage (among 13- to 17-year-olds) for individual vaccinations and concomitant vaccination. HPV vaccination outcomes were among female adolescents. Analyses used weighted longitudinal multivariable models. States with requirements for Tdap booster and meningococcal vaccination had 22 and 24 percentage point increases in coverage for these vaccines, respectively, compared with other states (both P < .05). States with HPV vaccination requirements had <1 percentage point increase in coverage for this vaccine (P < .05). Tdap booster and meningococcal vaccination requirements, respectively, were associated with 8 and 4 percentage point spillover increases for HPV vaccination coverage (both P < .05) and with increases for concomitant vaccination (all P < .05). Ensuring all states have meningococcal vaccination requirements could improve the nation's HPV vaccination coverage, given that many states already require Tdap booster but not meningococcal vaccination for school entry. Vaccination programs and clinicians should capitalize on changes in adolescent vaccination, including concomitant vaccination, that may arise after states adopt vaccination requirements. Additional studies are needed on the effects of HPV vaccination requirements and opt-out provisions. Copyright © 2016 by the American Academy of Pediatrics.

Too late to vaccinate? The incremental benefits and cost-effectiveness of a delayed catch-up program using the 4-valent human papillomavirus vaccine in Norway.

PubMed

Burger, Emily A; Sy, Stephen; Nygård, Mari; Kristiansen, Ivar S; Kim, Jane J

2015-01-15

Human papillomavirus (HPV) vaccines are ideally administered before HPV exposure; therefore, catch-up programs for girls past adolescence have not been readily funded. We evaluated the benefits and cost-effectiveness of a delayed, 1-year female catch-up vaccination program in Norway. We calibrated a dynamic HPV transmission model to Norwegian data and projected the costs and benefits associated with 8 HPV-related conditions while varying the upper vaccination age limit to 20, 22, 24, or 26 years. We explored the impact of vaccine protection in women with prior vaccine-targeted HPV infections, vaccine cost, coverage, and natural- and vaccine-induced immunity. The incremental benefits and cost-effectiveness decreased as the upper age limit for catch-up increased. Assuming a vaccine cost of $150/dose, vaccination up to age 20 years remained below Norway's willingness-to-pay threshold (approximately $83 000/quality-adjusted life year gained); extension to age 22 years was cost-effective at a lower cost per dose ($50-$75). At high levels of vaccine protection in women with prior HPV exposure, vaccinating up to age 26 years was cost-effective. Results were stable with lower coverage. HPV vaccination catch-up programs, 5 years after routine implementation, may be warranted; however, even at low vaccine cost per dose, the cost-effectiveness of vaccinating beyond age 22 years remains uncertain. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Human Papillomavirus Vaccination Coverage Among Girls Before 13 Years: A Birth Year Cohort Analysis of the National Immunization Survey-Teen, 2008-2013.

PubMed

Jeyarajah, Jenny; Elam-Evans, Laurie D; Stokley, Shannon; Smith, Philip J; Singleton, James A

2016-09-01

Routine human papillomavirus (HPV) vaccination is recommended at 11 or 12 years by the Advisory Committee on Immunization Practices. National Immunization Survey-Teen data were analyzed to evaluate, among girls, coverage with one or more doses of HPV vaccination, missed opportunities for HPV vaccination, and potential achievable coverage before 13 years. Results were stratified by birth year cohorts. HPV vaccination coverage before 13 years (≥1 HPV dose) increased from 28.4% for girls born in 1995 to 46.8% for girls born in 2000. Among girls born during 1999-2000 who had not received HPV vaccination before 13 years (57.2%), 80.1% had at least 1 missed opportunity to receive HPV vaccination before 13 years. Opportunities to vaccinate for HPV at age 11 to 12 years are missed. Strategies are needed to decrease these missed opportunities for HPV vaccination. This can be facilitated by the administration of all vaccines recommended for adolescents at the same visit. © The Author(s) 2015.

ERAP1 overexpression in HPV-induced malignancies: A possible novel immune evasion mechanism.

PubMed

Steinbach, Alina; Winter, Jan; Reuschenbach, Miriam; Blatnik, Renata; Klevenz, Alexandra; Bertrand, Miriam; Hoppe, Stephanie; von Knebel Doeberitz, Magnus; Grabowska, Agnieszka K; Riemer, Angelika B

2017-01-01

Immune evasion of tumors poses a major challenge for immunotherapy. For human papillomavirus (HPV)-induced malignancies, multiple immune evasion mechanisms have been described, including altered expression of antigen processing machinery (APM) components. These changes can directly influence epitope presentation and thus T-cell responses against tumor cells. To date, the APM had not been studied systematically in a large array of HPV + tumor samples. Therefore in this study, systematic expression analysis of the APM was performed on the mRNA and protein level in a comprehensive collection of HPV16 + cell lines. Subsequently, HPV + cervical tissue samples were examined by immunohistochemistry. ERAP1 (endoplasmic reticulum aminopeptidase 1) was the only APM component consistently altered - namely overexpressed - in HPV16 + tumor cell lines. ERAP1 was also found to be overexpressed in cervical intraepithelial neoplasia and cervical cancer samples; expression levels were increasing with disease stage. On the functional level, the influence of ERAP1 expression levels on HPV16 E7-derived epitope presentation was investigated by mass spectrometry and in cytotoxicity assays with HPV16-specific T-cell lines. ERAP1 overexpression did not cause a complete destruction of any of the HPV epitopes analyzed, however, an influence of ERAP1 overexpression on the presentation levels of certain HPV epitopes could be demonstrated by HPV16-specific CD8 + T-cells. These showed enhanced killing toward HPV16 + CaSki cells whose ERAP1 expression had been attenuated to normal levels. ERAP1 overexpression may thus represent a novel immune evasion mechanism in HPV-induced malignancies, in cases when presentation of clinically relevant epitopes is reduced by overactivity of this peptidase.

Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine.

PubMed

Gupta, Gaurav; Giannino, Viviana; Rishi, Narayan; Glueck, Reinhard

2016-09-07

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver. The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world. We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV. The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1. Copyright © 2016 Elsevier Ltd. All rights reserved.

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men.

PubMed

Van Damme, Pierre; Meijer, Chris J L M; Kieninger, Dorothee; Schuyleman, Anne; Thomas, Stephane; Luxembourg, Alain; Baudin, Martine

2016-07-29

A nine-valent human papilloma virus (9vHPV) vaccine has been developed to prevent infections and diseases related to HPV 6/11/16/18 (as per the licensed quadrivalent HPV (qHPV) vaccine) as well as to five additional oncogenic HPV types (HPV 31/33/45/52/58). The 9vHPV vaccine has the potential to prevent 90% of cervical cancers, HPV-related anal, vaginal and vulval cancers and anogenital warts. We compared the immunogenicity and safety of the 9vHPV vaccine versus the qHPV vaccine in 16-26-year-old men. Participants (N=500) were randomised to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6. Serology testing was performed on day 1 and month 7. HPV type-specific antibody titres (anti-HPV 6/11/16/18/31/33/45/52/58) were determined by competitive Luminex immunoassay and expressed as geometric mean titres and seroconversion rates. Vaccine safety was also assessed. The HPV 6/11/16/18 immune responses elicited by the 9vHPV vaccine were comparable with those elicited by the qHPV vaccine. All participants receiving the 9vHPV vaccine seroconverted for HPV 31/33/45/52/58. The 9vHPV and qHPV vaccines showed comparable safety profiles. In addition to immune responses to HPV 31/33/45/52/58, a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16-26years. The safety profile was also similar for the two vaccines. The results from this study support extending the efficacy findings with qHPV vaccine to 9vHPV vaccine in men aged 16-26years. NCT02114385. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Treatment failure in patients with HPV 16-induced vulvar intraepithelial neoplasia: understanding different clinical responses to immunotherapy.

PubMed

van Esch, Edith M G; Welters, Marij J P; Jordanova, Ekaterina S; Trimbos, J Baptist M Z; van der Burg, Sjoerd H; van Poelgeest, Mariëtte I E

2012-07-01

Failure of the immune system to launch a strong and effective immune response to high-risk HPV is related to viral persistence and the development of anogenital (pre)malignant lesions such as vulvar intraepithelial neoplasia (VIN). Different forms of immunotherapy, aimed at overcoming the inertia of the immune system, have been developed and met with clinical success. Unfortunately these, in principal successful, therapeutic approaches also fail to induce clinical responses in a substantial number of cases. In this review, the authors summarize the traits of the immune response to HPV in healthy individuals and in patients with HPV-induced neoplasia. The potential mechanisms involved in the escape of HPV-induced lesions from the immune system indicate gaps in our knowledge. Finally, the interaction between the immune system and VIN is discussed with a special focus on the different forms of immunotherapy applied to treat VIN and the potential causes of therapy failure. The authors conclude that there are a number of pre-existing conditions that determine the patients' responsiveness to immunotherapy. An immunotherapeutic strategy in which different aspects of immune failure are attacked by complementary approaches, will improve the clinical response rate.

Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era.

PubMed

Brickman, Cristina; Palefsky, Joel M

2015-03-01

Human papillomavirus (HPV) infection is associated with essentially all cervical cancers, 80-90 % of anal cancers, and a high proportion of oropharyngeal, vaginal, penile, and vulvar cancers. Malignancy is preceded by the development of precancerous lesions termed high-grade squamous intraepithelial lesions (HSIL). Men and women with human immunodeficiency virus (HIV) infection are at high risk of HPV-related malignancies. The incidence of anal cancer in particular has markedly risen during the antiretroviral era due to the increased longevity of patients with HIV and the absence of anal malignancy screening programs. HIV infection may facilitate initial HPV infection by disrupting epithelial cell tight junctions. Once infection is established, HIV may promote HSIL development via the up-regulation of HPV oncogene expression and impairment of the immune response needed to clear the lesion. HIV-infected women should be screened for cervical HSIL and cancer, and HIV-infected men and women should be considered for anal screening programs.

Human papillomavirus vaccine awareness, acceptability, and decision-making factors among Chinese college students.

PubMed

Wang, Shao-Ming; Zhang, Shao-Kai; Pan, Xiong-Fei; Ren, Ze-Fang; Yang, Chun-Xia; Wang, Zeng-Zhen; Gao, Xiao-Hong; Li, Man; Zheng, Quan-Qing; Ma, Wei; Zhao, Fang-Hui; Qiao, You-Lin; Sivasubramaniam, Priya

2014-01-01

College students are recommended as the target groups for catch-up human papillomavirus (HPV) vaccination. Systematical exploration of awareness, acceptability, and decision-making factors of HPV vaccination among Chinese college students has been limited. A multi-center survey was conducted in mainland China between November 2011 and May 2012. College students aged 18-22 years were stratified by their grade, gender, and major for sampling. Socio-demographic and HPV-related information such as knowledge, perceptions, acceptability, and attitudes were collected through a questionnaire. A total of 3,497 undergraduates completed the questionnaire, among which 1,686 were males. The acceptability of the HPV vaccine was high (70.8%). Undergraduates from high-level universities, at lower grade, or with greater prior knowledge of HPV vaccines showed higher acceptability of HPV vaccination (ptrend <0.001). Additionally, undergraduates with vaccination experience outside the National Expanded Program on Immunization (OR=1.29; 95%CI: 1.10-1.51) or fear of HPV-related diseases (OR=2.79; 95%CI: 2.28-3.41) were more willing to accept HPV vaccination. General knowledge of HPV vaccine was low among undergraduates, and safety was a major concern (71.05%). The majority of students wished to pay less than 300RMB for HPV vaccine and chose the Chinese Center for Disease Control and Prevention as the most appropriate venue for vaccination. Although most undergraduates demonstrate positive attitudes towards HPV vaccination, challenges pertaining to introduction exist in China. Corresponding proactive education and governmental subsidy to do so are urgently needed by this age-group population. Suggestions and potential strategies indicated may help shape the future HPV vaccination program in China.

Immune evasion mechanisms of human papillomavirus: An update.

PubMed

Steinbach, Alina; Riemer, Angelika B

2018-01-15

Human papillomavirus (HPV) is the most frequently sexually transmitted agent in the world. It can cause cervical and other anogenital malignancies, and oropharyngeal cancer. HPV has the unique ability to persist in the host's epithelium for a long time-longer than most viruses do-which is necessary to complete its replication cycle. To this end, HPV has developed a variety of immune evasion mechanisms, which unfortunately also favor the progression of the disease from infection to chronic dysplasia and eventually to cancer. This article summarizes the current knowledge about HPV immune evasion strategies. A special emphasis lies in HPV-mediated changes of the antigen processing machinery, which is generating epitopes for T cells and contributes to the detectability of infected cells. © 2017 UICC.

Optimization of heterologous DNA-prime, protein boost regimens and site of vaccination to enhance therapeutic immunity against human papillomavirus-associated disease.

PubMed

Peng, Shiwen; Qiu, Jin; Yang, Andrew; Yang, Benjamin; Jeang, Jessica; Wang, Joshua W; Chang, Yung-Nien; Brayton, Cory; Roden, Richard B S; Hung, Chien-Fu; Wu, T-C

2016-01-01

Human papillomavirus (HPV) has been identified as the primary etiologic factor of cervical cancer as well as subsets of anogenital and oropharyngeal cancers. The two HPV viral oncoproteins, E6 and E7, are uniquely and consistently expressed in all HPV infected cells and are therefore promising targets for therapeutic vaccination. Both recombinant naked DNA and protein-based HPV vaccines have been demonstrated to elicit HPV-specific CD8+ T cell responses that provide therapeutic effects against HPV-associated tumor models. Here we examine the immunogenicity in a preclinical model of priming with HPV DNA vaccine followed by boosting with filterable aggregates of HPV 16 L2E6E7 fusion protein (TA-CIN). We observed that priming twice with an HPV DNA vaccine followed by a single TA-CIN booster immunization generated the strongest antigen-specific CD8+ T cell response compared to other prime-boost combinations tested in C57BL/6 mice, whether naïve or bearing the HPV16 E6/E7 transformed syngeneic tumor model, TC-1. We showed that the magnitude of antigen-specific CD8+ T cell response generated by the DNA vaccine prime, TA-CIN protein vaccine boost combinatorial strategy is dependent on the dose of TA-CIN protein vaccine. In addition, we found that a single booster immunization comprising intradermal or intramuscular administration of TA-CIN after priming twice with an HPV DNA vaccine generated a comparable boost to E7-specific CD8+ T cell responses. We also demonstrated that the immune responses elicited by the DNA vaccine prime, TA-CIN protein vaccine boost strategy translate into potent prophylactic and therapeutic antitumor effects. Finally, as seen for repeat TA-CIN protein vaccination, we showed that the heterologous DNA prime and protein boost vaccination strategy is well tolerated by mice. Our results provide rationale for future clinical testing of HPV DNA vaccine prime, TA-CIN protein vaccine boost immunization regimen for the control of HPV-associated diseases.

Gender and age-specific seroprevalence of human papillomavirus 16 and 18 in general population in Tehran, Iran.

PubMed

Aghakhani, Arezoo; Mamishi, Setareh; Sabeti, Shahram; Bidari-Zerehpoosh, Farahnaz; Banifazl, Mohammad; Bavand, Anahita; Ramezani, Amitis

2017-04-01

The assessment of the gender and age-specific seroprevalence of human papillomavirus (HPV) is essential for planning of HPV vaccine implementation into the preventive programs. In this study, we aimed to determine the age-specific seroprevalence of HPV-16 and 18 in both males and females in Tehran, Iran. Three hundred and seventy-eight women (10-35 years) and 162 men (10-25 years) from Tehran, Iran, were enrolled. Anti-HPV IgG antibodies against HPV-16 and HPV-18 were detected by ELISA using papillomavirus type 16 and 18 L1-capsids as antigen. HPV-16 antibody was detected in 15.6 and 13.6% of women and men, respectively. Antibody against HPV-18 was found positive in 12.7 and 8% of women and men, respectively. The highest seroprevalence of HPV-16 and 18 were seen in women aged 26-30 years (22.2 and 19.4%, respectively), and the lowest HPV-16 and 18 seropositivity rates were seen in males and females aged 10-15 years (9.3 and 1.9%, respectively). In our cohort of study, in males, both anti-HPV-16 and 18 increased after age 15 years, peaking in men aged 21-25 years. In women, both HPV-16 and 18 seropositivity increased after 15 years, declined at 21-25 years, peaked in women aged 26-30 years and again decreased after 30 years. Our data showed increasing exposure rate to high-risk HPV vaccine types in our studied population over 15 years of age. In order to prevent the HPV-related cancers, implementation of HPV vaccine into the national immunization program in Iran and vaccination of females and males less than 15 years of age are suggested.

Pre-vaccine era cervical human papillomavirus infection among screening population of women in west Austria.

PubMed

Borena, Wegene; Grünberger, Margarethe; Widschwendter, Andreas; Kraxner, Karl Heinz; Marth, Elisabeth; Mayr, Peter; Meier, Joerg; Ruth, Norman; Guerrero, Aida Tort; Marth, Christian; Holm-von Laer, Dorothee

2016-08-26

In order to evaluate the newly implemented gender-neutral HPV vaccination program, knowledge on the pre-vaccine prevalence of HPV infection is of paramount importance. Data on HPV infection among the women with no known previous cytological abnormalities are inexistent in Austria. This study presents data on the prevalence and distribution of HPV genotypes among women with no known cytological abnormalities in west Austria. Women between 18 and 65 years of age attending annual cervical cancer screening examinations were included in the study. Data on socio-demographic and reproductive factors were collected using structured questionnaires. Corresponding cervical swab samples were tested for the presence of HPV DNA and were genotyped. Questionnaire data and HPV status were linked with the corresponding cytological findings. A total of 542 women were included in the study. The mean age of the study participants was 35.9 (SD = 11.5). The prevalence of HPV infection was 20.5 %. HPV 16 (6.5 %), HPV 33 (3.3 %) and HPV 31 (3.0 %) were the dominant genotypes detected. Multivariate analysis showed that women younger than 30 years of age, smokers, women with a higher number of lifetime sexual partners and those living in the eastern districts of the study region were at significantly higher risk of HPV infection. With this study we present the first data on the prevalence of cervical HPV genotypes among a screening population in Austria. The results not only fill the missing information on HPV infection in this group of women in the country, they also provide baseline data for a future evaluation of the impact of the Austrian gender-neutral HPV immunization program. Moreover, our finding of higher HPV prevalence in the eastern compared to the western district of the study region may - at least partly - explain the east-west gradient in the standardized incidence rate of cervical cancer in the region.

HPV Vaccination among Adolescent Males: Results from the National Immunization Survey-Teen

PubMed Central

Reiter, Paul L.; Gilkey, Melissa B.; Brewer, Noel T.

2013-01-01

US guidelines provided a permissive recommendation forHPV vaccine for males in 2009, with an updated recommendation for routine vaccination in 2011. Dataon vaccine uptake among males, however, remain sparse. We analyzed 2010–2011 data (collected mostlyprior to the recommendation for routine vaccination) from the National Immunization Survey-Teen for a nationally representative sample of adolescent males ages 13–17 (n=22,365). We examined HPV vaccine initiation( receipt of at least one doseba sed on healthcare provider records) as the primary outcome. Analyses used weighted logistic regression. HPV vaccine initiation increased from 1.4% in 2010 to 8.3% in 2011. Parents who reported receiving a healthcare provider recommendation to get their sons HPV vaccine were much more likely to have vaccinated sons (OR=19.02, 95% CI: 14.36–25.19). Initiation was also higher among sons who were Hispanic (OR=1.83, 95% CI: 1.24–2.71) or who were eligible for the Vaccines for Children program (OR=1.53, 95% CI: 1.01–2.31). Only31.0% of parents with unvaccinated sons indicatedtheir sons were “somewhat likely” or “very likely” to receive HPV vaccine in the next year. The most common main reasons for parents not intending to vaccinate were believing vaccination is not needed or not necessary (24.5%), not having received a provider recommendation (22.1%), and lack of knowledge (15.9%). HPV vaccination is low among adolescent males in the US, and provider recommendation for vaccination is likely keyto improv ingvaccine uptake. Given the updated recommendation for routine vaccination and the changes in health insurance coverage that are likely to follow, continued efforts are needed to monitor HPV vaccination among males. PMID:23602667

Introduction of human papillomavirus vaccination in Nordic countries.

PubMed

Sander, Bente Braad; Rebolj, Matejka; Valentiner-Branth, Palle; Lynge, Elsebeth

2012-02-14

Cervical screening has helped decrease the incidence of cervical cancer, but the disease remains a burden for women. Human Papillomavirus (HPV) vaccination is now a promising tool for control of cervical cancer. Nordic countries (Denmark, Finland, Greenland, Iceland, Norway and Sweden) are relatively wealthy with predominantly publicly paid health care systems. The aim of this paper was to provide an update of the current status of introduction of HPV vaccine into the childhood vaccination programs in this region. Data on cervical cancer, cervical screening programs, childhood immunization and HPV vaccination programs for Nordic countries were searched via PubMed and various organizations. We furthermore contacted selected experts for information. The incidence of cervical cancer is highest in Greenland (25 per 100,000, age standardized, World Standard Population, ASW) and lowest in Finland (4 per 100,000 ASW) and rates in the other Nordic countries vary between 7 and 11 per 100,000 ASW. Greenland and Denmark were first to introduce HPV vaccination, followed by Norway. Vaccination programs are underway in Sweden and Iceland, while Finland has just recently recommended introduction of vaccination. HPV vaccination has been intensively debated, in particular in Denmark and Norway. In Nordic countries with a moderate risk of cervical cancer and a publicly paid health care system, the introduction of HPV vaccination was a priority issue. Many players became active, from the general public to health professionals, special interest groups, and the vaccine manufacturers. These seemed to prioritize different health care needs and weighed differently the uncertainty about the long-term effects of the vaccine. HPV vaccination posed a pressure on public health authorities to consider the evidence for and against it, and on politicians to weigh the wish for cervical cancer protection against other pertinent health issues. Copyright © 2011 Elsevier Ltd. All rights reserved.

Trivalent Human Papillomavirus (HPV) VLP vaccine covering HPV type 58 can elicit high level of humoral immunity but also induce immune interference among component types.

PubMed

Zhang, Ting; Xu, Yufei; Qiao, Liang; Wang, Youchun; Wu, Xueling; Fan, Dongsheng; Peng, Qinglin; Xu, Xuemei

2010-04-26

Both Human Papillomavirus (HPV) type 16/18 bivalent vaccine and type 16/18/6/11 quadrivalent vaccine have been proved to be safe and effective, and licensed for public use. However, these two vaccines do not quite match the distribution of HPV types in China, Southeast Asia and Latin America, where HPV 58 is highly prevalent. Here we produced three types of virus-like particles (VLPs) in baculovirus expression system, formulated a trivalent vaccine containing HPV 16, 18, and 58 L1 VLPs and examined its in vitro neutralizing titers. This vaccine could induce high level and long-term humoral immunity against the component types. But immune interference was observed when comparing type specific neutralizing antibody levels induced by trivalent vaccine to those by corresponding monovalent vaccines. This kind of interference would become more obvious when formulating more types of VLPs into multivalent vaccines, but could be greatly overcome by decreasing the antigen dosage and adding a proper adjuvant. Copyright 2010 Elsevier Ltd. All rights reserved.

HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells

PubMed Central

Van den Bergh, Johan M J; Guerti, Khadija; Willemen, Yannick; Lion, Eva; Cools, Nathalie; Goossens, Herman; Vorsters, Alex; Van Tendeloo, Viggo F I; Anguille, Sébastien; Van Damme, Pierre; Smits, Evelien L J M

2014-01-01

Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposure of IL-15 DC to the HPV vaccine results in increased expression of phenotypic maturation markers, pro-inflammatory cytokine production and cytotoxic activity against HPV-positive tumour cells. These effects are mediated by the vaccine adjuvant, partly through Toll-like receptor 4 activation. Next, we demonstrate that vaccine-exposed IL-15 DC in turn induce phenotypic activation of NK cells, resulting in a synergistic cytotoxic action against HPV-infected tumour cells. Our study thus identifies a novel mode of action of the HPV vaccine in boosting innate immunity, including killing of HPV-infected cells by DC and NK cells. PMID:24979331

Tennessee’s 3-Star Report: Using Available Data Systems to Reduce Missed Opportunities to Vaccinate Preteens

PubMed Central

Moore, Kelly L.; Fankhauser, Melissa K.; Hull, Pamela C.

2016-01-01

All preteens should receive tetanus–diphtheria–pertussis vaccine (Tdap), quadrivalent meningococcal vaccine (Men-ACWY), and the human papillomavirus (HPV) cancer vaccine series. In Tennessee, HPV vaccination rates have stagnated at low levels for a decade. Three fundamental strategies to reduce missed opportunities for immunization include administering all recommended vaccines at the same visit, making strong recommendations for vaccines, and auditing and feedback. In Tennessee, during each summer, a surge of preteens visit local health departments (LHDs) to receive a required Tdap vaccine before entering seventh grade, presenting an opportunity to administer Men-ACWY and HPV. The Tennessee Immunization Program (TIP) coined the term “3-Star visit” for such encounters and developed a monthly report to track them using data from the Patient Tracking Billing Management Information System (PTBMIS) used by LHDs across Tennessee. Implementation of this quality improvement report has correlated with a substantial increase in 3-Star visits from 2013 to 2016, particularly during the summer months. PMID:27980415

Individual- and regional-level determinants of human papillomavirus (HPV) vaccine refusal: the Ontario Grade 8 HPV vaccine cohort study.

PubMed

Remes, Olivia; Smith, Leah M; Alvarado-Llano, Beatriz E; Colley, Lindsey; Lévesque, Linda E

2014-10-08

Studies on the determinants of human papillomavirus (HPV) vaccine use have generally focused on individual-level characteristics, despite the potentially important influence of regional-level characteristics. Therefore, we undertook a population-based, retrospective cohort study to identify individual- and regional-level determinants of HPV vaccine refusal (non-receipt) in Ontario's (Canada) Grade 8 HPV Immunization Program. Ontario's administrative health and immunization databases were used to identify girls eligible for free HPV vaccination in 2007-2011 and to ascertain individual-level characteristics of cohort members (socio-demographics, vaccination history, health care utilization, medical history). The social and material characteristics of the girl's region (health unit) were derived from the 2006 Canadian Census. Generalized estimating equations (binomial distribution, logit link) were used to estimate the population-average effects of individual- and regional-level characteristics on HPV vaccine refusal. Our cohort consisted of 144,047 girls, 49.3% of whom refused HPV vaccination. Factors associated with refusal included a previous diagnosis of Down's syndrome (OR = 1.37, 95% CI 1.16-1.63) or autism (OR = 1.60, 95% CI 1.34-1.90), few physician visits (OR = 1.45, 95% CI 1.35-1.55), and previous refusal of mandatory (OR = 2.23, 95% CI 2.07-2.40) and optional (OR = 3.96, 95% CI 3.87-4.05) vaccines. Refusal was highest among the lowest and highest income levels. Finally, a previous diagnosis of obesity and living in an area of high deprivation were associated with lower refusal (OR = 0.87, 95% CI 0.83-0.92 and OR = 0.82 95%, CI 0.79-0.86, respectively). Studies on HPV vaccine determinants should consider regional-level factors. Efforts to increase HPV vaccine acceptance should include vulnerable populations (such as girls of low income) and girls with limited contact with the healthcare system.

[HPV immunization for the prevention of cervical cancer].

PubMed

Mougin, Christiane; Bourgault-Villada, Isabelle; Coursaget, Pierre

2009-12-01

Human Papillomaviruses (HPV) infect epithelial cells of the skin and mucosae. Mucosal high-risk HPV types (mainly HPV 16 and 18) are involved in the development of cervical cancer, one of the most common cancers in young women. HPV infection is usually asymptomatic and clears spontaneously, but 10 - 15 % of high-risk HPV infections are persistent and increase the risk of precancerous and cancerous lesions of the cervix. Two HPV vaccines have been licensed to provide protection against cervical cancer. To report the different aspects of HPV infection in order to improve the understanding of the particular problems of HPV vaccination and to review the most recent findings related to HPV vaccines, particularly regarding the protective efficacy of vaccines and the roles of adjuvants and immune response in protection. Articles were selected from the PubMed database (National Library of Medicine- National Institute of Health) with the following Keywords "HPV", "Prevention", "HPV vaccines", "Immune response", "Antibody". Abstracts of oral presentations from international meetings were also selected for the more recent findings. a critical analysis of the majority of papers published was undertaken and relevant information summarized. Virus-like particle production by expressing the major protein of the HPV capsid was carried out in the early 90's, leading to the recent development of two HPV vaccines. These vaccines are now licensed in many countries and have been demonstrated to be highly immunogenic. In subjects that are non-infected at the time of vaccination, HPV vaccines are highly effective in preventing persistent HPV 16 - 18 infections (90 %) and precursors lesions of cervical cancer associated with these two HPV types (close to 100 %). Clinical trials have also confirmed that HPV vaccines are well tolerated by recipients. The present paper is a detailed review published in French on HPV vaccines, their efficacy in the prevention of HPV infections and unresolved questions regarding the use of HPV vaccines. This report also includes biological and immunological information to improve the understanding of HPV vaccination.

Cell-mediated immune response: a clinical review of the therapeutic potential of human papillomavirus vaccination.

PubMed

Meyer, Sonja Izquierdo; Fuglsang, Katrine; Blaakaer, Jan

2014-12-01

This clinical review aims to assess the efficacy of human papillomavirus 16/18 (HPV16/18) vaccination on the cell-mediated immune response in women with existing cervical intraepithelial neoplasia or cervical cancer induced by HPV16 or HPV18. A focused and thorough literature search conducted in five different databases found 996 publications. Six relevant articles were chosen for further review. In total, 154 patients (>18 years of age) were enrolled in prospective study trials with 3-15 months of follow up. The vaccine applications were administered two to four times. The vaccines contained different combinations of HPV16 and HPV18 and early proteins, E6 and E7. The primary outcome was the cell-mediated immune response. Correlation to clinical outcome (histopathology) and human leukocyte antigen genes were secondary endpoints. All vaccines triggered a detectable cell-mediated immune response, some of which were statistically significant. Correlations between immunological response and clinical outcome (histopathology) were not significant, so neoplasms may not be susceptible to vaccine-generated cytotoxic T cells (CD8(+)). Prophylactic HPV vaccines have been introduced to reduce the incidence of cervical cancer in young women. Women already infected with HPV could benefit from a therapeutic HPV vaccination. Hence, it is important to continue the development of therapeutic HPV vaccines to lower the rate of HPV-associated malignancies and crucial to evaluate vaccine efficacy clinically. This clinical review represents an attempt to elucidate the theories supporting the development of an HPV vaccine with a therapeutic effect on human papillomavirus-induced malignancies of the cervix. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Cervical Cancer Neoantigen Landscape and Immune Activity is Associated with Human Papillomavirus Master Regulators.

PubMed

Qin, Yong; Ekmekcioglu, Suhendan; Forget, Marie-Andrée; Szekvolgyi, Lorant; Hwu, Patrick; Grimm, Elizabeth A; Jazaeri, Amir A; Roszik, Jason

2017-01-01

Human papillomaviruses (HPVs) play a major role in development of cervical cancer, and HPV oncoproteins are being targeted by immunotherapies. Although these treatments show promising results in the clinic, many patients do not benefit or the durability is limited. In addition to HPV antigens, neoantigens derived from somatic mutations may also generate an effective immune response and represent an additional and distinct immunotherapy strategy against this and other HPV-associated cancers. To explore the landscape of neoantigens in cervix cancer, we predicted all possible mutated neopeptides in two large sequencing data sets and analyzed whether mutation and neoantigen load correlate with antigen presentation, infiltrating immune cell types, and a HPV-induced master regulator gene expression signature. We found that targetable neoantigens are detected in most tumors, and there are recurrent mutated peptides from known oncogenic driver genes (KRAS, MAPK1, PIK3CA, ERBB2, and ERBB3) that are predicted to be potentially immunogenic. Our studies show that HPV-induced master regulators are not only associated with HPV load but may also play crucial roles in relation to mutation and neoantigen load, and also the immune microenvironment of the tumor. A subset of these HPV-induced master regulators positively correlated with expression of immune-suppressor molecules such as PD-L1, TGFB1, and IL-10 suggesting that they may be involved in abrogating antitumor response induced by the presence of mutations and neoantigens. Based on these results, we predict that HPV master regulators identified in our study might be potentially effective targets in cervical cancer.

HPV detection rate in saliva may depend on the immune system efficiency.

PubMed

Adamopoulou, Maria; Vairaktaris, Eleftherios; Panis, Vassilis; Nkenke, Emeka; Neukam, Friedreich W; Yapijakis, Christos

2008-01-01

Human papilloma virus (HPV) has been established as a major etiological factor of anogenital cancer. In addition, HPV has also been implicated in oral carcinogenesis but its detection rates appear to be highly variable, depending on the patient population tested, the molecular methodology used, as well as the type of oral specimen investigated. For example, saliva is an oral fluid that may play a role in HPV transmission, although the detection rates of the virus are lower than tissue. Recent evidence has indicated that HPV-related pathology is increased in the oral cavity of human immunodeficiency virus (HIV)-positive individuals. In order to investigate whether the presence of different HPV types in saliva depends on immune system efficiency, oral fluid samples of patients with oral cancer and without any known immune deficiency were compared with those of HIV-positive individuals. Saliva samples were collected from 68 patients with oral squamous cell carcinoma and 34 HIV seropositive individuals. HPV DNA sequences were detected by L1 concensus polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP) analysis and DNA sequencing for HPV typing. HPV DNA was detected in 7/68 (10.3%) of the oral cancer patients and in 12/34 (35.3%) of the HIV-positive individuals, a highly significant difference (p = 0.006; odds ratio 4.753; 95% confidence interval 1.698-13.271). Among HPV-positive samples, the prevalence of HPV types associated with high oncogenic risk was similar in oral cancer and HIV-positive cases (71.4% and 66.7%, respectively). In both groups, the most common HPV type was high-risk 16 (50% and 42.8%, respectively). Although a similar pattern of HPV high-risk types was detected in oral cancer and HIV-positive cases, the quantitative detection of HPV in saliva significantly depended on immune system efficiency. Furthermore, the significantly increased detection rates of HPV in saliva of HIV-positive individuals may be associated with high risk for development of HPV-related oral lesions, including malignancy.

Characteristics of memory B cells elicited by a highly efficacious HPV vaccine in subjects with no pre-existing immunity.

PubMed

Scherer, Erin M; Smith, Robin A; Simonich, Cassandra A; Niyonzima, Nixon; Carter, Joseph J; Galloway, Denise A

2014-10-01

Licensed human papillomavirus (HPV) vaccines provide near complete protection against the types of HPV that most commonly cause anogenital and oropharyngeal cancers (HPV 16 and 18) when administered to individuals naive to these types. These vaccines, like most other prophylactic vaccines, appear to protect by generating antibodies. However, almost nothing is known about the immunological memory that forms following HPV vaccination, which is required for long-term immunity. Here, we have identified and isolated HPV 16-specific memory B cells from female adolescents and young women who received the quadrivalent HPV vaccine in the absence of pre-existing immunity, using fluorescently conjugated HPV 16 pseudoviruses to label antigen receptors on the surface of memory B cells. Antibodies cloned and expressed from these singly sorted HPV 16-pseudovirus labeled memory B cells were predominantly IgG (>IgA>IgM), utilized diverse variable genes, and potently neutralized HPV 16 pseudoviruses in vitro despite possessing only average levels of somatic mutation. These findings suggest that the quadrivalent HPV vaccine provides an excellent model for studying the development of B cell memory; and, in the context of what is known about memory B cells elicited by influenza vaccination/infection, HIV-1 infection, or tetanus toxoid vaccination, indicates that extensive somatic hypermutation is not required to achieve potent vaccine-specific neutralizing antibody responses.

Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis.

PubMed

Tjon Pian Gi, Robin E A; San Giorgi, Michel R M; Pawlita, Michael; Michel, Angelika; van Hemel, Bettien M; Schuuring, Ed M D; van den Heuvel, Edwin R; van der Laan, Bernard F A M; Dikkers, Frederik G

2016-10-01

Aim of this study was to explore influence of the quadrivalent HPV vaccine (Gardasil(®)) on the immune status of recurrent respiratory papillomatosis (RRP) patients. In retrospective observational study, six RRP patients who received the quadrivalent HPV vaccine and whose HPV seroreactivity was measured were included. Multiplex HPV Serology was used to determine HPV-specific antibodies pre- and post-vaccination. Surgical interventions and patient records were analyzed. Five HPV6 and 1 HPV11 infected patient were included. Mean antibody reactivity against the associated HPV type rose from 1125 median fluorescence intensity (MFI) pre-vaccination to 4690 MFI post-vaccination (p < 0.001). Median post-vaccination follow-up was 4 years. Poisson regression analysis showed that the quadrivalent HPV vaccine decreased the incidence rate of surgeries. The immune system of RRP patients is able to increase antibody reactivity against the associated HPV type. A double blind randomized controlled trial is needed to determine whether this immunological increase can cause decrease in number of surgeries.

First Aid: Warts

MedlinePlus

... on this topic for: Parents Kids Teens Warts Genital Warts (HPV) Your Child's Immunizations: Human Papillomavirus (HPV) Vaccine ... With Warts? Warts About Sexually Transmitted Diseases (STDs) Genital Warts (HPV) HPV Vaccine Molluscum Contagiosum View more Partner ...

HPV vaccination coverage of teen girls: the influence of health care providers.

PubMed

Smith, Philip J; Stokley, Shannon; Bednarczyk, Robert A; Orenstein, Walter A; Omer, Saad B

2016-03-18

Between 2010 and 2014, the percentage of 13-17 year-old girls administered ≥3 doses of the human papilloma virus (HPV) vaccine ("fully vaccinated") increased by 7.7 percentage points to 39.7%, and the percentage not administered any doses of the HPV vaccine ("not immunized") decreased by 11.3 percentage points to 40.0%. To evaluate the complex interactions between parents' vaccine-related beliefs, demographic factors, and HPV immunization status. Vaccine-related parental beliefs and sociodemographic data collected by the 2010 National Immunization Survey-Teen among teen girls (n=8490) were analyzed. HPV vaccination status was determined from teens' health care provider (HCP) records. Among teen girls either unvaccinated or fully vaccinated against HPV, teen girls whose parent was positively influenced to vaccinate their teen daughter against HPV were 48.2 percentage points more likely to be fully vaccinated. Parents who reported being positively influenced to vaccinate against HPV were 28.9 percentage points more likely to report that their daughter's HCP talked about the HPV vaccine, 27.2 percentage points more likely to report that their daughter's HCP gave enough time to discuss the HPV shot, and 43.4 percentage points more likely to report that their daughter's HCP recommended the HPV vaccine (p<0.05). Among teen girls administered 1-2 doses of the HPV vaccine, 87.0% had missed opportunities for HPV vaccine administration. Results suggest that an important pathway to achieving higher ≥3 dose HPV vaccine coverage is by increasing HPV vaccination series initiation though HCP talking to parents about the HPV vaccine, giving parents time to discuss the vaccine, and by making a strong recommendation for the HPV. Also, HPV vaccination series completion rates may be increased by eliminating missed opportunities to vaccinate against HPV and scheduling additional follow-up visits to administer missing HPV vaccine doses. Published by Elsevier Ltd.

Costs of introducing and delivering HPV vaccines in low and lower middle income countries: inputs for GAVI policy on introduction grant support to countries.

PubMed

Levin, Ann; Wang, Susan A; Levin, Carol; Tsu, Vivien; Hutubessy, Raymond

2014-01-01

In November 2011, the GAVI Alliance made the decision to add HPV vaccine as one of the new vaccines for which countries eligible for its funding (less than $1520 per capita income) could apply to receive support for national HPV vaccination, provided they could demonstrate the ability to deliver HPV vaccines. This paper describes the data and analysis shared with GAVI policymakers for this decision regarding GAVI HPV vaccine support. The paper reviews why strategies and costs for HPV vaccine delivery are different from other vaccines and what is known about the cost components from available data that originated primarily from HPV vaccine delivery costing studies in low and middle income-countries. Financial costs of HPV vaccine delivery were compared across three sources of data: 1) vaccine delivery costing of pilot projects in five low and lower-middle income countries; 2) cost estimates of national HPV vaccination in two low income countries; and 3) actual expenditure data from national HPV vaccine introduction in a low income country. Both costs of resources required to introduce the vaccine (or initial one-time investment, such as cold chain equipment purchases) and recurrent (ongoing costs that repeat every year) costs, such as transport and health personnel time, were analyzed. The cost per dose, cost per fully immunized girl (FIG) and cost per eligible girl were compared across studies. Costs varied among pilot projects and estimates of national programs due to differences in scale and service delivery strategy. The average introduction costs per fully immunized girl ranged from $1.49 to $18.94 while recurrent costs per girl ranged from $1.00 to $15.69, with both types of costs varying by delivery strategy and country. Evaluating delivery costs along programme characteristics as well as country characteristics (population density, income/cost level, existing service delivery infrastructure) are likely the most informative and useful for anticipating costs for HPV vaccine delivery. This paper demonstrates the importance of country level cost data to inform global donor policies for vaccine introduction support. Such data are also valuable for informing national decisions on HPV vaccine introduction.

To vaccinate or not to vaccinate? Perspectives on HPV vaccination among girls, boys, and parents in the Netherlands: a Q-methodological study.

PubMed

Patty, Nathalie J S; van Dijk, Hanna Maria; Wallenburg, Iris; Bal, Roland; Helmerhorst, Theo J M; van Exel, Job; Cramm, Jane Murray

2017-11-07

Despite the introduction of Human papillomavirus (HPV) vaccination in national immunization programs (NIPs), vaccination rates in most countries remain relatively low. An understanding of the reasons underlying decisions about whether to vaccinate is essential in order to promote wider spread of HPV vaccination. This is particularly important in relation to policies seeking to address shortfalls in current HPV campaigns. The aim of this study was to explore prevailing perspectives concerning HPV vaccination among girls, boys, and parents, and so to identify potential determinants of HPV vaccination decisions in these groups. Perspectives were explored using Q-methodology. Forty-seven girls, 39 boys, and 107 parents in the Netherlands were asked to rank a comprehensive set of 35 statements, assembled based on the health belief model (HBM), according to their agreement with them. By-person factor analysis was used to identify common patterns in these rankings, which were interpreted as perspectives on HPV vaccination. These perspectives were further interpreted and described using data collected with interviews and open-ended questions. The analysis revealed four perspectives: "prevention is better than cure," "fear of unknown side effects," "lack of information and awareness," and "my body, my choice." The first two perspectives and corresponding determinants of HPV vaccination decisions were coherent and distinct; the third and fourth perspectives were more ambiguous and, to some extent, incoherent, involving doubt and lack of awareness and information (perspective 3), and overconfidence (perspective 4). Given the aim of publically funded vaccination programs to minimize the spread of HPV infection and HPV-related disease and the concerns about current uptake levels, our results indicate that focus should be placed on increasing awareness and knowledge, in particular among those in a modifiable phase.

Human papillomavirus 16 E2-, E6- and E7-specific T-cell responses in children and their mothers who developed incident cervical intraepithelial neoplasia during a 14-year follow-up of the Finnish Family HPV cohort.

PubMed

Koskimaa, Hanna-Mari; Paaso, Anna E; Welters, Marij J P; Grénman, Seija E; Syrjänen, Kari J; van der Burg, Sjoerd H; Syrjänen, Stina M

2014-02-13

Human papillomavirus (HPV) infection has traditionally been regarded as a sexually transmitted disease (STD), but recent evidence implicates that an infected mother can transmit HPV to her newborn during pregnancy, at delivery, perinatal period or later. Given the lack of any studies on HPV-specific immune responses in children, we conducted HPV16-specific cell-mediated immune (CMI) monitoring of the mother-child pairs with known oral and genital HPV follow-up (FU) data since the delivery. In the Finnish Family HPV Study, 10 out of 331 mothers developed incident cervical intraepithelial neoplasia (CIN) during their 14-year FU. Our hypothesis according to the common dogma is that there is no HPV16 specific immune response in offspring of the CIN mother as she/he has not started the sexual life yet. We used overlapping 30-35 mer peptides covering the entire HPV16 E2, E6 and E7 protein sequences. Assays for lymphocyte proliferation capacity, cytokine production and HPV16-specific Foxp3 + CD25 + CD4+ regulatory T-cells were performed. HPV16-specific proliferative T-cell responses were broader in children than in their mothers. Nine of 10 children had responses against both E2 peptide pools compared to only 4 of the 10 mothers. Six of the 10 children and only 2 mothers displayed reactivity to E6 and/or E7. The cytokine levels of IL-2 (p = 0.023) and IL-5 (p = 0.028) induced by all peptide pools, were also higher among children than their mothers. The children of the mothers with incident CIN3 had significantly higher IFN-γ (p = 0.032) and TNF-α (p = 0.008) levels than other children. Our study is the first to show that also children could have HPV-specific immunity. These data indicate that the children have circulating HPV16-specific memory T-cells which might have been induced by previous HPV16 exposure or ongoing HPV 16 infection.

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV).

PubMed

Huber, Bettina; Schellenbacher, Christina; Shafti-Keramat, Saeed; Jindra, Christoph; Christensen, Neil; Kirnbauer, Reinhard

2017-01-01

Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa) 17-36) on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV) neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross-) protected against beta HPV5/20/24/38/96/16 (but not type 76), while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target cutaneous HPV infections.

Human papillomavirus-exposed Langerhans cells are activated by stabilized Poly-I:C.

PubMed

Da Silva, Diane M; Woodham, Andrew W; Rijkee, Laurie K; Skeate, Joseph G; Taylor, Julia R; Koopman, Maaike E; Brand, Heike E; Wong, Michael K; McKee, Greg M; Salazar, Andres M; Kast, W Martin

2015-12-01

Human papillomaviruses (HPV) establish persistent infections because of evolved immune evasion mechanisms, particularly HPV-mediated suppression of the immune functions of Langerhans cells (LC), the antigen presenting cells of the epithelium. Polyinosinic-polycytidilic acid (Poly-I:C) is broadly immunostimulatory with the ability to enhance APC expression of costimulatory molecules and inflammatory cytokines resulting in T cell activation. Here we investigated the activation of primary human LC derived from peripheral blood monocytes after exposure to HPV16 virus like particles followed by treatment with stabilized Poly-I:C compounds (s-Poly-I:C), and their subsequent induction of HPV16-specific T cells. Our results indicate that HPV16 particles alone were incapable of inducing LC activation as demonstrated by the lack of costimulatory molecules, inflammatory cytokines, chemokine-directed migration, and HPV16-specific CD8 + T cells in vitro . Conversely, s-Poly-I:C caused significant upregulation of costimulatory molecules and induction of chemokine-directed migration of LC that were pre-exposed to HPV16. In HLA-A*0201-positive donors, s-Poly-I:C treatment was able to induce CD8 + T cell immune responses against HPV16-derived peptides. Thus, s-Poly-I:C compounds are attractive for translation into therapeutics in which they could potentially mediate clearance of persistent HPV infection.

A pan-HPV vaccine based on bacteriophage PP7 VLPs displaying broadly cross-neutralizing epitopes from the HPV minor capsid protein, L2.

PubMed

Tumban, Ebenezer; Peabody, Julianne; Peabody, David S; Chackerian, Bryce

2011-01-01

Current human papillomavirus (HPV) vaccines that are based on virus-like particles (VLPs) of the major capsid protein L1 largely elicit HPV type-specific antibody responses. In contrast, immunization with the HPV minor capsid protein L2 elicits antibodies that are broadly cross-neutralizing, suggesting that a vaccine targeting L2 could provide more comprehensive protection against infection by diverse HPV types. However, L2-based immunogens typically elicit much lower neutralizing antibody titers than L1 VLPs. We previously showed that a conserved broadly neutralizing epitope near the N-terminus of L2 is highly immunogenic when displayed on the surface of VLPs derived from the bacteriophage PP7. Here, we report the development of a panel of PP7 VLP-based vaccines targeting L2 that protect mice from infection with carcinogenic and non-carcinogenic HPV types that infect the genital tract and skin. L2 peptides from eight different HPV types were displayed on the surface of PP7 bacteriophage VLPs. These recombinant L2 VLPs, both individually and in combination, elicited high-titer anti-L2 IgG serum antibodies. Immunized mice were protected from high dose infection with HPV pseudovirus (PsV) encapsidating a luciferase reporter. Mice immunized with 16L2 PP7 VLPs or 18L2 PP7 VLPs were nearly completely protected from both PsV16 and PsV18 challenge. Mice immunized with the mixture of eight L2 VLPs were strongly protected from genital challenge with PsVs representing eight diverse HPV types and cutaneous challenge with HPV5 PsV. VLP-display of a cross-neutralizing HPV L2 epitope is an effective approach for inducing high-titer protective neutralizing antibodies and is capable of offering protection from a spectrum of HPVs associated with cervical cancer as well as genital and cutaneous warts.

Cost-effectiveness of HPV vaccination in Belize.

PubMed

Walwyn, Leslie; Janusz, Cara Bess; Clark, Andrew David; Prieto, Elise; Waight, Eufemia; Largaespada, Natalia

2015-05-07

Among women in Belize, cervical cancer is both the leading cancer and the leading cause of cancer deaths. Both the quadrivalent and bivalent human papillomavirus (HPV) vaccines are licensed in Belize. The Ministry of Health of Belize convened a multidisciplinary team to estimate the costs, health benefits, and cost-effectiveness of adding an HPV vaccine to the national immunization schedule. The CERVIVAC cost-effectiveness model (Version 1.123) was used to assess the lifetime health and economic outcomes of vaccinating one cohort of girls aged 10 years against HPV. The comparator was no HPV vaccination. The PAHO Revolving Fund negotiated price of US$ 13.79 per dose was used (for the quadrivalent vaccine) and national data sources were used to define demography, cervical cancer incidence and mortality, cervical cancer treatment costs, and vaccine delivery costs. Estimates from international agencies were used in scenario analysis. In a cohort of ∼4000 Belizean girls tracked over a lifetime, HPV vaccination is estimated to prevent 69 new cases of cervical cancer (undiscounted), and 51 cervical cancer deaths (undiscounted). Considering the potential cervical cancer treatment costs and lost wages avoided by households (societal perspective), the cost per disability-adjusted life year (DALY) averted was estimated to be US$ 429. This increased to US$ 1320 when cervical cancer treatment costs and lost wages were excluded from the analysis. Both estimates are far below the gross domestic product (GDP) per capita of Belize (US$ 4795). The lifetime health care costs saved by the women and their families represent more than 60% of the investment cost needed by the Government for the vaccine. Routine HPV vaccination would be highly cost-effective in Belize. If affordable, efforts should be made to expedite the introduction of this vaccine into the Belizean national immunization program. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reversal of Human Papillomavirus-Specific T Cell Immune Suppression through TLR Agonist Treatment of Langerhans Cells Exposed to Human Papillomavirus Type 161

PubMed Central

Fahey, Laura M.; Raff, Adam B.; Da Silva, Diane M.; Kast, W. Martin

2009-01-01

Human papillomavirus (HPV) type 16 infects the epithelial layer of cervical mucosa and is causally associated with the generation of cervical cancer. Langerhans cells (LC) are the resident antigen-presenting cells at the site of infection and therefore are responsible for initiating an immune response against HPV16. On the contrary, LC exposed to HPV16 do not induce a specific T cell immune response, which leads to the immune evasion of HPV16. Demonstrating that Toll-like receptor 7 (TLR7) and TLR8 are expressed on human LC, we hypothesized that imidazoquinolines would activate LC exposed to HPV16, leading to the induction of an HPV16-specific cell-mediated immune response. Surprisingly both phenotypic and functional hallmarks of activation are not observed when LC are exposed to HPV16 virus-like particles (VLP) and treated with imiquimod (TLR7 agonist). However, we found that LC are activated by 3M-002 (TLR8 agonist) and resiquimod (TLR8/7 agonist). LC exposed to HPV16 VLP and subsequently treated with 3M-002 or resiquimod highly up-regulate surface activation markers, secrete pro-inflammatory cytokines and chemokines, induce CCL21-directed migration, and initiate an HPV16-specific CD8+ T cell response. These data strongly indicate that 3M-002 and resiquimod are promising therapeutics for treatment of HPV-infections and HPV-induced cervical lesions. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org.” PMID:19234187

Cost-effectiveness analysis of introducing universal human papillomavirus vaccination of girls aged 11 years into the National Immunization Program in Brazil.

PubMed

Novaes, Hillegonda Maria Dutilh; de Soárez, Patrícia Coelho; Silva, Gulnar Azevedo; Ayres, Andreia; Itria, Alexander; Rama, Cristina Helena; Sartori, Ana Marli Christovam; Clark, Andrew D; Resch, Stephen

2015-05-07

To evaluate the impact and cost-effectiveness of introducing universal human papillomavirus (HPV) vaccination into the National Immunization Program (NIP) in Brazil. The Excel-based CERVIVAC decision support model was used to compare two strategies: (1) status quo (with current screening program) and (2) vaccination of a cohort of 11-year-old girls. National parameters for the epidemiology and costs of cervical cancer were estimated in depth. The estimates were based on data from the health information systems of the public health system, the PNAD 2008 national household survey, and relevant scientific literature on Brazil. Costs are expressed in 2008 United States dollars (US$), and a 5% discount rate is applied to both future costs and future health benefits. Introducing the HPV vaccine would reduce the burden of disease. The model estimated there would be 229 deaths avoided and 6677 disability-adjusted life years (DALYs) averted in the vaccinated cohort. The incremental cost-effectiveness ratios (ICERs) per DALY averted from the perspectives of the government (US$ 7663), health system (US$ 7412), and society (US$ 7298) would be considered cost-effective, according to the parameters adopted by the World Health Organization. In the sensitivity analysis, the ICERs were most sensitive to variations in discount rate, disease burden, vaccine efficacy, and proportion of cervical cancer caused by types 16 and 18. However, universal HPV vaccination remained a cost-effective strategy in most variations of the key estimates. Vaccine introduction could contribute additional benefits in controlling cervical cancer, but it requires large investments by the NIP. Among the essential conditions for attaining the expected favorable results are immunization program sustainability, equity in a population perspective, improvement of the screening program, and development of a surveillance system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Human papillomavirus vaccines and vaccine implementation.

PubMed

de Sanjosé, Silvia; Alemany, Laia; Castellsagué, Xavier; Bosch, F Xavier

2008-11-01

Countries are now challenged by the rapid development of vaccines aimed at the primary prevention of infections. In the years to come, several vaccines will need to be considered as potential candidates in routine immunization programs. Recently, two new vaccines against two/four types of human papillomavirus (HPV) have been commercialized. Bivalent HPV 16 and 18 (Cervarix) and quadrivalent HPV 6, 11, 16 and 18 (Gardasil) vaccines are now extensively used in some countries. These vaccines will prevent infection and long-running complications, such as cervical cancer, other HPV-related cancers and genital warts (for the quadrivalent vaccine). The beneficial effect of these vaccines will be largely observed in women. This article summarizes the burden of HPV preventable disease worldwide and briefly describes the impact of secondary prevention and the most relevant aspects of the current available vaccines, their efficacy and safety. Finally, some major aspects that are likely to impact the introduction of these vaccines around the world are outlined, with particular emphasis on developing countries.

Therapeutic HPV vaccines.

PubMed

Hancock, Gemma; Hellner, Karin; Dorrell, Lucy

2018-02-01

High-risk human papillomavirus (HPV) infection is known to be a necessary factor for cervical and anogenital malignancies. Cervical cancers account for over a quarter of a million deaths annually. Despite the availability of prophylactic vaccines, HPV infections remain extremely common worldwide. Furthermore, these vaccines are ineffective at clearing pre-existing infections and associated preinvasive lesions. As cervical dysplasia can regress spontaneously, a therapeutic HPV vaccine that boosts host immunity could have a significant impact on the morbidity and mortality associated with HPV. Therapeutic vaccines differ from prophylactic vaccines in that they are aimed at generating cell-mediated immunity rather than neutralising antibodies. This review will cover various therapeutic vaccine strategies in development for the treatment of HPV-associated lesions and cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparatively low attendance during Human Papillomavirus catch-up vaccination among teenage girls in the Netherlands: Insights from a behavioral survey among parents.

PubMed

Gefenaite, Giedre; Smit, Marieke; Nijman, Hans W; Tami, Adriana; Drijfhout, Ingrid H; Pascal, Astrid; Postma, Maarten J; Wolters, Bert A; van Delden, Johannes J M; Wilschut, Jan C; Hak, Eelko

2012-07-02

The Dutch Human Papillomavirus (HPV) catch-up vaccination program in 2009 appeared less successful than expected. We aimed to identify the most important determinants of refusing the vaccination. Two thousand parents of girls born in 1996 targeted for HPV vaccination received an invitation letter to participate in a questionnaire study. Two study groups were defined: the first group consisted of parents of girls who had accepted the vaccine and already received the first dose of HPV vaccination. The second group consisted of parents whose daughters were not vaccinated. The questionnaire consisted of a broad spectrum of possible determinants that were revealed after literature search and discussions with the stakeholders. Four hundred sixty nine questionnaires (24%) were returned, 307 (31%) from those who accepted and 162 (16%) from those who declined the vaccine. The decision not to accept the vaccine was largely determined by: (i) perception that the information provided by the government about the vaccine was limited or biased (OR 13.27); (ii) limited trust, that the government would stop the vaccination program if there were serious side effects (OR 9.95); (iii) lack of knowledge about the effectiveness of the vaccine (OR 7.67); (iv) concerns about the side effects of the vaccine (OR 4.94); (v) lack of conviction that HPV can be extremely harmful (OR 3.78); (vi) perception that the government is strongly influenced by vaccine producers (OR 3.54); and (vii) religious convictions (OR 2.18). This study revealed several determinants for HPV vaccination uptake after implementation of the HPV vaccine for adolescent girls. These determinants should be taken into consideration in order to successfully implement HPV vaccination into National Immunization Programs.

Cost-Effectiveness Evaluation of Quadrivalent Human Papilloma Virus Vaccine for HPV-Related Disease in Iran

PubMed Central

Khatibi, Mohsen; Rasekh, Hamid Reza; Shahverdi, Zohreh; jamshidi, Hamid Reza

2014-01-01

Human Papilloma Virus (HPV) vaccine has been added recently to the Iran Drug List. So, decision makers need information beyond that available from RCTs to recommend funding for this vaccination program to add it to the National Immunization program in Iran. Modeling and economic studies have addressed some of those information needs in foreign countries. In order to determine the long term benefit of this vaccine and impact of vaccine program on the future rate of cervical cancer in Iran, we described a model, based on the available economic and health effects of human papilloma virus (HPV), to estimate the cost-effectiveness of HPV vaccination of 15-year-old girls in Iran. Our objective is to estimate the cost-effectiveness of HPV vaccination in Iran against cervical cancer based on available data; incremental cost-effectiveness ratio (ICER) calculations were based on a model comparing a cohort of 15-year-old girls with and without vaccination. We developed a static model based on available data in Iran on the epidemiology of HPV related health outcome. The model compared the cohort of all 15-year old girls alive in the year 2013 with and without vaccination. The cost per QALY, which was found based on our assumption for the vaccination of 15-years old girl to current situation was 439,000,000 Iranian Rial rate (IRR). By considering the key parameters in our sensitivity analysis, value varied from 251,000,000 IRR to 842,000,000 IRR. In conclusion, quadrivalent HPV vaccine (Gardasil) is not cost-effective in Iran based on the base-case parameters value. PMID:24711850

Efficacy of the HPV-16/18 AS04-Adjuvanted Vaccine Against Low-Risk HPV Types (PATRICIA Randomized Trial): An Unexpected Observation

PubMed Central

Szarewski, Anne; Skinner, S. Rachel; Garland, Suzanne M.; Romanowski, Barbara; Schwarz, Tino F.; Apter, Dan; Chow, Song-Nan; Paavonen, Jorma; Del Rosario-Raymundo, M. Rowena; Teixeira, Julio C.; De Carvalho, Newton S.; Castro-Sanchez, Maria; Castellsagué, Xavier; Poppe, Willy A. J.; De Sutter, Philippe; Huh, Warner; Chatterjee, Archana; Tjalma, Wiebren A.; Ackerman, Ronald T.; Martens, Mark; Papp, Kim A.; Bajo-Arenas, Jose; Harper, Diane M.; Torné, Aureli; David, Marie-Pierre; Struyf, Frank; Lehtinen, Matti; Dubin, Gary

2013-01-01

Background. Public Health England has reported a decrease of up to 20.8% in new diagnoses of external genital warts (GWs) among women aged <19 years since the national vaccination program with the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine began in 2008. A post hoc analysis of the phase III PATRICIA (PApilloma TRIal against Cancer In young Adults) trial (NCT00122681) was performed to ascertain whether protection against low-risk HPV types was apparent. Methods. Vaccine efficacy (VE) at 48 months was assessed against 6-month persistent infection (6MPI) with low-risk HPV types in the total vaccinated cohort (TVC) and in the TVC naive (for 25 HPV types tested) populations. Results. In the TVC naive cohort, VE against 6MPI (95% confidence interval) was 34.5% (11.3 to 51.8) for HPV-6/11, 34.9% (9.1 to 53.7) for HPV-6, 30.3% (−45.0 to 67.5) for HPV-11, and 49.5% (21.0 to 68.3) for HPV-74. Conclusions. The HPV-16/18 AS04-adjuvanted vaccine appears to have moderate efficacy against persistent infections with a number of low-risk HPV types (HPV-6/11/74), which are responsible for the majority of external GWs, and recently, antibody and cell-mediated immune response to HPV-6/11 have been observed. These findings may help to explain the decrease in external GW diagnoses seen in England. PMID:24092907

Human papilloma virus status of penile squamous cell carcinoma is associated with differences in tumour-infiltrating T lymphocytes.

PubMed

Lohneis, Philipp; Boral, Sengül; Kaufmann, Andreas M; Lehmann, Annika; Schewe, Christiane; Dietel, Manfred; Anagnostopoulos, Ioannis; Jöhrens, Korinna

2015-03-01

Meta-analyses show that approximately half of all squamous cell carcinomas (SCCs) of the penis are associated with a human papillomavirus (HPV) infection. As data about the tumour microenvironment of HPV-positive and HPV-negative penile carcinomas is scarce and conflicting, we examined tumour-infiltrating lymphocyte populations in such cases. The HPV status of 28 penile SCCs was determined by polymerase chain reaction, while the number and distribution of different lymphocyte populations were analysed by immunohistochemistry on whole sections of paraffin-embedded tumour specimens. The average number of tumour-infiltrating T cells in HPV-associated SCC was higher than in HPV-negative SCC, and their phenotype showed strong polarization towards a T helper 1 and cytotoxic immune response. In addition, we identified more tumour-infiltrating regulatory T cells in HPV-positive carcinomas, which might represent a mechanism of immune evasion. The present study provides further evidence that the tumour microenvironment of HPV-positive carcinomas differs from that of HPV-negative carcinomas.

Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series.

PubMed

Martínez-Lavín, Manuel; Amezcua-Guerra, Luis

2017-10-01

This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79–653) [DOSAGE ERROR CORRECTED] . The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms.

Human papilloma virus load and PD-1/PD-L1, CD8+ and FOXP3 in anal cancer patients treated with chemoradiotherapy: Rationale for immunotherapy

PubMed Central

Balermpas, Panagiotis; Martin, Daniel; Wieland, Ulrike; Rave-Fränk, Margret; Strebhardt, Klaus; Rödel, Claus; Fokas, Emmanouil; Rödel, Franz

2017-01-01

ABSTRACT We examined the prognostic role of immune markers programmed cell death protein-1 (PD-1) and its ligand (PD-L1), CD8+ tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell cancer (ASCC) treated with standard chemoradiotherapy (CRT). The baseline immunohistochemical expression of immune markers was correlated with clinicopathologic characteristics, and cumulative incidence of local failure, disease-free survival (DFS) and overall survival (OS) in 150 patients, also in the context of human papilloma virus 16 (HPV16) DNA load and p16INK4a expression. After a median follow-up of 40 mo (1–205 mo), the 5-y cumulative incidence of local failure and DFS was 19.4% and 67.2%, respectively. Strong immune marker expression was significantly more common in tumors with high HPV16 viral load. In multivariant analysis, high CD8+ and PD-1+ TILs expression predicted for improved local control (p = 0.023 and p = 0.007, respectively) and DFS (p = 0.020 and p = 0.014, respectively). Also, high p16INK4a (p = 0.011) and PD-L1 (p = 0.033) expression predicted for better local control, whereas high FOXP3+ Tregs (p = 0.050) and phosphorylated Caspase-8 (p = 0.031) expression correlated with superior DFS. Female sex and high HPV16 viral load correlated with favorable outcome for all three clinical endpoints. The present data provide, for the first time, robust explanation for the favorable clinical outcome of HPV16-positive ASCC patients harboring strong immune cell infiltration. Our findings are relevant for treatment stratification with immune PD-1/PD-L1 checkpoint inhibitors to complement CRT and should be explored in a clinical trial. PMID:28405521

Estimating the clinical benefits of vaccinating boys and girls against HPV-related diseases in Europe

PubMed Central

2013-01-01

Background HPV is related to a number of cancer types, causing a considerable burden in both genders in Europe. Female vaccination programs can substantially reduce the incidence of HPV-related diseases in women and, to some extent, men through herd immunity. The objective was to estimate the incremental benefit of vaccinating boys and girls using the quadrivalent HPV vaccine in Europe versus girls-only vaccination. Incremental benefits in terms of reduction in the incidence of HPV 6, 11, 16 and 18-related diseases (including cervical, vaginal, vulvar, anal, penile, and head and neck carcinomas and genital warts) were assessed. Methods The analysis was performed using a model constructed in Microsoft®Excel, based on a previously-published dynamic transmission model of HPV vaccination and published European epidemiological data on incidence of HPV-related diseases. The incremental benefits of vaccinating 12-year old girls and boys versus girls-only vaccination was assessed (70% vaccine coverage were assumed for both). Sensitivity analyses around vaccine coverage and duration of protection were performed. Results Compared with screening alone, girls-only vaccination led to 84% reduction in HPV 16/18-related carcinomas in females and a 61% reduction in males. Vaccination of girls and boys led to a 90% reduction in HPV 16/18-related carcinomas in females and 86% reduction in males versus screening alone. Relative to a girls-only program, vaccination of girls and boys led to a reduction in female and male HPV-related carcinomas of 40% and 65%, respectively and a reduction in the incidence of HPV 6/11-related genital warts of 58% for females and 71% for males versus girls-only vaccination. Conclusions In Europe, the vaccination of 12-year old boys and girls against HPV 6, 11, 16 and 18 would be associated with substantial additional clinical benefits in terms of reduced incidence of HPV-related genital warts and carcinomas versus girls-only vaccination. The incremental benefits of adding boys vaccination are highly dependent on coverage in girls. Therefore, further analyses should be performed taking into account the country-specific situation. In addition to clinical benefits, substantial economic benefits are also anticipated and warrant further investigation as do the social and ethical implications of including boys in vaccination programs. PMID:23298365

Estimating the clinical benefits of vaccinating boys and girls against HPV-related diseases in Europe.

PubMed

Marty, Rémi; Roze, Stéphane; Bresse, Xavier; Largeron, Nathalie; Smith-Palmer, Jayne

2013-01-08

HPV is related to a number of cancer types, causing a considerable burden in both genders in Europe. Female vaccination programs can substantially reduce the incidence of HPV-related diseases in women and, to some extent, men through herd immunity. The objective was to estimate the incremental benefit of vaccinating boys and girls using the quadrivalent HPV vaccine in Europe versus girls-only vaccination. Incremental benefits in terms of reduction in the incidence of HPV 6, 11, 16 and 18-related diseases (including cervical, vaginal, vulvar, anal, penile, and head and neck carcinomas and genital warts) were assessed. The analysis was performed using a model constructed in Microsoft(®)Excel, based on a previously-published dynamic transmission model of HPV vaccination and published European epidemiological data on incidence of HPV-related diseases. The incremental benefits of vaccinating 12-year old girls and boys versus girls-only vaccination was assessed (70% vaccine coverage were assumed for both). Sensitivity analyses around vaccine coverage and duration of protection were performed. Compared with screening alone, girls-only vaccination led to 84% reduction in HPV 16/18-related carcinomas in females and a 61% reduction in males. Vaccination of girls and boys led to a 90% reduction in HPV 16/18-related carcinomas in females and 86% reduction in males versus screening alone. Relative to a girls-only program, vaccination of girls and boys led to a reduction in female and male HPV-related carcinomas of 40% and 65%, respectively and a reduction in the incidence of HPV 6/11-related genital warts of 58% for females and 71% for males versus girls-only vaccination. In Europe, the vaccination of 12-year old boys and girls against HPV 6, 11, 16 and 18 would be associated with substantial additional clinical benefits in terms of reduced incidence of HPV-related genital warts and carcinomas versus girls-only vaccination. The incremental benefits of adding boys vaccination are highly dependent on coverage in girls. Therefore, further analyses should be performed taking into account the country-specific situation. In addition to clinical benefits, substantial economic benefits are also anticipated and warrant further investigation as do the social and ethical implications of including boys in vaccination programs.

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV)

PubMed Central

Huber, Bettina; Schellenbacher, Christina; Shafti-Keramat, Saeed; Jindra, Christoph; Christensen, Neil

2017-01-01

Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa) 17–36) on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV) neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross-) protected against beta HPV5/20/24/38/96/16 (but not type 76), while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target cutaneous HPV infections. PMID:28056100

Human papillomavirus 16 E2-, E6- and E7-specific T-cell responses in children and their mothers who developed incident cervical intraepithelial neoplasia during a 14-year follow-up of the Finnish Family HPV cohort

PubMed Central

2014-01-01

Background Human papillomavirus (HPV) infection has traditionally been regarded as a sexually transmitted disease (STD), but recent evidence implicates that an infected mother can transmit HPV to her newborn during pregnancy, at delivery, perinatal period or later. Given the lack of any studies on HPV-specific immune responses in children, we conducted HPV16-specific cell-mediated immune (CMI) monitoring of the mother-child pairs with known oral and genital HPV follow-up (FU) data since the delivery. In the Finnish Family HPV Study, 10 out of 331 mothers developed incident cervical intraepithelial neoplasia (CIN) during their 14-year FU. Our hypothesis according to the common dogma is that there is no HPV16 specific immune response in offspring of the CIN mother as she/he has not started the sexual life yet. Methods We used overlapping 30–35 mer peptides covering the entire HPV16 E2, E6 and E7 protein sequences. Assays for lymphocyte proliferation capacity, cytokine production and HPV16-specific Foxp3 + CD25 + CD4+ regulatory T-cells were performed. Results HPV16-specific proliferative T-cell responses were broader in children than in their mothers. Nine of 10 children had responses against both E2 peptide pools compared to only 4 of the 10 mothers. Six of the 10 children and only 2 mothers displayed reactivity to E6 and/or E7. The cytokine levels of IL-2 (p = 0.023) and IL-5 (p = 0.028) induced by all peptide pools, were also higher among children than their mothers. The children of the mothers with incident CIN3 had significantly higher IFN-γ (p = 0.032) and TNF-α (p = 0.008) levels than other children. Conclusions Our study is the first to show that also children could have HPV-specific immunity. These data indicate that the children have circulating HPV16-specific memory T-cells which might have been induced by previous HPV16 exposure or ongoing HPV 16 infection. PMID:24524328

Impact of Vaccination on 14 High-Risk HPV Type Infections: A Mathematical Modelling Approach

PubMed Central

Vänskä, Simopekka; Auranen, Kari; Leino, Tuija; Salo, Heini; Nieminen, Pekka; Kilpi, Terhi; Tiihonen, Petri; Apter, Dan; Lehtinen, Matti

2013-01-01

The development of high-risk human papillomavirus (hrHPV) infection to cervical cancer is a complicated process. We considered solely hrHPV infections, thus avoiding the confounding effects of disease progression, screening, and treatments. To analyse hrHPV epidemiology and to estimate the overall impact of vaccination against infections with hrHPVs, we developed a dynamic compartmental transmission model for single and multiple infections with 14 hrHPV types. The infection-related parameters were estimated using population-based sexual behaviour and hrHPV prevalence data from Finland. The analysis disclosed the important role of persistent infections in hrHPV epidemiology, provided further evidence for a significant natural immunity, and demonstrated the dependence of transmission probability estimates on the model structure. The model predicted that vaccinating girls at 80% coverage will result in a 55% reduction in the overall hrHPV prevalence and a higher 65% reduction in the prevalence of persistent hrHPV infections in females. In males, the reduction will be 42% in the hrHPV prevalence solely by the herd effect from the 80% coverage in girls. If such high coverage among girls is not reached, it is still possible to reduce the female hrHPV prevalence indirectly by the herd effect if also boys are included in the vaccination program. On the other hand, any herd effects in older unvaccinated cohorts were minor. Limiting the epidemiological model to infection yielded improved understanding of the hrHPV epidemiology and of mechanisms with which vaccination impacts on hrHPV infections. PMID:24009669

Impact of Louisiana's HPV Vaccine Awareness Policy on HPV Vaccination Among 13- to 17-Year-Old Females.

PubMed

Pierre-Victor, Dudith; Trepka, Mary Jo; Page, Timothy F; Li, Tan; Stephens, Dionne P; Madhivanan, Purnima

2017-08-01

The Advisory Committee on Immunization Practices recommends routine human papillomavirus (HPV) immunization for 11- to 12-year-old adolescents. In 2008, Louisiana required the school boards to distribute HPV vaccine information to parents or guardian of students in Grades 6 to 12. This article investigates the impact of this policy on HPV vaccination among 13- to 17-year-old female adolescents using National Immunization Survey-Teen (NIS-Teen) data. Drawing on the data from the 2008 to 2012 NIS-Teen, we compared the difference in proportions of females who have been vaccinated before and after the policy. Using difference-indifference estimation, we explored the change in vaccination rates before and after the policy implementation in Louisiana compared with Alabama and Mississippi, two states that did not have such a policy in place. The difference-in-differences estimates for HPV vaccination were not significant. Physician recommendation for HPV vaccination was significantly associated with vaccination among females in Louisiana and Alabama (adjusted odds ratio [aOR] = 7.74; 95% confidence interval [CI; 5.22, 11.5]), and for those in Louisiana and Mississippi (aOR = 7.05; 95% CI [4.6, 10.5]). Compared to the proportion of female adolescents who had received physician recommendation in Alabama or Mississippi, the proportion in Louisiana did not increase significantly in the postpolicy period. HPV vaccination rates did not increase significantly in Louisiana compared to Alabama or Mississippi following the implementation of the policy. Despite Louisiana's policy, physician recommendation remains the key determinant of HPV vaccination. HPV vaccine awareness does not necessarily result in HPV vaccination.

Type-specific human papillomavirus infections and Pap test findings in Inuit and non-Inuit women in Nunavut, Canada

PubMed Central

Totten, S; Severini, A; Jayaraman, GC; Faybush, ST; Johnson, G; Demers, AA; Sobol, I; Mao, Y; Wong, T

2015-01-01

Objective To determine the prevalence and distribution of type-specific human papillomavirus (HPV) infections and their association with cytological outcomes in women living in the Canadian territory of Nunavut. Methods Surveillance of type-specific HPV infection was conducted. Cervical specimens of all Inuit, First Nations and non-Aboriginal women in Nunavut who presented for a Pap test in any clinical setting between January 2008 and March 2009 were tested for HPV infection. The association between high-grade cervical lesions and HPV type was also examined. Results HPV results were available for 4,043 individual women (13 to 77 years). Of those with known ethnicity (N=4,033), 89.2% were Inuit, 0.4% were First Nations and 10.4% were non-Aboriginal. First Nations women were included in all analyses except those making comparisons by ethnicity, due to the small number of individuals in this group. Overall, 29.9% of women were found to be infected with HPV (any type) and 19.9% with any high-risk HPV (type 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 or 59). Most often, women were infected with HPV 16 (6.4%) followed by HPV 31 (3.1%). There were no statistically significant differences between Inuit and non-Aboriginal (reference group) women 20 years of age and older regarding the prevalence of any HPV (odds ratios (OR): 1.19, 95% confidence intervals (CI): 0.92-1.54), high-risk HPV (OR: 1.06, 95% CI: 0.78-1.44) or HPV 16 and 18 (OR: 0.81, 95% CI: 0.51-1.27). HPV 31 was the only type that was significantly more frequent among Inuit than non-Aboriginal women (OR: 3.95, 95% CI: 1.24-12.54). There was no difference in the overall occurrence of cervical abnormalities between non-Aboriginal and Inuit women (p-value = 0.17). HPV 16 was strongly associated with cervical dysplasia, being present in 50.9% of specimens with a high-grade lesion. Conclusion HPV is a significant public health issue in the territory of Nunavut. The findings presented in this article are similar to those in other studies among Inuit women, with prevalence of HPV being higher than in studies conducted among non-Inuit women in other regions of Canada. These results provide a baseline of HPV prevalence that precedes the introduction of the Nunavut HPV Immunization Program in 2010 and will allow for future evaluation. The high prevalence of HPV infection among women living in Nunavut can be reduced through immunization and associated high-grade cervical abnormalities mitigated by regular cervical screening.

Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases.

PubMed

Skeate, Joseph G; Woodham, Andrew W; Einstein, Mark H; Da Silva, Diane M; Kast, W Martin

2016-06-02

Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed.

Immune status does not predict high-risk HPV in anal condyloma.

PubMed

Lee, Janet T; Goldberg, Stanley M; Madoff, Robert D; Tawadros, Patrick S

2016-03-01

More than 90% of anal condyloma is attributed to nonhigh risk strains of human papillomavirus (HPV), thus patients with anal condyloma do not necessarily undergo HPV serotyping unless they are immunocompromised (IC). We hypothesized that IC patients with anal condyloma have a higher risk of high-risk HPV and dysplasia than nonimmunocompromised (NIC) patients. We performed a retrospective chart review of patients who underwent surgical treatment by a single surgeon for anal condyloma from 1/2000 to 1/2012. HPV serotyping was performed on all patient samples. We compared incidence of high-risk HPV and dysplasia in condyloma specimens from IC and NIC patients. High-risk HPV was identified in 14 specimens with serotypes 16, 18, 31, 33, 51, 52, and 67. Twenty-two cases (18.3%) had dysplasia. Invasive carcinoma was identified in one IC patient. The prevalence of dysplasia or high-risk HPV was not significantly different between IC and NIC groups. High-risk HPV was a significant independent predictor of dysplasia (odds ratio [OR] = 5.2; 95% CI = 1.24-21.62). Immune status, however, was not a significant predictor of high-risk HPV (OR = 1.11; 95% CI = 0.16-5.12) nor dysplasia (OR = 0.27; 95% CI = 0.037-1.17). IC patients did not have a significantly higher prevalence or risk of high-risk HPV or dysplasia in our study. HPV typing of all condylomata, regardless of immune status, should be considered as it may help predict risk of neoplastic transformation or identify NIC patients with an increased risk of developing anal intraepithelial neoplasia. Copyright © 2016 Elsevier Inc. All rights reserved.

The Interaction Between Human Papillomavirus and Other Viruses

PubMed Central

Guidry, J. T.; Scott, R. S.

2016-01-01

The etiological role of human papillomavirus (HPV) in anogenital tract and head and neck cancers is well established. However, only a low percentage of HPV-positive women develop cancer, indicating that HPV is necessary but not sufficient in carcinogenesis. Several biological and environmental cofactors have been implicated in the development of HPV-associated carcinoma that include immune status, hormonal changes, parity, dietary habits, tobacco usage, and co-infection with other sexually transmissible agents. Such cofactors likely contribute to HPV persistent infection through diverse mechanisms related to immune control, efficiency of HPV infection, and influences on tumor initiation and progression. Conversely, HPV co-infection with other factors may also harbor anti-tumor effects. Here, we review epidemiological and experimental studies investigating human immunodeficiency virus (HIV), herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), BK virus (BKV) JC virus (JCV), and adeno-associated virus (AAV) as viral cofactors in or therapeutic factors against the development of genital and oral HPV-associated carcinomas. PMID:27826043

Costs of Introducing and Delivering HPV Vaccines in Low and Lower Middle Income Countries: Inputs for GAVI Policy on Introduction Grant Support to Countries

PubMed Central

Levin, Ann; Wang, Susan A.; Levin, Carol; Tsu, Vivien; Hutubessy, Raymond

2014-01-01

Background In November 2011, the GAVI Alliance made the decision to add HPV vaccine as one of the new vaccines for which countries eligible for its funding (less than $1520 per capita income) could apply to receive support for national HPV vaccination, provided they could demonstrate the ability to deliver HPV vaccines. This paper describes the data and analysis shared with GAVI policymakers for this decision regarding GAVI HPV vaccine support. The paper reviews why strategies and costs for HPV vaccine delivery are different from other vaccines and what is known about the cost components from available data that originated primarily from HPV vaccine delivery costing studies in low and middle income-countries. Methods Financial costs of HPV vaccine delivery were compared across three sources of data: 1) vaccine delivery costing of pilot projects in five low and lower-middle income countries; 2) cost estimates of national HPV vaccination in two low income countries; and 3) actual expenditure data from national HPV vaccine introduction in a low income country. Both costs of resources required to introduce the vaccine (or initial one-time investment, such as cold chain equipment purchases) and recurrent (ongoing costs that repeat every year) costs, such as transport and health personnel time, were analyzed. The cost per dose, cost per fully immunized girl (FIG) and cost per eligible girl were compared across studies. Results Costs varied among pilot projects and estimates of national programs due to differences in scale and service delivery strategy. The average introduction costs per fully immunized girl ranged from $1.49 to $18.94 while recurrent costs per girl ranged from $1.00 to $15.69, with both types of costs varying by delivery strategy and country. Evaluating delivery costs along programme characteristics as well as country characteristics (population density, income/cost level, existing service delivery infrastructure) are likely the most informative and useful for anticipating costs for HPV vaccine delivery. Conclusions This paper demonstrates the importance of country level cost data to inform global donor policies for vaccine introduction support. Such data are also valuable for informing national decisions on HPV vaccine introduction. PMID:24968002

Achieving high uptake of human papillomavirus vaccine in Cameroon: lessons learned in overcoming challenges.

PubMed

Ogembo, Javier Gordon; Manga, Simon; Nulah, Kathleen; Foglabenchi, Lily H; Perlman, Stacey; Wamai, Richard G; Welty, Thomas; Welty, Edith; Tih, Pius

2014-07-31

Cameroon has the highest age-standardized incidence rate of cervical cancer (30/100,000 women) in Central Africa. In 2010-2011, the Cameroon Baptist Convention Health Services (CBCHS) received donated human papillomavirus (HPV) vaccine, Gardasil, from Merck & Co. Inc. through Axios Healthcare Development to immunize 6400 girls aged 9-13 years. The aim was to inform the Cameroon Ministry of Health (MOH) of the acceptability, feasibility, and optimal delivery strategies for HPV vaccine. Following approval by the MOH, CBCHS nurses educated girls, parents, and communities about HPV, cervical cancer, and HPV vaccine through multimedia coverage, brochures, posters, and presentations. Because educators were initially reluctant to allow immunization in schools, due to fear of adverse events, the nurses performed 40.7% of vaccinations in the clinics, 34.5% in community venues, and only 24.7% in schools. When no adverse events were reported, more schools and communities permitted HPV vaccine immunization on their premises. To recover administrative costs, CBCHS charged a fee of US$8 per 3-dose series only to those who were able to pay. Despite the fee, 84.6% of the 6,851 girls who received the first dose received all three doses. With adequate education of all stakeholders, HPV vaccination is acceptable and feasible in Cameroon. Following this demonstration project, in 2014 the Global Access to Vaccines and Immunization (GAVI) Alliance awarded the Cameroon MOH HPV vaccine at a price of US$4.50 per dose to immunize sixth grade girls and girls aged 10 years who are not in school in two districts of Cameroon. Copyright © 2014 Elsevier Ltd. All rights reserved.

Host control of human papillomavirus infection and disease.

PubMed

Doorbar, John

2018-02-01

Most human papillomaviruses cause inapparent infections, subtly affecting epithelial homeostasis, to ensure genome persistence in the epithelial basal layer. As with conspicuous papillomas, these self-limiting lesions shed viral particles to ensure population level maintenance and depend on a balance between viral gene expression, immune cell stimulation and immune surveillance for persistence. The complex immune evasion strategies, characteristic of high-risk HPV types, also allow the deregulated viral gene expression that underlies neoplasia. Neoplasia occurs at particular epithelial sites where vulnerable cells such as the reserve or cuboidal cells of the cervical transformation zone are found. Beta papillomavirus infection can also predispose an individual with immune deficiencies to the development of cancers. The host control of HPV infections thus involves local interactions between keratinocytes and the adaptive immune response. Effective immune detection and surveillance limits overt disease, leading to HPV persistence as productive microlesions or in a true latent state. Copyright © 2017. Published by Elsevier Ltd.

Studies towards the potential of poliovirus as a vector for the expression of HPV 16 virus-like-particles.

PubMed

van Kuppeveld, Frank J M; de Jong, Arjan; Dijkman, Henri B P M; Andino, Raul; Melchers, Willem J G

2002-11-15

Development of human cervical carcinomas is associated with infection by certain human papillomavirus (HPV) types. Thus, protection against HPV infection through vaccination may prevent development of cervical cancer. The purpose of this study was to investigate the possibility of using a poliovirus recombinant vector to induce immunity against HPV. A poliovirus recombinant was constructed which contained the complete coding sequence of the HPV 16 major capsid protein L1, between the P1 and P2 region of the poliovirus polyprotein. A replication-competent virus was obtained after transfection of the recombinant RNA into tissue culture cells. Electron microscopically examination of cells infected with the poliovirus-HPV L1 recombinant indicated that HPV 16 L1 self-assembles into virus-like particles. To investigate the immunological response in vivo, susceptible transgenic mice carrying the poliovirus receptor were infected with the recombinant poliovirus. In all mice a modest but consistent immune response against HPV 16 was observed. Based on these results, the potential for picornavirus-derived vectors in vaccine development against HPV infection is discussed.

Quality Improvement Initiative to Improve HPV Vaccine Initiation at Nine Years of Age,.

PubMed

Goleman, Martha J; Dolce, Millie; Morack, Jennifer

2018-05-26

Adolescent human papillomavirus (HPV) vaccine rates remain low. Early vaccination may improve the efficacy of the vaccine and immunization rates. However, clinicians have not routinely made a strong recommendation to younger adolescents. This study assessed the feasibility of routine vaccination at nine years of age. Three sequential quality improvement (QI) interventions were implemented to shift the initiation of the HPV vaccine to nine years of age in a primary care network in low-income neighborhoods in Columbus, Ohio. The first intervention changed the electronic medical record (EMR) alert for the HPV vaccine from eleven to nine years of age and focused on cancer prevention when discussing the vaccine with families. The second intervention was formation of an HPV QI team. The third intervention was a clinic incentive for HPV captured opportunity rates. Immunization rates were monitored using statistical process control charts to compare the HPV immunization rate in a sample of nine and ten-year-old children with a sample of 11 and 12-year-old children. The percentage of patients receiving an HPV vaccine before 11 years increased from 4.6% to 35.7% during the six months after the QI initiative began and to 60.8% 18 months after the project began. In comparison, the HPV vaccination rate in the sample of 11 and 12 year-olds increased from 78.7% to 82.8% 18 months later. This QI project used multiple interventions to increase HPV vaccination at nine years of age in a large primary care network serving a diverse low-income population. Copyright © 2018. Published by Elsevier Inc.

The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer.

PubMed

Wichmann, Gunnar; Rosolowski, Maciej; Krohn, Knut; Kreuz, Markus; Boehm, Andreas; Reiche, Anett; Scharrer, Ulrike; Halama, Dirk; Bertolini, Julia; Bauer, Ulrike; Holzinger, Dana; Pawlita, Michael; Hess, Jochen; Engel, Christoph; Hasenclever, Dirk; Scholz, Markus; Ahnert, Peter; Kirsten, Holger; Hemprich, Alexander; Wittekind, Christian; Herbarth, Olf; Horn, Friedemann; Dietz, Andreas; Loeffler, Markus

2015-12-15

Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient treatment decision. We characterize head and neck squamous cell carcinomas (HNSCC) with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited patients by gene expression profiling and targeted sequencing of 50 genes. We show that tumors with transcriptionally inactive HPV16 (DNA+ RNA-) are similar to HPV-negative (DNA-) tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). We also find that an immune response-related gene expression cluster is associated with lymph node metastasis, independent of HPV16 status and that disruptive TP53 mutations are associated with lymph node metastasis in HPV16 DNA- tumors. We validate each of these associations in another large data set. Four gene expression clusters which we identify differ moderately but significantly in overall survival. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53-mutation status for patient stratification and identify associations of an immune response-related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC. © 2015 UICC.

Comparison of the immunogenicity of Cervarix® and Gardasil® human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults.

PubMed

Toft, Lars; Tolstrup, Martin; Müller, Martin; Sehr, Peter; Bonde, Jesper; Storgaard, Merete; Østergaard, Lars; Søgaard, Ole S

2014-01-01

Individuals infected with human immunodeficiency virus (HIV) have excess risk of developing human papillomavirus (HPV)-related disease. A substantial fraction of HPV-associated cancers is caused by HPV serotypes not included in the currently available vaccines. Among healthy women, both Cervarix(®) (HPV-16/18, GlaxoSmithKline Biologicals, GSK) and Gardasil(®) (HPV-6/11/16/18, Merck) have demonstrated partial cross-protection against certain oncogenic non-vaccine HPV-types. Currently, there are no available data on vaccine-induced cross-protection in men and little is known about cross-reactive immunity after HPV-vaccination of HIV-infected individuals. In an investigator-initiated trial, we randomized 91 HIV-positive men and women to receive vaccination with Cervarix(®) or Gardasil(®). The HPV-DNA status of the participants was determined with pcr before and after immunization. Cross-reactive antibody responses against HPV-31, HPV-33, and HPV-45 were evaluated for up to 12 months using a pseudovirion-based neutralization assay (PBNA). Geometric mean antibody titers (GMTs) were compared among vaccine groups and genders at 7 and 12 months.: Both vaccines induced anti-HPV-31, -33, and -45 neutralizing antibodies in participants who were seronegative and HPV-DNA negative for those types at study entry. Geometric mean antibody titers were comparable between vaccine groups. Interestingly, anti-HPV-31 and -33 antibody titers were higher among women compared with men at 7 and 12 months.: In conclusion, both licensed HPV-vaccines induced cross-neutralizing antibodies against frequent oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults, and women had greater serological responses against HPV-31 and -33 compared with men.

[Introduction of vaccination against human papillomavirus in developing countries: update and perspectives].

PubMed

Hessel, L

2009-08-01

Cervical cancer and other diseases related to human papillomavirus (HPV) represent a global public health problem. Safe and effective vaccines are now available and already used in many industrialized countries. Immunization offers the best hope for protecting the population against a disease that is the second most deadly cancer in the developing world and the first most deadly in Africa. The World Health Organization currently recommends introduction of HVP vaccination in developing countries. Widespread vaccination could be beneficial in numerous domains other than primary prevention of cervical cancer. Efforts to overcome the numerous obstacles and speed up implementation of HVP vaccination programs are now underway in many areas ranging from related scientific issues such as epidemiology and clinical research to administrative concerns such as healthcare economics, vaccination guidelines, public acceptation, program funding, and universal access. Vaccine manufacturers have committed themselves to working in partnership with national and international organizations to ensure access to HPV vaccine for all countries regardless of economic level, Although numerous issues must be resolved to optimize the use of HPV vaccines and ensure synergistic integration of vaccination, screening and treatment, current initiatives and efforts should allow introduction of HPV vaccination in developing countries in a not too distant future.

HPV circulating tumor DNA to monitor the efficacy of anti-PD-1 therapy in metastatic squamous cell carcinoma of the anal canal: A case report.

PubMed

Cabel, Luc; Bidard, François-Clément; Servois, Vincent; Cacheux, Wulfran; Mariani, Pascale; Romano, Emanuela; Minsat, Mathieu; Bieche, Ivan; Farkhondeh, Fereshteh; Jeannot, Emmanuelle; Buecher, Bruno

2017-10-15

Squamous cell carcinoma of the anal canal (SCCA) is a rare HPV-associated cancer with limited sensitivity to standard chemotherapy. In a phase 2 study, nivolumab, an anti PD-1 immune checkpoint inhibitor, demonstrated significant efficacy as single-agent therapy in metastatic SCCA patients. Nevertheless, imaging assessment by standard RECIST criteria of the efficacy of immune therapy can be difficult in some patients due to tumor immune cell infiltration, and biomarkers of treatment efficacy are needed. We have previously developed a quantitative droplet digital PCR (ddPCR) technique to detect HPV circulating tumor DNA (HPV ctDNA), with excellent sensitivity and specificity. Here, we report, for the first time, the kinetics of HPV ctDNA during therapy in a patient with metastatic SCCA, who obtained sustained partial response to single-agent nivolumab. We observed an early and very significant decrease of HPV ctDNA during therapy from the baseline level of 3713 copies/ml plasma to 564 copies/ml plasma at 4 weeks, and 156 copies/ml at 6 weeks, followed by a plateau. This observation provides proof-of-concept that HPV ctDNA can be used as a noninvasive early dynamic biomarker to monitor the efficacy of new immunotherapy agents. © 2017 UICC.

Therapy of Human Papillomavirus-Related Disease

PubMed Central

Stern, Peter L.; van der Burg, Sjoerd H.; Hampson, Ian N.; Broker, Thomas; Fiander, Alison; Lacey, Charles J.; Kitchener, Henry C.; Einstein, Mark H.

2014-01-01

This chapter reviews the current treatment of chronic and neoplastic HPV-associated conditions and the development of novel therapeutic approaches. Surgical excision of HPV-associated lower genital tract neoplasia is very successful but largely depends on secondary prevention programmes for identification of disease. Only high-risk HPV-driven chronic, preneoplastic lesions and some very early cancers cannot be successfully treated by surgical procedures alone. Chemoradiation therapy of cervical cancer contributes to the 66–79% cervical cancer survival at 5 years. Outlook for those patients with persistent or recurrent cervical cancer following treatment is very poor. Topical agents such as imiquimod (immune response modifier), cidofovir (inhibition of viral replication; induction apoptosis) or photodynamic therapy (direct damage of tumour and augmentation of anti-tumour immunity) have all shown some useful efficacy (~50–60%) in treatment of high grade vulvar intraepithelial neoplasia. Provider administered treatments of genital warts include cryotherapy, trichloracetic acid, or surgical removal which has the highest primary clearance rate. Patient applied therapies include podophyllotoxin and imiquimod. Recurrence after “successful” treatment is 30–40%. Further improvements could derive from a rational combination of current therapy with new drugs targeting molecular pathways mediated by HPV in cancer. Small molecule inhibitors targeting the DNA binding activities of HPV E1/E2 or the anti-apoptotic consequences of E6/E7 oncogenes are in preclinical development. Proteasome and histone deacetylase inhibitors, which can enhance apoptosis in HPV positive tumour cells, are being tested in early clinical trials. Chronic high-risk HPV infection/neoplasia is characterised by systemic and/or local immune suppressive regulatory or escape factors. Recently two E6/E7 vaccines have shown some clinical efficacy in high grade VIN patients and this correlated with strong and broad systemic HPV-specific T cell response and modulation of key local immune factors. Treatments that can shift the balance of immune effectors locally in combination with vaccination are now being tested. This article forms part of a special supplement entitled “Opportunities for comprehensive control of HPV infections and related diseases” Vaccine Volume 30, Supplement X, 2012. PMID:23199967

Low proportion of high school senior athletes receiving recommended immunizations.

PubMed

Karpinos, Ashley Rowatt; Rizzone, Katherine H; Cribbs, Sarah P; Roumie, Christianne L

2014-05-01

The preparticipation physical evaluation (PPE) often serves as the only preventive health care visit for athletes, but immunization status is not uniformly addressed in such visits. Thus, athletes may not be receiving recommended immunizations. Our aim was to determine the proportion of high school senior athletes who received all recommended immunizations. Our hypothesis was that females would be less likely than males to receive all recommended immunizations given suboptimal human papillomavirus (HPV) vaccine uptake. We conducted a cross-sectional survey evaluation of the immunization status of high school senior athletes in Davidson County, TN. The primary composite outcome was receipt of recommended immunizations for tetanus, meningococcal, and seasonal influenza. For females, the primary outcome also included completion of the HPV series. A total of 162 participants, 104 males and 58 females, were included. More males than females received all recommended immunizations (15.4% vs 3.5%; P = 0.02). When HPV immunization was excluded from the composite outcome, there was no difference in the proportion of males and females who received all recommended immunizations (15.4% vs 15.5%; P = 0.98). The odds of receiving all recommended immunizations was 0.14 (95% CI, 0.03-0.72) for females compared with males when adjusted for covariates. Athletes seen at retail-based clinics for their PPE were less likely to receive all recommended immunizations compared with athletes seen in primary care (OR, 0.13; 95% CI, 0.02-0.69). Only 1 in 6 high school senior athletes received the recommended tetanus, meningococcal, and influenza immunizations. A lower proportion of females, only 1 in 28, received all recommended immunizations due to the HPV series. Policy changes requiring a review of immunizations at the PPE would benefit many high school athletes.

Risk of cervical HPV infection and prevalence of vaccine-type and other high-risk HPV types among sexually active teens and young women (13-26 years) enrolled in the VALHIDATE study.

PubMed

Orlando, Giovanna; Fasolo, Michela; Mazza, Francesca; Ricci, Elena; Esposito, Susanna; Frati, Elena; Zuccotti, Gian Vincenzo; Cetin, Irene; Gramegna, Maria; Rizzardini, Giuliano; Tanzi, Elisabetta

2014-01-01

HPV vaccination is expected to reduce the incidence of cervical cancer. The greatest and the earliest health gains will be ensured by high vaccine coverage among all susceptible people. The high costs and the risk of a reduced cost/effectiveness ratio in sexually active girls still represent the main obstacles for a more widespread use of HPV vaccination in many countries. Data on the rate, risk factors, and HPV types in sexually active women could provide information for the evaluation of vaccination policies extended to broader age cohorts. Sexually active women aged 13-26 years enrolled in an Italian cohort study were screened for cervical HPV infections; HPV-DNA positive samples were genotyped by InnoLipa HPV Genotyping Extra or by RFLP genotype analysis.: Among the 796 women meeting the inclusion criteria, 10.80% (95% CI 8.65-12.96) were HPV-DNA infected. Age>18 years, lifetime sexual partners>1, and history of STIs were associated to higher risk of HPV infection in the multivariable models adjusted for age, lifetime sexual partners, and time of sexual exposure. The global prevalence of the four HPV vaccine-types was 3.02% (95% CI 1.83-4.20) and the cumulative probability of infection from at least one vaccine-type was 12.82% in 26-years-old women and 0.78% in 18-years-old women.: Our data confirm most of the previously reported findings on the risk factors for HPV infections. The low prevalence of the HPV vaccine-types found may be useful for the evaluation of the cost/efficacy and the cost/effectiveness of broader immunization programs beyond the 12-years-old cohort.

Risk of cervical HPV infection and prevalence of vaccine-type and other high-risk HPV types among sexually active teens and young women (13–26 years) enrolled in the VALHIDATE study

PubMed Central

Orlando, Giovanna; Fasolo, Michela; Mazza, Francesca; Ricci, Elena; Esposito, Susanna; Frati, Elena; Zuccotti, Gian Vincenzo; Cetin, Irene; Gramegna, Maria; Rizzardini, Giuliano; Tanzi, Elisabetta; group, VALHIDATE study

2014-01-01

HPV vaccination is expected to reduce the incidence of cervical cancer. The greatest and the earliest health gains will be ensured by high vaccine coverage among all susceptible people. The high costs and the risk of a reduced cost/effectiveness ratio in sexually active girls still represent the main obstacles for a more widespread use of HPV vaccination in many countries. Data on the rate, risk factors, and HPV types in sexually active women could provide information for the evaluation of vaccination policies extended to broader age cohorts. Sexually active women aged 13–26 years enrolled in an Italian cohort study were screened for cervical HPV infections; HPV-DNA positive samples were genotyped by InnoLipa HPV Genotyping Extra or by RFLP genotype analysis. Among the 796 women meeting the inclusion criteria, 10.80% (95% CI 8.65–12.96) were HPV-DNA infected. Age >18 years, lifetime sexual partners >1, and history of STIs were associated to higher risk of HPV infection in the multivariable models adjusted for age, lifetime sexual partners, and time of sexual exposure. The global prevalence of the four HPV vaccine-types was 3.02% (95% CI 1.83–4.20) and the cumulative probability of infection from at least one vaccine-type was 12.82% in 26-years-old women and 0.78% in 18-years-old women. Our data confirm most of the previously reported findings on the risk factors for HPV infections. The low prevalence of the HPV vaccine-types found may be useful for the evaluation of the cost/efficacy and the cost/effectiveness of broader immunization programs beyond the 12-years-old cohort. PMID:24423757

Knowledge and beliefs regarding cervical cancer screening and HPV vaccination among urban and rural women in León, Nicaragua

PubMed Central

Lombardo, Alexandra R.; Tangoren, Caroline G.; Meyers, Sara J.; Muppala, Vishnu R.; Niccolai, Linda M.

2017-01-01

Background In Nicaragua, cervical cancer is the leading cause of cancer-related death for women ages 15–44, yet access to the HPV vaccine is limited to those with financial resources to pay for it. Cervical cytology is provided free of charge in public clinics; however, only 10% of women receive Pap smears at the nationally recommended frequency. Previous studies have not investigated how beliefs regarding cervical cancer screening may differ for urban and rural populations in Nicaragua. Furthermore, no investigation has assessed Nicaraguan women’s beliefs about a potential HPV immunization campaign. Given beliefs’ influence on health behavior, we investigated the structural, sociocultural, and knowledge-based factors influencing women’s beliefs regarding cervical cancer screening among urban and rural women in León, Nicaragua, and assessed acceptance of a potential HPV immunization program. Methods Our sequential explanatory mixed-methods study consisted of two phases: (1) a close-ended questionnaire, followed by (2) a qualitative, in-depth interview. Our quantitative sample contained 117 urban and 112 rural participants aged 18–49. We assessed beliefs regarding cervical cancer screening using a 22-item scale, with higher scores indicating screening-promoting beliefs in simple linear and multiple linear regressions. Twenty qualitative interviews, exploring the sociocultural dimensions of knowledge and attitudes indicated by our quantitative findings, were conducted with a sample of 13 urban and 7 rural women aged 19–46. Results The multiple linear regression indicates that greater knowledge of Pap smears, HPV, and cervical cancer is significantly associated with screening-promoting beliefs after adjusting for other relevant factors. There was no significant difference in screening knowledge and beliefs for urban and rural women. Four recurrent themes representing determinants of knowledge, beliefs, and attitudes regarding cervical cancer screening arose from interviews and built on quantitative findings: (1) women’s embarrassment due to the intimate nature of the Pap smear and male gender of exam provider discourages screening; (2) women believe Pap smears and cervical cancer are associated with sexual promiscuity, and this association stigmatizes women with the disease; (3) knowledge of cervical cancer prevention is limited to those who regularly attend health centers; and (4) women find screening inconvenient, believing understaffed clinics increase patient wait time, limit time patients spend with clinicians, and delay Pap results. A fifth theme indicates (5) participants’ acceptance of a potential HPV immunization program. Discussion Future interventions should focus on increasing access to information about cervical cancer prevention for women who do not regularly attend health centers. Furthermore, our results suggest that if funding were allocated to make the HPV vaccine accessible in Nicaragua, it would be well received. PMID:29085745

Knowledge and beliefs regarding cervical cancer screening and HPV vaccination among urban and rural women in León, Nicaragua.

PubMed

Rees, Hannah D; Lombardo, Alexandra R; Tangoren, Caroline G; Meyers, Sara J; Muppala, Vishnu R; Niccolai, Linda M

2017-01-01

In Nicaragua, cervical cancer is the leading cause of cancer-related death for women ages 15-44, yet access to the HPV vaccine is limited to those with financial resources to pay for it. Cervical cytology is provided free of charge in public clinics; however, only 10% of women receive Pap smears at the nationally recommended frequency. Previous studies have not investigated how beliefs regarding cervical cancer screening may differ for urban and rural populations in Nicaragua. Furthermore, no investigation has assessed Nicaraguan women's beliefs about a potential HPV immunization campaign. Given beliefs' influence on health behavior, we investigated the structural, sociocultural, and knowledge-based factors influencing women's beliefs regarding cervical cancer screening among urban and rural women in León, Nicaragua, and assessed acceptance of a potential HPV immunization program. Our sequential explanatory mixed-methods study consisted of two phases: (1) a close-ended questionnaire, followed by (2) a qualitative, in-depth interview. Our quantitative sample contained 117 urban and 112 rural participants aged 18-49. We assessed beliefs regarding cervical cancer screening using a 22-item scale, with higher scores indicating screening-promoting beliefs in simple linear and multiple linear regressions. Twenty qualitative interviews, exploring the sociocultural dimensions of knowledge and attitudes indicated by our quantitative findings, were conducted with a sample of 13 urban and 7 rural women aged 19-46. The multiple linear regression indicates that greater knowledge of Pap smears, HPV, and cervical cancer is significantly associated with screening-promoting beliefs after adjusting for other relevant factors. There was no significant difference in screening knowledge and beliefs for urban and rural women. Four recurrent themes representing determinants of knowledge, beliefs, and attitudes regarding cervical cancer screening arose from interviews and built on quantitative findings: (1) women's embarrassment due to the intimate nature of the Pap smear and male gender of exam provider discourages screening; (2) women believe Pap smears and cervical cancer are associated with sexual promiscuity, and this association stigmatizes women with the disease; (3) knowledge of cervical cancer prevention is limited to those who regularly attend health centers; and (4) women find screening inconvenient, believing understaffed clinics increase patient wait time, limit time patients spend with clinicians, and delay Pap results. A fifth theme indicates (5) participants' acceptance of a potential HPV immunization program. Future interventions should focus on increasing access to information about cervical cancer prevention for women who do not regularly attend health centers. Furthermore, our results suggest that if funding were allocated to make the HPV vaccine accessible in Nicaragua, it would be well received.

Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases

PubMed Central

Skeate, Joseph G.; Woodham, Andrew W.; Einstein, Mark H.; Da Silva, Diane M.; Kast, W. Martin

2016-01-01

ABSTRACT Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed. PMID:26835746

Human papillomavirus-driven immune deviation: challenge and novel opportunity for immunotherapy.

PubMed

Smola, Sigrun; Trimble, Connie; Stern, Peter L

2017-06-01

It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer. In these circumstances, a succession of interacting and self-reinforcing events mediated through modulation of different immune receptors, chemokine and cytokine responses (CCL20; CCL2; CCR2; IL-6; CCR7; IL-12) further promote the generation of an immune suppressive microenvironment [increased levels of Tregs, Th17, myeloid-derived suppressor cells (MDSCs) and PD-L1]. The overexpression of E6/E7 expression also compromises the ability to repair cellular DNA, leading to genomic instability, with the acquisition of genetic changes providing for the selection of advantaged cancer cells including additional strategies for immune escape. Therapeutic vaccines targeting the HPV oncogenes have shown some encouraging success in some recent early-phase clinical trials tested in patients with HPV-associated high-grade anogenital lesions. A significant hurdle to success in more advanced disease will be the local and systemic immune suppressive factors. Interventions targeting the different immunosuppressive components can provide opportunity to release existing or generate new and effective antitumour immunity. Treatments that alter the protumour inflammatory environment including toll-like receptor stimulation, inhibition of IL-6-related pathways, immune-checkpoint inhibition, direct modulation of MDSCs, Tregs and macrophages could all be useful in combination with therapeutic HPV vaccination. Future progress in delivering successful immunotherapy will depend on the configuration of treatment protocols in an insightful and timely combination.

Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Chinese girls and women aged 9 to 45 years

PubMed Central

Zhu, Fengcai; Li, Juan; Hu, Yuemei; Zhang, Xiang; Yang, Xiaoping; Zhao, Hui; Wang, Junzhi; Yang, Jianguo; Xia, Guodong; Dai, Qinyong; Tang, Haiwen; V Suryakiran, Pemmaraju; Datta, Sanjoy K; Descamps, Dominique; Bi, Dan; Struyf, Frank

2014-01-01

Immunogenicity and safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine were evaluated in healthy Chinese females aged 9–45 years in 2 phase IIIB, randomized, controlled trials. Girls aged 9–17 years (ClinicalTrials.gov, NCT00996125) received vaccine (n = 374) or control (n = 376) and women aged 26–45 years (NCT01277042) received vaccine (n = 606) or control (n = 606) at months 0, 1, and 6. The primary objective was to show non-inferiority of anti-HPV-16 and -18 immune responses in initially seronegative subjects at month 7, compared with Chinese women aged 18–25 years enrolled in a separate phase II/III trial (NCT00779766). Secondary objectives were to describe the anti-HPV-16 and -18 immune response, reactogenicity and safety. At month 7, immune responses were non-inferior for girls (9–17 years) vs. young women (18–25 years): the upper limit of the 95% confidence interval (CI) for the geometric mean titer (GMT) ratio (women/girls) was below the limit of 2 for both anti-HPV-16 (0.37 [95% CI: 0.32, 0.43]) and anti-HPV-18 (0.42 [0.36, 0.49]). Immune responses at month 7 were also non-inferior for 26–45 year-old women vs. 18–25 year-old women: the upper limit of the 95% CI for the difference in seroconversion (18–25 minus 26–45) was below the limit of 5% for both anti-HPV-16 (0.00% [–1.53, 1.10]) and anti-HPV-18 (0.21% [–1.36, 1.68]). GMTs were 2- to 3-fold higher in girls (9–17 years) as compared with young women (18–25 years). The HPV-16/18 AS04-adjuvanted vaccine had an acceptable safety profile when administered to healthy Chinese females aged 9–45 years. PMID:25424785

Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Chinese girls and women aged 9 to 45 years.

PubMed

Zhu, Fengcai; Li, Juan; Hu, Yuemei; Zhang, Xiang; Yang, Xiaoping; Zhao, Hui; Wang, Junzhi; Yang, Jianguo; Xia, Guodong; Dai, Qinyong; Tang, Haiwen; Suryakiran, Pemmaraju; Datta, Sanjoy K; Descamps, Dominique; Bi, Dan; Struyf, Frank

2014-01-01

Immunogenicity and safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine were evaluated in healthy Chinese females aged 9-45 years in 2 phase IIIB, randomized, controlled trials. Girls aged 9-17 years (ClinicalTrials.gov, NCT00996125) received vaccine (n = 374) or control (n = 376) and women aged 26-45 years (NCT01277042) received vaccine (n = 606) or control (n = 606) at months 0, 1, and 6. The primary objective was to show non-inferiority of anti-HPV-16 and -18 immune responses in initially seronegative subjects at month 7, compared with Chinese women aged 18-25 years enrolled in a separate phase II/III trial (NCT00779766). Secondary objectives were to describe the anti-HPV-16 and -18 immune response, reactogenicity and safety. At month 7, immune responses were non-inferior for girls (9-17 years) vs. young women (18-25 years): the upper limit of the 95% confidence interval (CI) for the geometric mean titer (GMT) ratio (women/girls) was below the limit of 2 for both anti-HPV-16 (0.37 [95% CI: 0.32, 0.43]) and anti-HPV-18 (0.42 [0.36, 0.49]). Immune responses at month 7 were also non-inferior for 26-45 year-old women vs. 18-25 year-old women: the upper limit of the 95% CI for the difference in seroconversion (18-25 minus 26-45) was below the limit of 5% for both anti-HPV-16 (0.00% [-1.53, 1.10]) and anti-HPV-18 (0.21% [-1.36, 1.68]). GMTs were 2- to 3-fold higher in girls (9-17 years) as compared with young women (18-25 years). The HPV-16/18 AS04-adjuvanted vaccine had an acceptable safety profile when administered to healthy Chinese females aged 9-45 years.

HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial.

PubMed

van Poelgeest, Mariette I E; Welters, Marij J P; van Esch, Edith M G; Stynenbosch, Linda F M; Kerpershoek, Gijs; van Persijn van Meerten, Els L; van den Hende, Muriel; Löwik, Margriet J G; Berends-van der Meer, Dorien M A; Fathers, Lorraine M; Valentijn, A Rob P M; Oostendorp, Jaap; Fleuren, Gert Jan; Melief, Cornelis J M; Kenter, Gemma G; van der Burg, Sjoerd H

2013-04-04

Human papilloma virus type 16 (HPV16)-induced gynecological cancers, in particular cervical cancers, are found in many women worldwide. The HPV16 encoded oncoproteins E6 and E7 are tumor-specific targets for the adaptive immune system permitting the development of an HPV16-synthetic long peptide (SLP) vaccine with an excellent treatment profile in animal models. Here, we determined the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in patients with advanced or recurrent HPV16-induced gynecological carcinoma. Patients with HPV16-positive advanced or recurrent gynecological carcinoma (n = 20) were subcutaneously vaccinated with an HPV16-SLP vaccine consisting of a mix of 13 HPV16 E6 and HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant. The primary endpoints were safety, toxicity and tumor regression as determined by RECIST. In addition, the vaccine-induced T-cell response was assessed by proliferation and associated cytokine production as well as IFNγ-ELISPOT. No systemic toxicity beyond CTCAE grade II was observed. In a few patients transient flu-like symptoms were observed. In 9 out of 16 tested patients vaccine-induced HPV16-specific proliferative responses were detected which were associated with the production of IFNγ, TNFα, IL-5 and/or IL-10. ELISPOT analysis revealed a vaccine-induced immune response in 11 of the 13 tested patients. The capacity to respond to the vaccine was positively correlated to the patient's immune status as reflected by their response to common recall antigens at the start of the trial. Median survival was 12.6 ± 9.1 months. No regression of tumors was observed among the 12 evaluable patients. Nineteen patients died of progressive disease. The HPV16-SLP vaccine was well tolerated and induced a broad IFNγ-associated T-cell response in patients with advanced or recurrent HPV16-induced gynecological carcinoma but neither induced tumor regression nor prevented progressive disease. We, therefore, plan to use this vaccine in combination with chemotherapy and immunomodulation.

Attitudes Regarding HPV Vaccinations of Children among Mothers with Adolescent Daughters in Korea.

PubMed

Lee, Kyong No; Chang, Kylie Hae Jin; Cho, Seong Sik; Park, Sung Ho; Park, Sung Taek

2017-01-01

The aim of this study, carried out before the beginning of human papillomavirus (HPV) vaccinations as a National Immunization Program (NIP) in Korea in 2016, is to assess the ranges of perceptions and personal experience and their influences on attitudes regarding HPV vaccinations of children, among mothers of adolescent (9-14 years of age) daughters in Korea. From November 2015 to February 2016, we distributed a written questionnaire to mothers who had daughters aged 9-14 years. The questionnaire consisted of several questions, related to knowledge of HPV, personal experiences of HPV vaccination, and attitudes toward HPV vaccinations of their adolescent daughters. Of the 260 questionnaires distributed, 140 participants returned answered ones. And although only 51% of participants were aware that cervical cancer is highly related with HPV infection, 70% said they were willing to vaccinate their daughters, showing that awareness does not coincide with intention to vaccinate. Among the participants showing negative attitudes, 50% were concerned about the vaccination side effects. The more the participants' pre-knowledge about HPV infection, and about the relationship of HPV to cervical cancer, the more positive their attitudes (P = 0.002, P < 0.001). Our study showed that, as the level of education rose, the proportion of mothers with negative attitudes toward vaccinating their adolescent daughters rose as well. Thus, the provision of correct education by health care providers and accurate information through active advertising may play an important role in increasing the vaccination rate among adolescent girls in Korea.

Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04-adjuvanted vaccine in preteen/adolescent girls and young women.

PubMed

Petäjä, Tiina; Pedersen, Court; Poder, Airi; Strauss, Gitte; Catteau, Gregory; Thomas, Florence; Lehtinen, Matti; Descamps, Dominique

2011-11-01

Vaccination against oncogenic human papillomavirus (HPV) types is one key intervention for cervical cancer prevention. This follow-up study assessed the persistence of the systemic and mucosal immune responses together with the safety profile of the HPV-16/18 AS04-adjuvanted vaccine administered to young women aged 10-25 years. Serum and cervicovaginal secretion (CVS) samples were collected at prespecified time-points during the 48-month follow-up period. Anti-HPV-16/18 antibody levels in serum and CVS were measured by enzyme-linked immunosorbent assay (ELISA). At Month 48, all subjects remained seropositive for serum anti-HPV-16 and -18 antibodies. As previously observed, anti-HPV-16 and -18 antibodies levels (ELISA Units/mL) were higher in subjects vaccinated at the age of 10-14 years (2862.2 and 940.8) compared to subjects vaccinated at the age of 15-25 years (1186.2 and 469.8). Moreover, anti-HPV-16 and -18 antibodies in CVS were still detectable for subjects aged 15-25 years (84.1% and 69.7%, respectively). There was a strong correlation between serum and CVS anti-HPV-16 and -18 antibodies levels (correlation coefficients = 0.84 and 0.90 at Month 48, respectively) supporting the hypothesis of transudation or exudation of serum immunoglobulin G antibodies through the cervical epithelium. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile. In conclusion, this follow-up study shows that the HPV-16/18 AS04-adjuvanted vaccine administered to preteen/adolescents girls and young women induces long-term systemic and mucosal immune response and has a clinically acceptable safety profile up to 4 years after the first vaccine dose. Copyright © 2010 UICC.

Less than 3 doses of the HPV vaccine – Review of efficacy against virological and disease end points

PubMed Central

Basu, Partha; Bhatla, Neerja; Ngoma, Twalib; Sankaranarayanan, Rengaswamy

2016-01-01

ABSTRACT World Health Organization (WHO) recommended 2 doses of the Human Papillomavirus (HPV) vaccine for girls below 15 y on the basis of the immune-bridging studies demonstrating non-inferior immune response of 2 doses in the adolescent girls compared to 3 doses in the young adult women in whom the efficacy against disease is established. The biological nature of the antigens (virus-like particles) constituting the HPV vaccine is responsible for the vigorous antibody response that may make the third dose redundant. The protection offered by 2 doses has been demonstrated in non-randomized clinical trials to be comparable to that offered by 3 doses against incident and persistent infections of vaccine targeted HPV types. However, results emerging from the ecological and nested case-control studies embedded in the population based screening programs of different countries indicate reduced efficacy of 2 doses against virological and disease end points. Some recent studies observed the protective effect of single dose of the vaccine against incident and persistent infections of the vaccine targeted HPV types to be similar to 3 doses in spite of immunological inferiority. The sample size, duration of follow-ups and number of events were limited in these studies. Longer follow ups of the less than 3 doses cohorts in the ongoing studies as well as appropriately designed and ethically justifiable randomized studies are needed to establish the protection offered by the alternative schedules at least beyond 10 y of vaccination. PMID:26933961

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.

PubMed

Morris, Van K; Salem, Mohamed E; Nimeiri, Halla; Iqbal, Syma; Singh, Preet; Ciombor, Kristen; Polite, Blase; Deming, Dustin; Chan, Emily; Wade, James L; Xiao, Lianchun; Bekaii-Saab, Tanios; Vence, Luis; Blando, Jorge; Mahvash, Armeen; Foo, Wai Chin; Ohaji, Chimela; Pasia, Manolo; Bland, Gail; Ohinata, Aki; Rogers, Jane; Mehdizadeh, Amir; Banks, Kimberly; Lanman, Richard; Wolff, Robert A; Streicher, Howard; Allison, James; Sharma, Padmanee; Eng, Cathy

2017-04-01

Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169. We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported. To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease. National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study

PubMed Central

Morris, Van K; Salem, Mohamed E; Nimeiri, Halla; Iqbal, Syma; Singh, Preet; Ciombor, Kristen; Polite, Blase; Deming, Dustin; Chan, Emily; Wade, James L; Xiao, Lianchun; Bekaii-Saab, Prof Tanios; Vence, Luis; Blando, Jorge; Mahvash, Armeen; Foo, Wai Chin; Ohaji, Chimela; Pasia, Manolo; Bland, Gail; Ohinata, Aki; Rogers, Jane; Mehdizadeh, Amir; Banks, Kimberly; Lanman, Richard; Wolff, Robert A; Streicher, Howard; Allison, Prof James; Sharma, Prof Padmanee; Eng, Prof Cathy

2018-01-01

Summary Background Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. Methods We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169. Findings We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15–33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported. Interpretation To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease. Funding National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor. PMID:28223062

[Review of the 2016 Swiss immunization schedule and technology update for improving vaccine management].

PubMed

Diana, Alessandro

2016-05-11

The 2016 immunization schedule published by the Swiss Federal Office of Public Health includes three new clauses: reimbursement of the additional Human Papillomavirus (HPV) vaccination in young males (11-26 years) as recommended by local canton programs, the end of franchise exemption for the measles, mumps and rubella (MMR) vaccination, and the creation of a new system of indemnities and moral compensation in the event of personal injury resulting from vaccinations. This article presents the main features of the 2016 immunization schedule with details of the technology available to physicians to improve vaccine management.

Warts and All: HPV in Primary Immunodeficiencies

PubMed Central

Leiding, Jennifer W.; Holland, Steven M.

2012-01-01

Infection with human papilloma virus (HPV) is almost universal and eventually asymptomatic, but pathologic infection with HPV is severe, recurrent, and recalcitrant to therapy. It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and DOCK8 are typically associated with extensive HPV infections, whereas several other primary immune defects have severe HPV much less frequently. We review immunodeficiencies with severe HPV infections and the mechanisms underlying them. PMID:23036745

Human papillomavirus in larynx.

PubMed

Aaltonen, Leena-Maija; Rihkanen, Heikki; Vaheri, Antti

2002-04-01

The core of the present clinical and basic research knowledge of laryngeal human papillomavirus (HPV) infection is described. Review. A computer-aided search of MEDLINE database supplemented by hand searches of key journals was conducted. One of the tumor-promoting factors in the larynx is the HPV found both in normal laryngeal epithelium and in laryngeal tumors. The most important manifestation of laryngeal HPV infection is laryngeal papillomatosis, a rare disease caused by HPV types 6 and 11. In laryngeal carcinogenesis, the role of HPV remains uncertain. The means of transmission of HPV are partly unknown, and the course of laryngeal HPV infection is unpredictable and variable. Treatment of laryngeal papillomatosis is based on surgery, especially on CO2 laser and shaver. Alpha-interferon is the drug of choice in patients whose response to surgery is poor. However, neither interferon nor other antiviral drugs are able to eradicate the virus from laryngeal mucosa. Little is known about immunological mechanisms involved in laryngeal HPV infection, but in defense against HPV cellular immunity is considered a more important mechanism than humoral immunity. A good experimental model of HPV infection is lacking in which the entire viral life cycle can take place. Organotypic cell cultures (collagen rafts) are useful, but the rate-limiting step in this method is the difficulties in culturing HPV-positive epithelial cells. Although laryngeal papillomatosis is clinically well defined, the mechanisms and treatment modalities of laryngeal HPV infection need further investigations.

Langerhans cells from women with cervical precancerous lesions become functionally responsive against human papillomavirus after activation with stabilized Poly-I:C.

PubMed

Da Silva, Diane M; Woodham, Andrew W; Skeate, Joseph G; Rijkee, Laurie K; Taylor, Julia R; Brand, Heike E; Muderspach, Laila I; Roman, Lynda D; Yessaian, Annie A; Pham, Huyen Q; Matsuo, Koji; Lin, Yvonne G; McKee, Greg M; Salazar, Andres M; Kast, W Martin

2015-12-01

Human papillomavirus (HPV)-mediated suppression of Langerhans cell (LC) function can lead to persistent infection and development of cervical intraepithelial neoplasia (CIN). Women with HPV-induced high-grade CIN2/3 have not mounted an effective immune response against HPV, yet it is unknown if LC-mediated T cell activation from such women is functionally impaired against HPV. We investigated the functional activation of in vitro generated LC and their ability to induce HPV16-specific T cells from CIN2/3 patients after exposure to HPV16 followed by treatment with stabilized Poly-I:C (s-Poly-I:C). LC from patients exposed to HPV16 demonstrated a lack of costimulatory molecule expression, inflammatory cytokine secretion, and chemokine-directed migration. Conversely, s-Poly-I:C caused significant phenotypic and functional activation of HPV16-exposed LC, which resulted in de novo generation of HPV16-specific CD8(+) T cells. Our results highlight that LC of women with a history of persistent HPV infection can present HPV antigens and are capable of inducing an adaptive T cell immune response when given the proper stimulus, suggesting that s-Poly-I:C compounds may be attractive immunomodulators for LC-mediated clearance of persistent HPV infection. Copyright © 2015 Elsevier Inc. All rights reserved.

Association of High-Risk Human Papillomavirus with Genital Tract Mucosal Immune Factors In HIV-Infected Women

PubMed Central

Buckley, Niall; Huber, Ashley; Lo, Yungtai; Castle, Philip E.; Kemal, Kimdar; Burk, Robert D.; Strickler, Howard D.; Einstein, Mark H.; Young, Mary; Anastos, Kathryn; Herold, Betsy C.

2015-01-01

Problem High-risk human papillomavirus (HR-HPV) is prevalent in HIV-infected women and may be associated with mucosal changes that promote HIV replication. Method of Study Innate immune molecules, antimicrobial activity, HIV RNA, and HPV DNA genotypes were measured in a cross-sectional study of 128 HIV-infected women categorized into HPV-16 (n=8), other HR-HPV (n=41), and non-HR-HPV controls (n=79). Results Compared to controls, HR-HPV groups had higher plasma viral loads (p=0.004), lower CD4 cells (p=0.02), more genital tract HIV RNA (p=0.03), greater number of different HPV types (p<0.001), higher cervicovaginal lavage (CVL) IL-1α (p=0.03) and human beta defensin 2 (HBD2) (p=0.049), and less anti-HIVBal activity (p=0.03). HPV-16 remained significantly associated with higher HBD2 (p=0.03), higher IL-1α (p=0.009), and lower anti-HIVBaL activity (p=0.03) compared to controls after adjusting for plasma viral load and CD4 T cell count. Conclusion HR-HPV is associated with mucosal changes in HIV-infected women that could adversely impact genital tract health. PMID:26685115

Summer peaks in uptake of human papillomavirus (HPV) and other adolescent vaccines in the United States

PubMed Central

Moss, Jennifer L.; Reiter, Paul L.; Rimer, Barbara K.; Ribisl, Kurt M.; Brewer, Noel T.

2015-01-01

Background Seasonality in human papillomavirus (HPV) vaccination could have a large impact on national cancer prevention efforts. We hypothesized that uptake of HPV vaccine and other adolescent vaccines in the United States would be highest in the summer. Methods Data came from healthcare provider-verified vaccination records for 70,144 adolescents (ages 13–17) from the 2008–2012 versions of the National Immunization Survey-Teen. Using the Edwards method for testing annual trends, we examined seasonal patterns in uptake of HPV and other recommended adolescent vaccines (tetanus, diphtheria, and pertussis (Tdap) booster and meningococcal vaccine). HPV vaccine initiation (receipt of the first of the three-dose series) data were for female adolescents. Results Uptake for HPV and other adolescent vaccines peaked in the summer across years and states (all p<.001). Uptake was 5 times as frequent at the peak as at the trough for HPV vaccine, and HPV vaccine initiation was highest in June, July, and August (percent of doses delivered in these months: 38.7%). The same pattern existed for Tdap booster and meningococcal vaccine. Concomitant (same-day) vaccination of HPV vaccine with other adolescent vaccines also demonstrated summer peaks each year nationally (all p<.001). Conclusion Uptake of adolescent vaccines increased dramatically in summer months. These summer peaks are an important opportunity for interventions focused on concomitant vaccination. Impact The potential cancer prevention impact of HPV vaccination programs could be increased, for example, by delivering messages about concomitant vaccination during the summer, when adolescents and their parents might be most open to them. PMID:26677211

IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia.

PubMed

Gosmann, Christina; Mattarollo, Stephen R; Bridge, Jennifer A; Frazer, Ian H; Blumenthal, Antje

2014-09-01

Persistent infection with high-risk human papillomaviruses (HPV) causes epithelial hyperplasia that can progress to cancer and is thought to depend on immunosuppressive mechanisms that prevent viral clearance by the host. IL-17 is a cytokine with diverse functions in host defense and in the pathology of autoimmune disorders, chronic inflammatory diseases, and cancer. We analyzed biopsies from patients with HPV-associated cervical intraepithelial neoplasia grade 2/3 and murine skin displaying HPV16 E7 protein-induced epithelial hyperplasia, which closely models hyperplasia in chronic HPV lesions. Expression of IL-17 and IL-23, a major inducer of IL-17, was elevated in both human HPV-infected and murine E7-expressing lesions. Using a skin-grafting model, we demonstrated that IL-17 in HPV16 E7 transgenic skin grafts inhibited effective host immune responses against the graft. IL-17 was produced by CD3(+) T cells, predominantly CD4(+) T cells in human, and CD4(+) and γδ T cells in mouse hyperplastic lesions. IL-23 and IL-1β, but not IL-18, induced IL-17 production in E7 transgenic skin. Together, these findings demonstrate an immunosuppressive role for IL-17 in HPV-associated epithelial hyperplasia and suggest that blocking IL-17 in persistent viral infection may promote antiviral immunity and prevent progression to cancer. Copyright © 2014 by The American Association of Immunologists, Inc.

Understanding Clinic Practices for Human Papilloma Virus Vaccination Series Completion in Clinics That Provide Primary Care: Survey of Clinic Managers in Iowa.

PubMed

Askelson, Natoshia M; Edmonds, Stephanie W; Momany, Elizabeth T; Tegegne, Mesay A

2016-07-01

Rates for human papilloma virus (HPV) vaccination are low across the United States. Evidence-based-practices to increase immunization coverage have been recommended by public health organizations, yet many primary care clinics do not follow these practices. The purpose of this study was to examine if primary care clinics use these best practices to promote completion of the HPV vaccine series for their adolescent patients. Understanding the prevalence of evidence-based immunization strategies is key to increasing vaccination coverage. We mailed 914 surveys to clinic managers of clinics that provide primary care in Iowa. The survey content was based on immunization strategies related to clinic practice and policies that have been proven effective to promote the completion of the HPV vaccination series. Survey responses from 127 clinics were used in the final analysis. Most clinics always used the state's immunization information system to record HPV vaccinations (89.4%). Over a quarter of clinics (27.6%) did not use any type of reminder or recall system to alert parents or providers that an HPV vaccine was due, and 35.0% did not give the vaccine at sick visits. Clinics need to focus more on the recommended logistics and processes to ensure that patients receive the entire HPV vaccination series. Survey results indicate that clinics are not consistently implementing the recommended best practices to ensure that vaccination series are completed.

Beta Human Papillomavirus Infection Is Prevalent in Elephantiasis and Exhibits a Productive Phenotype: A Case-Control Study.

PubMed

Carlson, John Andrew; Rady, Peter; Kadam, Pooja; He, Qin; Simonette, Rebecca; Tyring, Stephen

2017-06-01

Elephantiasis is considered a cutaneous region of immune deficiency with cobblestone-like surface caused by a wart-like eruption. Verrucosis is a diffuse human papillomavirus (HPV) infection linked to immunodeficiency disorders. The objective of this study was to examine the prevalence of HPV infection in lymphedema and its pathogenic role in elephantiasis. A retrospective case-control study was performed examining lymphedematous skin and controls of peritumoral normal skin. HPV infection was evaluated at the DNA, protein, and histopathologic levels by polymerase chain reaction, immunohistochemistry, and light microscopy, respectively. Overall, 540 HPV DNAs were detected in 120 of 122 cutaneous samples (median 4 HPV DNAs per sample, range 0-9). Compared with controls, no differences existed in type or number of HPVs identified. Instead, a diverse spectrum of HPV-related histopathologies were evident, likely reflecting the multiplicity of HPV genotypes detected. Most notably, increasing histopathologic lymphedema stage significantly correlated with markers of productive HPV infection such as altered keratohyaline granules and HPV L1 capsid expression. Limitations of this study are the absence of normal skin controls not associated with neoplasia or subclinical lymphedema, and lack of assessment of HPV copy number per keratinocyte infected. In conclusion, productive HPV infection, not HPV type or numbers detected, distinguished lymphedematous skin from controls. These findings support the theory that lymphedema creates a region of depressed immunity that permits productive HPV infection, manifested clinically by diffuse papillomatosis, characteristic of elephantiasis.

Systemic lupus erythematosus following HPV immunization or infection?

PubMed

Soldevilla, H F; Briones, S F R; Navarra, S V

2012-02-01

The link between autoimmunity and infectious agents has been strongly suggested by reports of lupus or lupus-like syndromes following immunization. This report describes three patients with either newly diagnosed systemic lupus erythematosus (SLE) or SLE flare, following vaccination for human papilloma virus (HPV). CASE 1: A 17-year-old female completed two doses of HPV vaccine uneventfully. Two months later, she developed arthralgias with pruritic rashes on both lower extremities, later accompanied by livedo reticularis, bipedal edema with proteinuria, anemia, leucopenia, hypocomplementemia and high titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA). Kidney biopsy showed International Society of Nephrology/Renal Pathology Society Class III lupus nephritis. She was started on high dose steroids followed by pulse cyclophosphamide therapy protocol for lupus nephritis, and subsequently went into remission. CASE 2: A 45-year-old housewife, previously managed for 11 years as having rheumatoid arthritis, had been in clinical remission for a year when she received two doses of HPV immunization. Four months later, she developed fever accompanied by arthritis, malar rash, oral ulcers, recurrent ascites with intestinal pseudo-obstruction, and behavioral changes. Cranial MRI showed vasculitic lesions on the frontal and parietal lobes. Laboratory tests showed anemia with leucopenia, hypocomplementemia, proteinuria, ANA positive at 1:320, and antibodies against dsDNA, Ro/SSA, La/SSB and histone. She improved following pulse methylprednisolone with subsequent oral prednisone combined with hydroxychloroquine. CASE 3: A 58-year-old housewife diagnosed with SLE had been in clinical remission for 8 years when she received two doses of HPV immunization. Three months later, she was admitted to emergency because of a 1-week history of fever, malar rash, easy fatigability, cervical lymph nodes, gross hematuria and pallor. Laboratory exams showed severe anemia, thrombocytopenia, active urine sediments, and hypocomplementemia. Despite pulse steroid therapy, blood transfusions, intravenous immunoglobulin and aggressive resuscitative measures, she expired a day after hospital admission. These cases narrate instances of the onset or exacerbation of lupus following HPV immunization suggesting adjuvant-induced autoimmunity. On the other hand, there are reports of higher incidence of HPV infection in SLE, with the infection per se possibly contributing to disease activity. Thus, the benefit of HPV immunization may still outweigh the risk among these individuals.

Effectiveness of a Web-Based Tailored Intervention With Virtual Assistants Promoting the Acceptability of HPV Vaccination Among Mothers of Invited Girls: Randomized Controlled Trial

PubMed Central

Paulussen, Theo GWM; Ruiter, Robert AC; Eekhout, Iris; de Melker, Hester E; Spoelstra, Maxine EA; van Keulen, Hilde M

2017-01-01

Background In 2010, the human papillomavirus (HPV) vaccination was introduced in the Dutch National Immunization Program for 12-year-old girls, aiming to reduce the incidence of cervical cancer in women. HPV vaccination uptake turned out to be lower than expected: 61% versus 70%, respectively. Mothers were shown to play the most important role in the immunization decision about this vaccination. They had also expressed their need for interactive personal information about the HPV vaccination over and above the existing universal general information. To improve the effectiveness of the existing education about the HPV vaccination, we systematically developed a Web-based tailored intervention with virtual assistants providing mothers of girls to be invited with tailored feedback on their decision making about the HPV vaccination. Objective The aim of this study was to evaluate the effectiveness of the Web-based tailored intervention for promoting HPV vaccination acceptance by means of a randomized controlled trial (RCT). Methods Mothers were recruited via the Dutch vaccination register (Praeventis) (n=36,000) and three Web-based panels (n=2483). Those who gave informed consent (N=8062) were randomly assigned to the control (n=4067) or intervention condition (n=3995). HPV vaccination uptake, as registered by Praeventis once the HPV vaccination round was completed, was used as the primary outcome. Secondary outcomes were differential scores across conditions between baseline (before the provided access to the new tailored intervention) and follow-up (just before the first vaccination) regarding the mothers’ degree of informed decision making (IDM), decisional conflict, and critical determinants of HPV vaccination uptake among which are intention, attitude, risk perception, and outcome beliefs. Results Intention-to-treat analysis (N=8062) showed a significant positive effect of the intervention on IDM, decisional conflict, and nearly all determinants of HPV vaccination uptake (P<.001). No effect was found on uptake (P=.60). This may be attributed to the overall high uptake rates in both conditions. Mothers evaluated the intervention as highly positive, including the website as well as the virtual assistants that were used to deliver the tailored feedback. Conclusions This computer-tailored intervention has the potential to improve HPV vaccination acceptability and IDM and to decrease decisional conflict among mothers of invited girls. Implications for future research are discussed. Trial Registration Trialregister.nl NTR4935; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4935 (Archived by WebCite at http://www.webcitation.org/6srT7l9EM) PMID:28877862

HPV Integration in HNSCC Correlates with Survival Outcomes, Immune Response Signatures, and Candidate Drivers.

PubMed

Koneva, Lada A; Zhang, Yanxiao; Virani, Shama; Hall, Pelle B; McHugh, Jonathan B; Chepeha, Douglas B; Wolf, Gregory T; Carey, Thomas E; Rozek, Laura S; Sartor, Maureen A

2018-01-01

The incidence of human papillomavirus (HPV)-related oropharynx cancer has steadily increased over the past two decades and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing deescalated treatment approaches for HPV + HNSCC patients. RNA sequencing (RNA-seq) data from HNSCC tumors ( n = 84) were used to identify and characterize expressed integration events, which were overrepresented near known head and neck, lung, and urogenital cancer genes. Five genes were recurrent, including CD274 (PD-L1) A significant number of genes detected to have integration events were found to interact with Tp63, ETS, and/or FOX1A. Patients with no detected integration had better survival than integration-positive and HPV - patients. Furthermore, integration-negative tumors were characterized by strongly heightened signatures for immune cells, including CD4 + , CD3 + , regulatory, CD8 + T cells, NK cells, and B cells, compared with integration-positive tumors. Finally, genes with elevated expression in integration-negative specimens were strongly enriched with immune-related gene ontology terms, while upregulated genes in integration-positive tumors were enriched for keratinization, RNA metabolism, and translation. Implications: These findings demonstrate the clinical relevancy of expressed HPV integration, which is characterized by a change in immune response and/or aberrant expression of the integration-harboring cancer-related genes, and suggest strong natural selection for tumor cells with expressed integration events in key carcinogenic genes. Mol Cancer Res; 16(1); 90-102. ©2017 AACR . ©2017 American Association for Cancer Research.

The Human Papillomavirus E6 Oncoprotein Targets USP15 and TRIM25 To Suppress RIG-I-Mediated Innate Immune Signaling.

PubMed

Chiang, Cindy; Pauli, Eva-Katharina; Biryukov, Jennifer; Feister, Katharina F; Meng, Melissa; White, Elizabeth A; Münger, Karl; Howley, Peter M; Meyers, Craig; Gack, Michaela U

2018-03-15

Retinoic acid-inducible gene I (RIG-I) is a key pattern recognition receptor that senses viral RNA and interacts with the mitochondrial adaptor MAVS, triggering a signaling cascade that results in the production of type I interferons (IFNs). This signaling axis is initiated by K63-linked ubiquitination of RIG-I mediated by the E3 ubiquitin ligase TRIM25, which promotes the interaction of RIG-I with MAVS. USP15 was recently identified as an upstream regulator of TRIM25, stabilizing the enzyme through removal of degradative K48-linked polyubiquitin, ultimately promoting RIG-I-dependent cytokine responses. Here, we show that the E6 oncoprotein of human papillomavirus type 16 (HPV16) as well as of other HPV types form a complex with TRIM25 and USP15 in human cells. In the presence of E6, the K48-linked ubiquitination of TRIM25 was markedly increased, and in line with this, TRIM25 degradation was enhanced. Our results further showed that E6 inhibited the TRIM25-mediated K63-linked ubiquitination of RIG-I and its CARD-dependent interaction with MAVS. HPV16 E6, but not E7, suppressed the RIG-I-mediated induction of IFN-β, chemokines, and IFN-stimulated genes (ISGs). Finally, CRISPR-Cas9 gene targeting in human keratinocytes showed that the TRIM25-RIG-I-MAVS triad is important for eliciting an antiviral immune response to HPV16 infection. Our study thus identifies a novel immune escape mechanism that is conserved among different HPV strains and further indicates that the RIG-I signaling pathway plays an important role in the innate immune response to HPV infection. IMPORTANCE Persistent infection and tumorigenesis by HPVs are known to require viral manipulation of a variety of cellular processes, including those involved in innate immune responses. Here, we show that the HPV E6 oncoprotein antagonizes the activation of the cytoplasmic innate immune sensor RIG-I by targeting its upstream regulatory enzymes TRIM25 and USP15. We further show that the RIG-I signaling cascade is important for an antiviral innate immune response to HPV16 infection, providing evidence that RIG-I, whose role in sensing RNA virus infections has been well characterized, also plays a crucial role in the antiviral host response to small DNA viruses of the Papillomaviridae family. Copyright © 2018 American Society for Microbiology.

Feasibility and acceptability of delivering adolescent health interventions alongside HPV vaccination in Tanzania

PubMed Central

Watson-Jones, Deborah; Lees, Shelley; Mwanga, Joseph; Neke, Nyasule; Changalucha, John; Broutet, Nathalie; Maduhu, Ibrahim; Kapiga, Saidi; Chandra-Mouli, Venkatraman; Bloem, Paul; Ross, David A

2016-01-01

Background: Human papillomavirus (HPV) vaccination offers an opportunity to strengthen provision of adolescent health interventions (AHI). We explored the feasibility of integrating other AHI with HPV vaccination in Tanzania. Methods: A desk review of 39 policy documents was preceded by a stakeholder meeting with 38 policy makers and partners. Eighteen key informant interviews (KIIs) with health and education policy makers and district officials were conducted to further explore perceptions of current programs, priorities and AHI that might be suitable for integration with HPV vaccination. Results: Fourteen school health interventions (SHI) or AHI are currently being implemented by the Government of Tanzania. Most are delivered as vertical programmes. Coverage of current programs is not universal, and is limited by financial, human resource and logistic constraints. Limited community engagement, rumours, and lack of strategic advocacy has affected uptake of some interventions, e.g. tetanus toxoid (TT) immunization. Stakeholder and KI perceptions and opinions were limited by a lack of experience with integrated delivery and AHI that were outside an individual’s area of expertise and experience. Deworming and educational sessions including reproductive health education were the most frequently mentioned interventions that respondents considered suitable for integrated delivery with HPV vaccine. Conclusions: Given programme constraints, limited experience with integrated delivery and concern about real or perceived side-effects being attributed to the vaccine, it will be very important to pilot-test integration of AHI/SHI with HPV vaccination. Selected interventions will need to be simple and quick to deliver since health workers are likely to face significant logistic and time constraints during vaccination visits. PMID:26768827

Human papillomavirus vaccine uptake, knowledge and attitude among 10th grade students in Berlin, Germany, 2010

PubMed Central

Stöcker, Petra; Dehnert, Manuel; Schuster, Melanie; Wichmann, Ole; Deleré, Yvonne

2013-01-01

Purpose: Since March 2007, the Standing Committee on Vaccination (STIKO) recommends HPV vaccination for all 12–17 y-old females in Germany. In the absence of an immunization register, we aimed at assessing HPV-vaccination coverage and knowledge among students in Berlin, the largest city in Germany, to identify factors influencing HPV-vaccine uptake. Results: Between September and December 2010, 442 students completed the questionnaire (mean age 15.1; range 14–19). In total 281/442 (63.6%) students specified HPV correctly as a sexually transmitted infection. Of 238 participating girls, 161 (67.6%) provided their vaccination records. Among these, 66 (41.0%) had received the recommended three HPV-vaccine doses. Reasons for being HPV-unvaccinated were reported by 65 girls: Dissuasion from parents (40.2%), dissuasion from their physician (18.5%), and concerns about side-effects (30.8%) (multiple choices possible). The odds of being vaccinated increased with age (Odds Ratio (OR) 2.19, 95% Confidence Interval (CI) 1.16, 4.15) and decreased with negative attitude toward vaccinations (OR = 0.33, 95%CI 0.13, 0.84). Methods: Self-administered questionnaires were distributed to 10th grade school students in 14 participating schools in Berlin to assess socio-demographic characteristics, knowledge, and statements on vaccinations. Vaccination records were reviewed. Multivariable statistical methods were applied to identify independent predictors for HPV-vaccine uptake among female participants. Conclusions: HPV-vaccine uptake was low among school girls in Berlin. Both, physicians and parents were influential regarding their HPV-vaccination decision even though personal perceptions played an important role as well. School programs could be beneficial to improve knowledge related to HPV and vaccines, and to offer low-barrier access to HPV vaccination. PMID:22995838

Frequencies and role of regulatory T cells in patients with (pre)malignant cervical neoplasia

PubMed Central

Visser, J; Nijman, H W; Hoogenboom, B-N; Jager, P; van Baarle, D; Schuuring, E; Abdulahad, W; Miedema, F; van der Zee, A G; Daemen, T

2007-01-01

Oncogenic human papillomavirus (HPV)-infection is crucial for developing cervical cancer and its precursor lesions [cervical intraepithelial neoplasia (CIN)]. Regulatory T cells (Tregs) might be involved in the failure of the immune system to control the development of HPV-induced cancer. We investigated frequencies, phenotype and activity of Tregs in patients with cervical neoplasia. CIN and cervical cancer patients showed increased CD4+/CD25high T cell frequencies in peripheral blood and CD4+ T cell fraction. These CD4+/CD25high T cells represent Tregs as demonstrated by their low proliferation rate, low interferon (IFN)-γ/interleukin (IL)-10 ratio, high expression of CD45RO, GITR, CTLA-4, forkhead box P3 (FoxP3) and low CD45RA expression. Moreover, in HPV16+ cervical cancer patients, in-vitro depletion of CD25+ T cells resulted in increased IFN-γ T cell responses against HPV16 E6- and E7 peptides. Thus, increased frequencies of Tregs in cervical cancer patients may indeed suppress HPV-specific immunity. Longitudinal analysis of CD4+/CD25high T cell frequencies in patients showed a modest decline 1 year after curative surgery or chemoradiation. This study demonstrates increased frequencies and suppressive activity of Tregs in cervical cancer. These results imply that Tregs may suppress the immune control of cervical neoplasia and furthermore that suppression of immunity by Tregs will be another hurdle to overcome in therapeutic immunization strategies against cervical neoplasia. PMID:17937675

Integration of Oncogenes via Sleeping Beauty as a Mouse Model of HPV16+ Oral Tumors and Immunologic Control.

PubMed

Lin, Yi-Hsin; Yang, Ming-Chieh; Tseng, Ssu-Hsueh; Jiang, Rosie; Yang, Andrew; Farmer, Emily; Peng, Shiwen; Henkle, Talia; Chang, Yung-Nien; Hung, Chien-Fu; Wu, T-C

2018-01-23

Human papillomavirus type 16 (HPV16) is the etiologic factor for cervical cancer and a subset of oropharyngeal cancers. Although several prophylactic HPV vaccines are available, no effective therapeutic strategies to control active HPV diseases exist. Tumor implantation models are traditionally used to study HPV-associated buccal tumors. However, they fail to address precancerous phases of disease progression and display tumor microenvironments distinct from those observed in patients. Previously, K14-E6/E7 transgenic mouse models have been used to generate spontaneous tumors. However, the rate of tumor formation is inconsistent, and the host often develops immune tolerance to the viral oncoproteins. We developed a preclinical, spontaneous, HPV16 + buccal tumor model using submucosal injection of oncogenic plasmids expressing HPV16-E6/E7, NRas G12V , luciferase, and sleeping beauty (SB) transposase, followed by electroporation in the buccal mucosa. We evaluated responses to immunization with a pNGVL4a-CRT/E7(detox) therapeutic HPV DNA vaccine and tumor cell migration to distant locations. Mice transfected with plasmids encoding HPV16-E6/E7, NRas G12V , luciferase, and SB transposase developed tumors within 3 weeks. We also found transient anti-CD3 administration is required to generate tumors in immunocompetent mice. Bioluminescence signals from luciferase correlated strongly with tumor growth, and tumors expressed HPV16-associated markers. We showed that pNGVL4a-CRT/E7(detox) administration resulted in antitumor immunity in tumor-bearing mice. Lastly, we demonstrated that the generated tumor could migrate to tumor-draining lymph nodes. Our model provides an efficient method to induce spontaneous HPV + tumor formation, which can be used to identify effective therapeutic interventions, analyze tumor migration, and conduct tumor biology research. Cancer Immunol Res; 6(3); 1-15. ©2018 AACR. ©2018 American Association for Cancer Research.

Measuring Adolescent Human Papillomavirus Vaccine Coverage: A Match of Sexually Transmitted Disease Clinic and Immunization Registry Data.

PubMed

Pathela, Preeti; Jamison, Kelly; Papadouka, Vikki; Kabir, Rezaul; Markowitz, Lauri E; Dunne, Eileen F; Schillinger, Julia A

2016-12-01

Human papillomavirus (HPV) vaccine is recommended for adolescents. By the end of 2013, 64% of female and 40% of male New York City residents aged 13-18 years had received ≥1 HPV vaccine dose. Adolescents attending sexually transmitted disease (STD) clinics are at high risk for HPV exposure and could benefit from vaccination. Our objective was to estimate HPV vaccination coverage for this population. We matched records of New York City's STD clinic patients aged 13-18 years during 2010-2013 with the Citywide Immunization Registry. We assessed HPV vaccine initiation (≥1 dose) and series completion (≥3 doses among those who initiated) as of clinic visit date and by patient demographics. We compared receipt of ≥1 dose for HPV, tetanus-diphtheria-acellular pertussis, and meningococcal conjugate vaccine. Eighty-two percent of clinic attendees (13,505/16,364) had records in the Citywide Immunization Registry. Receipt of ≥1 HPV dose increased during 2010-2013 (females: 57.6%-69.7%; males: 1.5%-36.3%). Among females, ≥1-dose coverage was lowest among whites (53.4%) and highest among Hispanics (73.3%); among males, ≥1-dose coverage was lowest among whites (6.9%) and highest among Asians (20.9%). Series completion averaged 57.7% (females) and 28.0% (males), with little variation by race/ethnicity or poverty level. Receipt of ≥1 dose was 59.7% for HPV, 82% for tetanus-diphtheria-acellular pertussis, and 76% for meningococcal conjugate vaccines. HPV vaccine initiation and completion were low among adolescent STD clinic patients; coverage was lower compared with other recommended vaccines. STD clinics may be good venues for delivering HPV vaccine, thereby enhancing efforts to improve HPV vaccination. Copyright © 2016 Society for Adolescent Health and Medicine. All rights reserved.

Human Papillomavirus Drives Tumor Development Throughout the Head and Neck: Improved Prognosis Is Associated With an Immune Response Largely Restricted to the Oropharynx

PubMed Central

Chakravarthy, Ankur; Henderson, Stephen; Thirdborough, Stephen M.; Ottensmeier, Christian H.; Su, Xiaoping; Lechner, Matt; Feber, Andrew; Thomas, Gareth J.

2016-01-01

Purpose In squamous cell carcinomas of the head and neck (HNSCC), the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCCs) is attributable to human papillomavirus (HPV) infection. Despite commonly presenting at late stage, HPV-driven OPSCCs are associated with improved prognosis compared with HPV-negative disease. HPV DNA is also detectable in nonoropharyngeal (non-OPSCC), but its pathogenic role and clinical significance are unclear. The objectives of this study were to determine whether HPV plays a causal role in non-OPSCC and to investigate whether HPV confers a survival benefit in these tumors. Methods Meta-analysis was used to build a cross-tissue gene-expression signature for HPV-driven cancer. Classifiers trained by machine-learning approaches were used to predict the HPV status of 520 HNSCCs profiled by The Cancer Genome Atlas project. DNA methylation data were similarly used to classify 464 HNSCCs and these analyses were integrated with genomic, histopathology, and survival data to permit a comprehensive comparison of HPV transcript-positive OPSCC and non-OPSCC. Results HPV-driven tumors accounted for 4.1% of non-OPSCCs. Regardless of anatomic site, HPV+ HNSCCs shared highly similar gene expression and DNA methylation profiles; nonkeratinizing, basaloid histopathological features; and lack of TP53 or CDKN2A alterations. Improved overall survival, however, was largely restricted to HPV-driven OPSCCs, which were associated with increased levels of tumor-infiltrating lymphocytes compared with HPV-driven non-OPSCCs. Conclusion Our analysis identified a causal role for HPV in transcript-positive non-OPSCCs throughout the head and neck. Notably, however, HPV-driven non-OPSCCs display a distinct immune microenvironment and clinical behavior compared with HPV-driven OPSCCs. PMID:27863190

Reasons for not vaccinating adolescents: National Immunization Survey of Teens, 2008-2010.

PubMed

Darden, Paul M; Thompson, David M; Roberts, James R; Hale, Jessica J; Pope, Charlene; Naifeh, Monique; Jacobson, Robert M

2013-04-01

To determine the reasons adolescents are not vaccinated for specific vaccines and how these reasons have changed over time. We analyzed the 2008-2010 National Immunization Survey of Teens examining reasons parents do not have their teens immunized. Parents whose teens were not up to date (Not-UTD) for Tdap/Td and MCV4 were asked the main reason they were not vaccinated. Parents of female teens Not-UTD for human papillomavirus vaccine (HPV) were asked their intent to give HPV, and those unlikely to get HPV were asked the main reason why not. The most frequent reasons for not vaccinating were the same for Tdap/Td and MCV4, including "Not recommended" and "Not needed or not necessary." For HPV, the most frequent reasons included those for the other vaccines as well as 4 others, including "Not sexually active" and "Safety concerns/Side effects." "Safety concerns/Side effects" increased from 4.5% in 2008 to 7.7% in 2009 to 16.4% in 2010 and, in 2010, approaching the most common reason "Not Needed or Not Necessary" at 17.4% (95% CI: 15.7-19.1). Although parents report that health care professionals increasingly recommend all vaccines, including HPV, the intent to not vaccinate for HPV increased from 39.8% in 2008 to 43.9% in 2010 (OR for trend 1.08, 95% CI: 1.04-1.13). Despite doctors increasingly recommending adolescent vaccines, parents increasingly intend not to vaccinate female teens with HPV. The concern about safety of HPV grew with each year. Addressing specific and growing parental concerns about HPV will require different considerations than those for the other vaccines.

The association of pre-treatment HPV subtypes with recurrence of VIN.

PubMed

Bogani, Giorgio; Martinelli, Fabio; Ditto, Antonino; Signorelli, Mauro; Taverna, Francesca; Lombardo, Claudia; Chiappa, Valentina; Leone Roberti Maggiore, Umberto; Recalcati, Dario; Scaffa, Cono; Perotto, Stefania; Sabatucci, Ilaria; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

2017-04-01

To assess whether pre-treatment HPV types are associated with recurrence of high-grade vulvar intraepithelial neoplasia (VIN2+). Data of consecutive patients with pretreatment HPV DNA test undergoing treatment for VIN2+ were retrospectively collected. Risk factors promoting the risk of VIN2+ persistence and recurrence were analyzed using Kaplan-Meier and Cox hazard proportional models. 64 patients had pretreatment vulvar-vaginal HPV DNA test. Two were excluded due to the presence of synchronous vulvar cancer, thus leaving 62 patients for the final analysis. HPV16, HPV18, HPV31 and HPV33 were the most common HPV genotype detected, occurring in 15 (24.2%), 4 (6.5%), 8 (12.9%) and 5 (8.0%) patients, respectively. HPV was not detected in 19 (30.6%) patients. During a mean (SD) follow up of 56.7 (±26.7) months, 10 (16.1%) patients had VIN2+ persistence/recurrence. Mean (SD) lesion-free interval was 51.7 (±31.4) months. Via multivariate analysis, pretreatment infection from HPV31 (HR:46.7(95%CI:4.21,518.4); p=0.02) and HPV33 (HR:77.0(95%CI:6.73,881.9); p<0.001) correlated with an increased risk of VIN2+ persistence/recurrence. Additionally, we observed that patients undergoing surgical excision followed by LASER ablation experienced a trend towards lower recurrence rate than patients undergoing other surgical or medical treatments (HR:0.20(95%CI:0.03,1.09); p=0.05). Two (3.2%) patients developed progression to vulvar cancer. Owing to the inherent biases of the retrospective study design and the small sample size, our data have to be corroborated by larger and prospective studies. HPV31 and HPV33 have a potential role in predicting VIN2+ persistence/recurrence. These findings will be paramount, owing to the implementation of new immunization programs. Copyright © 2017 Elsevier B.V. All rights reserved.

Human papilloma virus and lupus: the virus, the vaccine and the disease.

PubMed

Segal, Yahel; Calabrò, Michele; Kanduc, Darja; Shoenfeld, Yehuda

2017-07-01

Systemic lupus erythematosus (SLE) is a well known, widespread autoimmune disease, involving multiple organ systems, with a multifaceted, widely unmapped etiopathogenesis. Recently, a new aspect of morbidity has been described among SLE patients: infection with human papilloma virus (HPV). We set out to review data regarding the intricate relationship between the two and attempt to determine whether HPV may pose as a contributing factor to the development of SLE. We relate to epidemiological, molecular and clinical data. We have found evidence in all these fields suggesting HPV to be involved in the pathogenesis of SLE: increased prevalence of HPV infection among SLE patients; vast molecular homology between viral peptides and human proteins associated with SLE; several reports of SLE development post-HPV vaccination. Our findings suggest a possible involvement of HPV infection in the induction of SLE, via a mechanism of immune cross-reaction due to molecular homology. We review clinical, epidemiological and molecular data suggesting involvement of HPV infection in the pathogenesis of SLE. We suggest that these findings may justify the development of new HPV vaccines containing viral peptides that bear no homology to the human proteome, in order to avoid possible adverse immune cross-reactivity.

Economic evaluation of pediatric influenza immunization program compared with other pediatric immunization programs: A systematic review

PubMed Central

Gibson, Edward; Begum, Najida; Sigmundsson, Birgir; Sackeyfio, Alfred; Hackett, Judith; Rajaram, Sankarasubramanian

2016-01-01

ABSTRACT This study compared the economic value of pediatric immunisation programmes for influenza to those for rotavirus (RV), meningococcal disease (MD), pneumococcal disease (PD), human papillomavirus (HPV), hepatitis B (Hep B), and varicella reported in recent (2000 onwards) cost-effectiveness (CE) studies identified in a systematic review of PubMed, health technology, and vaccination databases. The systematic review yielded 51 economic evaluation studies of pediatric immunisation — 10 (20%) for influenza and 41 (80%) for the other selected diseases. The quality of the eligible articles was assessed using Drummond's checklist. Although inherent challenges and limitations exist when comparing economic evaluations of immunisation programmes, an overall comparison of the included studies demonstrated cost-effectiveness/cost saving for influenza from a European-Union-Five (EU5) and United States (US) perspective; point estimates for cost/quality-adjusted life-years (QALY) from dominance (cost-saving with more effect) to ≤45,444 were reported. The economic value of influenza programmes was comparable to the other vaccines of interest, with cost/QALY in general considerably lower than RV, Hep B, MD and PD. Independent of the perspective and type of analysis, the economic impact of a pediatric influenza immunisation program was influenced by vaccine efficacy, immunisation coverage, costs, and most significantly by herd immunity. This review suggests that pediatric influenza immunisation may offer a cost effective strategy when compared with HPV and varicella and possibly more value compared with other childhood vaccines (RV, Hep B, MD and PD). PMID:26837602

Economic evaluation of pediatric influenza immunization program compared with other pediatric immunization programs: A systematic review.

PubMed

Gibson, Edward; Begum, Najida; Sigmundsson, Birgir; Sackeyfio, Alfred; Hackett, Judith; Rajaram, Sankarasubramanian

2016-05-03

This study compared the economic value of pediatric immunisation programmes for influenza to those for rotavirus (RV), meningococcal disease (MD), pneumococcal disease (PD), human papillomavirus (HPV), hepatitis B (Hep B), and varicella reported in recent (2000 onwards) cost-effectiveness (CE) studies identified in a systematic review of PubMed, health technology, and vaccination databases. The systematic review yielded 51 economic evaluation studies of pediatric immunisation - 10 (20%) for influenza and 41 (80%) for the other selected diseases. The quality of the eligible articles was assessed using Drummond's checklist. Although inherent challenges and limitations exist when comparing economic evaluations of immunisation programmes, an overall comparison of the included studies demonstrated cost-effectiveness/cost saving for influenza from a European-Union-Five (EU5) and United States (US) perspective; point estimates for cost/quality-adjusted life-years (QALY) from dominance (cost-saving with more effect) to ≤45,444 were reported. The economic value of influenza programmes was comparable to the other vaccines of interest, with cost/QALY in general considerably lower than RV, Hep B, MD and PD. Independent of the perspective and type of analysis, the economic impact of a pediatric influenza immunisation program was influenced by vaccine efficacy, immunisation coverage, costs, and most significantly by herd immunity. This review suggests that pediatric influenza immunisation may offer a cost effective strategy when compared with HPV and varicella and possibly more value compared with other childhood vaccines (RV, Hep B, MD and PD).

Humoral, Mucosal, and Cell-Mediated Immunity Against Vaccine and Nonvaccine Genotypes After Administration of Quadrivalent Human Papillomavirus Vaccine to HIV-Infected Children

PubMed Central

Weinberg, Adriana; Song, Lin-Ye; Saah, Alfred; Brown, Martha; Moscicki, Anna B.; Meyer, William A.; Bryan, Janine; Levin, Myron J.

2012-01-01

Objectives. To characterize the immunogenicity of a quadrivalent human papillomavirus vaccine (QHPV) in human immunodeficiency virus (HIV)–infected children, we studied their immune responses to 3 or 4 doses. Methods. HIV-infected children aged 7–12 years with a CD4 cell percentage of ≥15% of lymphocytes, received 3 doses of QHPV with or without a fourth dose after 72 weeks. Type-specific and cross-reactive antibodies and cell-mediated immunity were measured. Results. Type-specific antibodies to HPV6, 11, and 16 were detected in 100% and ≥94% of children at 4 and 72 weeks, respectively, after the third QHPV dose. Corresponding numbers for HPV18 were 97% and 76%, respectively. A fourth QHPV dose increased seropositivity to ≥96% for all vaccine genotypes. Four weeks after the third QHPV dose, 67% of vaccinees seroconverted to HPV31, an HPV16-related genotype not in the vaccine; 69% and 39% of vaccinees developed mucosal HPV16 and 18 immunoglobulin G antibodies, respectively; and 60% and 52% of vaccinees developed cytotoxic T lymphocytes (CTLs) for HPV16 and 31, respectively. Conclusions. Three QHPV doses generated robust and persistent antibodies to HPV6, 11, and 16 but comparatively weaker responses to HPV18. A fourth dose increased antibodies against all vaccine genotypes in an anamnestic fashion. CTLs and mucosal antibodies against vaccine genotypes, as well as cross-reactive antibodies and CTL against nonvaccine genotypes, were detected. PMID:22859825

Service quality and parents' willingness to get adolescents HPV vaccine from pharmacists.

PubMed

Shah, Parth D; Calo, William A; Marciniak, Macary W; Golin, Carol E; Sleath, Betsy L; Brewer, Noel T

2018-04-01

We sought to examine whether pharmacy service quality was associated with parents' willingness to have immunizing pharmacists administer human papillomavirus (HPV) vaccine to their adolescent children. Participants were a national sample of 1504 US parents of adolescents ages 11 to 17 who completed an online survey in 2014. Analyses used structural equation modeling. Parents rated service quality and feelings of satisfaction with their pharmacies as moderate to high. Many (44%) were willing to get HPV vaccine from immunizing pharmacists for their adolescent children. Compared with parents who went to chain pharmacies, parents who went to independent pharmacies gave higher ratings of service quality (professionalism, confidentiality, milieu, all p < .001). Parents who went to clinic pharmacies, compared with parents who went to chain pharmacies gave lower ratings for milieu (p < .01). Parents who went to independent pharmacies had lower willingness to get HPV vaccine from pharmacists compared to parents who went to chain pharmacies (p = .001), but there was no difference in willingness for parents who went to clinic versus chain pharmacies. Service quality and satisfaction partially mediated the effect between independent pharmacies compared to chain pharmacies and willingness (p < .05). Parents who knew their pharmacists or expressed more confidence in HPV vaccine also had higher willingness to get their children HPV vaccine from pharmacist. Many parents were willing to go to immunizing pharmacists for their children's HPV vaccination. Pharmacies that are considering offering HPV vaccine may be able to improve vaccine uptake by increasing perception of service quality. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18-45 years.

PubMed

Einstein, Mark H; Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Lebacq, Marie; van der Most, Robbert; Moris, Philippe; Giannini, Sandra L; Schuind, Anne; Datta, Sanjoy K; Descamps, Dominique

2011-12-01

Protection against oncogenic non-vaccine types (cross-protection) offered by human papillomavirus (HPV) vaccines may provide a significant medical benefit. Available clinical efficacy data suggest the two licensed vaccines (HPV-16/18 vaccine, GlaxoSmithKline Biologicals (GSK), and HPV-6/11/16/18 vaccine, Merck & Co., Inc.) differ in terms of protection against oncogenic non-vaccine HPV types -31/45. The immune responses induced by the two vaccines against these two non-vaccine HPV types (cross-reactivity) was compared in an observer-blind study up to Month 24 (18 mo post-vaccination), in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed (HPV-010 [NCT00423046]). Geometric mean antibody titers (GMTs) measured by pseudovirion-based neutralization assay (PBNA) and enzyme-linked immunosorbent assay (ELISA) were similar between vaccines for HPV-31/45. Seropositivity rates for HPV-31 were also similar between vaccines; however, there was a trend for higher seropositivity with the HPV-16/18 vaccine (13.0-16.7%) versus the HPV-6/11/16/18 vaccine (0.0-5.0%) for HPV-45 with PBNA, but not ELISA. HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines. Circulating antigen-specific CD4+ T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (HPV-31 [geometric mean ratio [GMR] =2.0; p=0.0002] and HPV-45 [GMR=2.6; p=0.0092]), as were the proportion of T-cell responders (HPV-31, p=0.0009; HPV-45, p=0.0793). In conclusion, immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine. Considering the differences in cross-protective efficacy between the two vaccines, the results might provide insights into the underlying mechanism(s) of protection.

Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18–45 years

PubMed Central

Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Lebacq, Marie; van der Most, Robbert; Moris, Philippe; Giannini, Sandra L; Schuind, Anne; Datta, Sanjoy K; Descamps, Dominique

2011-01-01

Protection against oncogenic non-vaccine types (cross-protection) offered by human papillomavirus (HPV) vaccines may provide a significant medical benefit. Available clinical efficacy data suggest the two licensed vaccines [HPV-16/18 vaccine, GlaxoSmithKline Biologicals (GSK), and HPV-6/11/16/18 vaccine, Merck and Co., Inc.,] differ in terms of protection against oncogenic non-vaccine HPV types -31/45. The immune responses induced by the two vaccines against these two non-vaccine HPV types (cross-reactivity) was compared in an observer-blind study up to Month 24 (18 mo postvaccination), in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed [HPV-010 (NCT00423046)]. Geometric mean antibody titers (GMTs) measured by pseudovirion-based neutralization assay (PBNA) and enzyme-linked immunosorbent assay (ELISA ) were similar between vaccines for HPV-31/45. Seropositivity rates for HPV-31 were also similar between vaccines; however, there was a trend for higher seropositivity with the HPV-16/18 vaccine (13.0–16.7%) vs. the HPV-6/11/16/18 vaccine (0.0–5.0%) for HPV-45 with PBNA, but not ELISA . HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines. Circulating antigen-specific CD4+ T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine {HPV-31 [geometric mean ratio (GMR) = 2.0; p = 0.0002] and HPV-45 [GMR = 2.6; p = 0.0092]}, as were the proportion of T-cell responders (HPV-31, p = 0.0009; HPV-45, p = 0.0793). In conclusion, immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine. Considering the differences in cross-protective efficacy between the two vaccines, the results might provide insights into the underlying mechanism(s) of protection. PMID:22048172

Attitudes Regarding HPV Vaccinations of Children among Mothers with Adolescent Daughters in Korea

PubMed Central

2017-01-01

The aim of this study, carried out before the beginning of human papillomavirus (HPV) vaccinations as a National Immunization Program (NIP) in Korea in 2016, is to assess the ranges of perceptions and personal experience and their influences on attitudes regarding HPV vaccinations of children, among mothers of adolescent (9–14 years of age) daughters in Korea. From November 2015 to February 2016, we distributed a written questionnaire to mothers who had daughters aged 9–14 years. The questionnaire consisted of several questions, related to knowledge of HPV, personal experiences of HPV vaccination, and attitudes toward HPV vaccinations of their adolescent daughters. Of the 260 questionnaires distributed, 140 participants returned answered ones. And although only 51% of participants were aware that cervical cancer is highly related with HPV infection, 70% said they were willing to vaccinate their daughters, showing that awareness does not coincide with intention to vaccinate. Among the participants showing negative attitudes, 50% were concerned about the vaccination side effects. The more the participants’ pre-knowledge about HPV infection, and about the relationship of HPV to cervical cancer, the more positive their attitudes (P = 0.002, P < 0.001). Our study showed that, as the level of education rose, the proportion of mothers with negative attitudes toward vaccinating their adolescent daughters rose as well. Thus, the provision of correct education by health care providers and accurate information through active advertising may play an important role in increasing the vaccination rate among adolescent girls in Korea. PMID:27914142

Summer Peaks in Uptake of Human Papillomavirus and Other Adolescent Vaccines in the United States.

PubMed

Moss, Jennifer L; Reiter, Paul L; Rimer, Barbara K; Ribisl, Kurt M; Brewer, Noel T

2016-02-01

Seasonality in human papillomavirus (HPV) vaccination could have a large impact on national cancer prevention efforts. We hypothesized that uptake of HPV vaccine and other adolescent vaccines in the United States would be highest in the summer. Data came from health care provider-verified vaccination records for 70,144 adolescents (ages 13-17 years) from the 2008 to 2012 versions of the National Immunization Survey-Teen. Using the Edwards method for testing annual trends, we examined seasonal patterns in the uptake of HPV and other recommended adolescent vaccines [tetanus, diphtheria, and pertussis (Tdap) booster and meningococcal vaccine]. HPV vaccine initiation (receipt of the first of the three-dose series) data were for female adolescents. Uptake for HPV and other adolescent vaccines peaked in the summer across years and states (all P < 0.001). Uptake was five times as frequent at the peak as at the trough for HPV vaccine, and HPV vaccine initiation was highest in June, July, and August (percent of doses delivered in these months: 38.7%). The same pattern existed for Tdap booster and meningococcal vaccine. Concomitant (same-day) vaccination of HPV vaccine with other adolescent vaccines also demonstrated summer peaks each year nationally (all P < 0.001). Uptake of adolescent vaccines increased dramatically in summer months. These summer peaks are an important opportunity for interventions focused on concomitant vaccination. The potential cancer prevention impact of HPV vaccination programs could be increased, for example, by delivering messages about concomitant vaccination during the summer, when adolescents and their parents might be most open to them. ©2015 American Association for Cancer Research.

Random Network Models to Predict the Long-Term Impact of HPV Vaccination on Genital Warts

PubMed Central

Díez-Domingo, Javier; Sánchez-Alonso, Víctor; Acedo, Luis; Villanueva-Oller, Javier

2017-01-01

The Human papillomaviruses (HPV) vaccine induces a herd immunity effect in genital warts when a large number of the population is vaccinated. This aspect should be taken into account when devising new vaccine strategies, like vaccination at older ages or male vaccination. Therefore, it is important to develop mathematical models with good predictive capacities. We devised a sexual contact network that was calibrated to simulate the Spanish epidemiology of different HPV genotypes. Through this model, we simulated the scenario that occurred in Australia in 2007, where 12–13 year-old girls were vaccinated with a three-dose schedule of a vaccine containing genotypes 6 and 11, which protect against genital warts, and also a catch-up program in women up to 26 years of age. Vaccine coverage were 73% in girls with three doses and with coverage rates decreasing with age until 52% for 20–26 year-olds. A fast 59% reduction in the genital warts diagnoses occurred in the model in the first years after the start of the program, similar to what was described in the literature. PMID:29035332

Random Network Models to Predict the Long-Term Impact of HPV Vaccination on Genital Warts.

PubMed

Díez-Domingo, Javier; Sánchez-Alonso, Víctor; Villanueva, Rafael-J; Acedo, Luis; Moraño, José-Antonio; Villanueva-Oller, Javier

2017-10-16

The Human papillomaviruses (HPV) vaccine induces a herd immunity effect in genital warts when a large number of the population is vaccinated. This aspect should be taken into account when devising new vaccine strategies, like vaccination at older ages or male vaccination. Therefore, it is important to develop mathematical models with good predictive capacities. We devised a sexual contact network that was calibrated to simulate the Spanish epidemiology of different HPV genotypes. Through this model, we simulated the scenario that occurred in Australia in 2007, where 12-13 year-old girls were vaccinated with a three-dose schedule of a vaccine containing genotypes 6 and 11, which protect against genital warts, and also a catch-up program in women up to 26 years of age. Vaccine coverage were 73 % in girls with three doses and with coverage rates decreasing with age until 52 % for 20-26 year-olds. A fast 59 % reduction in the genital warts diagnoses occurred in the model in the first years after the start of the program, similar to what was described in the literature.

The Association of the Immune Response Genes to Human Papillomavirus-Related Cervical Disease in a Brazilian Population

PubMed Central

Marangon, Amanda Vansan; Guelsin, Gláucia Andreia Soares; Visentainer, Jeane Eliete Laguila; Borelli, Sueli Donizete; Watanabe, Maria Angélica Ehara; Consolaro, Márcia Edilaine Lopes; Caleffi-Ferracioli, Katiany Rizzieri; Rudnick, Cristiane Conceição Chagas; Sell, Ana Maria

2013-01-01

The genetic variability of the host contributes to the risk of human papillomavirus (HPV)-related cervical disease. Immune response genes to HPV must be investigated to define patients with the highest risk of developing malignant disease. The aim of this study was to investigate the association of polymorphic immune response genes, namely KIR, HLA class I and II, and single-nucleotide polymorphisms (SNPs) of cytokines with HPV-related cervical disease. We selected 79 non-related, admixed Brazilian women from the state of Paraná, southern region of Brazil, who were infected with high carcinogenic risk HPV and present cervical intraepithelial neoplasia grade 3 (CIN3), and 150 HPV-negative women from the same region matched for ethnicity. KIR genes were genotyped using an in-house PCR-SSP. HLA alleles were typed using a reverse sequence-specific oligonucleotide technique. SNPs of TNF −308G>A, IL6 −174G>C, IFNG +874T>A, TGFB1 +869T>C +915G>C, and IL10 −592C>A −819C>T −1082G>A were evaluated using PCR-SSP. The KIR genes were not associated with HPV, although some pairs of i(inhibitory)KIR-ligands occurred more frequently in patients, supporting a role for NK in detrimental chronic inflammatory and carcinogenesis. Some HLA haplotypes were associated with HPV. The associations of INFG and IL10 SNPs potentially reflect impaired or invalid responses in advanced lesions. PMID:23936772

Bicistronic DNA vaccines simultaneously encoding HIV, HSV and HPV antigens promote CD8⁺ T cell responses and protective immunity.

PubMed

Santana, Vinicius C; Diniz, Mariana O; Cariri, Francisco A M O; Ventura, Armando M; Cunha-Neto, Edécio; Almeida, Rafael R; Campos, Marco A; Lima, Graciela K; Ferreira, Luís C S

2013-01-01

Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8⁺ T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8⁺ T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses.

Comprehensive Control of Human Papillomavirus Infections and Related Diseases

PubMed Central

Bosch, F. Xavier; Broker, Thomas R.; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L.; Doorbar, John; Stern, Peter L.; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E.; Schiller, John T.; Markowitz, Lauri E.; Fisher, William A.; Canfell, Karen; Denny, Lynette A.; Franco, Eduardo L.; Steben, Marc; Kane, Mark A.; Schiffman, Mark; Meijer, Chris J.L.M.; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J.; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

2014-01-01

Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread—optimally universal—implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph ‘Comprehensive Control of HPV Infections and Related Diseases’ Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters. PMID:24229716

Fewer doses of HPV vaccine result in immune response similar to three-dose regimen

Cancer.gov

NCI scientists report that two doses of a human papillomavirus (HPV) vaccine, trademarked as Cervarix, resulted in similar serum antibody levels against two of the most carcinogenic types of HPV (16 and 18), compared to a standard three dose regimen.

Health and economic impact of HPV 16/18 vaccination and cervical cancer screening in Eastern Africa.

PubMed

Campos, Nicole G; Kim, Jane J; Castle, Philip E; Ortendahl, Jesse D; O'Shea, Meredith; Diaz, Mireia; Goldie, Sue J

2012-06-01

Eastern Africa has the world's highest cervical cancer incidence and mortality rates. We used epidemiologic data from Kenya, Mozambique, Tanzania, Uganda, and Zimbabwe to develop models of HPV-related infection and disease. For each country, we assessed HPV vaccination of girls before age 12 followed by screening with HPV DNA testing once, twice, or three times per lifetime (at ages 35, 40, 45). For women over age 30, we assessed only screening (with HPV DNA testing up to three times per lifetime or VIA at age 35). Assuming no waning immunity, mean reduction in lifetime cancer risk associated with vaccination ranged from 36 to 45%, and vaccination followed by screening once per lifetime at age 35 with HPV DNA testing ranged from 43 to 51%. For both younger and older women, the most effective screening strategy was HPV DNA testing three times per lifetime. Provided the cost per vaccinated girl was less than I$10 (I$2 per dose), vaccination had an incremental cost-effectiveness ratio [I$ (international dollars)/year of life saved (YLS)] less than the country-specific per capita GDP, a commonly cited heuristic for "very cost-effective" interventions. If the cost per vaccinated girl was between I$10 (I$2 per dose) and I$25 (I$5 per dose), vaccination followed by HPV DNA testing would save the most lives and would be considered good value for public health dollars. These results should be used to catalyze design and evaluation of HPV vaccine delivery and screening programs, and contribute to a dialogue on financing HPV vaccination in poor countries. Copyright © 2011 UICC.

Practices and Attitudes of Missouri School Nurses Regarding Immunization Records and Select Immunizations of Graduating High School Seniors.

PubMed

Rhodes, Darson L; Draper, Michele; Woolman, Kendra; Cox, Carol

2017-10-01

School nurses play a key role in maintaining a healthy student population, and one of their roles includes maintaining vaccination records. Further, they can play an important role in advocating for human papillomavirus (HPV) and meningococcal vaccination for students. All Missouri public high school nurses were sent an electronic survey addressing the knowledge, attitudes, and practices regarding immunization records and HPV and meningococcal vaccination of high school seniors. Approximately 75% of nurses reported their schools did not have or they did not know if the school had a written policy regarding the release of vaccination records. Approximately 1/2 and 1/3 of nurses do not communicate with parents/students about HPV or meningococcal vaccines, respectively. Although most favorable toward meningococcal, nurses had positive attitudes toward both vaccines. Recommendations include establishment of written policies regarding vaccination record release, and future research should focus on evaluating school nurses' communication methods regarding HPV and meningococcal vaccination.

Functional analysis of HPV-like particle-activated Langerhans cells in vitro.

PubMed

Yan, Lisa; Woodham, Andrew W; Da Silva, Diane M; Kast, W Martin

2015-01-01

Langerhans cells (LCs) are antigen-presenting cells responsible for initiating an immune response against human papillomaviruses (HPVs) entering the epithelial layer in vivo as they are the first immune cell that HPV comes into contact with. LCs become activated in response to foreign antigens, which causes internal signaling resulting in the increased expression of co-stimulatory molecules and the secretion of inflammatory cytokines. Functionally activated LCs are then capable of migrating to the lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response in vivo. However, HPV has evolved in a manner that suppresses LC function, and thus the induction of antigen-specific T cells is hindered. While many methods exist to monitor the activity of LCs in vitro, the migration and induction of cytotoxic T cells is ultimately indicative of a functional immune response. Here, methods in analyzing functional migration and induction of antigen-specific T cells after stimulation of LCs with HPV virus-like particles in vitro are described.

Quadrivalent human papillomavirus vaccination in girls and the risk of autoimmune disorders: the Ontario Grade 8 HPV Vaccine Cohort Study.

PubMed

Liu, Erin Y; Smith, Leah M; Ellis, Anne K; Whitaker, Heather; Law, Barbara; Kwong, Jeffrey C; Farrington, Paddy; Lévesque, Linda E

2018-05-28

Despite demonstrated effectiveness in real-world settings, concerns persist regarding the safety of the quadrivalent human papillomavirus (HPV4) vaccine. We sought to assess the risk of autoimmune disorders following HPV4 vaccination among grade 8 girls eligible for Ontario's school-based HPV vaccination program. We undertook a population-based retrospective cohort study using Ontario's administrative health and vaccination databases from 2007 to 2013. The self-controlled case series method was used to compare the rate of a composite end point of autoimmune disorders diagnosed during days 7-60 post-vaccination ("exposed" follow-up) to that at any other time ("unexposed"). The analysis was repeated to assess the effect of a history of immune-mediated diseases and time since vaccination. We also conducted an exploratory analysis of individual autoimmune disorders. Rate ratios and 95% confidence intervals (CIs) were estimated using conditional Poisson regression, adjusted for age, seasonality, concomitant vaccinations and infections. The study cohort consisted of 290 939 girls aged 12-17 years who were eligible for vaccination between 2007 and 2013. There was no significant risk for developing an autoimmune disorder following HPV4 vaccination ( n = 681; rate ratio 1.12, 95% CI 0.85-1.47), and the association was unchanged by a history of immune-mediated disorders and time since vaccination. Exploratory analyses of individual autoimmune disorders found no significant risks, including for Bell palsy ( n = 65; rate ratio 1.73, 95% CI 0.77-3.89), optic neuritis ( n = 67; rate ratio 1.57, 95% CI 0.74-3.33) and Graves disease ( n = 47; rate ratio 1.55, 95% CI 0.92-2.63). We did not observe an increased risk of autoimmune disorders following HPV4 vaccination among teenaged girls. These findings should reassure parents and health care providers. © 2018 Joule Inc. or its licensors.

Quadrivalent human papillomavirus vaccination in girls and the risk of autoimmune disorders: the Ontario Grade 8 HPV Vaccine Cohort Study

PubMed Central

Liu, Erin Y.; Smith, Leah M.; Ellis, Anne K.; Whitaker, Heather; Law, Barbara; Kwong, Jeffrey C.; Farrington, Paddy

2018-01-01

BACKGROUND: Despite demonstrated effectiveness in real-world settings, concerns persist regarding the safety of the quadrivalent human papillomavirus (HPV4) vaccine. We sought to assess the risk of autoimmune disorders following HPV4 vaccination among grade 8 girls eligible for Ontario’s school-based HPV vaccination program. METHODS: We undertook a population-based retrospective cohort study using Ontario’s administrative health and vaccination databases from 2007 to 2013. The self-controlled case series method was used to compare the rate of a composite end point of autoimmune disorders diagnosed during days 7–60 post-vaccination (“exposed” follow-up) to that at any other time (“unexposed”). The analysis was repeated to assess the effect of a history of immune-mediated diseases and time since vaccination. We also conducted an exploratory analysis of individual autoimmune disorders. Rate ratios and 95% confidence intervals (CIs) were estimated using conditional Poisson regression, adjusted for age, seasonality, concomitant vaccinations and infections. RESULTS: The study cohort consisted of 290 939 girls aged 12–17 years who were eligible for vaccination between 2007 and 2013. There was no significant risk for developing an autoimmune disorder following HPV4 vaccination (n = 681; rate ratio 1.12, 95% CI 0.85–1.47), and the association was unchanged by a history of immune-mediated disorders and time since vaccination. Exploratory analyses of individual autoimmune disorders found no significant risks, including for Bell palsy (n = 65; rate ratio 1.73, 95% CI 0.77–3.89), optic neuritis (n = 67; rate ratio 1.57, 95% CI 0.74–3.33) and Graves disease (n = 47; rate ratio 1.55, 95% CI 0.92–2.63). INTERPRETATION: We did not observe an increased risk of autoimmune disorders following HPV4 vaccination among teenaged girls. These findings should reassure parents and health care providers. PMID:29807937

One Dose of HPV Vaccine May Protect against Cervical Cancer | Frederick National Laboratory for Cancer Research

Cancer.gov

A single dose of the cancer-fighting human papillomavirus (HPV) vaccine Cervarix™ appears to induce an immune response that remains stable in the blood four years after vaccination. This may be enough to protect women from two strains of HPV and, u

Cervical Intraepithelial Neoplasia Is Associated With Genital Tract Mucosal Inflammation

PubMed Central

Mhatre, Mohak; McAndrew, Thomas; Carpenter, Colleen; Burk, Robert D.; Einstein, Mark H.; Herold, Betsy C.

2013-01-01

Background Clinical studies demonstrate increased prevalence of human papillomavirus (HPV)-associated disease in HIV-infected individuals and an increased risk of HIV acquisition in HPV-infected individuals. The mechanisms underlying this synergy are not defined. We hypothesize that women with cervical intraepithelial neoplasia (CIN) will exhibit changes in soluble mucosal immunity that may promote HPV persistence and facilitate HIV infection. Methods The concentrations of immune mediators and endogenous anti-Escherichia coli activity in genital tract secretions collected by cervicovaginal lavage were compared in HIV-negative women with high-risk HPV-positive (HRHPV+) CIN-3 (n = 37), HRHPV+ CIN-1 (n = 12), or PAP-negative control subjects (n = 57). Results Compared with control subjects, women with CIN-3 or CIN-1 displayed significantly higher levels of proinflammatory cytokines including interleukin (IL)-1α, IL-1β, and IL-8 (P < 0.002) and significantly lower levels of anti-inflammatory mediators and antimicrobial peptides, including IL-1 receptor antagonist, secretory leukocyte protease inhibitor (P < 0.01), and human β defensins 2 and 3 (P < 0.02). There was no significant difference in endogenous anti-E. coli activity after controlling for age and sample storage time. Conclusion HRHPV+ CIN is characterized by changes in soluble mucosal immunity that could contribute to HPV persistence. The observed mucosal inflammation suggests a mechanism that may also contribute to the epidemiologic link between persistent HPV and HIV. PMID:22801340

Feasibility and acceptability of delivering adolescent health interventions alongside HPV vaccination in Tanzania.

PubMed

Watson-Jones, Deborah; Lees, Shelley; Mwanga, Joseph; Neke, Nyasule; Changalucha, John; Broutet, Nathalie; Maduhu, Ibrahim; Kapiga, Saidi; Chandra-Mouli, Venkatraman; Bloem, Paul; Ross, David A

2016-07-01

Human papillomavirus (HPV) vaccination offers an opportunity to strengthen provision of adolescent health interventions (AHI). We explored the feasibility of integrating other AHI with HPV vaccination in Tanzania. A desk review of 39 policy documents was preceded by a stakeholder meeting with 38 policy makers and partners. Eighteen key informant interviews (KIIs) with health and education policy makers and district officials were conducted to further explore perceptions of current programs, priorities and AHI that might be suitable for integration with HPV vaccination. Fourteen school health interventions (SHI) or AHI are currently being implemented by the Government of Tanzania. Most are delivered as vertical programmes. Coverage of current programs is not universal, and is limited by financial, human resource and logistic constraints. Limited community engagement, rumours, and lack of strategic advocacy has affected uptake of some interventions, e.g. tetanus toxoid (TT) immunization. Stakeholder and KI perceptions and opinions were limited by a lack of experience with integrated delivery and AHI that were outside an individual's area of expertise and experience. Deworming and educational sessions including reproductive health education were the most frequently mentioned interventions that respondents considered suitable for integrated delivery with HPV vaccine. Given programme constraints, limited experience with integrated delivery and concern about real or perceived side-effects being attributed to the vaccine, it will be very important to pilot-test integration of AHI/SHI with HPV vaccination. Selected interventions will need to be simple and quick to deliver since health workers are likely to face significant logistic and time constraints during vaccination visits. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Human Papillomavirus (HPV) Vaccination Motivators, Barriers, and Brochure Preferences Among Parents in Multicultural Hawai'i: a Qualitative Study.

PubMed

Dela Cruz, May Rose Isnec; Tsark, Jo Ann Umilani; Chen, John Jiangtian; Albright, Cheryl Lynn; Braun, Kathryn Lenzner

2017-09-01

The human papillomavirus (HPV) vaccine can prevent cervical and other cancers. Unfortunately, according to the National Immunization Survey-Teen 2014 data, completion of the HPV vaccine was only 38 % for 13- to 17-year-old girls and 31 % for 13- to17-year-old boys in the USA, and prevalence was similar in Hawai'i. Parents' acceptability of the HPV vaccine is critical for the vaccine uptake, and this can be increased by educational materials and interventions. However, HPV materials are not widely distributed in Hawai'i. The purpose of this qualitative study was to identify HPV vaccination barriers, motivators, and brochure preferences among parents of teens in multicultural Hawai'i. Twenty parents were interviewed in person or by telephone. Four major themes emerged: (1) the physician is critical in the decision to vaccinate, (2) parental perception of the child's sexual activity guides the timing of their willingness to vaccinate, (3) HPV health education materials should be provided and discussed by the physician, and (4) parents would prefer an educational brochure that features local faces and testimonials, includes an immunization chart, and addresses barriers to vaccination. These findings informed the development of HPV health education materials tailored to Asian Americans and Pacific Islanders in Hawai'i.

A Non-oncogenic HPV 16 E6/E7 Vaccine Enhances Treatment of HPV Expressing Tumors

PubMed Central

Wieking, Bryant G.; Vermeer, Daniel W.; Spanos, William C.; Lee, Kimberly M.; Vermeer, Paola; Lee, Walter T.; Xu, Younong; Gabitzsch, Elizabeth S.; Balcaitis, Stephanie; Balint, Joseph P.; Jones, Frank R.; Lee, John H.

2012-01-01

Human papillomaviruses (HPVs) are the causative factor for greater than 90% of cervical cancers and 25% of head and neck cancers. The incidence of HPV positive (+) head and neck squamous cell carcinomas (HNSCCs) has greatly increased in the last 30 years. E6 and E7 are the two key viral oncoproteins that induce and propagate cellular transformation. An immune response generated during cisplatin/radiation therapy improves tumor clearance of HPV(+) cancers. Augmenting this induced response during therapy with an adenoviral HPV16 E6/E7 vaccine improves long term survival in preclinical models. Here we describe the generation of an HPV16 E6/E7 construct, which contains mutations that render E6/E7 non-oncogenic, while preserving antigenicity. These mutations do not allow E6/E7 to degrade p53, pRb, PTPN13, or activate telomerase. Non-oncogenic E6/E7 (E6Δ/E7Δ) expressed as a stable integrant, or in the [E1-, E2b-] adenovirus, lacks the ability to transform human cells while retaining the ability to induce an HPV specific immune response. Moreover, E6Δ/E7Δ plus chemotherapy/radiation statistically enhances clearance of established HPV(+) cancer in vivo. PMID:22918471

HPV16 seropositivity and subsequent HPV16 infection risk in a naturally infected population: comparison of serological assays.

PubMed

Lin, Shih-Wen; Ghosh, Arpita; Porras, Carolina; Markt, Sarah C; Rodriguez, Ana Cecilia; Schiffman, Mark; Wacholder, Sholom; Kemp, Troy J; Pinto, Ligia A; Gonzalez, Paula; Wentzensen, Nicolas; Esser, Mark T; Matys, Katie; Meuree, Ariane; Quint, Wim; van Doorn, Leen-Jan; Herrero, Rolando; Hildesheim, Allan; Safaeian, Mahboobeh

2013-01-01

Several serological assays have been developed to detect antibodies elicited against infections with oncogenic human papillomavirus (HPV) type 16. The association between antibody levels measured by various assays and subsequent HPV infection risk may differ. We compared HPV16-specific antibody levels previously measured by a virus-like particle (VLP)-based direct enzyme-linked immunoassay (ELISA) with levels measured by additional assays and evaluated the protection against HPV16 infection conferred at different levels of the assays. Replicate enrollment serum aliquots from 388 unvaccinated women in the control arm of the Costa Rica HPV vaccine trial were measured for HPV16 seropositivity using three serological assays: a VLP-based direct ELISA; a VLP-based competitive Luminex immunoassay (cLIA); and a secreted alkaline phosphatase protein neutralization assay (SEAP-NA). We assessed the association of assay seropositivity and risk of subsequent HPV16 infection over four years of follow-up by calculating sampling-adjusted odds ratios (OR) and HPV16 seropositivity based on standard cutoff from the cLIA was significantly associated with protection from subsequent HPV16 infection (OR = 0.48, CI = 0.27-0.86, compared with seronegatives). Compared with seronegatives, the highest seropositive tertile antibody levels from the direct ELISA (OR = 0.53, CI = 0.28-0.90) as well as the SEAP-NA (OR = 0.20, CI = 0.06, 0.64) were also significantly associated with protection from HPV16 infection. Enrollment HPV16 seropositivity by any of the three serological assays evaluated was associated with protection from subsequent infection, although cutoffs for immune protection were different. We defined the assays and seropositivity levels after natural infection that better measure and translate to protective immunity.

Mothers' support for voluntary provision of HPV vaccine in schools.

PubMed

Kadis, Jessica A; McRee, Annie-Laurie; Gottlieb, Sami L; Lee, Morgan R; Reiter, Paul L; Dittus, Patricia J; Brewer, Noel T

2011-03-21

HPV vaccination rates among adolescents in the United States lag behind some other developed countries, many of which routinely offer the vaccine in schools. We sought to assess mothers' willingness to have their adolescent daughters receive HPV vaccine at school. A national sample of mothers of adolescent females ages 11-14 completed our internet survey (response rate=66%). The final sample (n=496) excluded mothers who did not intend to have their daughters receive HPV vaccine in the next year. Overall, 67% of mothers who intended to vaccinate their daughters or had vaccinated their daughters reported being willing to have their daughters receive HPV vaccine at school. Mothers were more willing to allow their daughters to receive HPV vaccine in schools if they had not yet initiated the vaccine series for their daughters or resided in the Midwest or West (all p<.05). The two concerns about voluntary school-based provision of HPV vaccine that mothers most frequently cited were that their daughters' doctors should keep track of her shots (64%) and that they wished to be present when their daughters were vaccinated (40%). Our study suggests that most mothers who support adolescent vaccination for HPV find school-based HPV vaccination an acceptable option. Ensuring communication of immunization records with doctors and allowing parents to be present during immunization may increase parental support. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effectiveness of a Web-Based Tailored Intervention With Virtual Assistants Promoting the Acceptability of HPV Vaccination Among Mothers of Invited Girls: Randomized Controlled Trial.

PubMed

Pot, Mirjam; Paulussen, Theo Gwm; Ruiter, Robert Ac; Eekhout, Iris; de Melker, Hester E; Spoelstra, Maxine Ea; van Keulen, Hilde M

2017-09-06

In 2010, the human papillomavirus (HPV) vaccination was introduced in the Dutch National Immunization Program for 12-year-old girls, aiming to reduce the incidence of cervical cancer in women. HPV vaccination uptake turned out to be lower than expected: 61% versus 70%, respectively. Mothers were shown to play the most important role in the immunization decision about this vaccination. They had also expressed their need for interactive personal information about the HPV vaccination over and above the existing universal general information. To improve the effectiveness of the existing education about the HPV vaccination, we systematically developed a Web-based tailored intervention with virtual assistants providing mothers of girls to be invited with tailored feedback on their decision making about the HPV vaccination. The aim of this study was to evaluate the effectiveness of the Web-based tailored intervention for promoting HPV vaccination acceptance by means of a randomized controlled trial (RCT). Mothers were recruited via the Dutch vaccination register (Praeventis) (n=36,000) and three Web-based panels (n=2483). Those who gave informed consent (N=8062) were randomly assigned to the control (n=4067) or intervention condition (n=3995). HPV vaccination uptake, as registered by Praeventis once the HPV vaccination round was completed, was used as the primary outcome. Secondary outcomes were differential scores across conditions between baseline (before the provided access to the new tailored intervention) and follow-up (just before the first vaccination) regarding the mothers' degree of informed decision making (IDM), decisional conflict, and critical determinants of HPV vaccination uptake among which are intention, attitude, risk perception, and outcome beliefs. Intention-to-treat analysis (N=8062) showed a significant positive effect of the intervention on IDM, decisional conflict, and nearly all determinants of HPV vaccination uptake (P<.001). No effect was found on uptake (P=.60). This may be attributed to the overall high uptake rates in both conditions. Mothers evaluated the intervention as highly positive, including the website as well as the virtual assistants that were used to deliver the tailored feedback. This computer-tailored intervention has the potential to improve HPV vaccination acceptability and IDM and to decrease decisional conflict among mothers of invited girls. Implications for future research are discussed. Trialregister.nl NTR4935; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4935 (Archived by WebCite at http://www.webcitation.org/6srT7l9EM). ©Mirjam Pot, Theo GWM Paulussen, Robert AC Ruiter, Iris Eekhout, Hester E de Melker, Maxine EA Spoelstra, Hilde M van Keulen. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.09.2017.

Safety and Immunogenicity of the HPV-16/18 AS04-adjuvanted Vaccine in 4-6-year-old Girls: Results to Month 12 From a Randomized Trial.

PubMed

Lin, Lan; Parra, Mercedes Macias; Sierra, Victor Y; Cespedes, Albino Salas; Granados, Maria Angelica; Luque, Adriana; Damaso, Silvia; Castrejon Alba, Maria Mercedes; Romano-Mazzotti, Luis; Struyf, Frank

2018-04-01

The burden of cervical cancer caused by human papillomavirus (HPV) is high in Latin America. The suboptimal HPV vaccination coverage in adolescents could be improved by pediatric immunization. HPV vaccination has not yet been reported in girls <9 years of age. This ongoing phase III, controlled, randomized, single-blind, multicenter study conducted in Colombia, Mexico and Panama (NCT01627561) evaluated the safety and immunogenicity of AS04-HPV-16/18 vaccine in 4-6-year-old girls. Healthy girls (randomized 1:1) received either 2 doses of AS04-HPV-16/18 vaccine (HPV group, N=74) or 1 dose of each measles-mumps-rubella and diphtheria-tetanus-acellular-pertussis vaccines (control group, N=74) 6 months apart. We report the safety and serum anti-HPV-16 and anti-HPV-18 antibodies (measured by enzyme-linked immunosorbent assay) up to 6 months postvaccination, that is, month (M) 12. Injection site pain was the most frequently reported solicited local symptom in HPV vaccinees. The incidence of other solicited and unsolicited symptoms after each vaccination was similar between the HPV and control group. Until M12, 1 girl in the HPV group and 2 in the control group reported serious adverse events; all serious adverse events were assessed as unrelated to study vaccines. No potential immune-mediated diseases were identified. All girls seroconverted for both antigens after 2 doses of AS04-HPV-16/18. In initially seronegative girls, anti-HPV-16 geometric mean concentrations were 20080.0 enzyme-linked immunosorbent assay units (EU)/mL at M7 and 3246.5 EU/mL at M12; anti-HPV-18 geometric mean concentrations were 10621.8 EU/mL at M7 and 1216.6 EU/mL at M12. Two-dose vaccination with AS04-HPV-16/18 was well tolerated and induced adequate antibody responses in 4-6-year-old girls.

Human papillomavirus vaccine policy and delivery in Latin America and the Caribbean.

PubMed

Andrus, Jon Kim; Lewis, Merle J; Goldie, Sue J; García, Patricia J; Winkler, Jennifer L; Ruiz-Matus, Cuauhtémoc; de Quadros, Ciro A

2008-08-19

Cervical cancer caused by human papillomavirus (HPV) is a major preventable public health problem. Two vaccines are now available for primary prevention of HPV infection and their introduction offers new opportunities to enhance comprehensive cervical cancer prevention and control. Currently, HPV vaccine price is a significant barrier to rapid vaccine introduction and access. Therefore, making evidence-based decisions about whether and how to introduce HPV vaccine into the immunization schedule in the countries of Latin America and the Caribbean (LAC) requires a rigorous analysis of several factors. These include: estimates of disease burden, cost-effectiveness, operational feasibility of reaching a population of adolescent females and other key analyses that have been used in recent years to support the introduction of other vaccines, such as rotavirus and pneumococcal conjugate vaccines. Given the large number of public health priorities that are competing for limited public resources, developing and using a sound evidence base is of particular importance for vaccines, like HPV, which are currently available only at prices higher than other vaccines now in use. HPV vaccination provides the opportunity to dramatically improve women's health and partnerships must also be broad-based and effectively coordinated. This can be achieved by developing programs based on the lessons learned from vaccination strategies used to eliminate rubella and neonatal tetanus and for scaling up influenza vaccination in countries of LAC.

Are HPV vaccination services accessible to high-risk communities? A spatial analysis of HPV-associated cancer and Chlamydia rates and safety-net clinics.

PubMed

Tsui, Jennifer; Rodriguez, Hector P; Gee, Gilbert C; Escobedo, Loraine A; Kominski, Gerald F; Bastani, Roshan

2013-12-01

While HPV vaccines can greatly benefit adolescents and young women from high-risk areas, little is known about whether safety-net immunization services are geographically accessible to communities at greatest risk for HPV-associated diseases. We explore the spatial relationship between areas with high HPV risk and proximity to safety-net clinics from an ecologic perspective. We used cancer registry data and Chlamydia surveillance data to identify neighborhoods within Los Angeles County with high risk for HPV-associated cancers. We examined proximity to safety-net clinics among neighborhoods with the highest risk. Proximity was measured as the shortest distance between each neighborhood center and the nearest clinic and having a clinic within 3 miles of each neighborhood center. The average 5-year non-age-adjusted rates were 1,940 cases per 100,000 for Chlamydia and 60 per 100,000 for HPV-associated cancers. A large majority, 349 of 386 neighborhoods with high HPV-associated cancer rates and 532 of 537 neighborhoods with high Chlamydia rates, had a clinic within 3 miles of the neighborhood center. Clinics were more likely to be located within close proximity to high-risk neighborhoods in the inner city. High-risk neighborhoods outside of this urban core area were less likely to be near accessible clinics. The majority of high-risk neighborhoods were geographically near safety-net clinics with HPV vaccination services. Due to low rates of vaccination, these findings suggest that while services are geographically accessible, additional efforts are needed to improve uptake. Programs aimed to increase awareness about the vaccine and to link underserved groups to vaccination services are warranted.

Are HPV vaccination services accessible to high-risk communities?: A spatial analysis of HPV-associated cancer and Chlamydia rates and safety-net clinics

PubMed Central

Tsui, Jennifer; Rodriguez, Hector P.; Gee, Gilbert C.; Escobedo, Loraine A.; Kominski, Gerald F.; Bastani, Roshan

2013-01-01

Purpose While HPV vaccines can greatly benefit adolescents and young women from high-risk areas, little is known about whether safety-net immunization services are geographically accessible to communities at greatest risk for HPV-associated diseases. We explore the spatial relationship between areas with high HPV risk and proximity to safety-net clinics from an ecologic perspective. Methods We used cancer registry data and Chlamydia surveillance data to identify neighborhoods within Los Angeles County with high risk for HPV-associated cancers. We examined proximity to safety-net clinics among neighborhoods with the highest risk. Proximity was measured as the shortest distance between each neighborhood center and the nearest clinic and having a clinic within 3 miles of each neighborhood center. Results The average 5-year non-age-adjusted rates were 1,940 cases per 100,000 for Chlamydia and 60 per 100,000 for HPV-associated cancers. A large majority, 349 of 386 neighborhoods with high HPV-associated cancer rates and 532 of 537 neighborhoods with high Chlamydia rates had a clinic within 3 miles of the neighborhood center. Clinics were more likely to be located within close proximity to high-risk neighborhoods in the inner city. High-risk neighborhoods outside of this urban core area were less likely to be near accessible clinics. Conclusions The majority of high-risk neighborhoods were geographically near safety-net clinics with HPV vaccination services. Due to low rates of vaccination, these findings suggest that while services are geographically accessible, additional efforts are needed to improve uptake. Programs aimed to increase awareness about the vaccine and to link underserved groups to vaccination services are warranted. PMID:24043448

Evaluation of HPV-16 and HPV-18 specific antibody measurements in saliva collected in oral rinses and merocel® sponges.

PubMed

Parker, Katherine H; Kemp, Troy J; Pan, Yuanji; Yang, Zhen; Giuliano, Anna R; Pinto, Ligia A

2018-05-03

Current Human papillomavirus (HPV) L1 VLP vaccines protect against HPV-16 and HPV-18-associated cancers, in females and males. Although correlates of protection have not been identified, HPV-specific antibodies at sites of infection are thought to be the main mechanism of protection afforded by vaccination. Oral sampling has gained increased attention as a potential alternative to serum in monitoring immunity to vaccination and understanding local immunity in oral cancers. Serum was collected via venipuncture, and saliva was collected via oral rinses and Merocel® sponges from healthy volunteers: 16 unvaccinated females, 6 females (ages 24-41) and 6 mid-adult aged males (ages 27-45) recipients of three doses of the HPV-16/18/6/11 vaccine (Gardasil®). Mid-adult male vaccine trial participants were compared to female participants. Samples were tested for anti-HPV-16 and anti-HPV-18 immunoglobulin G levels by an L1 virus-like particle-based enzyme-linked immunosorbent assay (ELISA). All vaccinated participants had detectable serum anti-HPV-16 and anti-HPV-18 antibodies. Optimal standard concentration range and sample serial dilutions for oral rinses were determined. The standard curve was not affected by the type of solution examined. Reproducibility of HPV-16 and HPV-18 antibody titers in mouthwash (overall CV < 10%) or in Merocel® extraction buffer was robust (CV < 13%). Excellent assay linearity (R 2  > 0.9) was observed for sera spiked controls in both solutions. HPV-16 and HPV-18 specific antibodies were detectable in saliva from vaccine recipients, both in mouthwash and in Merocel® sponges but levels were several logs lower than those in serum. This study confirms the application of HPV-16 and HPV-18 ELISAs currently used in sero-epidemiological studies of immunogenicity of HPV vaccines for use with oral samples. Oral samples may be a useful resource for the detection of HPV-16 and HPV-18-specific antibodies in saliva following vaccination. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cost-Effectiveness Analysis of the Introduction of HPV Vaccination of 9-Year-Old-Girls in Iran.

PubMed

Yaghoubi, Mohsen; Nojomi, Marzieh; Vaezi, Atefeh; Erfani, Vida; Mahmoudi, Susan; Ezoji, Khadijeh; Zahraei, Seyed Mohsen; Chaudhri, Irtaza; Moradi-Lakeh, Maziar

2018-04-23

To estimate the cost effectiveness of introducing the quadrivalent human papillomavirus (HPV) vaccine into the national immunization program of Iran. The CERVIVAC cost-effectiveness model was used to calculate incremental cost per averted disability-adjusted life-year by vaccination compared with no vaccination from both governmental and societal perspectives. Calculations were based on epidemiologic parameters from the Iran National Cancer Registry and other national data sources as well as from literature review. We estimated all direct and indirect costs of cervical cancer treatment and vaccination program. All future costs and benefits were discounted at 3% per year and deterministic sensitivity analysis was used. During a 10-year period, HPV vaccination was estimated to avert 182 cervical cancer cases and 20 deaths at a total vaccination cost of US $23,459,897; total health service cost prevented because of HPV vaccination was estimated to be US $378,646 and US $691,741 from the governmental and societal perspective, respectively. Incremental cost per disability-adjusted life-year averted within 10 years was estimated to be US $15,205 and US $14,999 from the governmental and societal perspective, respectively, and both are higher than 3 times the gross domestic product per capita of Iran (US $14,289). Sensitivity analysis showed variation in vaccine price, and the number of doses has the greatest volatility on the incremental cost-effectiveness ratio. Using a two-dose vaccination program could be cost-effective from the societal perspective (incremental cost-effectiveness ratio = US $11,849). Introducing a three-dose HPV vaccination program is currently not cost-effective in Iran. Because vaccine supplies cost is the most important parameter in this evaluation, considering a two-dose schedule or reducing vaccine prices has an impact on final conclusions. Copyright © 2018. Published by Elsevier Inc.

Comparison of quality of internet pages on human papillomavirus immunization in Italian and in English.

PubMed

Tozzi, Alberto Eugenio; Buonuomo, Paola Sabrina; Ciofi degli Atti, Marta Luisa; Carloni, Emanuela; Meloni, Marco; Gamba, Fiorenza

2010-01-01

Information available on the Internet about immunizations may influence parents' perception about human papillomavirus (HPV) immunization and their attitude toward vaccinating their daughters. We hypothesized that the quality of information on HPV available on the Internet may vary with language and with the level of knowledge of parents. To this end we compared the quality of a sample of Web pages in Italian with a sample of Web pages in English. Five reviewers assessed the quality of Web pages retrieved with popular search engines using criteria adapted from the Good Information Practice Essential Criteria for Vaccine Safety Web Sites recommended by the World Health Organization. Quality of Web pages was assessed in the domains of accessibility, credibility, content, and design. Scores in these domains were compared through nonparametric statistical tests. We retrieved and reviewed 74 Web sites in Italian and 117 in English. Most retrieved Web pages (33.5%) were from private agencies. Median scores were higher in Web pages in English compared with those in Italian in the domain of accessibility (p < .01), credibility (p < .01), and content (p < .01). The highest credibility and content scores were those of Web pages from governmental agencies or universities. Accessibility scores were positively associated with content scores (p < .01) and with credibility scores (p < .01). A total of 16.2% of Web pages in Italian opposed HPV immunization compared with 6.0% of those in English (p < .05). Quality of information and number of Web pages opposing HPV immunization may vary with the Web site language. High-quality Web pages on HPV, especially from public health agencies and universities, should be easily accessible and retrievable with common Web search engines. Copyright 2010 Society for Adolescent Medicine. Published by Elsevier Inc. All rights reserved.

Current State in the Development of Candidate Therapeutic HPV Vaccines

PubMed Central

Yang, Andrew; Jeang, Jessica; Cheng, Kevin; Cheng, Ting; Yang, Benjamin; Wu, T.-C.; Hung, Chien-Fu

2016-01-01

Summary The identification of human papillomavirus (HPV) as an etiological factor for HPV-associated malignancies creates the opportunity to control these cancers through vaccination. Currently, available preventive HPV vaccines have not yet demonstrated strong evidences for therapeutic effects against established HPV infections and lesions. Furthermore, HPV infections remain extremely common. Thus, there is urgent need for therapeutic vaccines to treat existing HPV infections and HPV-associated diseases. Therapeutic vaccines differ from preventive vaccines in that they are aimed at generating cell-mediated immunity rather than neutralizing antibodies. The HPV-encoded early proteins, especially oncoproteins E6 and E7, form ideal targets for therapeutic HPV vaccines since they are consistently expressed in HPV-associated malignancies and precancerous lesions, playing crucial roles in the generation and maintenance of HPV-associated disease. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we review strategies to enhance vaccine efficacy and the latest clinical trials on therapeutic HPV vaccines. PMID:26901118

A human papillomavirus type 16 vaccine by oral delivery of L1 protein.

PubMed

Sasagawa, Toshiyuki; Tani, Mayuko; Basha, Walid; Rose, Robert C; Tohda, Hideki; Giga-Hama, Yuko; Azar, Khadijeh K; Yasuda, Hideyo; Sakai, Akemi; Inoue, Masaki

2005-06-01

To establish an edible HPV16 vaccine, we constructed a recombinant HPV16 L1-expressing Schizosaccharomyces pombe yeast strain (HPV16L1 yeast). A preliminary study revealed that freeze-dried yeast cells could be delivered safely, and were digested in the mouse intestine. The freeze-dried HPV16 L1 yeast was administered orally as an edible vaccine, with or without the mucosal adjuvant heat-labile toxin LT (R192G), to 18 female BALB/c mice. After the third immunization, none of the mice that received the edible HPV16 vaccine showed specific antibody responses, whereas all of the positive controls that were administered intranasally with 5 microg of HPV16-virus-like particles (VLP) had serum IgG, and genital IgA and IgG that reacted with HPV16-VLP in enzyme-linked immunosorbent assays (ELISAs). When a suboptimal dose (1 microg) of HPV16-VLP was administered to all the mice, including the negative control mice, 50% of the mice that were pre-immunized with the edible HPV16 vaccine showed positive serum IgG responses, while none of the negative controls showed any response. Vaginal IgG and IgA antibodies were also elicited in 33 and 39%, respectively, of the mice that were given with the edible HPV16 vaccine and the intranasal boost. All of the antibodies reacted more strongly to intact HPV16-VLP than to denatured HPV16-L1 protein suggesting that the edible vaccine primes for antibody responses against conformation-dependent epitopes. The inclusion of adjuvant in the vaccine formulation marginally increased the genital IgA response (P=0.06). HPV16-L1 protein in the yeast might induce tolerance in the vaccinated animals that could be recovered by intranasal boosting with a suboptimal dose of HPV-VLP. This freeze-dried yeast system may be useful as an oral delivery of HPV 16 L1 protein.

Immune cells and prognosis in HPV-associated oropharyngeal squamous cell carcinomas: Review of the literature.

PubMed

Saber, Camelia Nami; Grønhøj Larsen, Christian; Dalianis, Tina; von Buchwald, Christian

2016-07-01

Currently, oropharyngeal squamous cell carcinomas (OPSCC) are treated based on the traditional TNM-classification, although this scheme might be inadequate for the subgroup of human papillomavirus (HPV)-associated OPSCCs. It remains debatable whether this subgroup of patients with favorable prognosis should be offered altered treatment. Besides the well-known biomarkers of HPV and p16, new promising immune cells and markers might nuance the prognosis and treatment for patients with HPV+ OPSCC. We systematically reviewed the literature on immunological features of HPV-associated OPSCCs, and report that a high number of cytotoxic T cells (CD8s) and a low number of CD98 positive cells is associated with better outcome, while an increased CD4/CD8 ratio and a high human leukocyte antigen 1 (HLA1) intensity is most likely associated with worse outcome. These findings might contribute to future OPSCC staging and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human papillomavirus vaccination coverage using two-dose or three-dose schedule criteria.

PubMed

Lin, Xia; Rodgers, Loren; Zhu, Liping; Stokley, Shannon; Meites, Elissa; Markowitz, Lauri E

2017-10-13

In October 2016, the Advisory Committee on Immunization Practices (ACIP) updated the human papillomavirus (HPV) vaccination recommendation to include a 2-dose schedule for U.S. adolescents initiating the vaccine series before their 15th birthday. We analyzed records for >4million persons aged 9-17years receiving any HPV vaccine by the end of each quarter during January 1, 2014-September 30, 2016 from six Immunization Information Systems Sentinel Sites, and reclassified HPV vaccination up-to-date coverage according to the updated recommendations. Compared with HPV vaccination up-to-date coverage by the 3-dose schedule only, including criteria for either a 2-dose or 3-dose schedule increased up-to-date coverage in 11-12, 13-14, and 15-17 year-olds by 4.5-8.5 percentage points. The difference between 3-dose up-to-date coverage and 2- or 3-dose up-to-date coverage was greatest in late 2016. These data provide baseline HPV vaccination coverage using current ACIP recommendations. Published by Elsevier Ltd.

The ImmProve Project: Leveraging electronic health record data to promote immunization delivery

PubMed Central

Bundy, David G.; Persing, Nichole M.; Solomon, Barry S.; King, Tracy M.; Murakami, Peter; Thompson, Richard E.; Engineer, Lilly D.; Lehmann, Christoph U.; Miller, Marlene R.

2013-01-01

Objective Though an essential pediatric preventive service, immunizations are challenging to deliver reliably. Our objective was to measure the impact on pediatric immunization rates of providing clinicians with electronic health record-derived immunization prompting. Methods Operating in a large, urban, hospital-based pediatric primary care clinic, we evaluated 2 interventions to improve immunization delivery to children ages 2, 6, and 13 years: point-of-care, patient-specific electronic clinical decision support (CDS) when children overdue for immunizations presented for care and provider-specific bulletins listing children overdue for immunizations. Results Overall, the proportion of children up-to-date for a composite of recommended immunizations at ages 2, 6, and 13 years was not different in the intervention (CDS active) and historical control (CDS not active) periods; historical immunization rates were high. The proportion of children receiving 2 doses of hepatitis A immunization prior to their second birthday was significantly improved during the intervention period. Human papilloma virus (HPV) immunization delivery was low during both control and intervention periods and was unchanged for 13-year-olds. For 14-year-olds, however, 4 of the 5 highest quarterly rates of complete HPV immunization occurred in the final year of the intervention. Provider-specific bulletins listing children overdue for immunizations increased the likelihood of identified children receiving catch-up hepatitis A immunizations (hazard ratio: 1.32 [95% confidence interval (CI): 1.12–1.56]); results for HPV and the composite of recommended immunizations were of a similar magnitude but not statistically significant. Conclusions In our patient population, with high baseline uptake of recommended immunizations, electronic health record-derived immunization prompting had a limited effect on immunization delivery. Benefit was more clearly demonstrated for newer immunizations with lower baseline uptake. PMID:23726754

Improving immunization delivery using an electronic health record: the ImmProve project.

PubMed

Bundy, David G; Persing, Nichole M; Solomon, Barry S; King, Tracy M; Murakami, Peter N; Thompson, Richard E; Engineer, Lilly D; Lehmann, Christoph U; Miller, Marlene R

2013-01-01

Though an essential pediatric preventive service, immunizations are challenging to deliver reliably. Our objective was to measure the impact on pediatric immunization rates of providing clinicians with electronic health record-derived immunization prompting. Operating in a large, urban, hospital-based pediatric primary care clinic, we evaluated 2 interventions to improve immunization delivery to children ages 2, 6, and 13 years: point-of-care, patient-specific electronic clinical decision support (CDS) when children overdue for immunizations presented for care, and provider-specific bulletins listing children overdue for immunizations. Overall, the proportion of children up to date for a composite of recommended immunizations at ages 2, 6, and 13 years was not different in the intervention (CDS active) and historical control (CDS not active) periods; historical immunization rates were high. The proportion of children receiving 2 doses of hepatitis A immunization before their second birthday was significantly improved during the intervention period. Human papillomavirus (HPV) immunization delivery was low during both control and intervention periods and was unchanged for 13-year-olds. For 14-year-olds, however, 4 of the 5 highest quarterly rates of complete HPV immunization occurred in the final year of the intervention. Provider-specific bulletins listing children overdue for immunizations increased the likelihood of identified children receiving catch-up hepatitis A immunizations (hazard ratio 1.32; 95% confidence interval 1.12-1.56); results for HPV and the composite of recommended immunizations were of a similar magnitude but not statistically significant. In our patient population, with high baseline uptake of recommended immunizations, electronic health record-derived immunization prompting had a limited effect on immunization delivery. Benefit was more clearly demonstrated for newer immunizations with lower baseline uptake. Copyright © 2013 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Epidemiology of virus infection and human cancer.

PubMed

Chen, Chien-Jen; Hsu, Wan-Lun; Yang, Hwai-I; Lee, Mei-Hsuan; Chen, Hui-Chi; Chien, Yin-Chu; You, San-Lin

2014-01-01

The International Agency for Research on Cancer (IARC) has comprehensively assessed the human carcinogenicity of biological agents. Seven viruses including Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency virus, type-1 (HIV-1), human T cell lymphotrophic virus, type-1 (HTLV-1), and human papillomavirus (HPV) have been classified as Group 1 human carcinogens by IARC. The conclusions are based on the findings of epidemiological and mechanistic studies. EBV, HPV, HTLV-1, and KSHV are direct carcinogens; HBV and HCV are indirect carcinogens through chronic inflammation; HIV-1 is an indirect carcinogen through immune suppression. Some viruses may cause more than one cancer, while some cancers may be caused by more than one virus. However, only a proportion of persons infected by these oncogenic viruses will develop specific cancers. A series of studies have been carried out to assess the viral, host, and environmental cofactors of EBV-associated nasopharyngeal carcinoma, HBV/HCV-associated hepatocellular carcinoma, and HPV-associated cervical carcinoma. Persistent infection and high viral load are important risk predictors of these virus-caused cancers. Risk calculators incorporating host and viral factors have also been developed for the prediction of long-term risk of hepatocellular carcinoma. These risk calculators are useful for the triage and clinical management of infected patients. Both clinical trials and national programs of immunization or antiviral therapy have demonstrated a significant reduction in the incidence of cancers caused by HBV, HCV, and HPV. Future researches on gene-gene and gene-environment interaction of oncogenic viruses and human host are in urgent need.

A Content Analysis of Online HPV Immunization Information

ERIC Educational Resources Information Center

Pappa, Sara T.

2016-01-01

The Human Papillomavirus (HPV) can cause some types of cancer and is the most common sexually transmitted infection in the US. Because most people turn to the internet for health information, this study analyzed HPV information found online. A content analysis was conducted on 69 web search results (URLs) from Google, Yahoo, Bing and Ask. The…

Correlates of HPV vaccine initiation and provider recommendation among male adolescents, 2014 NIS-Teen.

PubMed

Landis, Kathryn; Bednarczyk, Robert A; Gaydos, Laura M

2018-05-08

Vaccination is a safe and effective way to prevent Human Papillomavirus (HPV) infection and related cancers; however, HPV vaccine uptake remains low in the US. After the 2011 Advisory Committee on Immunization Practices (ACIP) recommendation for routine HPV vaccination of adolescent males, several studies have examined predictors for initiating the vaccine series in this population of interest, particularly with regard to provider recommendations. This study examined racial and ethnic differences for HPV vaccine initiation and provider recommendation in male adolescents. Based on prior HPV vaccine uptake estimates and healthcare utilization data, we hypothesized that minority adolescents would be more likely to initiate HPV vaccines, but less likely to receive a provider recommendation compared to white counterparts. We analyzed the 2014 National Immunization Survey-Teen (NIS-Teen), which included 10,753 male adolescents with provider-verified vaccination data in 50 US states, using multivariate logistic regression models to evaluate racial/ethnic differences in HPV vaccine initiation and provider recommendation. The odds of HPV vaccine initiation were 76 percent higher for Hispanic adolescents and 43 percent higher for non-Hispanic Other or Multiple race adolescents compared to white adolescents. Approximately half of parents reported receiving a provider recommendation for vaccination, with no significant difference in the odds of receiving a provider recommendation across racial/ethnic groups. Despite similar frequency of recommendations across racial and ethnic groups, male adolescents who are racial/ethnic minorities are more likely to initiate vaccination. Future research should focus on developing tailored interventions to increase HPV vaccine receipt among males of all racial/ethnic groups. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functional characterization of CD4 and CD8 T cell responses among human papillomavirus infected patients with ano-genital warts.

PubMed

Singh, Manjula; Thakral, Deepshi; Rishi, Narayan; Kar, Hemanta Kumar; Mitra, Dipendra Kumar

2017-06-01

Ano-genital warts are considered one of the commonest and highly infectious sexually transmitted infections. These warts are primarily caused by the human papillomavirus (HPV) of the family Papillomaviridae , genus alpha - papillomavirus , species 10 and types 6 and 11. However the high recurrence rate of warts is a matter of serious concern to the patients and a challenge for the treating physician. The conventional treatment options are targeted only to the local site of warts. There is no systemic treatment modality as there is limited understanding of the disease immune-pathogenesis. The role of cell-mediated immunity in combating HPV infection is not clearly defined. Hence the present study is aimed at investigating the CD4 + T helper (Th1 and Th2) and CD8 + T cell responses among wart patients. In this study, we compared HPV6 and HPV11 antigen-specific T cell responses among venereal wart patients relative to healthy controls. Significant decrease in percent frequencies of IFN-γ producing CD4 + and CD8 + T cells were observed in HPV infected wart patients. On the other hand, the frequency of CD4 + T cells expressing IL-4 was significantly increased in these patients as compared to healthy controls. The observed functional skewing of HPV specific T cells from Th1 to Th2 response in patients indicated suppressed immunity against the HPV. Moreover, decrease in CD8 T cell function correlated with poor wart clearance. Our findings open future avenues for exploring potential immunomodulation strategies as an adjunct to standard treatment for better management of these patients and prevention of recurrence.

Acceptability of HPV vaccines and associations with perceptions related to HPV and HPV vaccines among male baccalaureate students in Hong Kong

PubMed Central

2018-01-01

Objectives The highly infectious human papillomavirus (HPV) causes both genital warts and cervical cancer in women. In 2009, the prevalence of genital warts in Hong Kong was 203.7 per 100,000 person-years. Cervical cancer, more seriously, was the eight most common cancer among women and girls in Hong Kong, accounting for 2.3% of all new cancer cases in females in 2014. Cervical cancer is a significant global public health problem and HPV is a major risk factor leading to the development of cervical cancer. HPV is also the most common sexually transmitted disease among university students. This is the first study to examine the acceptability of HPV vaccines and associations with perceptions related to HPV and HPV vaccines among the male baccalaureate student population locally. Methods A self-administrative cross-sectional survey was used to assess whether male baccalaureate students from eight local Hong Kong universities intended to be immunized for HPV. The study also asked questions concerning how its subjects perceived HPV and HPV vaccines using the Health Belief Model. Data collection spanned from June to September 2015. A multiple stepwise regression model was used to examine associations between cognitive factors and subjects’ intention to take up the HPV vaccine. Results A total of 1,004 (83.7%) students aged 18 and 26 participated in this study. 23.3% found vaccinating for HPV acceptable, a level correlating with a number of indicators. Subjects were more likely to find vaccinating acceptable if 1) they knew something about HPV vaccines; 2) they understood that men were susceptible to infection by HPV; 3) they realised they could benefit by HPV vaccination, and 4) they were aware of the arguments for and against HPV vaccination, as disseminated by either the media or peers. Conclusions HPV remains a significant public health concern in Hong Kong and China more broadly. This study’s findings show a disconnect between the perceived and actual risk of being infected with the HPV vaccine among male baccalaureate students. This disconnect may be bridged by informing young men of the benefits of their being vaccinated against HPV, by removing the psychological and financial barriers that prevent them from taking up the vaccine and by improving how primary healthcare providers motivate them to get immunized. PMID:29912883

White, affluent, educated parents are least likely to choose HPV vaccination for their children: a cross-sectional study of the National Immunization Study - teen.

PubMed

Warner, Echo L; Ding, Qian; Pappas, Lisa M; Henry, Kevin; Kepka, Deanna

2017-12-01

Human Papillomavirus (HPV) vaccination coverage is below national goals in the United States. Research is needed to inform strategically designed interventions that target sociodemographic groups with underutilization of HPV vaccination. Secondary data analysis of the National Immunization Survey-Teen 2013 measured association of sociodemographic factors (e.g., ethnicity/race, insurance) with HPV vaccination among females and males ages 13-17 (N = 18,959). Chi-square and multivariable Poisson regressions were conducted using survey-weighted statistics. Having a mother ≥35 years, a mother with some college, being of "Other" ethnicity/race, and having no providers who order vaccines from health departments was negatively associated with females initiating HPV vaccination. Having a mother with some college, being of Non-Hispanic White or "Other" ethnicity/race, and having some or no providers who order vaccines from health departments was negatively associated with males initiating HPV vaccination. These same factors were negatively associated with males completing HPV vaccination with the exception of "Other" ethnicity/race. In contrast, having an unmarried mother, being ages 15-17, having a hospital based provider, and receiving other adolescent vaccinations were positively associated with females initiating and completing HPV vaccination. Having an unmarried mother, health insurance that is not employer or union sponsored, and influenza and meningitis vaccinations was positively associated with male's initiating HPV vaccination. For males, being 15 or 17 years old and having other adolescent vaccinations was positively associated with vaccine completion. All findings p ≤ 0.05. Future HPV vaccination interventions may benefit from targeting certain sociodemographic groups that were negatively associated with HPV vaccination in this study.

Human Papillomavirus (HPV) L1 Serum Antibodies and the Risk of Subsequent Oral HPV Acquisition in Men: The HIM Study.

PubMed

Pierce Campbell, Christine M; Viscidi, Raphael P; Torres, B Nelson; Lin, Hui-Yi; Fulp, William; Abrahamsen, Martha; Lazcano-Ponce, Eduardo; Villa, Luisa L; Kreimer, Aimée R; Giuliano, Anna R

2016-07-01

The role of antibody-mediated immunity in preventing newly acquired oral human papillomavirus (HPV) is not well understood. Among 1618 men participating in the HPV Infection in Men (HIM) Study, we evaluated oral rinses for HPV DNA and baseline sera for HPV-6, -11, -16, and -18 L1 antibodies. Thirty percent of men (486) were seropositive for ≥1 HPV type, and 25 men developed incident oral HPV infection (HPV-6 was detected in 7, HPV-11 in 0, HPV-16 in 17, and HPV-18 in 1). Cox models revealed that men with circulating antibodies to HPV-6, -11, -16, or -18 were not less likely to acquire type-specific oral HPV than men without antibodies (hazard ratio for the risk of acquiring HPV-6, -11, -16, or -18, 1.63; 95% confidence interval, .56-4.76). © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Should I or shouldn't I: decision making, knowledge and behavioral effects of quadrivalent HPV vaccination in men who have sex with men.

PubMed

Thomas, Emily A; Goldstone, Stephen E

2011-01-10

Prior to FDA licensure in men, a surgical practice (SG) offered the quadrivalent HPV vaccine (qHPV) off-label to men who have sex with men (MSM). We administered a written or telephone survey to MSM to elicit drivers and barriers to vaccination, sexual behavior changes post-vaccination, and knowledge. 191 subjects enrolled: 68 refused qHPV, 71 received qHPV <1 year ago, and 52 received qHPV >1 year ago. History of HPV infection (86%, n=164) and level of HPV and qHPV knowledge were high, with a mean of 10.8 of 13 knowledge questions correct. Ninety-seven percent of participants understood that qHPV does not cure present infection or disease. MSM refused qHPV for reasons including cost and not FDA approved; prevention of future HPV infection was the paramount driver for immunization. Vaccination did not affect sexual behavior. Copyright © 2010 Elsevier Ltd. All rights reserved.

Assessing the effectiveness of a community-based sensitization strategy in creating awareness about HPV, cervical cancer and HPV vaccine among parents in North West Cameroon.

PubMed

Wamai, Richard G; Ayissi, Claudine Akono; Oduwo, Geofrey O; Perlman, Stacey; Welty, Edith; Manga, Simon; Ogembo, Javier Gordon

2012-10-01

In 2010, the Cameroon Baptist Convention Health Services (CBCHS) received a donation of HPV vaccine (Gardasil®) to immunize girls of ages 9-13 years in the North West Region of Cameroon. We evaluated the effectiveness of the CBCHS campaign program in sensitizing parents/guardians to encourage HPV vaccine uptake, identified factors that influence parents' decisions to vaccinate girls, and examined the uptake of cervical cancer screening among mothers. We conducted a cross-sectional survey in four healthcare facilities run by CBCHS, churches and other social settings. A total of 350 questionnaires were distributed and 317 were used for the analysis. There were high levels of awareness about cervical cancer, HPV and HPV vaccine. 75.5% understood HPV is sexually transmitted and 90.3% were aware of the use of vaccine as a preventive measure. Effectiveness of the vaccine (31.8%) and side effects/safety (18.4%) were the major barriers for parents to vaccinate their daughters. Bivariate analysis further revealed that the level of education (p = 0.0006), income level (p = 0.0044) and perceived risks (p = 0.0044) are additional factors influencing parents' decisions to vaccinate girls. 35.3% of women had sought a cervical cancer screening, significantly higher than the general estimated rate of screening (<10%) in other parts of Cameroon and sub-Saharan Africa. These results support the viability of a community-tailored sensitization strategy to increase awareness among the targeted audience of parents/guardians, who are critical decision-makers for vaccine delivery to children.

A qualitative analysis of South African women's knowledge, attitudes, and beliefs about HPV and cervical cancer prevention, vaccine awareness and acceptance, and maternal-child communication about sexual health.

PubMed

Francis, Shelley A; Battle-Fisher, Michele; Liverpool, Joan; Hipple, Lauren; Mosavel, Maghboehba; Soogun, Soji; Mofammere, Nokuthula

2011-11-03

In South Africa, cervical cancer is the second leading cause of death among women. Black South Africa women are disproportionately affected by cervical cancer and have one of the highest mortality rates from this disease. Although the body of literature that examines HPV and cervical cancer prevention is growing in the developing world; there is still a need for a better understanding of women's knowledge and beliefs around HPV and cervical cancer prevention. Therefore, this formative study sought to examine women's attitudes, beliefs and knowledge of HPV and cervical cancer, HPV vaccine acceptance, maternal-child communication about sexuality, and healthcare decision-making and gender roles within an urban community in South Africa. Women ages 18-44 were recruited from an antenatal clinic in a Black township outside of Johannesburg during the fall of 2008. Twenty-four women participated in three focus groups. Findings indicated that the women talked to their children about a variety of sexual health issues; had limited knowledge about HPV, cervical cancer, and the HPV vaccine. Women were interested in learning more about the vaccine although they had reservations about the long-term affect; they reinforced that grandmothers played a key role in a mother's decisions' about her child's health, and supported the idea that government should provide the HPV vaccine as part of the country's immunization program. Our findings indicate the need to develop primary prevention strategies and materials that will provide women with basic cervical cancer prevention messages, including information about HPV, cervical cancer, the HPV vaccine, screening, and how to talk to their children about these topics. Prevention strategies should also consider the cultural context and the role that grandmothers play in the family unit. Copyright © 2011 Elsevier Ltd. All rights reserved.

Antagonist-mediated down-regulation of toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus

PubMed Central

2012-01-01

Introduction Prevalence of an abnormal Papanicolaou smear was significantly increased in lupus patients in cross-sectional studies, associated with a higher prevalence of high-risk human papillomavirus (HPV) infection. The nucleic acid-specific Toll-like receptors (TLRs) locate at the endolysosomal compartments and trigger the induction of cytokines for the innate immune response. This study evaluated whether abnormal host innate immune response in lupus patients may enhance HPV persistence. Methods Protein levels of TLRs 3, 7, 8 and 9 in cervical epithelial cells of lupus patients and controls with or without HPV infection were assessed using flow cytometry. Characteristics associated with the differential expression of TLRs in systemic lupus erythematosus (SLE) were elucidated. The effect and interferon-stimulated genes (ISGs) (ISG15 and Mx-1) gene expressions were then measured in oncogenic HeLa (HPV18), CaSki (HPV) and C33A (HPV negative) cell lines using flow cytometry and quantitative real-time PCR. Ex vivo productions of cytokines and interferon-gamma (IFN-γ) upon TLR ligands stimulations were subsequently measured using cytometric bead array and ELISA. Results For subjects with HPV infection, levels of TLR3 and TLR7 were significantly lower in lupus patients compared with controls. Significantly decreased TLRs 7, 8 and 9 levels were observed in HPV-negative SLE compared to healthy controls. For SLE with and without HPV infection, TLR7 and 9 levels were significantly lower in infected SLE than those in HPV-negative patients. Independent explanatory variables associated with down-regulation of TLR7 level included HPV infection and a higher cumulative dose of prednisolone; while a higher cumulative dose of hydroxychloroquine and HPV infection were associated with down-regulation of TLR9 level. In cervical cell lines, TLRs 3, 7, 8, 9 protein levels and antiviral ISG15 and Mx-1 gene expressions were inhibited in two oncogenic HPV types. Functional data showed that the induction of pro-inflammatory cytokines by TLR ligands (R837, ssRNA and ODN2395) was greatly impaired in CaSki and HeLa than C33A cells. Conclusions In conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate protein levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response against HPV infection. Upon infection, HPV further down-regulate TLR7 and 9 levels for viral persistence. Furthermore, reduction of nucleic acid-sensing TLRs 7, 8 and 9 in carcinogenic HPVs ensures that the expression of inducible pro-inflammatory cytokines is minimized to prevent the expression of antiviral ISGs (ISG15 and Mx-1) on a biologically relevant antiviral response. PMID:22513098

The role of vaccines in the control of STDs: HPV vaccines.

PubMed Central

Frazer, I H

1996-01-01

Prophylactic vaccines for genital human papillomavirus (HPV) infection have been shown to be feasible in animal models, and suitable vaccine material based on virus-like particles can be produced in bulk at reasonable cost. Initiation of phase III clinical trials will follow definition of trial outcome measures through further epidemiological studies, and development of assays of host protective immunity. Vaccines could in principle eliminate HPV-related disease, as the human race is the only natural host for the relevant papillomaviruses (PVs). Therapeutic vaccines for genital HPV infection are also possible, but have not yet been demonstrated as feasible in practice because the choice of vaccine antigens is difficult, the method of their optimal delivery is uncertain, and the nature of the relevant antiviral immunity is unknown. PV species specificity will require trials to be conducted in man, which will slow definition of an ideal vaccine. PMID:9038634

The current state of therapeutic and T cell-based vaccines against human papillomaviruses

PubMed Central

Yang, Andrew; Farmer, Emily; Lin, John; Wu, T-C.; Hung, Chien-Fu

2016-01-01

Human papillomavirus (HPV) is known to be a necessary factor for many gynecologic malignancies and is also associated with a subset of head and neck malignancies. This knowledge has created the opportunity to control these HPV-associated cancers through vaccination. However, despite the availability of prophylactic HPV vaccines, HPV infections remain extremely common worldwide. In addition, while prophylactic HPV vaccines have been effective in preventing infection, they are ineffective at clearing pre-existing HPV infections. Thus, there is an urgent need for therapeutic and T cell-based vaccines to treat existing HPV infections and HPV-associated lesions and cancers. Unlike prophylactic vaccines, which generate neutralizing antibodies, therapeutic, and T cell-based vaccines enhance cell-mediated immunity against HPV antigens. Our review will cover various therapeutic and T cell-based vaccines in development for the treatment of HPV-associated diseases. Furthermore, we review the strategies to enhance the efficacy of therapeutic vaccines and the latest clinical trials on therapeutic and T cell-based HPV vaccines. PMID:27932207

Immunization with mutant HPV16 E7 protein inhibits the growth of TC-1 cells in tumor-bearing mice.

PubMed

Li, Yan-Li; Ma, Zhong-Liang; Zhao, Yue; Zhang, Jing

2015-04-01

Two human papillomavirus (HPV) 16 oncogenic proteins, E6 and E7, are co-expressed in the majority of HPV16-induced cervical cancer cells. Thus, the E6 and E7 proteins are good targets for developing therapeutic vaccines for cervical cancer. In the present study, immunization with the mutant non-transforming HPV16 E7 (mE7) protein was demonstrated to inhibit the growth of TC-1 cells in the TC-1 mouse model. The HPV16 mE7 gene was amplified by splicing overlap extension polymerase chain reaction using pET-28a(+)-E7 as a template, and the gene was cloned into pET-28a(+) to form pET-28a(+)-mE7. Compared with the E7 protein, mE7 lacks amino acid residues 94-98, and at residue 24, there is a Cys to Gly substitution. pET-28a(+)-mE7 was then introduced into Escherichia coli Rosetta. The expression of mE7 was induced by isopropyl β-D-1-thiogalactopyranoside. The mE7 protein was purified using Ni-NTA agarose and detected by SDS-PAGE and western blot analysis. In the tumor prevention model, no tumor was detected in the mice vaccinated with the mE7 protein. After 40 days, the tumor-free mice and control mice were challenged with 2×10 5 TC-1 cells. All control mice developed tumors six days later, but mE7 immunized mice were tumor free until 90 days. In the tumor therapy model, the TC-1 cells were initially injected subcutaneously, and the mice were subsequently vaccinated. Vaccination against the mE7 protein may significantly inhibit TC-1 cell growth compared to the control. These results demonstrated that immunization with the HPV16 mE7 protein elicited a long-term protective immunity against TC-1 tumor growth and generated a significant inhibition of TC-1 growth in a TC-1 mouse model.

Differential misclassification between self-reported status and official HPV vaccination records in Japan: Implications for evaluating vaccine safety and effectiveness.

PubMed

Yamaguchi, Manako; Sekine, Masayuki; Kudo, Risa; Adachi, Sosuke; Ueda, Yutaka; Miyagi, Etsuko; Hara, Megumi; Hanley, Sharon J B; Enomoto, Takayuki

2018-05-25

Japan has no national vaccine registry and approximately 1700 municipalities manage the immunization records independently. In June 2013, proactive recommendations for the human papillomavirus (HPV) vaccine were suspended after unconfirmed reports of adverse events following immunization in the media, despite no vaccine safety signal having been raised. Furthermore, studies assessing HPV vaccine safety and effectiveness published post suspension are predominantly based on self-reported information. Our aim was to examine the accuracy of self-reported vaccination status compared with official municipal records. Participants were women aged 20-22 yrs, who were attending for cervical screening in Niigata city. Among the 1230 eligible registrants, vaccine uptake, defined as any dose, was 75.0% and 77.2% according to a self-reported questionnaire and municipal records, respectively. The accuracy rate of self-reported information was as follows: positive predictive value (PPV) was 87.7%; negative predictive value (NPV) was 54.5%; sensitivity was 85.2%; and specificity was 59.8%. The validity of self-reported information was only moderate (Kappa statistic = 0.44, 95% confidence interval 0.37-0.50). This combined with the low NPV may lead to reduced estimation of effectiveness and safety. A more reliable method, such as a national HPV vaccine registry, needs to be established for assessing HPV immunization status in Japan. Copyright © 2018. Published by Elsevier B.V.

Cost-effectiveness of human papillomavirus vaccination for adolescent girls in Punjab state: Implications for India's universal immunization program.

PubMed

Prinja, Shankar; Bahuguna, Pankaj; Faujdar, Dharmjeet Singh; Jyani, Gaurav; Srinivasan, Radhika; Ghoshal, Sushmita; Suri, Vanita; Singh, Mini P; Kumar, Rajesh

2017-09-01

Introduction of human papillomavirus (HPV) vaccination for adolescent girls is being considered in the Punjab state of India. However, evidence regarding cost-effectiveness is sought by policy makers when making this decision. The current study was undertaken to evaluate the incremental cost per quality-adjusted life-years (QALYs) gained with introduction of the HPV vaccine compared with a no-vaccination scenario. A static progression model, using a combination of decision tree and Markov models, was populated using epidemiological, cost, coverage, and effectiveness data to determine the cost-effectiveness of HPV vaccination. Using a societal perspective, lifetime costs and consequences (in terms of QALYs) among a cohort of 11-year-old adolescent girls in Punjab state were modeled in 2 alternate scenarios with and without vaccination. All costs and consequences were discounted at a rate of 3%. Although immunizing 1 year's cohort of 11-year-old girls in Punjab state costs Indian National Rupees (INR) 135 million (US dollars [USD] 2.08 million and International dollars [Int$] 6.25 million) on an absolute basis, its net cost after accounting for treatment savings is INR 38 million (USD 0.58 million and Int$ 1.76 million). Incremental cost per QALY gained for HPV vaccination was found to be INR 73 (USD 1.12 and Int$ 3.38). Given all the data uncertainties, there is a 90% probability for the vaccination strategy to be cost-effective in Punjab state at a willingness-to-pay threshold of INR 10,000, which is less than one-tenth of the per capita gross domestic product. HPV vaccination appears to be a very cost-effective strategy for Punjab state, and is likely to be cost-effective for other Indian states. Cancer 2017;123:3253-60. © 2017 American Cancer Society. © 2017 American Cancer Society.

Determinants of HPV vaccination intentions among Dutch girls and their mothers: a cross-sectional study

PubMed Central

2013-01-01

Background The Dutch government recently added universal Human Papilloma Virus (HPV) vaccination for 12-year-old girls to the existing national immunization program. The participation rate for the initial catch-up campaign for girls aged 13 to 16 years in 2009 was lower (47%) than expected (70%). To inform future HPV information campaigns, this paper examines the social and psychological determinants of the HPV vaccination intentions of girls aged 13 to 16 years and their mothers who were targeted by the Dutch catch-up campaign of 2009. Methods A random sample of girls and their mothers was chosen from the Dutch vaccination register and received a letter inviting them to participate (n = 5,998 mothers and daughters). In addition, a random sample was recruited via an online panel by a marketing research company (n = 650 mothers; n = 350 daughters). Both groups were asked to complete a web-based questionnaire with questions on social demographic characteristics, social-psychological factors and HPV vaccination intention. Backward linear regression analyses were conducted to examine which social-psychological factors were most dominantly associated with vaccination intention. Results Data from 952 mothers (14%) and 642 daughters (10%) were available for the intended analyses. The contribution of social demographic variables to the explained variance of HPV vaccination intention was small but significant for mothers (ΔR2 = .01; p = .007), but not significant for daughters (ΔR2 = .02; p = .17) after controlling for HPV vaccination uptake and the sample. In addition, social-psychological determinants largely contributed to the explained variance of HPV vaccination intention of mothers (ΔR2 = .35; p < .001) and daughters (ΔR2 = .34; p < .001). Attitudes, beliefs, subjective norms and habit strength were significantly associated with participants’ HPV vaccination intentions. Conclusions Because of the large contribution of social-psychological variables to the explained variance of HPV vaccination intentions among the mothers and daughters, future communication strategies targeting HPV vaccination uptake should address attitudes, beliefs, subjective norms and habit strength. There is a need for longitudinal research to confirm the causality of the association between these determinants and HPV vaccination behavior indicated by this study. PMID:23388344

Evaluation of human papilloma virus (HPV) vaccination strategies and vaccination coverage in adolescent girls worldwide.

PubMed

Owsianka, Barbara; Gańczak, Maria

2015-01-01

An analysis of HPV vaccination strategies and vaccination coverage in adolescent girls worldwide for the last eight years with regard to potential improvement of vaccination coverage rates in Poland. Literature search, covering the period 2006-2014, was performed using Medline. Comparative analysis of HPV vaccination strategies and coverage between Poland and other countries worldwide was conducted. In the last eight years, a number of countries introduced HPV vaccination for adolescent girls to their national immunization programmes. Vaccination strategies differ, consequently affecting vaccination coverage, ranging from several percent to more than 90%. Usually, there are also disparities at national level. The highest HPV vaccination coverage rates are observed in countries where vaccines are administered in school settings and funded from the national budget. Poland is one of the eight EU countries where HPV vaccination has not been introduced to mandatory immunization programme and where paid vaccination is only provided in primary health care settings. HPV vaccination coverage in adolescent girls is estimated at 7.5-10%. Disparities in HPV vaccination coverage rates in adolescent girls worldwide may be due to different strategies of vaccination implementation between countries. Having compared to other countries, the low HPV vaccination coverage in Polish adolescent girls may result from the lack of funding at national level and the fact that vaccines are administered in a primary health care setting. A multidimensional approach, involving the engagement of primary health care and school personnel as well as financial assistance of government at national and local level and the implementation of media campaigns, particularly in regions with high incidence of cervical cancer, could result in an increase of HPV vaccination coverage rates in Poland.

Risk of Delayed Human Papillomavirus Vaccination in Inner-City Adolescent Women

PubMed Central

Schlecht, Nicolas F.; Diaz, Angela; Shankar, Viswanathan; Szporn, Arnold H.; Wu, Maoxin; Nucci-Sack, Anne; Peake, Ken; Strickler, Howard D.; Burk, Robert D.

2016-01-01

Background. Uptake of human papillomavirus (HPV) vaccine in the United States is slow, and the effectiveness of the vaccine has not been assessed in high-risk adolescent populations. Methods. We conducted a longitudinal study of 1139 sexually active, inner-city adolescent women receiving the 3-dose quadrivalent (4vHPV) vaccine. Cervical and anal specimens collected semiannually were tested using an L1-specific polymerase chain reaction assay. Postvaccination incidence of 4vHPV vaccine and nonvaccine HPV types, and risk of cervical cytological abnormalities, were assessed in relation to time to completion of all 3 vaccine doses. Results. Compared to vaccine naive women at enrollment, vaccinated women had significantly lower incidence rate ratios of cervical infection with HPV6/11/16/18 (0.2; 95% confidence interval [CI], .1–.4) and the related types HPV31 and HPV45 (0.4 [95% CI, .2–1.0] and 0.3 [95% CI, .1–.6], respectively), as well as significantly lower incidence rate ratios of anal infection with HPV6/11/16/18 (0.4; 95% CI, .2–.7). Notably, we observed higher risks of cervical HPV6/11/16/18 infection (hazards ratio [HR], 2.9; 95% CI, 1.0–8.0) and associated cytological abnormalities (HR, 4.5; 95% CI, .7–26.0) among women immunized at ≥15 years of age who took ≥12 months (vs <12 months) to complete the 3-dose regimen. Conclusions. Among adolescents immunized at ≥15 years of age, a longer time to complete the 3-dose schedule was associated with an increased risk of anogenital HPV6/11/16/18 infection and an increased incidence of associated cervical cytological abnormalities. PMID:27738056

Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15-55 years of age.

PubMed

Schwarz, Tino F; Galaj, Andrzej; Spaczynski, Marek; Wysocki, Jacek; Kaufmann, Andreas M; Poncelet, Sylviane; Suryakiran, Pemmaraju V; Folschweiller, Nicolas; Thomas, Florence; Lin, Lan; Struyf, Frank

2017-11-01

Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15-25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26-45-year olds and 45-55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15-25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15-55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

PD-L1 expression on immune cells is a favorable prognostic factor for vulvar squamous cell carcinoma patients.

PubMed

Sznurkowski, Jacek J; Żawrocki, Anton; Sznurkowska, Katarzyna; Pęksa, Rafał; Biernat, Wojciech

2017-10-27

Anti-immune programmed death-ligand 1 (PD-L1) pathway is used by the tumor to overcome immune system and serves as immunotherapy target in various malignancies. To investigate the expression of PD-L1 in vulvar squamous cell carcinoma (vSCC) and to assess it's clinicopathological and prognostic significance. Immunohistochemical PD-L1 expression was evaluated in 84 vSCCs with previously defined status of p16 and DNA-HPV, infiltration of immune cells: CD8+, CD4+, FOXP3+, CD56+, CD68+, and GZB+ cells. PD-L1 positivity was defined as ≥5% of PD-L1-positive cells. Survival analyses included the Kaplan-Meier method, log-rank test and Cox proportional hazards model. PD-L1 expression was detected on cancer and peritumoral immune cells. PD-L1-positivity of cancer nests (27/84, 32.1%) was correlated with higher infiltration of CD4+ (p=0.037), CD8+ (p=0.02), FOXP3+ (p=0.007), CD68+ (p=0.021) cells, while PD-L1 positivity of peritumoral immune cells (51/84, 60.7%) was correlated with higher infiltration of intraepithelial FOXP3+ cells only (p=0.037).PD-L1-positivity of cancer cells but not immune cells, was more frequently observed in p16-negative tumors (p=0.004). High-risk HPV-status did not correlate with the PD-L1 status of cancer and immune cells (p=1.000) and (p=1.000) respectively). Median follow up was 89.20 months (range 1.7-189.5). PD-L1 positivity of peritumoral immune cells was found to be an independent favorable prognostic factor for OS. Conclusion: This study highlights the importance of comprehensive PD-L1 assessment in both cancer and immune cells. PD-L1 expression on peritumoral immune cells seems to be an additional prognostic factor in vSCC patients and may influence the results by anti-PD-L1 treatment.

Topical herpes simplex virus 2 (HSV-2) vaccination with human papillomavirus vectors expressing gB/gD ectodomains induces genital-tissue-resident memory CD8+ T cells and reduces genital disease and viral shedding after HSV-2 challenge.

PubMed

Çuburu, Nicolas; Wang, Kening; Goodman, Kyle N; Pang, Yuk Ying; Thompson, Cynthia D; Lowy, Douglas R; Cohen, Jeffrey I; Schiller, John T

2015-01-01

No herpes simplex virus 2 (HSV-2) vaccine has been licensed for use in humans. HSV-2 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and T cells, but clinical trials involving intramuscular (i.m.) injection of HSV-2 gB and gD in adjuvants have not been effective. Here we evaluated intravaginal (ivag) genetic immunization of C57BL/6 mice with a replication-defective human papillomavirus pseudovirus (HPV PsV) expressing HSV-2 gB (HPV-gB) or gD (HPV-gD) constructs to target different subcellular compartments. HPV PsV expressing a secreted ectodomain of gB (gBsec) or gD (gDsec), but not PsV expressing a cytoplasmic or membrane-bound form, induced circulating and intravaginal-tissue-resident memory CD8(+) T cells that were able to secrete gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) as well as moderate levels of serum HSV neutralizing antibodies. Combined immunization with HPV-gBsec and HPV-gDsec (HPV-gBsec/gDsec) vaccines conferred longer survival after vaginal challenge with HSV-2 than immunization with HPV-gBsec or HPV-gDsec alone. HPV-gBsec/gDsec ivag vaccination was associated with a reduced severity of genital lesions and lower levels of viral shedding in the genital tract after HSV-2 challenge. In contrast, intramuscular vaccination with a soluble truncated gD protein (gD2t) in alum and monophosphoryl lipid A (MPL) elicited high neutralizing antibody titers and improved survival but did not reduce genital lesions and viral shedding. Vaccination combining ivag HPV-gBsec/gDsec and i.m. gD2t-alum-MPL improved survival and reduced genital lesions and viral shedding. Finally, high levels of circulating HSV-2-specific CD8(+) T cells, but not serum antibodies, correlated with reduced viral shedding. Taken together, our data underscore the potential of HPV PsV as a platform for a topical mucosal vaccine to control local manifestations of primary HSV-2 infection. Genital herpes is a highly prevalent chronic disease caused by HSV infection. To date, there is no licensed vaccine against HSV infection. This study describes intravaginal vaccination with a nonreplicating HPV-based vector expressing HSV glycoprotein antigens. The data presented in this study underscore the potential of HPV-based vectors as a platform for the induction of genital-tissue-resident memory T cell responses and the control of local manifestations of primary HSV infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Topical Herpes Simplex Virus 2 (HSV-2) Vaccination with Human Papillomavirus Vectors Expressing gB/gD Ectodomains Induces Genital-Tissue-Resident Memory CD8+ T Cells and Reduces Genital Disease and Viral Shedding after HSV-2 Challenge

PubMed Central

Çuburu, Nicolas; Wang, Kening; Goodman, Kyle N.; Pang, Yuk Ying; Thompson, Cynthia D.; Lowy, Douglas R.; Cohen, Jeffrey I.

2014-01-01

ABSTRACT No herpes simplex virus 2 (HSV-2) vaccine has been licensed for use in humans. HSV-2 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and T cells, but clinical trials involving intramuscular (i.m.) injection of HSV-2 gB and gD in adjuvants have not been effective. Here we evaluated intravaginal (ivag) genetic immunization of C57BL/6 mice with a replication-defective human papillomavirus pseudovirus (HPV PsV) expressing HSV-2 gB (HPV-gB) or gD (HPV-gD) constructs to target different subcellular compartments. HPV PsV expressing a secreted ectodomain of gB (gBsec) or gD (gDsec), but not PsV expressing a cytoplasmic or membrane-bound form, induced circulating and intravaginal-tissue-resident memory CD8+ T cells that were able to secrete gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) as well as moderate levels of serum HSV neutralizing antibodies. Combined immunization with HPV-gBsec and HPV-gDsec (HPV-gBsec/gDsec) vaccines conferred longer survival after vaginal challenge with HSV-2 than immunization with HPV-gBsec or HPV-gDsec alone. HPV-gBsec/gDsec ivag vaccination was associated with a reduced severity of genital lesions and lower levels of viral shedding in the genital tract after HSV-2 challenge. In contrast, intramuscular vaccination with a soluble truncated gD protein (gD2t) in alum and monophosphoryl lipid A (MPL) elicited high neutralizing antibody titers and improved survival but did not reduce genital lesions and viral shedding. Vaccination combining ivag HPV-gBsec/gDsec and i.m. gD2t-alum-MPL improved survival and reduced genital lesions and viral shedding. Finally, high levels of circulating HSV-2-specific CD8+ T cells, but not serum antibodies, correlated with reduced viral shedding. Taken together, our data underscore the potential of HPV PsV as a platform for a topical mucosal vaccine to control local manifestations of primary HSV-2 infection. IMPORTANCE Genital herpes is a highly prevalent chronic disease caused by HSV infection. To date, there is no licensed vaccine against HSV infection. This study describes intravaginal vaccination with a nonreplicating HPV-based vector expressing HSV glycoprotein antigens. The data presented in this study underscore the potential of HPV-based vectors as a platform for the induction of genital-tissue-resident memory T cell responses and the control of local manifestations of primary HSV infection. PMID:25320297

Human papillomavirus prevalence and type-distribution, cervical cancer screening practices and current status of vaccination implementation in Central and Eastern Europe.

PubMed

Poljak, Mario; Seme, Katja; Maver, Polona J; Kocjan, Boštjan J; Cuschieri, Kate S; Rogovskaya, Svetlana I; Arbyn, Marc; Syrjänen, Stina

2013-12-31

We present a review of current cervical cancer screening practices, the implementation status of vaccination against human papillomaviruses (HPV) and available data concerning the burden of HPV infection and HPV type-specific distribution in 16 Central and Eastern European countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia and the Former Yugoslav Republic (FYR) of Macedonia. Since published data were relatively scarce, two detailed surveys were conducted during August-October 2011 and in January 2013 to obtain relevant and updated information. The mean prevalence of HPV infection in 8610 women with normal cervical cytology from the region was 12.6%, with HPV16 being the most frequent HPV type. The overall HPV DNA prevalence in women with high-grade cervical lesions was 78.1%. HPV DNA was found in 86.6% of cervical cancers; the combined prevalence of HPV16/18 among HPV positive cases was 87.5%. The overall HPV DNA prevalence in genital warts and laryngeal papillomas was 94.8% and 95.2%, respectively, with HPV6 and HPV11 being the most frequent types. Opportunistic and organized cervical screening, mainly based on conventional cytology, is performed in nine and seven countries in the region, respectively, with the proposed age of the start of screening ranging from 20 to 30 years and the estimated coverage ranging from a few percent to over 70%. At least one of the current HPV prophylactic vaccines is registered in all Central and Eastern European countries except Montenegro. Only Bulgaria, Czech Republic, FYR Macedonia, Latvia, Romania and Slovenia have actually integrated HPV vaccination into their national immunization programme and currently provide routine vaccination free of charge to the primary target population. The key reasons for lack of implementation of HPV vaccination into the national immunization programme are high vaccine cost and negative public perception. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Central and Eastern Europe and Central Asia Region" Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of varying antigens and adjuvant systems on the immunogenicity and safety of investigational tetravalent human oncogenic papillomavirus vaccines: results from two randomized trials.

PubMed

Van Damme, Pierre; Leroux-Roels, Geert; Simon, Philippe; Foidart, Jean-Michel; Donders, Gilbert; Hoppenbrouwers, Karel; Levin, Myron; Tibaldi, Fabian; Poncelet, Sylviane; Moris, Philippe; Dessy, Francis; Giannini, Sandra L; Descamps, Dominique; Dubin, Gary

2014-06-17

A prophylactic human papillomavirus (HPV) vaccine targeting oncogenic HPV types in addition to HPV-16 and -18 may broaden protection against cervical cancer. Two Phase I/II, randomized, controlled studies were conducted to compare the immunogenicity and safety of investigational tetravalent HPV L1 virus-like particle (VLP) vaccines, containing VLPs from two additional oncogenic genotypes, with the licensed HPV-16/18 AS04-adjuvanted vaccine (control) in healthy 18-25 year-old women. In one trial (NCT00231413), subjects received control or one of 6 tetravalent HPV-16/18/31/45 AS04 vaccine formulations at months (M) 0,1,6. In a second trial (NCT00478621), subjects received control or one of 5 tetravalent HPV-16/18/33/58 vaccines formulated with different adjuvant systems (AS04, AS01 or AS02), administered on different schedules (M0,1,6 or M0,3 or M0,6). One month after the third injection (Month 7), there was a consistent trend for lower anti-HPV-16 and -18 geometric mean antibody titers (GMTs) for tetravalent AS04-adjuvanted vaccines compared with control. GMTs were statistically significantly lower for an HPV-16/18/31/45 AS04 vaccine containing 20/20/10/10 μg VLPs for both anti-HPV-16 and anti-HPV-18 antibodies, and for an HPV-16/18/33/58 AS04 vaccine containing 20/20/20/20 μg VLPs for anti-HPV-16 antibodies. There was also a trend for lower HPV-16 and -18-specific memory B-cell responses for tetravalent AS04 vaccines versus control. No such trends were observed for CD4(+) T-cell responses. Immune interference could not always be overcome by increasing the dose of HPV-16/18 L1 VLPs or by using a different adjuvant system. All formulations had acceptable reactogenicity and safety profiles. Reactogenicity in the 7-day post-vaccination period tended to increase with the introduction of additional VLPs, especially for formulations containing AS01. HPV-16 and -18 antibody responses were lower when additional HPV L1 VLPs were added to the HPV-16/18 AS04-adjuvanted vaccine. Immune interference is a complex phenomenon that cannot always be overcome by changing the antigen dose or adjuvant system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Accumulation of invariant NKT cells with increased IFN-γ production in persistent high-risk HPV-infected high-grade cervical intraepithelial neoplasia.

PubMed

Hu, Ting; Yang, Pei; Zhu, Hongmei; Chen, Xinlian; Xie, Xiaoyan; Yang, Mei; Liu, Shanling; Wang, He

2015-04-02

Persistent high-risk human papillomavirus (HR-HPV) infection has been implicated in the development of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. Invariant natural killer T (iNKT) cells produce large amounts of cytokines to regulate immune responses. However, the role of iNKT cells in human persistent HPV-infected cervical tissues is unknown. In our study, 201 patients with diagnoses ranging from normal ectocervical tissue to CINIII from June 2010 to May 2012 were enrolled. HPV DNA and HPV types were detected using the hybrid capture-2 HPV DNA test. Flow cytometry was used to investigate iNKT and CD3+ T cell infiltration into cervical tissues. Real-time quantitative reverse transcription-polymerase chain reaction was used to study IFN-γ expression and immunohistochemistry was used to determine CD3+ T cell distribution. A significant increase in iNKT cells was observed in HPV-positive cervical tissues (p < 0.05), especially in CINII-III (p < 0.01). IFN-γ expression was also increased in HPV-positive cervical tissues (p < 0.05). CD3+ T cells were detected among both epithelium and stromal layers in cervical tissues, and the percentage of CD3+ T cells in HPV-positive cervical tissues was similar to that in HPV-negative cervical tissues (p > 0.05). The iNKT cell aggregation in cervical tissues during the progression from HPV infection to CIN indicates that iNKT cells might play an important role in suppressing immunity. IFN-γ expression could also be related to the HPV infection status. Preventing the accumulation or functioning of iNKT cells in cervical tissues may be a viable method to prevent the development of CIN. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2521874671514142.

Voluntary or Mandatory? The Valence Framing Effect of Attitudes Regarding HPV Vaccination.

PubMed

Gesser-Edelsburg, Anat; Walter, Nathan; Shir-Raz, Yaffa; Green, Manfred S

2015-01-01

This study addresses the issue of valence framing effect in the context of immunization, a preventive behavior often addressed by the equation of benefit versus risk. The authors examined how framing (support vs. oppose) the issue of HPV vaccination in Israel's immunization routine affects attitudes regarding vaccine regulations. The study also examined issue involvement as a moderator of valence framing effect. The results demonstrate that participants in the positive framing condition tended to express greater support for voluntary immunization than participants in the negative framing condition (77.5% and 48.5%, respectively). Among those who supported the mandatory HPV immunization policy, the negative framing condition was more prominent than the positive condition (51.5% and 22.5%, respectively). The analysis of interaction between valence framing and issue involvement showed that the latter tends to moderate the direct effect of framing on attitudes towards vaccination. Findings indicate that even attitudes towards such consequential preventive behaviors as vaccination could be affected by different framing of the issue, especially for those who are less involved. Implications of predilection for freedom of choice regarding vaccination are also discussed.

Seroconversion Following Anal and Genital HPV Infection in Men: The HIM Study.

PubMed

Giuliano, Anna R; Viscidi, Raphael; Torres, B Nelson; Ingles, Donna J; Sudenga, Staci L; Villa, Luisa L; Baggio, Maria Luiza; Abrahamsen, Martha; Quiterio, Manuel; Salmeron, Jorge; Lazcano-Ponce, Eduardo

2015-12-01

Protection from naturally acquired human papillomavirus (HPV) antibodies may influence HPV infection across the lifespan. This study describes seroconversion rates following genital, anal, and oral HPV 6/11/16/18 infections in men and examines differences by HPV type and anatomic site. Men with HPV 6/11/16/18 infections who were seronegative for those genotypes at the time of DNA detection were selected from the HPV Infection in Men (HIM) Study. Sera specimens collected ≤36 months after detection were analyzed for HPV 6/11/16/18 antibodies using a virus-like particle-based ELISA. Time to seroconversion was separately assessed for each anatomic site, stratified by HPV type. Seroconversion to ≥1 HPV type (6/11/16/18) in this sub-cohort (N=384) varied by anatomic site, with 6.3, 18.9, and 0.0% seroconverting following anal, genital, and oral HPV infection, respectively. Regardless of anatomic site, seroconversion was highest for HPV 6 (19.3%). Overall, seroconversion was highest following anal HPV 6 infection (69.2%). HPV persistence was the only factor found to influence seroconversion. Low seroconversion rates following HPV infection leave men susceptible to recurrent infections that can progress to HPV-related cancers. This emphasizes the need for HPV vaccination in men to ensure immune protection against new HPV infections and subsequent disease.

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas.

PubMed

Campbell, Joshua D; Yau, Christina; Bowlby, Reanne; Liu, Yuexin; Brennan, Kevin; Fan, Huihui; Taylor, Alison M; Wang, Chen; Walter, Vonn; Akbani, Rehan; Byers, Lauren Averett; Creighton, Chad J; Coarfa, Cristian; Shih, Juliann; Cherniack, Andrew D; Gevaert, Olivier; Prunello, Marcos; Shen, Hui; Anur, Pavana; Chen, Jianhong; Cheng, Hui; Hayes, D Neil; Bullman, Susan; Pedamallu, Chandra Sekhar; Ojesina, Akinyemi I; Sadeghi, Sara; Mungall, Karen L; Robertson, A Gordon; Benz, Christopher; Schultz, Andre; Kanchi, Rupa S; Gay, Carl M; Hegde, Apurva; Diao, Lixia; Wang, Jing; Ma, Wencai; Sumazin, Pavel; Chiu, Hua-Sheng; Chen, Ting-Wen; Gunaratne, Preethi; Donehower, Larry; Rader, Janet S; Zuna, Rosemary; Al-Ahmadie, Hikmat; Lazar, Alexander J; Flores, Elsa R; Tsai, Kenneth Y; Zhou, Jane H; Rustgi, Anil K; Drill, Esther; Shen, Ronglei; Wong, Christopher K; Stuart, Joshua M; Laird, Peter W; Hoadley, Katherine A; Weinstein, John N; Peto, Myron; Pickering, Curtis R; Chen, Zhong; Van Waes, Carter

2018-04-03

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+) and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the ΔNp63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacy of immune therapy. These findings support possibilities for molecular classification and therapeutic approaches. Published by Elsevier Inc.

Immunogenicity of quadrivalent HPV and combined hepatitis A and B vaccine when co-administered or administered one month apart to 9-10 year-old girls according to 0-6 month schedule.

PubMed

Gilca, Vladimir; Sauvageau, Chantal; Boulianne, Nicole; De Serres, Gaston; Couillard, Michel; Krajden, Mel; Ouakki, Manale; Murphy, Donald; Trevisan, Andrea; Dionne, Marc

2014-01-01

No immunogenicity data has been reported after a single dose of the quadrivalent HPV vaccine (qHPV-Gardasil®) and no data are available on co-administration of this vaccine with the HAV/HBV vaccine (Twinrix-Junior®). Two pre-licensure studies reported similar anti-HPV but lower anti-HBs titers when co-administering HPV and HBV vaccines. To assess the immunogenicity of the qHPV and HAV/HBV vaccine when co-administered (Group-Co-adm) or given one month apart (Group-Sep) and to measure the persistence of HPV antibodies three years post-second dose of qHPV vaccine in both study groups. 416 9-10 year-old girls were enrolled. Vaccination schedule was 0-6 months. Anti-HAV and anti-HBs were measured in all subjects 6 months post-first dose and 1 month post-second dose. Anti-HPV were measured 6 months post-first dose in Group-Co-adm and in all subjects 1 and 36 months post-second dose. Six months post-first dose: 100% of subjects had detectable anti-HAV and 56% and 73% had detectable anti-HBs in Group-Co-Adm and Group-Sep, respectively. In Group-Co-adm 94, 100, 99 and 96% had detectable antibodies to HPV 6, 11, 16 and 18, respectively. One month post-second dose of qHPV and HAV/HBV vaccine, in both study groups 99.5-100% of subjects had an anti-HAV titer ≥ 20IU/L, 97.5-97.6% an anti-HBs level ≥ 10IU/L, and 100% had an anti-HPV titer ≥ 3LU. Thirty-six months post-second dose of qHPV all but four subjects (99%) had antibodies to HPV18 and 100% had antibodies to HPV6, 11 and 16. The great majority (97-100%) had an anti-HPV titer ≥ 3 LU. Post-second dose administration of qHPV and HAV/HBV, no meaningful difference was observed in the immune response in the two study groups to any component of vaccines. The results indicate that qHPV and HAV/HBV can be given during the same vaccination session. Two doses of of qHPV and HAV/HBV vaccines induce a strong immune response. Three years post-second dose of qHPV, the great majority of subjects had antibodies to HPV types included in the vaccine. A two-dose schedule for pre-adolescents might be a reasonable alternative to the currently approved three-dose schedules.

STING activation enhances cetuximab-mediated NK cell activation and DC maturation and correlates with HPV+ status in head and neck cancer.

PubMed

Lu, Shanhong; Concha-Benavente, Fernando; Shayan, Gulidanna; Srivastava, Raghvendra M; Gibson, Sandra P; Wang, Lin; Gooding, William E; Ferris, Robert L

2018-03-01

The intracellular DNA sensor stimulator of interferon genes (STING) has recently been shown to play a vital role in anti-viral and anti-tumor immune responses stimulating cytokine production. While human papillomavirus (HPV) is a causative agent for a subset of head and neck squamous cell carcinoma (HNSCC) with unique etiology and clinical outcome, how the STING pathway is regulated in a virus-induced tumor microenvironment is not well understood. Since STING inactivation likely reflects immunoescape via innate immunity, we hypothesized that its restoration would improve efficacy of the immune modulatory monoclonal antibody (mAb), cetuximab. We correlated STING protein expression with clinical parameters by immunohistochemistry (n = 106) and its mRNA expression from The Cancer Genome Atlas (TCGA) in HNSCC tissue specimens. STING protein expression was tested for association with cancer-specific survival (CSS). We further examined the impact of STING activation on cetuximab-mediated immunity using an in vitro NK:DC:tumor cells co-culture system. In this study, we found that expression of STING both at the protein and mRNA level was higher in HPV positive (HPV + ) specimens but unrelated to TNM stage or cancer-specific survival. Our in vitro studies verified that STING activation enhanced cetuximab mediated NK cell activation and DC maturation. Our findings suggest a novel role of STING in HPV-related carcinogenesis, in which activation of the STING signaling pathway may facilitate anti-tumor response in HNSCC patients, particularly in combination with therapeutic monoclonal antibodies (mAbs) such as cetuximab, an epidermal growth factor receptor (EGFR) inhibitor. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Intramuscular Therapeutic Vaccination Targeting HPV16 Induces T Cell Responses That Localize in Mucosal Lesions

PubMed Central

Jotova, Iveta; Wu, T. C.; Wang, Chenguang; Desmarais, Cindy; Boyer, Jean D.; Tycko, Benjamin; Robins, Harlan S.; Clark, Rachael A.; Trimble, Cornelia L.

2014-01-01

About 25% of high-grade cervical intraepithelial neoplasias (CIN2/3) caused by human papillomavirus serotype 16 (HPV16) undergo complete spontaneous regression. However, to date, therapeutic vaccination strategies for HPV disease have yielded limited success when measured by their ability to induce robust peripheral blood T cell responses to vaccine antigen. We report marked immunologic changes in the target lesion microenvironment after intramuscular therapeutic vaccination targeting HPV16 E6/E7 antigens, in subjects with CIN2/3 who had modest detectable responses in circulating T lymphocytes. Histologic and molecular changes, including markedly (average threefold) increased intensity of CD8+ T cell infiltrates in both the stromal and epithelial compartments, suggest an effector response to vaccination. Postvaccination cervical tissue immune infiltrates included organized tertiary lymphoid-like structures in the stroma subjacent to residual intraepithelial lesions and, unlike infiltrates in unvaccinated lesions, showed evidence of proliferation induced by recognition of cognate antigen. At a molecular level, these histologic changes in the stroma were characterized by increased expression of genes associated with immune activation (CXCR3) and effector function (Tbet and IFNβ), and were also associated with an immunologic signature in the overlying dysplastic epithelium. High-throughput T cell receptor sequencing of unmanipulated specimens identified clonal expansions in the tissue that were not readily detectable in peripheral blood. Together, these findings indicate that peripheral therapeutic vaccination to HPV antigens can induce a robust tissue-localized effector immune response, and that analyses of immune responses at sites of antigen are likely to be much more informative than analyses of cells that remain in the circulation. PMID:24477000

HPV vaccination impact on a cervical cancer screening program: methods of the FASTER-Tlalpan Study in Mexico.

PubMed

Salmerón, Jorge; Torres-Ibarra, Leticia; Bosch, F Xavier; Cuzick, Jack; Lörincz, Attila; Wheeler, Cosette M; Castle, Philip E; Robles, Claudia; Lazcano-Ponce, Eduardo

2016-04-01

To outline the design of a clinical trial to evaluate the impact of HPV vaccination as part of a hrHPV-based primary screening program to extend screening intervals. A total of 18,000 women aged 25-45 years, attending the regular cervical cancer-screening program in primary health care services in Tlalpan, Mexico City, will be invited to the study. Eligible participants will be assigned to one of three comparison groups: 1) HPV16/18 vaccine and hrHPV-based screening; 2) HPV6/11/16/18 vaccine and hrHPV-based screening; 3) Control group who will receive only hrHPV-based screening. Strict surveillance of hrHPV persistent infection and occurrence of precancerous lesions will be conducted to estimate safety profiles at different screening intervals; participants will undergo diagnosis confirmation and treatment as necessary. The FASTER-Tlalpan Study will provide insights into new approaches of cervical cancer prevention programs. It will offer valuable information on potential benefits of combining HPV vaccination and hrHPV-based screening to safety extend screening intervals.

[Acceptability of vaccination against human papillomavirus (HPV) by pediatricians, mothers and young women in Ho Chi Minh City, Vietnam].

PubMed

Phan, D P T; Pham, Q T; Strobel, M; Tran, D S; Tran, T L; Buisson, Y

2012-12-01

Cervical cancer (CC) is almost always induced by some oncogenic types of human papillomavirus (HPV). In Vietnam, it is the first leading cause of cancer in women, with highest prevalence in Ho Chi Minh City (HCMC). Since 2006, prevention of the CC has been improved by licensure of recombinant vaccines directed against HPV 16 and 18, effective when administered before the age of first sexual intercourse. A national program for routine immunization of pre-adolescent girls in addition to cytological screening of adult women would greatly reduce the impact of CC in Vietnam but vaccines remain expensive and it is unclear how this strategy would be accepted by the target population. The aim of this study was to assess the acceptability of HPV vaccination by pediatricians, mothers with a daughter aged 9-15 years and young women aged 16-26 years in HCMC. Between March and June 2010, a cross-sectional survey of knowledge and attitudes was administered to 115 pediatricians in the pediatric hospital, 210 mothers and 400 young women attending the gynecology department of the University Hospital. Pediatricians generally had a good perception of the risk but they still lacked knowledge about HPV vaccination, given by 66% of them. Among mothers, 18% knew the relationship between HPV infection and CC, 43% had heard of HPV vaccination and 40% agreed to vaccinate their daughter. Among young women, 35% knew the risk, 49% knew the vaccine and 38% wanted to be vaccinated. Level of education, amount of income and celibacy were positively related to intention to be vaccinated. The lack of information on HPV vaccination and the high cost of vaccines were the main causes of refusal or indecision. Routine HPV vaccination of girls in HCMC will be well accepted by the population if a large campaign of health education is implemented by the government and if the affordability of vaccines is facilitated. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Is expanding HPV vaccination programs to include school-aged boys likely to be value-for-money: a cost-utility analysis in a country with an existing school-girl program.

PubMed

Pearson, Amber L; Kvizhinadze, Giorgi; Wilson, Nick; Smith, Megan; Canfell, Karen; Blakely, Tony

2014-06-26

Similar to many developed countries, vaccination against human papillomavirus (HPV) is provided only to girls in New Zealand and coverage is relatively low (47% in school-aged girls for dose 3). Some jurisdictions have already extended HPV vaccination to school-aged boys. Thus, exploration of the cost-utility of adding boys' vaccination is relevant. We modeled the incremental health gain and costs for extending the current girls-only program to boys, intensifying the current girls-only program to achieve 73% coverage, and extension of the intensive program to boys. A Markov macro-simulation model, which accounted for herd immunity, was developed for an annual cohort of 12-year-olds in 2011 and included the future health states of: cervical cancer, pre-cancer (CIN I to III), genital warts, and three other HPV-related cancers. In each state, health sector costs, including additional health costs from extra life, and quality-adjusted life-years (QALYs) were accumulated. The model included New Zealand data on cancer incidence and survival, and other cause mortality (all by sex, age, ethnicity and deprivation). At an assumed local willingness-to-pay threshold of US$29,600, vaccination of 12-year-old boys to achieve the current coverage for girls would not be cost-effective, at US$61,400/QALY gained (95% UI $29,700 to $112,000; OECD purchasing power parities) compared to the current girls-only program, with an assumed vaccine cost of US$59 (NZ$113). This was dominated though by the intensified girls-only program; US$17,400/QALY gained (95% UI: dominant to $46,100). Adding boys to this intensified program was also not cost-effective; US$128,000/QALY gained, 95% UI: $61,900 to $247,000).Vaccination of boys was not found to be cost-effective, even for additional scenarios with very low vaccine or program administration costs - only when combined vaccine and administration costs were NZ$125 or lower per dose was vaccination of boys cost-effective. These results suggest that adding boys to the girls-only HPV vaccination program in New Zealand is highly unlikely to be cost-effective. In order for vaccination of males to become cost-effective in New Zealand, vaccine would need to be supplied at very low prices and administration costs would need to be minimised.

Is expanding HPV vaccination programs to include school-aged boys likely to be value-for-money: a cost-utility analysis in a country with an existing school-girl program

PubMed Central

2014-01-01

Background Similar to many developed countries, vaccination against human papillomavirus (HPV) is provided only to girls in New Zealand and coverage is relatively low (47% in school-aged girls for dose 3). Some jurisdictions have already extended HPV vaccination to school-aged boys. Thus, exploration of the cost-utility of adding boys’ vaccination is relevant. We modeled the incremental health gain and costs for extending the current girls-only program to boys, intensifying the current girls-only program to achieve 73% coverage, and extension of the intensive program to boys. Methods A Markov macro-simulation model, which accounted for herd immunity, was developed for an annual cohort of 12-year-olds in 2011 and included the future health states of: cervical cancer, pre-cancer (CIN I to III), genital warts, and three other HPV-related cancers. In each state, health sector costs, including additional health costs from extra life, and quality-adjusted life-years (QALYs) were accumulated. The model included New Zealand data on cancer incidence and survival, and other cause mortality (all by sex, age, ethnicity and deprivation). Results At an assumed local willingness-to-pay threshold of US$29,600, vaccination of 12-year-old boys to achieve the current coverage for girls would not be cost-effective, at US$61,400/QALY gained (95% UI $29,700 to $112,000; OECD purchasing power parities) compared to the current girls-only program, with an assumed vaccine cost of US$59 (NZ$113). This was dominated though by the intensified girls-only program; US$17,400/QALY gained (95% UI: dominant to $46,100). Adding boys to this intensified program was also not cost-effective; US$128,000/QALY gained, 95% UI: $61,900 to $247,000). Vaccination of boys was not found to be cost-effective, even for additional scenarios with very low vaccine or program administration costs – only when combined vaccine and administration costs were NZ$125 or lower per dose was vaccination of boys cost-effective. Conclusions These results suggest that adding boys to the girls-only HPV vaccination program in New Zealand is highly unlikely to be cost-effective. In order for vaccination of males to become cost-effective in New Zealand, vaccine would need to be supplied at very low prices and administration costs would need to be minimised. PMID:24965837

Clinical trial tests first-in-class bifunctional immunotherapy drug in HPV-associated cancers | Center for Cancer Research

Cancer.gov

HPV-associated cancers that spread or do not respond to treatment are often incurable. Julius Strauss, M.D., of the Laboratory of Tumor Immunology and Biology is testing a first-in-class bifunctional immunotherapy to see if it can control the growth of HPV-associated tumors by restoring and improving the immune system’s ability to kill cancer cells.

Factors influencing HPV vaccine delivery by healthcare professionals at public health posts in São Paulo, Brazil.

PubMed

Figueroa-Downing, Daniella; Baggio, Maria Luiza; Baker, Misha L; Dias De Oliveira Chiang, Ellen; Villa, Luisa L; Eluf Neto, Jose; Evans, Dabney P; Bednarczyk, Robert A

2017-01-01

To assess the association between Brazilian healthcare providers' characteristics and their knowledge, perceptions, and practices regarding the HPV vaccine. An observational cross-sectional study was conducted at five public health posts in São Paulo between July 28 and August 8, 2014. Healthcare professionals directly involved in patient care were asked to complete a written survey. Factors associated with routine verification of HPV vaccination status were evaluated using Poisson regression. Among 200 participants included, 74 (38.5%) reported never and 70 (36.5%) reported always asking about HPV immunization status. Doctors were significantly less likely to report always asking than were community health agents (5/39 [12.8%] vs 32/60 [53.3%]; adjusted prevalence ratio [aPR] 0.25 [95% confidence interval (CI) 0.07-0.91]). Knowledge about the correct dosing schedule was associated with always rather than never verifying vaccination status (aPR 2.46 [95% CI 1.06-5.70]). Knowledge and attitude played secondary roles in influencing HPV vaccine verification. Community health agents were crucial for vaccine promotion; continued education and support of this group is essential for the sustained success of HPV immunization efforts in Brazil. © 2016 International Federation of Gynecology and Obstetrics.

Provider-Verified HPV Vaccine Coverage among a National Sample of Hispanic Adolescent Females

PubMed Central

Reiter, Paul L.; Gupta, Kunal; Brewer, Noel T.; Gilkey, Melissa B.; Katz, Mira L.; Paskett, Electra D.; Smith, Jennifer S.

2014-01-01

Background Hispanic females have the highest cervical cancer incidence rate of any racial or ethnic group in the US, yet relatively little research has examined HPV vaccination among this fast-growing population. We examined HPV vaccination among a national sample of Hispanic adolescent females. Methods We analyzed provider-verified vaccination data from the 2010-2011 National Immunization Survey-Teen for Hispanic females ages 13-17 (n=2,786). We used weighted logistic regression to identify correlates of HPV vaccine initiation (receipt of one or more doses), completion (receipt of three doses), and follow-through (receipt of three doses among those who initiated the series). Results HPV vaccine initiation was 60.9%, completion was 36.0%, and follow-through was 59.1%. Initiation and completion were more common among older daughters and those whose parents had received a provider recommendation to vaccinate (all p<0.05). Completion was less common among daughters who had moved from their birth state (p<0.05). All vaccination outcomes were less common among daughters without health insurance (all p<0.05). Vaccination did not differ by parents’ preferred language (all p>0.05), although intent to vaccinate was higher among Spanish-speaking parents (p<0.01). Spanish-speaking parents were more likely to indicate lack of provider recommendation (20.2% vs. 5.3%) and cost (10.9% vs. 1.8%) as main reasons for not intending to vaccinate (both p<0.05). Conclusions Many Hispanic females have not received HPV vaccine. Several factors, including provider recommendation and health insurance, are key correlates of vaccination. Impact HPV vaccination programs targeting Hispanics are needed and should consider how potential barriers to vaccination may differ by preferred language. PMID:24633142

Screening women for cervical cancer carcinoma with a HPV mRNA test: first results from the Venice pilot program.

PubMed

Maggino, Tiziano; Sciarrone, Rocco; Murer, Bruno; Dei Rossi, Maria Rosa; Fedato, Chiara; Maran, Michela; Lorio, Melania; Soldà, Marika; Zago, Fiorella; Giorgi Rossi, Paolo; Zorzi, Manuel

2016-08-23

HPV DNA-based screening is more effective than a Pap test in preventing cervical cancer, but the test is less specific. New HPV tests have been proposed for primary screening. The HPV mRNA test showed a similar or slightly lower sensitivity than the HPV DNA tests but with a higher specificity. We report the results of an organised HPV mRNA-based screening pilot program in Venice, Italy. From October 2011 to May 2014, women aged 25-64 years were invited to undergo a HPV mRNA test (Aptima). Those testing positive underwent cytological triage. Women with positive cytology were referred to colposcopy, whereas those with negative cytology were referred to repeat the HPV mRNA test 1 year later. The results of the HPV mRNA test program were compared with both the local historical cytology-based program and with four neighbouring DNA HPV-based pilot projects. Overall, 23 211 women underwent a HPV mRNA test. The age-standardised positivity rate was 7.0%, higher than in HPV DNA programs (6.8%; relative rate (RR) 1.11, 95% confidence interval (CI) 1.05-1.17). The total colposcopy referral was 5.1%, double than with cytology (2.6%; RR 2.02, 95% CI 1.82-2.25) but similar to the HPV DNA programs (4.8%; RR 1.02; 95% CI 0.96-1.08). The cervical intraepithelial neoplasia grade 2+ detection rate with HPV mRNA was greater than in the HPV DNA programs at baseline (RR 1.50; 95% CI 1.19-1.88) and not significantly lower at the 1-year repeat (RR 0.70; 95% CI 0.40-1.16). The overall RR was 1.29 (95% CI 1.05-1.59), which was much higher than with cytology (detection rate 5.5‰ vs 2.1‰; RR 2.50, 95% CI 1.76-3.62). A screening programme based on the HPV mRNA obtained results similar to those observed with the HPV DNA test. In routine screening programmes, even a limited increase in HPV prevalence may conceal the advantage represented by the higher specificity of HPV mRNA.

Rationale and design of a community-based double-blind randomized clinical trial of an HPV 16 and 18 vaccine in Guanacaste, Costa Rica

PubMed Central

Herrero, Rolando; Hildesheim, Allan; Rodríguez, Ana C; Wacholder, Sholom; Bratti, Concepción; Solomon, Diane; González, Paula; Porras, Carolina; Jiménez, Silvia; Guillen, Diego; Morales, Jorge; Alfaro, Mario; Cyr, Jean; Morrisey, Kerrygrace; Estrada, Yenory; Cortés, Bernal; Morera, Lidia Ana; Freer, Enrique; Schussler, John; Schiller, John; Lowy, Douglas; Schiffman, Mark

2008-01-01

We report the rationale, design, methods and details of participation of a community-based, double blind, randomized clinical trial of an HPV 16 and 18 vaccine conducted in two provinces of Costa Rica to investigate the efficacy and population impact of the vaccine in the prevention of cervical cancer precursors. More than 24,000 women between 18 and 25 years of age were invited to participate and pre-screened for eligibility, with recruitment of 7,466 women (30% of those prescreened, 59% of those eligible) who were randomized to receive 3 doses of the HPV vaccine or hepatitis A vaccine as control. A complex protocol of data and specimen collection was applied, including an interview, pelvic exam for sexually active women, blood for serology and cell-mediated immunity, cervical secretions for local immunity and cells for HPV, Chlamydia trachomatis and Gonorrhea testing. Eighty percent of the women received 3 doses, 12.4% two doses and 7.4% one dose. At visits, compliance with data and specimen collection was close to 100%. Baseline characteristics and age-specific prevalence of HPV and cervical neoplasia are reported. Overall prevalence of HPV was high (50%), with 8.3% of women having HPV 16 and 3.2% HPV 18. LSIL was detected in 12.7% of women at baseline and HSIL in 1.9%. Prevalence of Chlamydia was 14.2%. There was very good agreement in HPV detection between clinician-collected and self-collected specimens (89.4% agreement for all types, kappa 0.59). Follow up will continue with yearly or more frequent examinations for at least 4 years for each participant. PMID:18640170

The current state of therapeutic and T cell-based vaccines against human papillomaviruses.

PubMed

Yang, Andrew; Farmer, Emily; Lin, John; Wu, T-C; Hung, Chien-Fu

2017-03-02

Human papillomavirus (HPV) is known to be a necessary factor for many gynecologic malignancies and is also associated with a subset of head and neck malignancies. This knowledge has created the opportunity to control these HPV-associated cancers through vaccination. However, despite the availability of prophylactic HPV vaccines, HPV infections remain extremely common worldwide. In addition, while prophylactic HPV vaccines have been effective in preventing infection, they are ineffective at clearing pre-existing HPV infections. Thus, there is an urgent need for therapeutic and T cell-based vaccines to treat existing HPV infections and HPV-associated lesions and cancers. Unlike prophylactic vaccines, which generate neutralizing antibodies, therapeutic, and T cell-based vaccines enhance cell-mediated immunity against HPV antigens. Our review will cover various therapeutic and T cell-based vaccines in development for the treatment of HPV-associated diseases. Furthermore, we review the strategies to enhance the efficacy of therapeutic vaccines and the latest clinical trials on therapeutic and T cell-based HPV vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

Epidemiologic natural history and clinical management of Human Papillomavirus (HPV) Disease: a critical and systematic review of the literature in the development of an HPV dynamic transmission model

PubMed Central

2009-01-01

Background Natural history models of human papillomavirus (HPV) infection and disease have been used in a number of policy evaluations of technologies to prevent and screen for HPV disease (e.g., cervical cancer, anogenital warts), sometimes with wide variation in values for epidemiologic and clinical inputs. The objectives of this study are to: (1) Provide an updated critical and systematic review of the evidence base to support epidemiologic and clinical modeling of key HPV disease-related parameters in the context of an HPV multi-type disease transmission model which we have applied within a U.S. population context; (2) Identify areas where additional studies are particularly needed. Methods Consistent with our and other prior HPV natural history models, the literature review was confined to cervical disease and genital warts. Between October 2005 and January 2006, data were gathered from the published English language medical literature through a search of the PubMed database and references were examined from prior HPV natural history models and review papers. Study design and data quality from individual studies were compared and analyses meeting pre-defined criteria were selected. Results Published data meeting review eligibility criteria were most plentiful for natural history parameters relating to the progression and regression of cervical intraepithelial neoplasia (CIN) without HPV typing, and data concerning the natural history of HPV disease due to specific HPV types were often lacking. Epidemiologic evidence to support age-dependency in the risk of progression and regression of HPV disease was found to be weak, and an alternative hypothesis concerning the time-dependence of transition rates is explored. No data were found on the duration of immunity following HPV infection. In the area of clinical management, data were observed to be lacking on the proportion of clinically manifest anogenital warts that are treated and the proportion of cervical cancer cases that become symptomatic by stage. Conclusion Knowledge of the natural history of HPV disease has been considerably enhanced over the past two decades, through the publication of an increasing number of relevant studies. However, considerable opportunity remains for advancing our understanding of HPV natural history and the quality of associated models, particularly with respect to examining HPV age- and type-specific outcomes, and acquired immunity following infection. PMID:19640281

Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia

PubMed Central

Daayana, S; Elkord, E; Winters, U; Pawlita, M; Roden, R; Stern, P L; Kitchener, H C

2010-01-01

Background: Vulval intraepithelial neoplasia (VIN) is a premalignant condition, which is frequently associated with type HPV16 infection, and multifocal disease has high rates of surgical treatment failure. Methods: We report a phase II clinical trial of the topical immunomodulator, imiquimod, for 8 weeks, followed by 3 doses (weeks 10, 14 and 18) of therapeutic human papillomavirus (HPV) vaccination (TA-CIN, fusion protein HPV16 E6E7L2) in 19 women with VIN grades 2 and 3. Histology and HPV testing of biopsies were performed at weeks 0, 10, 20 and 52. Intralesional infiltration of T-cell subsets and lymphocyte proliferation for HPV systemic immune responses were also assessed. Results: Lesion response (complete regression of VIN on histology) was observed in 32% (6 out of 19) of women at week 10, increasing to 58% (11 out of 19) at week 20 and 63% (12 out of 19) at week 52. At this time, 36% (5 out of 14) of lesions showed HPV16 clearance and 79% (15 out of 19) of women were symptom free. At week 20, after treatment with imiquimod and vaccination, there was significantly increased local infiltration of CD8 and CD4 T cells in lesion responders; in contrast, non-responders (persistent VIN by histology) showed an increased density of T regulatory cells. After vaccination, only lesion responders had significantly increased lympho-proliferation to the HPV vaccine antigens. Conclusion: The therapeutic effect of treatment depends on the differential immune response of responders and non-responders with affect locally and systemically. PMID:20234368

Sexual behavior and factors associated with young age at first intercourse and HPV vaccine uptake among young women in Germany: implications for HPV vaccination policies.

PubMed

Remschmidt, Cornelius; Fesenfeld, Michaela; Kaufmann, Andreas M; Deleré, Yvonne

2014-12-05

In Germany, immunization against human papillomaviruses (HPV) is free of charge for all females aged 12 to 17 years. Since HPV infection rates rise soon after first intercourse, immunization against HPV should be completed before sexual debut. Knowledge of country-specific data on age at first intercourse and related risk factors is important to optimize prevention of HPV and other sexually transmitted infections. Therefore, the primary aim of this study was to describe sexual behavior in young women in Germany. Secondary aims were to identify factors that are (i) associated with younger age at first intercourse and (ii) with HPV vaccine uptake. Between 2010 and 2012, we conducted a cross-sectional study among randomly selected women aged 20 to 25 years in Germany. We used a structured, self-administered questionnaire to collect sociodemographic data, information on sexual habits such as age at first intercourse, and information on HPV vaccine uptake. We used univariate and multivariate logistic regression analyses to identify factors associated with younger age at first intercourse and with HPV vaccine uptake. A total of 823 women (response rate: 14.2%) participated, 785 (95.4%) of which reported having had intercourse already. 70% of these women experienced first intercourse before the age of 18 years. However, less than 5% were younger than 14 years at sexual debut. Younger age at first intercourse was independently associated with a higher number of sexual partners, smoking, and past pregnancies. HPV vaccine uptake was associated with higher education, whereas smoking and a migrant background reduced the chance of being vaccinated. In Germany, only a small proportion of women experienced first intercourse before the age of 14 years. Younger age at first intercourse was associated with behavior that might increase the risk of HPV infections or other sexually transmitted infections. Therefore, to optimize the HPV vaccination strategy, HPV vaccination series should be completed before the age of 14 years in Germany.

Persistence of memory B-cell and T-cell responses to the quadrivalent HPV vaccine in HIV-infected children.

PubMed

Weinberg, Adriana; Huang, Sharon; Moscicki, Anna-Barbara; Saah, Afred; Levin, Myron J

2018-04-24

To determine the magnitude and persistence of quadrivalent human papillomavirus (HPV)16 and HPV18 B-cell and T-cell memory after three or four doses of quadrivalent HPV vaccine (QHPV) in HIV-infected children. Seventy-four HIV-infected children immunized with four doses and 23 with three doses of QHPV had HPV16 and HPV18 IgG B-cell and IFNγ and IL2 T-cell ELISPOT performed at 2, 3.5 and 4-5 years after the last dose. HPV16 and HPV18 T-cell responses were similar in both treatment groups, with higher responses to HPV16 vs. HPV18. These HPV T-cell responses correlated with HIV disease characteristics at the study visits. Global T-cell function declined over time as measured by nonspecific mitogenic stimulation. B-cell memory was similar across treatment groups and HPV genotypes. There was a decline in HPV-specific B-cell memory over time that reached statistical significance for HPV16 in the four-dose group. B-cell and T-cell memory did not significantly differ after either three or four doses of QHPV in HIV-infected children. The clinical consequences of decreasing global T-cell function and HPV B-cell memory over time in HIV-infected children requires further investigation.

Use of the Carolina HPV Immunization Attitudes and Beliefs Scale (CHIAS) in young adult women.

PubMed

Dempsey, Amanda F; Fuhrel-Forbis, Andrea; Konrath, Sara

2014-01-01

Validated measures that can accurate describe young adults' HPV vaccination attitudes and how these relate to vaccination intention and receipt are needed for developing interventions to improve low HPV vaccination levels. The Carolina HPV Immunization Attitudes Scale (CHIAS) is a validated measure of these outcomes that was originally designed for parents. To assess the performance of the CHIAS among young adult women using an exploratory factor analysis. A convenience sample of 139 young adult women (age 18-26 years) were given the CHIAS measure at baseline. Factor analysis was used to determine attitudinal factor groupings and the association of these factors with HPV vaccination intention. A 6-month follow up assessment examined the stability of the CHIAS over time and the association of baseline vaccine factors with vaccine receipt. Five factors loaded on to the CHIAS in young adults - "Barriers," "Harms," "Effectiveness," "Risk Denial" and "Uncertainty," - which was similar to the factor loadings of CHIAS for parents. "Harms" was the factor most consistently associated with vaccination intention at all time points assessed. Only 5 women had received or made an appointment to receive the vaccine at the 6-month follow-up. In terms of categorizing HPV vaccination attitudes, the CHIAS appears to have similar performance among young adults as in parents. However, additional studies are needed to assess the utility of the CHIAS for predicting HPV vaccine receipt among the young adult population.

Marketing HPV vaccine: implications for adolescent health and medical professionalism.

PubMed

Rothman, Sheila M; Rothman, David J

2009-08-19

The new vaccine against 4 types of human papillomavirus (HPV), Gardasil, like other immunizations appears to be a cost-effective intervention with the potential to enhance both adolescent health and the quality of their adult lives. However, the messages and the methods by which the vaccine was marketed present important challenges to physician practice and medical professionalism. By making the vaccine's target disease cervical cancer, the sexual transmission of HPV was minimized, the threat of cervical cancer to adolescents was maximized, and the subpopulations most at risk practically ignored. The vaccine manufacturer also provided educational grants to professional medical associations (PMAs) concerned with adolescent and women's health and oncology. The funding encouraged many PMAs to create educational programs and product-specific speakers' bureaus to promote vaccine use. However, much of the material did not address the full complexity of the issues surrounding the vaccine and did not provide balanced recommendations on risks and benefits. As important and appropriate as it is for PMAs to advocate for vaccination as a public good, their recommendations must be consistent with appropriate and cost-effective use.

Experiences and lessons learned from 29 HPV vaccination programs implemented in 19 low and middle-income countries, 2009-2014.

PubMed

Ladner, Joël; Besson, Marie-Hélène; Audureau, Etienne; Rodrigues, Mariana; Saba, Joseph

2016-10-13

Cervical cancer is the greatest cause of age-weighted years of life lost in the developing world. Human papillomavirus (HPV) infection is associated with a high proportion of cervical cancers, and HPV vaccination may help to reduce the incidence of cancer. The aim of the study was to identify barriers, obstacles, and strategies and to analyze key concerns and lessons learned with respect to the implementation of HPV vaccination program in low- and middle-income countries. The Gardasil Access Program (GAP) is a donation program established to enable organizations and institutions in eligible low-resource countries to gain operational experience designing and implementing HPV vaccination programs. This study used an online survey to capture the experiences and insights of program managers participating in the GAP. Different factors related to HPV vaccination program management were collected. A mixed-method approach enabled the presentation of both quantitative measurements and qualitative insights. Twenty-nine programs implemented by 23 institutions in 19 low- and middle-income countries were included. Twenty programs managers (97.7 %) reported that their institution implemented sensitization strategies about vaccination prior to the launch of vaccination campaign. The most frequently reported obstacles to HPV vaccination by the program managers were erroneous perceptions of population related to the vaccine's safety and efficacy. Reaching and maintaining follow-up with target populations were identified as challenges. Insufficient infrastructure and human resources financing and the vaccine delivery method were identified as significant health system barriers. Coupling HPV vaccination with other health interventions for mothers of targeted girls helped to increase vaccination and cervical cancer screening. The majority of program managers reported that their programs had a positive impact on national HPV vaccination policy. The majority of institutions had national and international partners that provided support for human resources, technical assistance, and training and financial support for health professionals. Local organizations and institutions can implement successful HPV vaccination campaigns. Adequate and adapted planning and resources that support information sharing, sensitization, and mobilization are essential for such success. These results can inform the development of programs and policies related to HPV vaccination in low- and middle-income countries.

Development of chimeric candidate vaccine against HPV18: a proof of concept.

PubMed

Wahiduzzaman, Mohammed; Sharma, Chandresh; Dey, Bindu; Bhatla, Neerja; Singh, Neeta

2015-06-01

Human papillomaviruses (HPVs) are prerequisite for the development of cervical cancer, with HPV16 and HPV18 being the most prevalent. Despite the fact that two prophylactic vaccines against HPVs are in the market, wide-scale application of the vaccine in developing countries is a major problem as far as cost of the vaccine and lack of therapeutic efficacy are concerned. Hence, the aim of our study was to develop HPV18 L1E7 chimeric virus-like particles (CVLPs) vaccine candidate possessing both, prophylactic and therapeutic potential against HPV18-associated cervical cancer. In this study, we have developed a potential candidate vaccine against HPV18 involving HPV18 L1E7 CVLPs, which was expressed in E. coli and assembled in vitro. These CVLPs were able to induce a neutralizing antibody response as well as a cell-mediated immune response in mice.

Laboratory audit as part of the quality assessment of a primary HPV-screening program.

PubMed

Hortlund, Maria; Sundström, Karin; Lamin, Helena; Hjerpe, Anders; Dillner, Joakim

2016-02-01

As primary HPV screening programs are rolled out, methods are needed for routine quality assurance of HPV laboratory analyzes. To explore the use of similar design for audit as currently used in cytology-based screening, to estimate the clinical sensitivity to identify women at risk for CIN 3 or worse (CIN3+). Population-based cohort study conducted within the cervical screening program in Stockholm, Sweden, in 2011-2012. All women with histopathologically confirmed CIN3+ in the following two years were identified by registry analysis. Primary HPV and cytology screening results were collected. For women who had not been HPV tested, biobanked cytology samples were HPV-tested. If the original HPV result had been negative, the sample and subsequent biopsies were analyzed with broad HPV typing (general primer PCR and Luminex). 154 women had a biobanked prediagnostic cytology sample taken up to 2 years before a histopathologically confirmed CIN3+. The high-risk HPV-positivity was 97% (148/154 women), whereas 143/154 (94%) women had had a cytological abnormality. Among the six HPV-negative samples, one sample was HPV 33 positive in repeat testing whereas the other five cases were HPV-negative also on repeat testing, but HPV-positive in the subsequent tumor tissue. A sensitivity of the HPV test that is higher than the sensitivity of cytology suggests adequate quality of the testing. Regular audits of clinical sensitivity, similar to those of cytology-based screening, should be used also in HPV-based screening programs, in order to continuously monitor the performance of the analyzes. Copyright © 2015 Elsevier B.V. All rights reserved.

Nationwide Survey of Knowledge and Health Beliefs regarding Human Papillomavirus among HPV-Vaccinated Female Students in Malaysia

PubMed Central

Wong, Li Ping; Raja Muhammad Yusoff, Raja Nur Amalina; Edib, Zobaida; Sam, I-Ching; Zimet, Gregory D.

2016-01-01

The National HPV Immunization Programme, which offers free human papillomavirus (HPV) vaccines to teenaged female students, was launched in Malaysia in 2010. HPV vaccination paired with adequate knowledge about HPV infection provides the best protection against cervical cancer. To identify the level of knowledge and the health beliefs towards HPV and the HPV vaccine among HPV-vaccinated female students in Malaysia. A nationwide cross-sectional survey among 14 years old female students who had received three doses of the HPV vaccine was conducted in 32 randomly selected schools from 13 states and 3 federal territories in Malaysia between February 2013 and April 2013. Among 2482 respondents, knowledge about HPV infection and the HPV vaccine was extremely poor. The mean total knowledge score was only 3.56 (SD ± 1.76), out of a possible score of 10. The majority of respondents were unaware that vaccinating boys with HPV can help protect girls against HPV infection (91.6%), HPV cannot be cured (81.6%) and that HPV is a sexually transmitted infection (70.3%). Most of the respondents had the misconception that only females get HPV (95.1%), and that the HPV vaccine eliminates the need for Pap smear tests (68.3%). Most respondents (91.6%) believed that they would not get an HPV infection. Almost half of the respondents (42.9%) held the misconception that HPV infection could not lead to serious illness. Findings revealed poor knowledge about both HPV and the HPV vaccine, low perceived susceptibility to HPV infection and misinformation about HPV infection among HPV-vaccinated girls. Therefore, it is essential to increase the knowledge and awareness of health risks regarding HPV infection among teenaged girls who have received the HPV vaccine. PMID:27656876

Nationwide Survey of Knowledge and Health Beliefs regarding Human Papillomavirus among HPV-Vaccinated Female Students in Malaysia.

PubMed

Wong, Li Ping; Raja Muhammad Yusoff, Raja Nur Amalina; Edib, Zobaida; Sam, I-Ching; Zimet, Gregory D

The National HPV Immunization Programme, which offers free human papillomavirus (HPV) vaccines to teenaged female students, was launched in Malaysia in 2010. HPV vaccination paired with adequate knowledge about HPV infection provides the best protection against cervical cancer. To identify the level of knowledge and the health beliefs towards HPV and the HPV vaccine among HPV-vaccinated female students in Malaysia. A nationwide cross-sectional survey among 14 years old female students who had received three doses of the HPV vaccine was conducted in 32 randomly selected schools from 13 states and 3 federal territories in Malaysia between February 2013 and April 2013. Among 2482 respondents, knowledge about HPV infection and the HPV vaccine was extremely poor. The mean total knowledge score was only 3.56 (SD ± 1.76), out of a possible score of 10. The majority of respondents were unaware that vaccinating boys with HPV can help protect girls against HPV infection (91.6%), HPV cannot be cured (81.6%) and that HPV is a sexually transmitted infection (70.3%). Most of the respondents had the misconception that only females get HPV (95.1%), and that the HPV vaccine eliminates the need for Pap smear tests (68.3%). Most respondents (91.6%) believed that they would not get an HPV infection. Almost half of the respondents (42.9%) held the misconception that HPV infection could not lead to serious illness. Findings revealed poor knowledge about both HPV and the HPV vaccine, low perceived susceptibility to HPV infection and misinformation about HPV infection among HPV-vaccinated girls. Therefore, it is essential to increase the knowledge and awareness of health risks regarding HPV infection among teenaged girls who have received the HPV vaccine.

Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies

PubMed Central

Vici, P; Pizzuti, L; Mariani, L; Zampa, G; Santini, D; Di Lauro, L; Gamucci, T; Natoli, C; Marchetti, P; Barba, M; Maugeri-Saccà, M; Sergi, D; Tomao, F; Vizza, E; Di Filippo, S; Paolini, F; Curzio, G; Corrado, G; Michelotti, A; Sanguineti, G; Giordano, A; De Maria, R; Venuti, A

2016-01-01

ABSTRACT Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease. PMID:27063030

Oral Human Papillomavirus Detection in Older Adults Who Have Human Immunodeficiency Virus Infection

PubMed Central

Fatahzadeh, Mahnaz; Schlecht, Nicolas F.; Chen, Zigui; Bottalico, Danielle; McKinney, Sharod; Ostoloza, Janae; Dunne, Anne; Burk, Robert D.

2014-01-01

Objective To evaluate reproducibility of oral rinse self-collection for HPV detection and investigate associations between oral HPV, oral lesions, immune and sociodemographic factors, we performed a cross-sectional study of older adults with HIV infection. Study Design We collected oral rinse samples from 52 subjects at two different times of day followed by an oral examination and interview. We identified HPV using PCR platforms optimized for detection of mucosal and cutaneous types. Results Eighty seven percent of individuals had oral HPV, of which 23% had oncogenic alpha, 40% had non-oncogenic alpha, and 46% had beta or gamma HPV. Paired oral specimens were concordant in all parameters tested. Significant associations observed for oral HPV with increased HIV viral load, hepatitis-C seropositivity, history of sexually transmitted diseases and lifetime number of sexual partners. Conclusions Oral cavity may be a reservoir of subclinical HPV in older adults who have HIV infection. Understanding natural history, transmission and potential implications of oral HPV warrants further investigations. PMID:23375488

Multimodal Counseling Interventions: Effect on Human Papilloma Virus Vaccination Acceptance

PubMed Central

Salisbury, Helen; Bay, Curtis

2017-01-01

Human papilloma virus (HPV) vaccine was developed to reduce HPV-attributable cancers, external genital warts (EGW), and recurrent respiratory papillomatosis. Adolescent HPV vaccination series completion rates are less than 40% in the United States of America, but up to 80% in Australia and the United Kingdom. Population-based herd immunity requires 80% or greater vaccination series completion rates. Pro-vaccination counseling facilitates increased vaccination rates. Multimodal counseling interventions may increase HPV vaccination series non-completers’ HPV-attributable disease knowledge and HPV-attributable disease prophylaxis (vaccination) acceptance over a brief 14-sentence counseling intervention. An online, 4-group, randomized controlled trial, with 260 or more participants per group, found that parents were more likely to accept HPV vaccination offers for their children than were childless young adults for themselves (68.2% and 52.9%). A combined audiovisual and patient health education handout (PHEH) intervention raised knowledge of HPV vaccination purpose, p = 0.02, and HPV vaccination acceptance for seven items, p < 0.001 to p = 0.023. The audiovisual intervention increased HPV vaccination acceptance for five items, p < 0.001 to p = 0.006. That HPV causes EGW, and that HPV vaccination prevents HPV-attributable diseases were better conveyed by the combined audiovisual and PHEH than the control 14-sentence counseling intervention alone. PMID:29113137

Multimodal Counseling Interventions: Effect on Human Papilloma Virus Vaccination Acceptance.

PubMed

Nwanodi, Oroma; Salisbury, Helen; Bay, Curtis

2017-11-06

Human papilloma virus (HPV) vaccine was developed to reduce HPV-attributable cancers, external genital warts (EGW), and recurrent respiratory papillomatosis. Adolescent HPV vaccination series completion rates are less than 40% in the United States of America, but up to 80% in Australia and the United Kingdom. Population-based herd immunity requires 80% or greater vaccination series completion rates. Pro-vaccination counseling facilitates increased vaccination rates. Multimodal counseling interventions may increase HPV vaccination series non-completers' HPV-attributable disease knowledge and HPV-attributable disease prophylaxis (vaccination) acceptance over a brief 14-sentence counseling intervention. An online, 4-group, randomized controlled trial, with 260 or more participants per group, found that parents were more likely to accept HPV vaccination offers for their children than were childless young adults for themselves (68.2% and 52.9%). A combined audiovisual and patient health education handout (PHEH) intervention raised knowledge of HPV vaccination purpose, p = 0.02, and HPV vaccination acceptance for seven items, p < 0.001 to p = 0.023. The audiovisual intervention increased HPV vaccination acceptance for five items, p < 0.001 to p = 0.006. That HPV causes EGW, and that HPV vaccination prevents HPV-attributable diseases were better conveyed by the combined audiovisual and PHEH than the control 14-sentence counseling intervention alone.

Evaluation of Cytokines in Endocervical Secretion and Vaginal pH from Women with Bacterial Vaginosis or Human Papillomavirus

PubMed Central

Campos, Ana Claudia Camargo; Murta, Eddie Fernando Candido; Michelin, Márcia Antoniazi; Reis, Cleomenes

2012-01-01

Objective. To verify the relationship between vaginal pH and human papillomavirus (HPV) infection and to measure cytokine levels in endocervical secretions of women with bacterial vaginosis (BV) or HPV. Methods. 173 women (16–48 years old) were enrolled and divided into groups: BV, HPV, and controls. Microbiological culture and vaginal pH were measured. HPV detect by PCR, and cytokines by ELISA (IL-2, IL-6, IL-10, IL-12, TNF-α, and IFN-γ cytokines). Results. Of 173 women, 60 were control group (34.7%) and 113 were distributed in HPV (n=36, 20.8%), BV (n=36, 20.8%), vaginitis (n=30, 17.3%) and, BV and HPV-associated groups (n=11, 6.4%). Vaginal pH > 4.5 was related with HPV infection. IL-2 and IL-12 were increased in BV and HPV groups, and IL-6 (only BV group), compared to control group. IL-12 and IFN-γ were higher in HPV than BV group. Conclusion. The increase of vaginal pH was associated with HPV infection; BV and HPV groups had a Th1 cytokines immune response. PMID:22550593

DNA plasmid vaccine carrying Chlamydia trachomatis (Ct) major outer membrane and human papillomavirus 16L2 proteins for anti-Ct infection.

PubMed

Wang, Ledan; Cai, Yiqi; Xiong, Yirong; Du, Wangqi; Cen, Danwei; Zhang, Chanqiong; Song, Yiling; Zhu, Shanli; Xue, Xiangyang; Zhang, Lifang

2017-05-16

Chlamydia trachomatis (Ct) is one of the most frequently encountered sexual infection all over the world, yielding tremendous reproductive problems (e.g. infertility and ectopic pregnancy) in the women. This work described the design of a plasmid vaccine that protect mice from Ct infection, and reduce productive tract damage by generating effective antibody and cytotoxic T cell immunity. The vaccine, s was composed of MOMP multi-epitope and HPV16L2 genes carried in pcDNA plasmid (i.e. pcDNA3.1/MOMP/HPV16L). In transfection, the vaccine expressed the chimeric genes (i.e. MOMP and HPV16L2), as demonstrated via western blot, RT-PCR and fluorescence imaging. In vitro, the vaccine transfected COS-7 cells and expressed the proteins corresponding to the genes carried in the vaccine. Through intramuscular immunization in BALB/c mice, the vaccine induced higher levels of anti-Ct IgG titer, anti-HPV16L2 IgG titer in serum and IgA titer in local mucosal secretions, compared to plasmid vaccines that carry only Ct MOMP multi-epitope or HPV16L2 chimeric component only. In mice intravaginally challenged with Ct, the vaccines pcDNA3.1/MOMP/HPV16L2 generated a higher level of genital protection compared to other vaccine formulations. Additionally, histochemical staining indicated that pcDNA3.1/MOMP/HPV16L2 eliminated mouse genital tract tissue pathologies induced by Ct infection. This work demonstrated that pcDNA/MOMP/HPV16L2 vaccine can protect against Ct infection by regulating antibody production, cytotoxic T cell killing functions and reducing pathological damage in mice genital tract. This work can potentially offer us a new vaccine platform against Ct infection.

An open-label, randomized study of a 9-valent human papillomavirus vaccine given concomitantly with diphtheria, tetanus, pertussis and poliomyelitis vaccines to healthy adolescents 11-15 years of age.

PubMed

Kosalaraksa, Pope; Mehlsen, Jesper; Vesikari, Timo; Forstén, Aino; Helm, Klaus; Van Damme, Pierre; Joura, Elmar A; Ciprero, Karen; Maansson, Roger; Luxembourg, Alain; Sobanjo-ter Meulen, Ajoke

2015-06-01

A 9-valent human papillomavirus (9vHPV) vaccine has recently been reported to be safe and highly efficacious against infection and disease related to HPV6/11/16/18/31/33/45/52/58. We evaluated the immunogenicity and safety of the 9vHPV vaccine administered concomitantly with REPEVAX (diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis vaccine). This open-label, randomized, multicenter study enrolled 1054 males and females ages 11-15 years. Subjects were randomly assigned to each group in a 1:1 ratio. Subjects received a 0.5 mL dose of 9vHPV vaccine intramuscularly at day 1, months 2 and 6 and a 0.5 mL dose of REPEVAX either on day 1 (concomitant vaccination group; n = 526) or at month 1 (nonconcomitant vaccination group, n = 528). Serologic responses for each vaccine component were tested by 1-sided tests of noninferiority between groups. Systemic and injection-site adverse experiences (AEs) and serious AEs were monitored. Noninferiority of anti-HPV geometric mean titers and seroconversion rates for all 9vHPV antigens were demonstrated for the concomitant group compared with the nonconcomitant group. Seroconversion rates for the 9vHPV vaccine types were ≥99.8% in both groups at month 7. For REPEVAX, noninferiority of immune response was established for diphtheria, tetanus, all polio and pertussis antigens for both groups. There were no vaccine-related serious AEs. Overall, concomitant administration of 9vHPV vaccine and REPEVAX was generally well tolerated and did not interfere with the immune response to either vaccine. This strategy would minimize the number of visits required to deliver each vaccine individually.

High rates of incident and prevalent anal human papillomavirus infection among young men who have sex with men.

PubMed

Glick, Sara Nelson; Feng, Qinghua; Popov, Viorica; Koutsky, Laura A; Golden, Matthew R

2014-02-01

There are few published estimates of anal human papillomavirus (HPV) infection rates among young men who have sex with men (YMSM). We estimated incidence and prevalence of type-specific anal HPV infection using clinician-collected anal swabs for HPV DNA testing obtained during a 1-year prospective study of 94 YMSM (mean age, 21 years) in Seattle. Seventy percent of YMSM had any HPV infection detected during the study, and HPV-16 and/or -18 were detected in 37%. The incidence rate for any new HPV infection was 38.5 per 1000 person-months and 15.3 per 1000 person-months for HPV-16/18; 19% had persistent HPV-16/18 infection. No participant tested positive for all 4 HPV types in the quadrivalent vaccine. The number of lifetime male receptive anal sex partners was significantly associated with HPV infection. The prevalence of HPV-16/18 was 6% among YMSM with a history of 1 receptive anal sex partner and 31% among YMSM with ≥ 2 partners. Although the high prevalence of HPV among YMSM highlights the desirability of vaccinating all boys as a strategy to avert the morbidity of HPV infection, most YMSM appear to remain naive to either HPV-16 or -18 well into their sexual lives and would benefit from HPV immunization.

Barriers and Facilitators of HPV Vaccination in the VFC Program.

PubMed

Fleming, Wayne S; Sznajder, Kristin K; Nepps, Margaret; Boktor, Sameh W

2018-06-01

This study determined facilitators and barriers to human papillomavirus (HPV) vaccination perceived by providers of healthcare in the federally funded Pennsylvania Vaccines for Children (PA VFC) program. The cross-sectional study gathered descriptive data through a survey research design. Providers of healthcare were recruited through an email containing a link to an 18-question online survey. The survey was divided into four main sections which assessed the perceived facilitators and barriers to HPV vaccination of PA VFC program-eligibles. Survey respondents represented 65 of 66 Pennsylvania counties covered by the PA VFC Program. The study recruited 772 PA VFC participating healthcare facilities for a response rate of 52%. Ninety eight percent of the responding facilities reported that they offered the HPV vaccine. The most common barriers to vaccine administration were the parental belief that HPV vaccination is associated with sexual activity and parent/patient refusal of the HPV vaccination which together accounted for (44%) of responses. The majority of respondents (75.6%) indicated counseling parents and adolescents on the benefits of HPV vaccination was a very important factor in HPV vaccination uptake. Healthcare provider facility based training (32%) and web-based training for healthcare providers (22%) were the most recommended avenues for HPV training. The most common barrier to HPV vaccination was identified as the parental misconception that HPV vaccination is associated with sexual activity. Providers believed that the best way to increase HPV vaccination is through counseling parents and adolescents on the benefits of HPV vaccination and to correct misconceptions and change attitudes. Providers are desirous of receiving HPV web-based or workplace training.

HPV vaccination syndrome: A clinical mirage, or a new tragic fibromyalgia model.

PubMed

Martínez-Lavín, Manuel

2018-03-13

Independent investigators have described the onset of a chronic painful dysautonomic syndrome soon after human papillomavirus (HPV) vaccination. The veracity of this syndrome is hotly debated. Many of the reported post-HPV vaccination cases fullfill fibromyalgia diagnostic criteria. This article discusses the arguments favoring the existence of a syndrome associated to HPV vaccination. We propose that fibromyalgia dysautonomic-neuropathic model could help in the diagnostic and therapeutic process in those patients in whom the onset of a painful chronic illness began after HPV immunization. On the other hand, if its veracity is corroborated, HPV vaccination syndrome may become a new tragic fibromyalgia model. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Assessing genital human papillomavirus genoprevalence in young Australian women following the introduction of a national vaccination program.

PubMed

Osborne, Sarah L; Tabrizi, Sepehr N; Brotherton, Julia M L; Cornall, Alyssa M; Wark, John D; Wrede, C David; Jayasinghe, Yasmin; Gertig, Dorota M; Pitts, Marian K; Garland, Suzanne M

2015-01-01

Following the implementation of Australia's National HPV Vaccination Program in April 2007, this study evaluated the prevalence of vaccine-targeted human papillomavirus (HPV) genotypes (HPV 6, 11, 16, 18) amongst vaccine-eligible young women. Between September 2011 and August 2013, women from Victoria, Australia aged 18-25 were recruited through targeted advertising on the social networking website Facebook. Participants completed an online questionnaire, and sexually active women were asked to provide a self-collected vaginal swab for HPV deoxyribonucleic acid (DNA) detection and genotyping. Samples positive for HPV were genotyped using the Linear Array HPV genotyping test (Roche Diagnostics). Self-reported HPV vaccination details were verified with the National HPV Vaccination Program Register (NHVPR). Of 431 vaginal swabs, 24.8% were positive for HPV DNA. Vaccine-targeted HPV genotypes were detected in only seven (1.6%) samples; all HPV 16 (of the six HPV 16 positive vaccinated women, all had received the vaccine after sexual debut). There were no cases of HPV 6, 11 or 18 identified. HPV types 51, 59, 73, 84, and 89 were the most prevalent genotypes. Vaccination rates were high, with 77.3% of participants having received all three doses of the vaccine, and there was an 89.8% concordance between self-reported and registry-reported HPV vaccination status. Strong associations were observed between vaccination status, age, language spoken at home and country of birth, as well as between HPV detection and the number of male sexual partners. Preliminary data from this study demonstrate a very low prevalence of vaccine-related HPV genotypes amongst vaccine-eligible women from Victoria, Australia. We were able to use Facebook to effectively reach and recruit young women to participate in the assessment of the impact of Australia's HPV vaccination program. Copyright © 2014 Elsevier Ltd. All rights reserved.

HPV Vaccination Coverage of Male Adolescents in the United States

PubMed Central

Lu, Peng-jun; Yankey, David; Jeyarajah, Jenny; O’Halloran, Alissa; Elam-Evans, Laurie D.; Smith, Philip J.; Stokley, Shannon; Singleton, James A.; Dunne, Eileen F.

2018-01-01

Background In 2011, the Advisory Committee for Immunization Practices (ACIP) recommended routine use HPV vaccine for male adolescents. Methods We used the 2013 National Immunization Survey-Teen (NIS-Teen) data to assess HPV vaccine uptake (≥1 dose) and series completion (≥3 doses). Multivariable logistic regression analysis and a predictive marginal model were conducted to identify independent predictors of vaccination among adolescent males aged 13–17 years. Results HPV vaccination coverage with ≥1 dose was 34.6% while series completion (≥3 doses) was 13.9%. Coverage was significantly higher among non-Hispanic blacks and Hispanics compared with non-Hispanic white males. Multivariable logistic regression showed that characteristics independently associated with a higher likelihood of HPV vaccination (≥1 dose) included: being non-Hispanic black race or Hispanic ethnicity, having mothers who were widowed, divorced, or separated, having 1–3 physician contacts in the past 12 months, a well-child visit at age 11–12 years, having one or two vaccination providers, living in urban or suburban areas, and receiving vaccinations from more than one type of facility (p<0.05). Having mothers with some college or college education, having a higher family income to poverty ratio, living in South or Midwest, and receiving vaccinations from all STD/school/teen clinics or other facilities were independently associated with a lower likelihood of HPV vaccination (p<0.05). Conclusions Following recommendations for routine HPV vaccination among male adolescents, uptake in 2013 was low in males. Increased efforts are needed to improve vaccination coverage, especially for those who are least likely to be vaccinated. PMID:26504124

Prevalence of Anal High-Risk Human Papillomavirus Infections Among HIV-Positive and HIV-Negative Men Who Have Sex With Men in Nigeria.

PubMed

Nowak, Rebecca G; Gravitt, Patti E; He, Xin; Ketende, Sosthenes; Dauda, Wuese; Omuh, Helen; Blattner, William A; Charurat, Manhattan E

2016-04-01

Prevalence estimates of anal high-risk human papillomavirus (HR-HPV) are needed in sub-Saharan Africa where HIV is endemic. This study evaluated anal HR-HPV in Nigeria among HIV-positive and HIV-negative men who have sex with men (MSM) for future immunization recommendations. We conducted a cross-sectional study to compare the prevalence of anal HR-HPV infections between 64 HIV-negative and 90 HIV-positive MSM. Multivariate Poisson regression analyses were used to examine demographic and behavioral risk factors associated with any HR-HPV infections. The median age of the 154 participants was 25 years (interquartile range, 22-28 years; range, 16-38 years), and the median age at initiation of anal sex with another man was 16 years (interquartile range, 13-18 years; range, 7-29 years). The prevalence of anal HR-HPV was higher among HIV-positive than HIV-negative MSM (91.1% vs. 40.6%, P < 0.001). In the multivariate analysis, HIV infection (adjusted prevalence ratio [aPR], 2.02; 95% confidence interval [CI], 1.49-2.72), 10 years or more since anal sexual debut (aPR, 1.26; 95% CI, 1.07-1.49), and concurrent relationships with men (aPR, 1.32; 95% CI, 1.04-1.67) were associated with increased anal HR-HPV prevalence. Anal HR-HPV infection is high for young Nigerian MSM, and rates are amplified in those coinfected with HIV. Providing universal coverage as well as catch-up immunization for young MSM may be an effective anal cancer prevention strategy in Nigeria.

[Papillomavirus and cervical cancer in Chile].

PubMed

O'Ryan, Miguel; Valenzuela, María Teresa

2008-11-01

Molecular, clinical and epidemiological studies have established beyond doubt that human papiloma viruses (HPV) cause cervical cancer. The virus is also associated with genital warts and other less common cancers in oropharynx, vulva, vagina and penis. Worldwide, VPH genotypes 16 and 18 are the most common high risk genotypes, detected in near 70% of women with cervical cancer. The discovery of a cause-effect relationship between several carcinogenic microorganisms and cancer open avenues for new diagnostic, treatment and prevention strategies. In this issue of Revista Médica de Chile, two papers on HPV are presented. Guzman and colleagues demonstrate that HPV can be detected in 66% to 77% of healthy male adolescents bypolymerase chain reaction and that positivity depends on the site of the penis that is sampled. These results support the role of male to female transmission of high risk HPVs in Chile and should lead to even more active educational campaigns. The second paper provides recommendations for HPV vaccine use in Chile, generated by the Immunization Advisory Committee of the Chilean Infectious Disease Society. To issue these recommendations, the Committee analyzes the epidemiological information available on HPV infection and cervical cancer in Chile, vaccine safety and effectiveness data, and describes cost-effectiveness studies. Taking into account that universal vaccination is controversial, the Committee favors vaccine use in Chile and it's incorporation into a national program. However, there is an indication that the country requires the implementation of an integrated surveillance approach including cross matching of data obtained from HPV genotype surveillance, monitoring of vaccination coverage, and surveillance of cervical cancer. The final decision of universal vaccine use in Chile should be based on a through analysis of information.ev Mid Chile

PD-L1 expression on immune cells is a favorable prognostic factor for vulvar squamous cell carcinoma patients

PubMed Central

Sznurkowski, Jacek J.; Żawrocki, Anton; Sznurkowska, Katarzyna; Pęksa, Rafał; Biernat, Wojciech

2017-01-01

Background Anti-immune programmed death-ligand 1 (PD-L1) pathway is used by the tumor to overcome immune system and serves as immunotherapy target in various malignancies. Aim To investigate the expression of PD-L1 in vulvar squamous cell carcinoma (vSCC) and to assess it's clinicopathological and prognostic significance. Methods Immunohistochemical PD-L1 expression was evaluated in 84 vSCCs with previously defined status of p16 and DNA-HPV, infiltration of immune cells: CD8+, CD4+, FOXP3+, CD56+, CD68+, and GZB+ cells. PD-L1 positivity was defined as ≥5% of PD-L1-positive cells. Survival analyses included the Kaplan–Meier method, log-rank test and Cox proportional hazards model. Results PD-L1 expression was detected on cancer and peritumoral immune cells. PD-L1-positivity of cancer nests (27/84, 32.1%) was correlated with higher infiltration of CD4+ (p=0.037), CD8+ (p=0.02), FOXP3+ (p=0.007), CD68+ (p=0.021) cells, while PD-L1 positivity of peritumoral immune cells (51/84, 60.7%) was correlated with higher infiltration of intraepithelial FOXP3+ cells only (p=0.037). PD-L1-positivity of cancer cells but not immune cells, was more frequently observed in p16-negative tumors (p=0.004). High-risk HPV-status did not correlate with the PD-L1 status of cancer and immune cells (p=1.000) and (p=1.000) respectively). Median follow up was 89.20 months (range 1.7-189.5). PD-L1 positivity of peritumoral immune cells was found to be an independent favorable prognostic factor for OS. Conclusion: This study highlights the importance of comprehensive PD-L1 assessment in both cancer and immune cells. PD-L1 expression on peritumoral immune cells seems to be an additional prognostic factor in vSCC patients and may influence the results by anti-PD-L1 treatment. PMID:29163797

Knowledge, Attitude, Practice and Barriers on Vaccination against Human Papillomavirus Infection: A Cross-Sectional Study among Primary Care Physicians in Hong Kong

PubMed Central

Wong, Martin C. S.; Lee, Albert; Ngai, Karry L. K.; Chor, Josette C. Y.; Chan, Paul K. S.

2013-01-01

This study explored the knowledge, attitude, practice and barriers to prescribe human papillomavirus (HPV) vaccines among private primary care physicians in Hong Kong. A self-administered questionnaire survey was conducted by sending letters to doctors who had joined a vaccination program for school girls. From 720 surveys sent, 444 (61.7%) completed questionnaires were returned and analyzed. For knowledge, few responded to questions accurately on the prevalence of cervical HPV (27.9%) and genital wart infection (13.1%) among sexually active young women in Hong Kong, and only 44.4% correctly answered the percentage of cervical cancers caused by HPV. For attitude, most agreed that HPV vaccination should be fully paid by the Government (68.3%) as an important public health strategy. Vaccination against HPV was perceived as more important than those for genital herpes (52.2%) and Chlamydia (50.1%) for adolescent health, and the majority selected adolescents aged 12–14 years as the ideal group for vaccination. Gardasil® (30.9%) and Cervarix® (28.0%) were almost equally preferred. For practice, the factors influencing the choice of vaccine included strength of vaccine protection (61.1%), long-lasting immunity (56.8%) and good antibody response (55.6%). The most significant barriers to prescribe HPV vaccines consisted of parental refusal due to safety concerns (48.2%), and their practice of advising vaccination was mostly affected by local Governmental recommendations (78.7%). A substantial proportion of physicians had recommended HPV vaccines for their female clients/patients aged 18–26 years for protection of cervical cancer (83.8%) or both cervical cancer and genital warts (85.5%). The knowledge on HPV infection was low among physicians in Hong Kong. Prescription of HPV vaccine was hindered by the perceived parental concerns and was mostly relied on Governmental recommendations. Educational initiatives should be targeted towards both physicians and parents, and the Government should consider full subsidy to enhance vaccine uptake rate. PMID:23990994

Characterization of tumor-associated T-lymphocyte subsets and immune checkpoint molecules in head and neck squamous cell carcinoma

PubMed Central

Thelen, Martin; Reuter, Sabrina; Zentis, Peter; Shimabukuro-Vornhagen, Alexander; Theurich, Sebastian; Wennhold, Kerstin; Garcia-Marquez, Maria; Tharun, Lars; Quaas, Alexander; Schauss, Astrid; Isensee, Jörg; Hucho, Tim; Huebbers, Christian

2017-01-01

The composition of tumor-infiltrating lymphocytes (TIL) reflects biology and immunogenicity of cancer. Here, we characterize T-cell subsets and expression of immune checkpoint molecules in head and neck squamous cell carcinoma (HNSCC). We analyzed TIL subsets in primary tumors (n = 34), blood (peripheral blood mononuclear cells (PBMC); n = 34) and non-cancerous mucosa (n = 7) of 34 treatment-naïve HNSCC patients and PBMC of 15 healthy controls. Flow cytometry analyses revealed a highly variable T-cell infiltration mainly of an effector memory phenotype (CD45RA−/CCR7−). Naïve T cells (CD45RA+/CCR7+) were decreased in the microenvironment compared to PBMC of patients, while regulatory T cells (CD4+/CD25+/CD127low and CD4+/CD39+) were elevated. Furthermore, we performed digital image analyses of entire cross sections of HNSCC to define the ‘Immunoscore’ (CD3+ and CD8+ cell infiltration in tumor core and invasive margin) and quantified MHC class I expression on tumor cells by immunohistochemistry. Immune checkpoint molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) were increased in TILs compared to peripheral T cells in flow-cytometric analysis. Human papillomavirus (HPV) positive tumors showed higher numbers of TILs, but a similar composition of T-cell subsets and checkpoint molecule expression compared to HPV negative tumors. Taken together, the tumor microenvironment of HNSCC is characterized by a strong infiltration of regulatory T cells and high checkpoint molecule expression on T-cell subsets. In view of increasingly used immunotherapies, a detailed knowledge of TILs and checkpoint molecule expression on TILs is of high translational relevance. PMID:28574843

Vaccinating women previously exposed to human papillomavirus: a cost-effectiveness analysis of the bivalent vaccine.

PubMed

Turner, Hugo C; Baussano, Iacopo; Garnett, Geoff P

2013-01-01

Recent trials have indicated that women with prior exposure to Human papillomavirus (HPV) subtypes 16/18 receive protection against reinfection from the HPV vaccines. However, many of the original models investigating the cost effectiveness of different vaccination strategies for the protection of cervical cancer assumed, based on the trial results at that time, that these women received no protection. We developed a deterministic, dynamic transmission model that incorporates the vaccine-induced protection of women with prior exposure to HPV. The model was used to estimate the cost effectiveness of progressively extending a vaccination programme using the bivalent vaccine to older age groups both with and without protection of women with prior exposure. We did this under a range of assumptions on the level of natural immunity. Our modelling projections indicate that including the protection of women with prior HPV exposure can have a profound effect on the cost effectiveness of vaccinating adults. The impact of this protection is inversely related to the level of natural immunity. Our results indicate that adult vaccination strategies should potentially be reassessed, and that it is important to include the protection of non-naive women previously infected with HPV in future studies. Furthermore, they also highlight the need for a more thorough investigation of this protection.

Initial results of population based cervical cancer screening program using HPV testing in one million Turkish women.

PubMed

Gultekin, Murat; Zayifoglu Karaca, Mujdegul; Kucukyildiz, Irem; Dundar, Selin; Boztas, Guledal; Semra Turan, Hatice; Hacikamiloglu, Ezgi; Murtuza, Kamil; Keskinkilic, Bekir; Sencan, Irfan

2018-05-01

To evaluate the Turkey's nationwide HPV DNA screening program on the basis of first 1 million screened women. Women over age 30 were invited for population based screening via HPV DNA and conventional cytology. Samples were collected by family physicians and the evaluations and reports had been performed in the National Central HPV laboratories. The acceptance rate for HPV based cervical cancer screening after first invitation was nearly 36.5%. Since HPV DNA tests have been implemented, cervical cancer screening rates have shown 4-5-fold increase in primary level. Through the evaluation of all, HPV positivity was seen in 3.5%. The commonest HPV genotypes were 16, followed by 51, 31, 52 and 18. Among the 37.515 HPV positive cases, cytological abnormality rate was 19.1%. Among HPV positive cases, 16.962 cases had HPV 16 or 18 or other oncogenic HPV types with abnormal cytology (>ASC-US). These patients were referred to colposcopy. The colposcopy referral rate was 1.6%. Among these, final clinico-pathological data of 3.499 patients were normal in 1.985 patients, CIN1 in 708, CIN2 in 285, CIN3 in 436 and cancer in 85 patients and only pap-smear program could miss 45.9% of ≥CIN3 cases. The results of 1 million women including the evaluation of 13 HPV genotypes with respect to prevalence, geographic distribution and abnormal cytology results shows that HPV DNA can be used in primary level settings to have a high coverage rated screening program and is very effective compared to conventional pap-smear. © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Initial results of population based cervical cancer screening program using HPV testing in one million Turkish women

PubMed Central

Zayifoglu Karaca, Mujdegul; Kucukyildiz, Irem; Dundar, Selin; Boztas, Guledal; Semra Turan, Hatice; Hacikamiloglu, Ezgi; Murtuza, Kamil; Keskinkilic, Bekir; Sencan, Irfan

2017-01-01

To evaluate the Turkey's nationwide HPV DNA screening program on the basis of first 1 million screened women. Women over age 30 were invited for population based screening via HPV DNA and conventional cytology. Samples were collected by family physicians and the evaluations and reports had been performed in the National Central HPV laboratories. The acceptance rate for HPV based cervical cancer screening after first invitation was nearly 36.5%. Since HPV DNA tests have been implemented, cervical cancer screening rates have shown 4–5‐fold increase in primary level. Through the evaluation of all, HPV positivity was seen in 3.5%. The commonest HPV genotypes were 16, followed by 51, 31, 52 and 18. Among the 37.515 HPV positive cases, cytological abnormality rate was 19.1%. Among HPV positive cases, 16.962 cases had HPV 16 or 18 or other oncogenic HPV types with abnormal cytology (>ASC‐US). These patients were referred to colposcopy. The colposcopy referral rate was 1.6%. Among these, final clinico‐pathological data of 3.499 patients were normal in 1.985 patients, CIN1 in 708, CIN2 in 285, CIN3 in 436 and cancer in 85 patients and only pap‐smear program could miss 45.9% of ≥CIN3 cases. The results of 1 million women including the evaluation of 13 HPV genotypes with respect to prevalence, geographic distribution and abnormal cytology results shows that HPV DNA can be used in primary level settings to have a high coverage rated screening program and is very effective compared to conventional pap‐smear. PMID:29235108

E6D25E, HPV16 Asian variant shows specific proteomic pattern correlating in cells transformation and suppressive innate immune response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chopjitt, Peechanika; Pientong, Chamsai; Sunthamala, Nuchsupha

HPV16 Asian variant (HPV16As) containing E6D25E oncogene, is commonly associated with cervical cancers of Asian populations. To explore a mechanism of E6D25E oncoprotein in carcinogenesis, we compared protein profiles in human keratinocytes expressing E6D25E with E6 of HPV16 prototype (E6Pro). A human cervical keratinocyte cell line, HCK1T, was transduced with retroviruses containing E6D25E or E6Pro genes. Biological properties of E6D25E or E6Pro transduced HCK1T cells were characterized. Protein profiles of the transduced HCK1T cells were analyzed using 2D-PAGE and characterized by mass spectrometry and western blotting. Reactomes of modulated proteins were analyzed by using the Reactome Knowledgebase. The E6D25E andmore » E6Pro oncoproteins were comparable for their abilities to degrade p53 and suppress the induction of p21, and induce cell proliferation. Interestingly, the protein profiles of the HCK1T cells transduced with E6D25E showed specific proteomic patterns different from those with E6Pro. Among altered proteins, more than 1.5-fold up- or down- regulation was observed in E6D25E-expressing cells for gp96 and keratin7 which involved in activation of TLR signaling and transformation of squamocolumnar junction cells, respectively. This report describes new cellular proteins specifically targeted by E6D25E oncoprotein that may contribute to impair immune response against viral infection and cell transformation associated with oncogenic property of HPV16As variant. - Highlights: • E6D25E HPV16 specifically modulates protein profile of human keratinocytes. • E6D25E HPV16 modulates protein profile which involves in TLR signalling and transformation of squamocolumnar junction cells. • E6D25E oncoprotein may correlate to impair of immune response against viral infection and cells transformation.« less

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

PubMed

North, Anna L; Niccolai, Linda M

2016-10-01

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.

The Relationship of Health Beliefs with Information Sources and HPV Vaccine Acceptance among Young Adults in Korea.

PubMed

Kim, Jarim

2018-04-04

Despite the HPV vaccine’s efficacy in preventing cervical cancer, its coverage rates among Asians are very low. To increase immunization coverage among these populations, understanding the psychological factors that affect HPV acceptability is critical. To this end, this study examined the relationships between multidimensional health beliefs and HPV vaccine acceptance, and what information sources effectively foster HPV vaccination-related health beliefs. Data were collected using a survey of 323 undergraduate students in Korea. Results showed that perceived susceptibility, perceived severity, perceived benefits, and perceived vaccine safety concerns predicted vaccine acceptance. Multiple dimensions of perceived barriers showed differing impacts on vaccine acceptance. In addition, interpersonal information sources were effective in boosting various health beliefs for HPV vaccination. The Internet also was effective in reducing social barriers, but the effects were opposite to those of social media. Theoretical and practical implications are discussed.

The Relationship of Health Beliefs with Information Sources and HPV Vaccine Acceptance among Young Adults in Korea

PubMed Central

Kim, Jarim

2018-01-01

Despite the HPV vaccine’s efficacy in preventing cervical cancer, its coverage rates among Asians are very low. To increase immunization coverage among these populations, understanding the psychological factors that affect HPV acceptability is critical. To this end, this study examined the relationships between multidimensional health beliefs and HPV vaccine acceptance, and what information sources effectively foster HPV vaccination-related health beliefs. Data were collected using a survey of 323 undergraduate students in Korea. Results showed that perceived susceptibility, perceived severity, perceived benefits, and perceived vaccine safety concerns predicted vaccine acceptance. Multiple dimensions of perceived barriers showed differing impacts on vaccine acceptance. In addition, interpersonal information sources were effective in boosting various health beliefs for HPV vaccination. The Internet also was effective in reducing social barriers, but the effects were opposite to those of social media. Theoretical and practical implications are discussed. PMID:29617313

Human Papilloma Virus Vaccination Among Adolescents in a Community Clinic Before and After Intervention.

PubMed

Varman, M; Sharlin, C; Fernandez, C; Vasudevan, J; Wichman, C

2018-06-01

Human Papilloma Virus (HPV) is the most common sexually transmitted disease with over 14 million infections in 2008. Certain HPV types have been identified in up to 70% of cases of cervical and anal cancers. Despite being safe and effective, HPV vaccination rates remain low. Vaccination and demographic data was collected pre-and post-intervention. Among 13 thru 17-year-old cohort females were significantly more likely to be fully vaccinated. Assessment also found that patients insured by Medicaid were significantly more likely to be fully vaccinated than patients insured privately. Post-intervention vaccination rate is similar to baseline rates. There was non-significant improvement in HPV vaccination coverage after intervention. Male and privately insured patients of Creighton's Pediatric Clinic have lower HPV vaccination coverage than their counterparts. More direct efforts are needed in vaccination process and policy in the clinic to improve immunization against HPV among children and adolescents.

The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcγRIIIA and augments anti-HPV immunity after nasal immunization.

PubMed

Fang, Y; Zhang, T; Lidell, L; Xu, X; Lycke, N; Xiang, Z

2013-11-01

We have previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, we have extended these studies and demonstrate that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. Importantly, CTA1-DD/IgE immune complexes did not activate mast cells. Interestingly, only connective tissue, but not mucosal, mast cells could be activated by CTA1-DD/IgG immune complexes. This effect was mediated by FcγRIIIA, only expressed on connective tissue mast cells, and found in the nasal submucosa. FcγRIIIA-deficient mice had compromised responses to immunization adjuvanted by CTA1-DD/IgG. Proof-of-concept studies revealed that IN immunized mice with human papillomavirus (HPV) type 16 L1 virus-like particles (VLP) and CTA1-DD/IgG immune complexes demonstrated strong and sustained specific antibody titers in serum and vaginal secretions. From a mast cell perspective, CTA1-DD/IgG immune complexes appear to be safe and effective mucosal adjuvants.

Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

PubMed

Arguedas, A; Soley, C; Loaiza, C; Rincon, G; Guevara, S; Perez, A; Porras, W; Alvarado, O; Aguilar, L; Abdelnour, A; Grunwald, U; Bedell, L; Anemona, A; Dull, P M

2010-04-19

This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity. Copyright 2010 Elsevier Ltd. All rights reserved.

Smoking and human papillomavirus (HPV) infection in the HPV in Men (HIM) study.

PubMed

Schabath, Matthew B; Villa, Luisa L; Lazcano-Ponce, Eduardo; Salmerón, Jorge; Quiterio, Manuel; Giuliano, Anna R

2012-01-01

The influence of smoking on the natural history of HPV infection in men is not well understood. Smoking could influence the incidence and persistence of HPV infections by suppressing local immune function, increased cellular proliferation, upregulated proinflammatory factors, or induced host DNA damage resulting in increased susceptibility to infection. The purpose of this analysis is to assess prevalent HPV infections by smoking status in men, and to determine baseline risk of HPV infection associated with smoking. The HPV in Men (HIM) study is a multinational prospective study of the natural history of HPV infections in men. Samples from the coronal sulcus, glans penis, shaft, and scrotum were combined for HPV DNA testing. Multivariable logistic regression was used to assess the association between smoking and any-, oncogenic-, and nononcogenic HPV infections. Our analyses revealed that current smoking was associated with an increased risk of any HPV infection (OR = 1.19; 95% CI: 1.01-1.41) and oncogenic HPV infection (OR = 1.24; 95% CI: 1.05-1.47). However, the association between smoking and any HPV infection (OR = 1.35; 95% CI: 1.05-1.73) and oncogenic HPV infection (OR = 1.46; 95% CI: 1.11-1.92) was only evident among men reporting fewer lifetime sexual partners. These results suggest that current smokers with the fewest number of sexual partners are associated with an increased risk for oncogenic HPV infection. The relationship between smoking and HPV infection remains understudied in men; these data shed new light on the interplay between smoking, sexual activity, and risk of HPV infection.

Combining MPDL3280A with adoptive cell immunotherapy exerts better antitumor effects against cervical cancer.

PubMed

Zheng, Yi; Yang, Yicheng; Wu, Shu; Zhu, Yongqiang; Tang, Xiaolong; Liu, Xiaopeng

2017-07-04

As the second most common gynecologic malignant tumors with a high mortality rate, cervical cancer jeopardizes women's life worldwide. The low cure rate in cervical cancer patients is mainly attributed to the lack of effective therapies. One feasible novel strategy is to develop immune-based approaches such as adoptive cell immunotherapy of DCCIKs which represents a promising nontoxic antineoplastic immunotherapy preferred in clinic practice. However, the therapeutic effect is not as efficient as anticipated. Possible explanations are tumors exploit immunoregulatory check-points such as programmed death 1(PD1)/PDL1 which provides tumor cells an escape strategy of circumventing immunologic rejection from immune surveillance by hampering activated tumor-specific T cell activities and rendering them functionally exhausted. With reduced transformation activity and enhanced antigenicity, a modified HPV16 E7 (HPV16mE7) was used to load DCs with silenced SOCS1 mediated by a recombinant adenovirus to improve the targetability and efficiency against cervical cancer. Combined with anti-PDL1 antibody MPDL3280A therapy, the co-cultured DCCIKs were transfused into murine models bearing tumor of HPV16 E6/E7 expressing CaSki cells for in vitro/in vivo antitumor activity assay. Although all of the animals succumbed to CaSki tumors even after adoptive DCCIKs transfer or MPDL3280A immunotherapy, the infusion of PDL1 blocking monoclonal antibody with activated T cells cured 40% of animals. These data support PDL1 blockade improves the efficacy of adoptive DCCIKs therapy, providing a new approach of immunotherapy against cervical cancer.

Combining MPDL3280A with adoptive cell immunotherapy exerts better antitumor effects against cervical cancer

PubMed Central

Zheng, Yi; Yang, Yicheng; Wu, Shu; Zhu, Yongqiang; Tang, Xiaolong; Liu, Xiaopeng

2017-01-01

ABSTRACT As the second most common gynecologic malignant tumors with a high mortality rate, cervical cancer jeopardizes women's life worldwide. The low cure rate in cervical cancer patients is mainly attributed to the lack of effective therapies. One feasible novel strategy is to develop immune-based approaches such as adoptive cell immunotherapy of DCCIKs which represents a promising nontoxic antineoplastic immunotherapy preferred in clinic practice. However, the therapeutic effect is not as efficient as anticipated. Possible explanations are tumors exploit immunoregulatory check-points such as programmed death 1(PD1)/PDL1 which provides tumor cells an escape strategy of circumventing immunologic rejection from immune surveillance by hampering activated tumor-specific T cell activities and rendering them functionally exhausted. With reduced transformation activity and enhanced antigenicity, a modified HPV16 E7 (HPV16mE7) was used to load DCs with silenced SOCS1 mediated by a recombinant adenovirus to improve the targetability and efficiency against cervical cancer. Combined with anti-PDL1 antibody MPDL3280A therapy, the co-cultured DCCIKs were transfused into murine models bearing tumor of HPV16 E6/E7 expressing CaSki cells for in vitro/in vivo antitumor activity assay. Although all of the animals succumbed to CaSki tumors even after adoptive DCCIKs transfer or MPDL3280A immunotherapy, the infusion of PDL1 blocking monoclonal antibody with activated T cells cured 40% of animals. These data support PDL1 blockade improves the efficacy of adoptive DCCIKs therapy, providing a new approach of immunotherapy against cervical cancer. PMID:27754760

Monitoring vaccine and non-vaccine HPV type prevalence in the post-vaccination era in women living in the Basilicata region, Italy.

PubMed

Carozzi, Francesca; Puliti, Donella; Ocello, Cristina; Anastasio, Pasquale Silvio; Moliterni, Espedito Antonio; Perinetti, Emilia; Serradell, Laurence; Burroni, Elena; Confortini, Massimo; Mantellini, Paola; Zappa, Marco; Dominiak-Felden, Géraldine

2018-01-15

A large free-of-charge quadrivalent HPV (qHPV) vaccination program, covering four cohorts annually (women 11, 14, 17 and 24 years), has been implemented in Basilicata since 2007. This study evaluated vaccine and non-vaccine HPV prevalence 5-7 years post-vaccination program implementation in vaccinated and unvaccinated women. This population-based, cross-sectional study was conducted in the public screening centers of the Local Health Unit in Matera between 2012 and 2014. Cervical samples were obtained for Pap and HPV testing (HC2, LiPA Extra® assay) and participants completed a sociodemographic and behavioral questionnaire. Detailed HPV vaccination status was retrieved from the official HPV vaccine registry. HPV prevalence was described overall, by type and vaccination status. The association between HPV type-detection and risk/protective factors was studied. Direct vaccine protection (qHPV vaccine effectiveness [VE]), cross-protection, and type-replacement were evaluated in cohorts eligible for vaccination, by analyzing HPV prevalence of vaccine and non-vaccine types according to vaccination status. Overall, 2793 women (18-50 years) were included, 1314 of them having been in birth cohorts eligible for the HPV vaccination program (18- to 30-year-old women at enrolment). Among the latter, qHPV vaccine uptake was 59% (at least one dose), with 94% completing the schedule; standardized qHPV type prevalence was 0.6% in vaccinated versus 5.5% in unvaccinated women (P <0.001); adjusted VE against vaccine type infections was 90% (95% CI: 73%-96%) for all fully vaccinated women and 100% (95% CI not calculable) in women vaccinated before sexual debut. No statistically significant difference in overall high-risk HPV, high-risk non-vaccine HPV, or any single non-vaccine type prevalence was observed between vaccinated and unvaccinated women. These results, conducted in a post-vaccine era, suggest a high qHPV VE and that a well-implemented catch-up vaccination program may be efficient in reducing vaccine-type infections in a real-world setting. No cross-protective effect or evidence of type-replacement was observed a few years after HPV vaccine introduction.

Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer.

PubMed

Wang, Sophia S; Bratti, M Concepcion; Rodríguez, Ana Cecilia; Herrero, Rolando; Burk, Robert D; Porras, Carolina; González, Paula; Sherman, Mark E; Wacholder, Sholom; Lan, Z Elizabeth; Schiffman, Mark; Chanock, Stephen J; Hildesheim, Allan

2009-01-01

We examined host genetic factors to identify those more common in individuals whose human papillomavirus (HPV) infections were most likely to persist and progress to cervical intraepithelial neoplasia grade 3 (CIN3) and cancer. We genotyped 92 single-nucleotide polymorphisms (SNPs) from 49 candidate immune response and DNA repair genes obtained from 469 women with CIN3 or cancer, 390 women with persistent HPV infections (median duration, 25 months), and 452 random control subjects from the 10,049-woman Guanacaste Costa Rica Natural History Study. We calculated odds ratios and 95% confidence intervals (CIs) for the association of SNP and haplotypes in women with CIN3 or cancer and HPV persistence, compared with random control subjects. A SNP in the Fanconi anemia complementation group A gene (FANCA) (G501S) was associated with increased risk of CIN3 or cancer. The AG and GG genotypes had a 1.3-fold (95% CI, 0.95-1.8-fold) and 1.7-fold (95% CI, 1.1-2.6-fold) increased risk for CIN3 or cancer, respectively (P(trend) = .008; referent, AA). The FANCA haplotype that included G501S also conferred increased risk of CIN3 or cancer, as did a different haplotype that included 2 other FANCA SNPs (G809A and T266A). A SNP in the innate immune gene IRF3 (S427T) was associated with increased risk for HPV persistence (P(trend) = .009). Our results require replication but support the role of FANCA variants in cervical cancer susceptibility and of IRF3 in HPV persistence.

A history of allergies is associated with reduced risk of oral squamous cell carcinoma.

PubMed

Stott-Miller, Marni; Chen, Chu; Doody, David R; Carter, Joseph L; Galloway, Denise A; Madeleine, Margaret M; Schwartz, Stephen M

2012-12-01

A history of allergies is associated with a decreased risk of several types of cancers. Potential mechanisms include enhanced immune surveillance against tumor cells early in disease development and/or carcinogenic infectious agents. We tested whether allergies are inversely associated with oral squamous cell carcinoma (OSCC), accounting for factors that may modify the association, such as tumor site, stage, and HPV infection. We estimated odds ratios (OR) and 95 % confidence intervals (CI) for the association between allergy history (including different types of allergies) and OSCC, adjusted for potential confounders, among 400 cases and 613 controls. Analyses were also stratified by site, stage, and measures of HPV infection. We observed a weak inverse association between history of any allergy and OSCC (OR = 0.81, 95 % CI 0.61-1.08). This association was present only for allergies to airborne allergens (dust/pollen/mold) (OR = 0.67; 95 % CI 0.48-0.93). The inverse associations with airborne allergies were slightly stronger for oropharyngeal SCC (OR = 0.56; 95 % CI 0.35-0.90) than for oral cavity SCC (OR = 0.71; 95 % CI 0.49-1.05) and present only for later-stage cancers (OR = 0.42; 95 % CI 0.26-0.66) as opposed to earlier-stage cancers (OR = 0.98; 95 % CI 0.66-1.46). Inverse associations were not particularly present or stronger among HPV-16-seropositive individuals or for HPV DNA-positive OSCC. There is an inverse association between history of allergies to dust, pollen, or mold and OSCC. Whether the inverse association involves heightened immune surveillance, increased immune response to HPV or other antigen, or other carcinogenic mechanism remains to be determined in more definitive studies.

A history of allergies is associated with reduced risk of oral squamous cell carcinoma

PubMed Central

Stott-Miller, Marni; Chen, Chu; Doody, David R; Carter, Joseph L.; Galloway, Denise A.; Madeleine, Margaret M.; Schwartz, Stephen M.

2012-01-01

Purpose A history of allergies is associated with a decreased risk of several types of cancers. Potential mechanisms include enhanced immune surveillance against tumor cells early in disease development and/or carcinogenic infectious agents. We tested whether allergies are inversely associated with oral squamous cell carcinoma (OSCC), accounting for factors that may modify the association, such as tumor site, stage, and HPV infection. Methods We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between allergy history (including different types of allergies) and OSCC, adjusted for potential confounders, among 400 cases and 613 controls. Analyses were also stratified by site, stage, and measures of HPV infection. Results We observed a weak inverse association between history of any allergy and OSCC (OR=0.81, 95% CI, 0.61–1.08). This association was present only for allergies to airborne allergens (dust/pollen/mold); OR=0.67; 95% CI, 0.48–0.93. The inverse associations with airborne allergies were slightly stronger for oropharyngeal SCC (OR=0.56; 95% CI, 0.35–0.90) than for oral cavity SCC (OR=0.71; 95% CI, 0.49–1.05), and present only for later stage cancers (OR=0.42; 95% CI, 0.26–0.66) as opposed to earlier stage cancers (OR=0.98; 95% CI, 0.66–1.46). Inverse associations were not particularly present or stronger among HPV-16 seropositive individuals or for HPV DNA positive OSCC. Conclusions There is an inverse association between history of allergies to dust, pollen or mold and OSCC. Whether the inverse association involves heightened immune surveillance, increased immune response to HPV or other antigen, or other carcinogenic mechanism, remains to be determined in more definitive studies. PMID:23011537

Use of the nonavalent HPV vaccine in individuals previously fully or partially vaccinated with bivalent or quadrivalent HPV vaccines.

PubMed

Van Damme, Pierre; Bonanni, Paolo; Bosch, F Xavier; Joura, Elmar; Kjaer, Susanne Krüger; Meijer, Chris J L M; Petry, Karl-Ulrich; Soubeyrand, Benoit; Verstraeten, Thomas; Stanley, Margaret

2016-02-03

With the availability of the nonavalent human papillomavirus (HPV) vaccine, vaccinees, parents and healthcare providers need guidance on how to complete an immunization course started with the bi- or quadrivalent vaccine and whether to revaccinate individuals who have completed a full immunization course with the bi- or quadrivalent vaccine. To answer these questions three parameters should be considered: age at the start of vaccination (9 to 14 years of age versus 15 years and older, the cut-off for 2 or 3 doses schedule), the number of doses already received and the time interval between doses. Based on a number of scenarios, we propose that the 9-valent vaccine can be used to complete an incomplete vaccination regimen or might be added to a previous completed schedule to extend protection. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Effect of History of Abnormal Pap Smear or Preceding HPV infection on the Humoral Immune Response to Quadrivalent Human Papilloma virus (qHPV) Vaccine in Women with Systemic Lupus Erythematosus.

PubMed

Dhar, J Patricia; Essenmacher, Lynnette; Dhar, Renee; Magee, Ardella; Ager, Joel; Sokol, Robert J

2018-04-30

To determine if natural human papillomavirus (HPV) infection would induce an anamnestic response to quadrivalent (qHPV) vaccine in women with Systemic Lupus Erythematosus (SLE). Thirty four women (19-50 years) with mild to moderate and minimally active or inactive SLE received standard qHPV vaccine. Neutralizing antibody titers to HPV 6, 11, 16 and18 were evaluated pre- and post- vaccine using HPV competitive Luminex Immunoassay. For each HPV type, logistic regressions were performed to explore the relationship between a positive titer at baseline with their final geometric mean titer and with the rise in titer. Fisher's Exact Test was used to assess the association of at least one positive HPV antibody test at baseline and history of abnormal pap. History of abnormal pap smear/cervical neoplasia occurred in 52.9%. Baseline anti HPV antibody titers: 21% = negative for all 4 HPV types, 79% = positive for ≥1 of the HPV types. Statistical analysis showed: those with a history of abnormal pap smear/cervical neoplasia were likely to have a positive anti-HPV antibody result pre-vaccine to ≥ 1 of the 4 types, p = 0.035 Fisher's Exact Test. In general, HPV exposed women showed higher post vaccine GMTs than HPV unexposed women with higher point estimates. However, when examining the rise in titers using logistic regression, there was no evidence of an anamnestic response. Prior HPV infection and cervical neoplasia in SLE are linked with no anamnestic response to HPV vaccine. This supports not checking HPV-antibodies pre-vaccine. Women with SLE should be vaccinated for HPV.

RNASeq analysis of differentiated keratinocytes reveals a massive response to late events during human papillomavirus type 16 infection, including loss of epithelial barrier function.

PubMed

Klymenko, T; Gu, Q; Herbert, I; Stevenson, A; Iliev, V; Watkins, G; Pollock, C; Bhatia, R; Cuschieri, K; Herzyk, P; Gatherer, D; Graham, S V

2017-10-11

The human papillomavirus (HPV) replication cycle is tightly linked to epithelial cell differentiation. To examine HPV-associated changes in the keratinocyte transcriptome, RNAs isolated from undifferentiated and differentiated cell populations of normal, spontaneously immortalised, keratinocytes (NIKS), and NIKS stably transfected with HPV16 episomal genomes (NIKS16), were compared using RNASeq. HPV16 infection altered expression of 2862 cellular genes. Next, to elucidate the role of keratinocyte gene expression in late events during the viral life cycle, RNASeq was carried out on triplicate differentiated populations of NIKS (uninfected) and NIKS16 (infected). Of the top 966 genes altered (>log 2 = 1.8, 3.5-fold change) 670 genes were downregulated and 296 genes were up-regulated. HPV down-regulated many genes involved in epithelial barrier function that involves structural resistance to the environment and immunity to infectious agents. For example, HPV infection repressed expression of the differentiated keratinocyte-specific pattern recognition receptor TLR7, the Langerhans cell chemoattractant, CCL20, and proinflammatory cytokines, IL1A and IL1B. However, IRF1, IFNκ and viral restriction factors (IFIT1, 2, 3, 5, OASL, CD74, RTP4) were up-regulated. HPV infection abrogated gene expression associated with the physical epithelial barrier, including keratinocyte cytoskeleton, intercellular junctions and cell adhesion. qPCR and western blotting confirmed changes in expression of seven of the most significantly altered mRNAs. Expression of three genes showed statistically significant changes during cervical disease progression in clinical samples. Taken together, the data indicate that HPV infection manipulates the differentiating keratinocyte transcriptome to create an environment conducive to productive viral replication and egress. IMPORTANCE Human papillomavirus (HPV) genome amplification and capsid formation takes place in differentiated keratinocytes. The viral life cycle is intimately associated with host cell differentiation. Deep sequencing (RNASeq) of RNA from undifferentiated and differentiated uninfected and HPV16-positive keratinocytes showed that almost 3000 genes were differentially expressed in keratinocyte due to HPV16 infection. Strikingly, the epithelial barrier function of differentiated keratinocytes, comprising keratinocyte immune function and cellular structure, was found to be disrupted. These data provide new insights into virus-host interaction crucial for production of infectious virus and reveal that HPV infection remodels keratinocytes for completion of the virus replication cycle. Copyright © 2017 American Society for Microbiology.

Willingness of reproductive-aged women in a Nigerian community to accept human papillomavirus vaccination for their children.

PubMed

Morhason-Bello, Imran O; Wallis, Selina; Adedokun, Babatunde O; Adewole, Isaac F

2015-10-01

The aim of this study was to determine the willingness of reproductive-aged women in a Nigerian community to allow human papillomavirus (HPV) vaccination in their children and the associated factors with this decision. A multistage household survey of 1002 women who participated in the HPV Vaccine and Cervical Cancer Prevention Survey from 26 August to 29 September 2012 at Ibadan North Local Government Area, Mokola Ibadan, Nigeria. Descriptive, bivariate and multivariable analyses were performed, and statistical significance was set at 95% confidence level (CI). There was high willingness (88.6%) to vaccinate, and this attitude was associated with previous history of genital discharge or sores (adjusted odds ratio, 1.91; 95%CI, 1.05-3.45), and knowledge that cervical cancer is preventable (adjusted odds ratio, 1.67; 95%CI, 1.07-2.59). On the likely acceptability of Nigerian HPV vaccine policy, about two-thirds strongly agreed to its incorporation into the routine immunization program (66.9%), it being free (66.7%) and mandatory (64.3%), amongst other factors. The commonest concerns raised were cost/expenses (10.2%), that it might encourage promiscuity (9.9%), or stimulate early sexual debut (6.7%), and fear of infertility (6.3%). This study found that the majority of Nigerian women are willing to vaccinate their children against HPV infection and would prefer free universal HPV vaccination with regulation to ensure better uptake. The concerns expressed would need to be addressed by policy-makers to increase its acceptability. © 2015 Japan Society of Obstetrics and Gynecology.

Investigating Stakeholder Attitudes and Opinions on School-Based Human Papillomavirus Vaccination Programs

PubMed Central

Nodulman, Jessica A.; Starling, Randall; Kong, Alberta S.; Buller, David B.; Wheeler, Cosette M.; Woodall, W. Gill

2015-01-01

BACKGROUND In several countries worldwide, school-based human papillomavirus (HPV) vaccination programs have been successful; however, little research has explored US stakeholders’ acceptance toward school-based HPV vaccination programs. METHODS A total of 13 focus groups and 12 key informant interviews (N = 117; 85% females; 66% racial/ethnic minority) were conducted with 5 groups of stakeholders: parents of adolescent girls, parents of adolescent boys, adolescent girls, middle school nurses, and middle school administrators throughout the 5 public health regions of New Mexico. RESULTS All groups of stakeholders lacked knowledge on HPV and HPV vaccines. Stakeholders were interested in—but apprehensive about—the benefits of HPV vaccination. Despite previous literature showing the benefits of using middle schools as an HPV vaccination site, stakeholders did not deem middle schools as a viable site for vaccination. Nurses reported that using the school as an HPV vaccination site had not occurred to them; parents and adolescents stated they were uncertain about using this type of program. School administrators indicated that they lacked implementation authority. CONCLUSIONS Our study uncovered barriers to using middle schools as a site of HPV vaccination. Resources should be directed toward increased support and education for middle school nurses who function as opinion leaders relevant to the uptake of HPV vaccination. PMID:25846308

Human papillomavirus-associated oropharynx cancer (HPV-OPC): treatment options.

PubMed

Chau, Nicole G; Rabinowits, Guilherme; Haddad, Robert I

2014-12-01

Human papillomavirus-associated oropharynx cancer (HPV-OPC) is growing in incidence and has distinct clinical, pathologic, molecular, and epidemiologic features. However, the management of HPV-OPC does not presently differ from HPV-negative OPC based on the current evidence and requires complex multidisciplinary approaches. The superior prognosis of HPV-OPC and the toxicities of current multimodality treatment in a young population serve as the impetus to evaluate de-intensification treatment regimens aimed at reducing toxicity while maintaining therapeutic efficacy. Clinical trials are underway to evaluate reduced doses of radiation or less toxic systemic therapy regimens in HPV-OPC. Minimally invasive surgical approaches in the HPV-OPC population with early tumor stage also are being investigated. De-intensification strategies should only be employed in the context of clinical trials, and HPV-OPC patients should be offered clinical trials' participation. Appropriate patient selection is critical to the development of de-intensification regimens, and this requires greater understanding of risk factors within the HPV-OPC population, HPV-OPC biology, and how HPV modulates response to specific therapies. Smoking history and bulky nodal disease have been shown to impact negatively the favorable prognosis of HPV association. Validated biomarkers within the HPV-OPC population are lacking, although alterations in the PI3K pathway and markers of immune response may emerge as important considerations in the future. Novel therapeutic strategies are desperately needed particularly for HPV-OPC patients who fail definitive therapy, and select patients with recurrent or metastatic disease may benefit from aggressive approaches.

Strategies to Make Immunization Status Visible During Patient Encounters at Naval Medical Center San Diego

DTIC Science & Technology

2007-10-29

for non- cancerous genital warts (World Health Organization, 2006). A second vaccine, developed by GSK, covers HPV types 16 and 18 alone and is...to HPV through sexual activity; howevr women who are sexuafy at the tine ofacute disease); 4) history of herpes zoster based on health-care active sh

The impact and cost-effectiveness of nonavalent HPV vaccination in the United States: Estimates from a simplified transmission model.

PubMed

Chesson, Harrell W; Markowitz, Lauri E; Hariri, Susan; Ekwueme, Donatus U; Saraiya, Mona

2016-06-02

The objective of this study was to assess the incremental costs and benefits of the 9-valent HPV vaccine (9vHPV) compared with the quadrivalent HPV vaccine (4vHPV). Like 4vHPV, 9vHPV protects against HPV types 6, 11, 16, and 18. 9vHPV also protects against 5 additional HPV types 31, 33, 45, 52, and 58. We adapted a previously published model of the impact and cost-effectiveness of 4vHPV to include the 5 additional HPV types in 9vHPV. The vaccine strategies we examined were (1) 4vHPV for males and females; (2) 9vHPV for females and 4vHPV for males; and (3) 9vHPV for males and females. In the base case, 9vHPV cost $13 more per dose than 4vHPV, based on available vaccine price information. Providing 9vHPV to females compared with 4vHPV for females (assuming 4vHPV for males in both scenarios) was cost-saving regardless of whether or not cross-protection for 4vHPV was assumed. The cost per quality-adjusted life year (QALY) gained by 9vHPV for both sexes (compared with 4vHPV for both sexes) was < $0 (cost-saving) when assuming no cross-protection for 4vHPV and $8,600 when assuming cross-protection for 4vHPV. Compared with a vaccination program of 4vHPV for both sexes, a vaccination program of 9vHPV for both sexes can improve health outcomes and can be cost-saving.

Statewide analysis of missed opportunities for human papillomavirus vaccination using vaccine registry data.

PubMed

Kepka, Deanna; Spigarelli, Michael G; Warner, Echo L; Yoneoka, Yukiko; McConnell, Nancy; Balch, Alfred

2016-12-01

Human papillomavirus (HPV) vaccine 3-dose completion rates among adolescent females in the US are low. Missed opportunities impede HPV vaccination coverage. A population-based secondary data analysis of de-identified vaccination and demographic data from the Utah Statewide Immunization Information System (USIIS) was conducted. Records were included from 25,866 females ages 11-26 years at any time during 2008-2012 who received at least one of the following adolescent vaccinations documented in the USIIS: Tdap (Tetanus, Diphtheria, Pertussis), meningococcal, and/or influenza. A missed opportunity for HPV vaccination was defined as a clinical encounter where the patient received at least one adolescent vaccination, but not a HPV vaccine. Of 47,665 eligible visits, there were 20,911 missed opportunities (43.87%). Age group, race/ethnicity, and rurality were significantly associated with missed opportunity (p<0.0001). In a multivariable mixed-effects logistic regression model that included ethnicity, location and age, as fixed effects and subject as a random effect, Hispanics were less likely to have a missed opportunity than whites OR 0.59 (95% CI: 0.52-0.66), small rural more likely to have a missed opportunity than urban youth OR 1.8 (95% CI: 1.5-2.2), and preteens more likely than teens OR 2.4 (95% CI: 2.2-2.7). Missed clinical opportunities are a significant barrier to HPV vaccination among female adolescents. Interventions targeted at providers who serve patient groups with the highest missed opportunities are needed to achieve adequate protection from HPV-associated illnesses. This is one of the first studies to utilize state immunization information system data to assess missed opportunities for HPV vaccination.

Prevalence of anal high-risk human papillomavirus infections among HIV-positive and HIV-negative men who have sex with men (MSM) in Nigeria

PubMed Central

Nowak, Rebecca G.; Gravitt, Patti E.; He, Xin; Ketende, Sosthenes; Anom, Wuese; Omuh, Helen; Blattner, William A.; Charurat, Manhattan E.

2016-01-01

Background Prevalence estimates of anal high-risk human papillomavirus (HR-HPV) are needed in sub-Saharan Africa where HIV is endemic. This study evaluated anal HR-HPV in Nigeria among HIV-positive and HIV-negative men who have sex with men (MSM) for future immunization recommendations. Methods We conducted a cross-sectional study to compare the prevalence of anal HR-HPV infections between 64 HIV-negative and 90 HIV-positive MSM. Multivariate Poisson regression analyses were used to examine demographic and behavioral risk factors associated with any HR-HPV infections. Results The median age of the 154 participants was 25 years (interquartile range [IQR]: 22-28, range: 16-38) and the median age at initiation of anal sex with another man was 16 years (IQR: 13-18, range: 7-29). The prevalence of anal HR-HPV was higher among HIV-positive than HIV-negative MSM (91.1% vs. 40.6%, p<0.001). In the multivariate analysis, HIV infection (adjusted prevalence ratio [aPR]: 2.02, 95% CI: 1.49-2.72), ten years or more since anal sexual debut (aPR: 1.26, 95% CI: 1.07-1.49), and concurrent relationships with men (aPR: 1.32, 95% CI: 1.04-1.67) were associated with increased anal HR-HPV prevalence. Conclusions Anal HR-HPV infection is high for young Nigerian MSM and rates are amplified in those co-infected with HIV. Providing universal coverage as well as catchup immunization for young MSM may be an effective anal cancer prevention strategy in Nigeria. PMID:26967301

Factors associated with parental reasons for "no-intent" to vaccinate female adolescents with human papillomavirus vaccine: National Immunization Survey - Teen 2008-2012.

PubMed

Cheruvu, Vinay K; Bhatta, Madhav P; Drinkard, Lauren N

2017-02-13

1) To identify socio-demographic factors associated with parental "no-intent" for their 13-17 year old unvaccinated daughter to receive the human papillomavirus (HPV) vaccine series within the next twelve months, 2) to describe patterns in "no-intent" by socio-demographic factors, and 3) to identify socio-demographic factors associated with parental reasons for "no-intent". Data from 2008-2012 National Immunization Survey - Teen (NIS - Teen) were examined in this study. Parents with "no-intent" to vaccinate their daughters were asked to identify reasons for their decision. All responses were categorized into five domains identified as barriers to receive the HPV vaccine series: 1) Safety and Effectiveness Concerns; 2) Systemic Barriers; 3) Vaccine Misinformation; 4) Lack of Knowledge about the Vaccine; and 5) Socio-cultural Barriers. Multivariable logistic regression models were performed to address the study objectives. Number of people in the household, household income, mother's age, education, health insurance, recommendation of a health care provider, and the survey year were significantly associated with parental "no-intent". Race/ethnicity, mother's education, marital status, recommendation of a health care provider, household income, age of the unvaccinated daughter, and the survey year, were significantly associated with one or more domains identified as barriers to receive the HPV vaccine. This study identified sub-groups of parents across different socio-demographic factors with "no-intent" for their adolescent daughters to receive the HPV vaccine. Developing strategies that target educational tools towards the identified sub-groups of parents about the purpose, safety, and efficacy of the HPV vaccine, and HPV infection, may help increase HPV vaccine acceptance, initiation and completion rates.

RECENT ADVANCES IN STRATEGIES FOR IMMUNOTHERAPY OF HUMAN PAPILLOMAVIRUS-INDUCED LESIONS

PubMed Central

Kanodia, Shreya; Da Silva, Diane M.; Kast, W. Martin

2016-01-01

Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for “proof of concept” studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. PMID:17973257

Feasibility of a Catch-Up HPV Vaccination Program among College Students Attending a Large Rural University in the South

ERIC Educational Resources Information Center

Richman, Alice R.; Haithcox-Dennis, Melissa J.; Allsbrook, Ashley R.

2012-01-01

Our study explored the eligibility and willingness of students to participate in a university-wide catch-up Human papillomavirus (HPV) vaccination program. A total of 1804 electronic surveys (82% response) assessing demographics, HPV knowledge, eligibility, and willingness were gathered. HPV knowledge was moderate, with just over a quarter (26%)…

A Population-Based Evaluation of a Publicly Funded, School-Based HPV Vaccine Program in British Columbia, Canada: Parental Factors Associated with HPV Vaccine Receipt

PubMed Central

Ogilvie, Gina; Anderson, Maureen; Marra, Fawziah; McNeil, Shelly; Pielak, Karen; Dawar, Meena; McIvor, Marilyn; Ehlen, Thomas; Dobson, Simon; Money, Deborah; Patrick, David M.; Naus, Monika

2010-01-01

Background Information on factors that influence parental decisions for actual human papillomavirus (HPV) vaccine receipt in publicly funded, school-based HPV vaccine programs for girls is limited. We report on the level of uptake of the first dose of the HPV vaccine, and determine parental factors associated with receipt of the HPV vaccine, in a publicly funded school-based HPV vaccine program in British Columbia, Canada. Methods and Findings All parents of girls enrolled in grade 6 during the academic year of September 2008–June 2009 in the province of British Columbia were eligible to participate. Eligible households identified through the provincial public health information system were randomly selected and those who consented completed a validated survey exploring factors associated with HPV vaccine uptake. Bivariate and multivariate analyses were conducted to calculate adjusted odds ratios to identify the factors that were associated with parents' decision to vaccinate their daughter(s) against HPV. 2,025 parents agreed to complete the survey, and 65.1% (95% confidence interval [CI] 63.1–67.1) of parents in the survey reported that their daughters received the first dose of the HPV vaccine. In the same school-based vaccine program, 88.4% (95% CI 87.1–89.7) consented to the hepatitis B vaccine, and 86.5% (95% CI 85.1–87.9) consented to the meningococcal C vaccine. The main reasons for having a daughter receive the HPV vaccine were the effectiveness of the vaccine (47.9%), advice from a physician (8.7%), and concerns about daughter's health (8.4%). The main reasons for not having a daughter receive the HPV vaccine were concerns about HPV vaccine safety (29.2%), preference to wait until the daughter is older (15.6%), and not enough information to make an informed decision (12.6%). In multivariate analysis, overall attitudes to vaccines, the impact of the HPV vaccine on sexual practices, and childhood vaccine history were predictive of parents having a daughter receive the HPV vaccine in a publicly funded school-based HPV vaccine program. By contrast, having a family with two parents, having three or more children, and having more education was associated with a decreased likelihood of having a daughter receive the HPV vaccine. Conclusions This study is, to our knowledge, one of the first population-based assessments of factors associated with HPV vaccine uptake in a publicly funded school-based program worldwide. Policy makers need to consider that even with the removal of financial and health care barriers, parents, who are key decision makers in the uptake of this vaccine, are still hesitant to have their daughters receive the HPV vaccine, and strategies to ensure optimal HPV vaccine uptake need to be employed. Please see later in the article for the Editors' Summary PMID:20454567

Suppression of Innate Immune Response by Primary Human Keratinocytes Expressing HPV-16 E6 and E7

DTIC Science & Technology

2005-01-01

respectively. High-risk HPVs have been correlated with at least 90% of cervical cancers and more than 50% of other anogenital cancers (113). 10 An in vitro...substantiated by the lack of p53 mutations discovered in HPV -related cancers . Through the binding and degradation of p53, E6 can drive cells with chromosomal...of class I molecules and accessory proteins, such as TAP-1, are down-regulated in HPV infections and cervical cancers [reviewed in (71, 108

HPV vaccine for teen boys: Dyadic analysis of parents' and sons' beliefs and willingness

PubMed Central

Moss, Jennifer L.; Reiter, Paul L.; Brewer, Noel T.

2015-01-01

Objective Parents and adolescents often decide together whether the child should receive human papillomavirus (HPV) vaccine. However, few studies have investigated the dyadic nature of beliefs that affect this process. Method Data came from the 2010 HPV Immunization in Sons (HIS) Study, a national sample of 412 parents and their adolescent sons. We conducted dyadic multivariate logistic regression to test the relationships between parents' and sons' HPV vaccine beliefs and their willingness to have the son receive the vaccine. Results Fewer than half of parents and sons were willing to have the sons receive HPV vaccine (43% and 29%, respectively). Willing parents and sons anticipated greater regret if the son did not receive HPV vaccine but later contracted an HPV infection (parent odds ratio [OR]=1.72, 95% confidence interval [CI]=1.24-2.40; son OR=1.51, 95% CI=1.04-2.19) (both p<.05). Lower concerns about side effects, such as pain and fainting, were also associated with willingness. Conclusion Parents and sons were more willing to have the son receive HPV vaccine if they had higher anticipated regret about potential HPV infection and lower concerns about side effects. Communication campaigns should target these beliefs to increase parents' and sons' willingness to seek HPV vaccination. PMID:26190364

HPV vaccine for teen boys: Dyadic analysis of parents' and sons' beliefs and willingness.

PubMed

Moss, Jennifer L; Reiter, Paul L; Brewer, Noel T

2015-09-01

Parents and adolescents often decide together whether the child should receive human papillomavirus (HPV) vaccine. However, few studies have investigated the dyadic nature of beliefs that affect this process. Data came from the 2010 HPV Immunization in Sons (HIS) Study, a national sample of 412 parents and their adolescent sons. We conducted dyadic multivariate logistic regression to examine the relationships between parents' and sons' HPV vaccine beliefs and their willingness to have the son receive the vaccine. Less than half of parents and sons were willing to have the sons receive HPV vaccine (43% and 29%, respectively). Willing parents and sons anticipated greater regret if the son did not receive HPV vaccine but later contracted an HPV infection (parent odds ratio [OR]=1.72, 95% confidence interval [CI]=1.24-2.40; son OR=1.51, 95% CI=1.04-2.19) (both p<.05). Lower concerns about side effects, such as pain and fainting, were also associated with willingness. Parents and sons were more willing to have the son receive HPV vaccine if they had higher anticipated regret about potential HPV infection and lower concerns about side effects. Communication campaigns may be able to target these beliefs to increase parents' and sons' willingness to seek HPV vaccination. Copyright © 2015 Elsevier Inc. All rights reserved.

Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota

PubMed Central

Shannon, B; Yi, TJ; Perusini, S; Gajer, P; Ma, B; Humphrys, MS; Thomas-Pavanel, J; Chieza, L; Janakiram, P; Saunders, M; Tharao, W; Huibner, S; Shahabi, K; Ravel, J; Rebbapragada, A; Kaul, R

2016-01-01

Cervical human papillomavirus (HPV) infection may increase HIV risk. Since other genital infections enhance HIV susceptibility by inducing inflammation, we assessed the impact of HPV infection and clearance on genital immunology and the cervico-vaginal microbiome. Genital samples were collected from 65 women for HPV testing, immune studies and microbiota assessment; repeat HPV testing was performed after 6 months. All participants were HIV-uninfected and free of bacterial STIs. Cytobrush-derived T cell and dendritic cell subsets were assessed by multiparameter flow cytometry. Undiluted cervico-vaginal secretions were used to determine cytokine levels by multiplex ELISA, and to assess bacterial community composition and structure by 16S rRNA gene sequence analysis. Neither HPV infection nor clearance were associated with broad differences in cervical T cell subsets or cytokines, although HPV clearance was associated with increased Langerhans cells and HPV infection with elevated IP-10 and MIG. Individuals with HPV more frequently had a high diversity cervico-vaginal microbiome (community state type IV) and were less likely to have an L. gasseri predominant microbiome. In summary, HPV infection and/or subsequent clearance was not associated with inflammation or altered cervical T cell subsets, but associations with increased Langerhans cells and the composition of the vaginal microbiome warrant further exploration. PMID:28120845

[Knowledge of HPV-related genital lesions and of anti-HPV vaccination in a sample of women of north-eastern Italy].

PubMed

Sopracordevole, F; Cigolot, F; Lucia, E; Marchesoni, D

2009-04-01

Knowledge of human papilloma virus (HPV) infection and related genital lesions and vaccine is related to the success of the vaccination program. Authors have assessed knowledge, attitudes and beliefs on HPV and vaccination in a sample of women, in order to optimize any educational interventions. This study enrolled 212 consecutive women with no history of HPV-related genital lesions by means of an anonymous questionnaire. The questionnaire included 21 questions (19 with a multiple choice and 2 with open answers) to check awareness of HPV infection and related lesions, HPV transmission, vaccine and vaccination program expectations, sexual/precautionary behaviours after vaccination and the need felt for more information. Forty-two percent of women in the study population know about HPV-related genital lesions, and 43% are aware of the right way of transmission; 75% have learned about the vaccine. In this last group 28% know that the vaccine efficiency is mainly limited to the HPV types included in the vaccine, 19.8% know that one of the vaccines can also prevent genital condylomata and 88% have heard about this vaccination program. There is still a lack of information or access to information about HPV and more needs to be done to raise awareness of HPV vaccination. A percentage of 74.4 of women wish to receive more information and thinks that schools and family planning clinics should play a central role in teenagers' health education. There is a need to further train healthcare workers involved in the vaccination program in order to optimize their counselling to teenagers and parents.

A Cross-Sectional Study to Assess HPV Knowledge and HPV Vaccine Acceptability in Mali

PubMed Central

Poole, Danielle N.; Tracy, J. Kathleen; Levitz, Lauren; Rochas, Mali; Sangare, Kotou; Yekta, Shahla; Tounkara, Karamoko; Aboubacar, Ben; Koita, Ousmane; Lurie, Mark; De Groot, Anne S.

2013-01-01

Despite a high prevalence of oncogenic human papilloma virus (HPV) infection and cervical cancer mortality, HPV vaccination is not currently available in Mali. Knowledge of HPV and cervical cancer in Mali, and thereby vaccine readiness, may be limited. Research staff visited homes in a radial pattern from a central location to recruit adolescent females and males aged 12–17 years and men and women aged ≥18 years (N = 51) in a peri-urban village of Bamako, Mali. Participants took part in structured interviews assessing knowledge, attitudes, and practices related to HPV, cervical cancer, and HPV vaccination. We found low levels of HPV and cervical cancer knowledge. While only 2.0% of respondents knew that HPV is a sexually transmitted infection (STI), 100% said they would be willing to receive HPV vaccination and would like the HPV vaccine to be available in Mali. Moreover, 74.5% said they would vaccinate their child(ren) against HPV. Men were found to have significantly greater autonomy in the decision to vaccinate themselves than women and adolescents (p = 0.005), a potential barrier to be addressed by immunization campaigns. HPV vaccination would be highly acceptable if the vaccine became widely available in Bamako, Mali. This study demonstrates the need for a significant investment in health education if truly informed consent is to be obtained for HPV vaccination. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine. Barriers to vaccination, including the significantly lower ability of the majority of the target population to autonomously decide to get vaccinated, must also be addressed in future HPV vaccine campaigns. PMID:23431375

A cross-sectional study to assess HPV knowledge and HPV vaccine acceptability in Mali.

PubMed

Poole, Danielle N; Tracy, J Kathleen; Levitz, Lauren; Rochas, Mali; Sangare, Kotou; Yekta, Shahla; Tounkara, Karamoko; Aboubacar, Ben; Koita, Ousmane; Lurie, Mark; De Groot, Anne S

2013-01-01

Despite a high prevalence of oncogenic human papilloma virus (HPV) infection and cervical cancer mortality, HPV vaccination is not currently available in Mali. Knowledge of HPV and cervical cancer in Mali, and thereby vaccine readiness, may be limited. Research staff visited homes in a radial pattern from a central location to recruit adolescent females and males aged 12-17 years and men and women aged ≥ 18 years (N = 51) in a peri-urban village of Bamako, Mali. Participants took part in structured interviews assessing knowledge, attitudes, and practices related to HPV, cervical cancer, and HPV vaccination. We found low levels of HPV and cervical cancer knowledge. While only 2.0% of respondents knew that HPV is a sexually transmitted infection (STI), 100% said they would be willing to receive HPV vaccination and would like the HPV vaccine to be available in Mali. Moreover, 74.5% said they would vaccinate their child(ren) against HPV. Men were found to have significantly greater autonomy in the decision to vaccinate themselves than women and adolescents (p = 0.005), a potential barrier to be addressed by immunization campaigns. HPV vaccination would be highly acceptable if the vaccine became widely available in Bamako, Mali. This study demonstrates the need for a significant investment in health education if truly informed consent is to be obtained for HPV vaccination. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine. Barriers to vaccination, including the significantly lower ability of the majority of the target population to autonomously decide to get vaccinated, must also be addressed in future HPV vaccine campaigns.

Female students receiving post-secondary education in Greece: the results of a collaborative human papillomavirus knowledge survey.

PubMed

Michail, G; Smaili, M; Vozikis, A; Jelastopulu, E; Adonakis, G; Poulas, K

2014-12-01

Contrary to the optimistic forecasts, existing until 2008 and despite the incorporation of the vaccine into the Greek National Immunization Program, six years later, the percentage of HPV vaccination coverage in Greece remains disappointingly low. The aim of this extended study was to investigate the knowledge, behaviour and attitude of a representative sample of the initial target group; young female students of Greek higher education institutions to Pap cervical screening, biology of HPV infection and principles of HPV vaccination. Cross-sectional study. One thousand two hundred ten (1210) questionnaires were completed by young female students aged 17-24 years. The survey questionnaire sought data relating to sociodemographic characteristics, health behaviour and knowledge about HPV, as well as vaccination status. 79.6% of the sample reported at least one annual gynaecologic examination and 92.6% were familiar with the rationale of cervical screening; however only 52.9% had undergone a Pap smear. 69.7% reported adequate knowledge about HPV and 89.3% were aware of the possible course of HPV infection. Despite most (95.9%) were aware of vaccine availability, vaccinated students represented only 33.1%. According to the multivariate analysis, vaccination status was associated with university studies (OR 1.96; 95% CI: 1.19-3.20), parental area of expertise (OR 2.77; 95% CI: 1.18-6.53, OR 2.03; 95% CI: 1.05-3.94), and adequate knowledge of the reasons for which women should undergo regular cervical screening (OR 4.23; 85% CI: 1.55-11.55). Fear of side-effects and equivocal information were the main reasons of non-vaccination (52.2% and 33.1% respectively). Finally, the majority of unvaccinated individuals showed a positive attitude towards prospective HPV vaccination, providing they received well-documented advising. Young women attending Greek higher education exhibit a good level of knowledge about HPV and its correlation with cervical cancer. These data highlight the need for further sensitization of the general population. Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Early direct and indirect impact of quadrivalent HPV (4HPV) vaccine on genital warts: a systematic review.

PubMed

Mariani, Luciano; Vici, Patrizia; Suligoi, Barbara; Checcucci-Lisi, Giovanni; Drury, Rosybel

2015-01-01

Since 2007, many countries have implemented national human papillomavirus (HPV) vaccination programs with the quadrivalent HPV (4HPV) vaccine that has been shown to be efficacious in clinical trials involving 25,000 subjects. Two vaccine serotypes, HPV16 and 18, are responsible for cervical cancer and other HPV-related cancers, but the impact of the 4HPV vaccine on these cancers cannot be seen immediately as there is a considerable lag between infection with HPV and cancer development. The other two serotypes, HPV6 and 11, are responsible for genital warts (GWs), which develop within a few months after infection, making GWs an early clinical endpoint for the assessment of the impact of 4HPV vaccination. We performed a systematic literature search in PubMed to identify all published studies on 4HPV vaccination, including those that assessed the impact of 4HPV vaccination programs on the incidence of GWs at a population level around the world. A total of 354 records were identified in the PubMed search. After screening and obtaining full papers for 56 publications, 16 publications presenting data on the impact or effectiveness of 4HPV vaccination on GWs were identified. These reported data on the impact or effectiveness of 4HPV in six countries [Australia (n = 6), New Zealand (n = 2), United States (n = 3), Denmark (n = 2), Germany (n = 1), and Sweden (n = 2)]. In Australia, no GWs were diagnosed in women aged <21 years who reported being vaccinated. A 92.6% reduction in GWs incidence was reported for all women in this age group, where the vaccine uptake rate (VUR) was 70% for 3 doses. The highest reductions were reported in countries with high VURs, mostly through school-based vaccination programs, although high VURs were obtained with some non-school-based programs. The results are coherent with the GWs incidence reduction reported in clinical trials and are an early indicator of what can be expected for the long-term clinical impact on vaccine-type HPV-related cancers.

Multiple Human Papilloma Virus Infections and Their Impact on the Development of High-Risk Cervical Lesions.

PubMed

Salazar, Katrina L; Zhou, Haijun Steve; Xu, Jiaqiong; Peterson, Leif E; Schwartz, Mary R; Mody, Dina R; Ge, Yimin

2015-01-01

Individuals are often infected with multiple genotypes of human papillomavirus (HPV) simultaneously, but the role these infections play in the development of cervical disease is not well established. This study aimed to determine the association of multiple HPV infections with high-risk cervical lesions (hrCLs). HPV genotyping was performed on 798 SurePath specimens collected between December 1, 2009, and April 30, 2011. The cases were classified as hrCL (n = 90) or non-hrCL (n = 708) based on cytology diagnoses. The association between hrCL and HPV infection patterns was analyzed. Multiple HPV infections were frequently encountered (38.2%) in the cohort. Increased frequency of hrCLs was associated with a single high-risk HPV (hrHPV) infection. An additive or synergistic effect was not observed for hrCL in multiple HPV infections. The hrCL rates appeared to decrease in various patterns of multiple HPV infections, but the reduction was not statistically significant. Multiple HPV infections are common with no additive or synergistic effect on the development of hrCL. Conversely, reduced hrCL rates were observed in various patterns of multiple HPV infections compared to their single-genotype infection counterparts, suggestive of possible intergenotypic competition or more effective immune response triggered by multiple infections. Further studies in larger cohorts are needed. © 2015 S. Karger AG, Basel.

Engineered outer membrane vesicle is potent to elicit HPV16E7-specific cellular immunity in a mouse model of TC-1 graft tumor.

PubMed

Wang, Shijie; Huang, Weiwei; Li, Kui; Yao, Yufeng; Yang, Xu; Bai, Hongmei; Sun, Wenjia; Liu, Cunbao; Ma, Yanbing

2017-01-01

Currently, therapeutic tumor vaccines under development generally lack significant effects in human clinical trials. Exploring a powerful antigen delivery system is a potential approach to improve vaccine efficacy. We sought to explore engineered bacterial outer membrane vesicles (OMVs) as a new vaccine carrier for efficiently delivering tumor antigens and provoking robust antitumor immune responses. First, the tumoral antigen human papillomavirus type 16 early protein E7 (HPV16E7) was presented on Escherichia coli -derived OMVs by genetic engineering methods, acquiring the recombinant OMV vaccine. Second, the ability of recombinant OMVs delivering their components and the model antigen green fluorescent protein to antigen-presenting cells was investigated in the macrophage Raw264.7 cells and in bone marrow-derived dendritic cells in vitro. Third, it was evaluated in TC-1 graft tumor model in mice that the recombinant OMVs displaying HPV16E7 stimulated specific cellular immune response and intervened the growth of established tumor. E. coli DH5α-derived OMVs could be taken up rapidly by dendritic cells, for which vesicle structure has been proven to be important. OMVs significantly stimulated the expression of dendritic cellmaturation markers CD80, CD86, CD83 and CD40. The HPV16E7 was successfully embedded in engineered OMVs through gene recombinant techniques. Subcutaneous immunization with the engineered OMVs induced E7 antigen-specific cellular immune responses, as shown by the increased numbers of interferon-gamma-expressing splenocytes by enzyme-linked immunospot assay and interferon-gamma-expressing CD4 + and CD8 + cells by flow cytometry analyses. Furthermore, the growth of grafted TC-1 tumors in mice was significantly suppressed by therapeutic vaccination. The recombinant E7 proteins presented by OMVs were more potent than those mixed with wild-type OMVs or administered alone for inducing specific cellular immunity and suppressing tumor growth. The results indicated that the nano-grade OMVs might be a useful vaccine platform for antigen delivery in cancer immunotherapy.

Therapeutic Vaccination for HPV Induced Cervical Cancers

PubMed Central

Brinkman, Joeli A.; Hughes, Sarah H.; Stone, Pamela; Caffrey, Angela S.; Muderspach, Laila I.; Roman, Lynda D.; Weber, Jeffrey S.; Kast, W. Martin

2007-01-01

Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV) infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence. PMID:17627067

Impact of school-entry and education mandates by states on HPV vaccination coverage: Analysis of the 2009-2013 National Immunization Survey-Teen.

PubMed

Perkins, Rebecca B; Lin, Mengyun; Wallington, Sherrie F; Hanchate, Amresh D

2016-06-02

To determine the effectiveness of existing school entry and education mandates on HPV vaccination coverage, we compared coverage among girls residing in states and jurisdictions with and without education and school-entry mandates. Virginia and the District of Columbia enacted school entry mandates, though both laws included liberal opt-out provisions. Ten additional states had mandates requiring distribution of education to parents or provision of education within school curricula. Using data from the National Immunization Survey-Teen from 2009-2013, we estimated multilevel logistic regression models to compare coverage with HPV vaccines for girls ages 13-17 residing in states and jurisdictions with and without school entry and education mandates, adjusting for demographic factors, healthcare access, and provider recommendation. Girls residing in states and jurisdictions with HPV vaccine school entry mandates (DC and VA) and education mandates (LA, MI, CO, IN, IA, IL, NJ, NC, TX, and WA) did not have higher HPV vaccine series initiation or completion than those living in states without mandates for any year (2009-2013). Similar results were seen when comparing girls ages 13-14 to those ages 15-17, and after adjustment for known covariates of vaccination. States and jurisdictions with school-entry and education mandates do not currently have higher HPV vaccination coverage than states without such legislation. Liberal opt-out language in existing school entry mandates may weaken their impact. Policy-makers contemplating legislation to improve vaccination coverage should be aware of the limitations of existing mandates.

The Cervicovaginal Microbiota and Its Associations With Human Papillomavirus Detection in HIV-Infected and HIV-Uninfected Women

PubMed Central

Reimers, Laura L.; Mehta, Supriya D.; Massad, L. Stewart; Burk, Robert D.; Xie, Xianhong; Ravel, Jacques; Cohen, Mardge H.; Palefsky, Joel M.; Weber, Kathleen M.; Xue, Xiaonan; Anastos, Kathryn; Minkoff, Howard; Atrio, Jessica; D'Souza, Gypsyamber; Ye, Qian; Colie, Christine; Zolnik, Christine P.; Spear, Gregory T.; Strickler, Howard D.

2016-01-01

Background. Bacterial vaginosis (BV) is characterized by low abundance of Lactobacillus species, high pH, and immune cell infiltration and has been associated with an increased risk of human papillomavirus (HPV) infection. We molecularly assessed the cervicovaginal microbiota over time in human immunodeficiency virus (HIV)–infected and HIV-uninfected women to more comprehensively study the HPV-microbiota relationship, controlling for immune status. Methods. 16S ribosomal RNA gene amplicon pyrosequencing and HPV DNA testing were conducted annually in serial cervicovaginal lavage specimens obtained over 8–10 years from African American women from Chicago, of whom 22 were HIV uninfected, 22 were HIV infected with a stable CD4+ T-cell count of > 500 cells/mm3, and 20 were HIV infected with progressive immunosuppression. Vaginal pH was serially measured. Results. The relative abundances of Lactobacillus crispatus and other Lactobacillus species were inversely associated with vaginal pH (all P < .001). High (vs low) L. crispatus relative abundance was associated with decreased HPV detection (odds ratio, 0.48; 95% confidence interval, .24–.96; Ptrend = .03) after adjustment for repeated observation and multiple covariates, including pH and study group. However, there were no associations between HPV and the relative abundance of Lactobacillus species as a group, nor with Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii individually. Conclusions. L. crispatus may have a beneficial effect on the burden of HPV in both HIV-infected and HIV-uninfected women (independent of pH). PMID:27521363

Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-world Experience

PubMed Central

Garland, Suzanne M.; Kjaer, Susanne K.; Muñoz, Nubia; Block, Stan L.; Brown, Darron R.; DiNubile, Mark J.; Lindsay, Brianna R.; Kuter, Barbara J.; Perez, Gonzalo; Dominiak-Felden, Geraldine; Saah, Alfred J.; Drury, Rosybel; Das, Rituparna; Velicer, Christine

2016-01-01

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. PMID:27230391

[HPV Vaccination Program - The History and Recent Progress].

PubMed

Yoshikawa, Hiroyuki

2017-09-01

Four years have passed since HPV vaccination "crisis" occurred in June 2013. In Japan,a publicly funded HPV vaccination program for adolescent females aged 12-16 years began in December 2010. However,the Japanese government withdrew its recommendation for HPV vaccination in June, 2013 because news reports on potential adverse effects of HPV vaccines without any medical evidence appeared repeatedly. The vaccination coverage among adolescent females decreased quickly from around 70%in females born between 1994 and 1999 to only 1%in females born since 2001 over the country. The suspension of recommendation for vaccination has continued to the present,though there is no scientific or epidemiologic evidence to demonstrate the causal linkage between post-vaccination symptoms and the HPV vaccines. Very recently,an ecological investigation reported that similar symptoms also occur in unvaccinated adolescents in Japan. Medical organizations in Japan are also calling for a resumption of the HPV vaccination program. Now,the resumption of the recommendation needs a political judgment.

Area-based socioeconomic factors and Human Papillomavirus (HPV) vaccination among teen boys in the United States.

PubMed

Henry, Kevin A; Swiecki-Sikora, Allison L; Stroup, Antoinette M; Warner, Echo L; Kepka, Deanna

2017-07-14

This study is the first to examine associations between several area-based socioeconomic factors and human papillomavirus (HPV) vaccine uptake among boys in the United States (U.S.). Data from the 2012-2013 National Immunization Survey-Teen restricted-use data were analyzed to examine associations of HPV vaccination initiation (receipt of ≥1 dose) and series completion (receipt of three doses) among boys aged 13-17 years (N = 19,518) with several individual-level and ZIP Code Tabulation Area (ZCTA) census measures. Multivariable logistic regression was used to estimate the odds of HPV vaccination initiation and series completion separately. In 2012-2013 approximately 27.9% (95% CI 26.6%-29.2%) of boys initiated and 10.38% (95% CI 9.48%-11.29%) completed the HPV vaccine series. Area-based poverty was not statistically significantly associated with HPV vaccination initiation. It was, however, associated with series completion, with boys living in high-poverty areas (≥20% of residents living below poverty) having higher odds of completing the series (AOR 1.22, 95% CI 1.01-1.48) than boys in low-poverty areas (0-4.99%). Interactions between race/ethnicity and ZIP code-level poverty indicated that Hispanic boys living in high-poverty areas had a statistically significantly higher odds of  HPV vaccine initiation (AOR 1.43, 95% CI 1.03-1.97) and series completion (AOR 1.56, 95% CI 1.05-2.32)  than Hispanic boys in  low-poverty areas. Non-Hispanic Black boys in high poverty areas had higher odds of initiation (AOR 2.23, 95% CI 1.33-3.75) and completion (AOR 2.61, 95% CI 1.06-6.44) than non-Hispanic Black boys in low-poverty areas. Rural/urban residence and population density were also significant factors, with boys from urban or densely populated areas having higher odds of initiation and completion compared to boys living in non-urban, less densely populated areas. Higher HPV vaccination coverage in urban areas and among racial/ethnic minorities in areas with high poverty may be attributable to factors such as vaccine acceptance, health-care practices, and their access to HPV vaccines through the Vaccines for Children Program, which provides free vaccines to uninsured and under-insured children. Given the low HPV vaccination rates among boys in the U.S., these results provide important evidence to inform public health interventions to increase HPV vaccination.

[Human papillomavirus vaccines].

PubMed

Brun, J-L

2008-02-01

To assess the efficacy, the tolerance, the duration of protection and the limitations of papillomavirus vaccines and to determine the potential indications for prophylactic vaccination. Medline, Biosis and Pascal contents were searched to July 2007. Of 546 abstracts, 30 studies were selected. Prophylactic vaccines are composed of L1 virus-like particles. They are well-tolerated and effective in preventing HPV 16/18 infections and related cervical diseases in young women who are naive to HPV 16/18 after five years of follow-up. In addition, the quadrivalent vaccine prevents HPV 6/11 infections and their consequences. The bivalent vaccine may also prevent HPV 31/45 infections by cross-protection. Young girls before sexual debut are the main target for prophylactic vaccines. Indeed, they demonstrate an excellent immune response after injection and the prevalence of HPV infection increases dramatically after the first sexual intercourse. However, vaccines are ineffective in healthy HPV 16/18 carriers or on existing lesions. Prophylactic vaccines are not effective in women infected by other oncogenic HPV. Therapeutic vaccine effects against cervical dysplasia are currently being assessed. Prophylactic vaccination against HPV is effective, well-tolerated, and should be associated with screening to optimize the prevention of cervical cancer.

Chronic Inflammation-Related HPV: A Driving Force Speeds Oropharyngeal Carcinogenesis

PubMed Central

Liu, Xin; Ma, Xiangrui; Lei, Zhengge; Feng, Hao; Wang, Shasha; Cen, Xiao; Gao, Shiyu; Jiang, Yaping; Jiang, Jian; Chen, Qianming; Tang, Yajie; Tang, Yaling; Liang, Xinhua

2015-01-01

Oropharyngeal squamous cell carcinoma (OPSCC) has been known to be a highly aggressive disease associated with human papilloma virus (HPV) infection. To investigate the relationship between HPV and chronic inflammation in oropharyngeal carcinogenesis, we collected 140 oral mucous fresh specimens including 50 OPSCC patients, 50 cancer in situ, 30 precancerous lesions, and 10 normal oral mucous. Our data demonstrated that there was a significantly higher proportion of severe chronic inflammation in dysplastic epithelia in comparison with that in normal tissues (P<0.001). The positive rate of HPV 16 was parallel with the chronic inflammation degrees from mild to severe inflammation (P<0.05). The positive rate of HPV 16 was progressively improved with the malignant progression of oral mucous (P<0.05). In addition, CD11b+ LIN- HLA-DR-CD33+ MDSCs were a critical cell population that mediates inflammation response and immune suppression in HPV-positive OPSCC. These indicated that persistent chronic inflammation-related HPV infection might drive oropharyngeal carcinogenesis and MDSCs might pay an important role during this process. Thus, a combination of HPV infection and inflammation expression might become a helpful biomedical marker to predict oropharyngeal carcinogenesis. PMID:26193368

Chronic Inflammation-Related HPV: A Driving Force Speeds Oropharyngeal Carcinogenesis.

PubMed

Liu, Xin; Ma, Xiangrui; Lei, Zhengge; Feng, Hao; Wang, Shasha; Cen, Xiao; Gao, Shiyu; Jiang, Yaping; Jiang, Jian; Chen, Qianming; Tang, Yajie; Tang, Yaling; Liang, Xinhua

2015-01-01

Oropharyngeal squamous cell carcinoma (OPSCC) has been known to be a highly aggressive disease associated with human papilloma virus (HPV) infection. To investigate the relationship between HPV and chronic inflammation in oropharyngeal carcinogenesis, we collected 140 oral mucous fresh specimens including 50 OPSCC patients, 50 cancer in situ, 30 precancerous lesions, and 10 normal oral mucous. Our data demonstrated that there was a significantly higher proportion of severe chronic inflammation in dysplastic epithelia in comparison with that in normal tissues (P<0.001). The positive rate of HPV 16 was parallel with the chronic inflammation degrees from mild to severe inflammation (P<0.05). The positive rate of HPV 16 was progressively improved with the malignant progression of oral mucous (P<0.05). In addition, CD11b+ LIN- HLA-DR-CD33+ MDSCs were a critical cell population that mediates inflammation response and immune suppression in HPV-positive OPSCC. These indicated that persistent chronic inflammation-related HPV infection might drive oropharyngeal carcinogenesis and MDSCs might pay an important role during this process. Thus, a combination of HPV infection and inflammation expression might become a helpful biomedical marker to predict oropharyngeal carcinogenesis.

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12-24 in a Phase III randomized study of healthy women aged 18-45 years.

PubMed

Einstein, Mark H; Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Meric, Dorothée; Dessy, Francis J; Datta, Sanjoy K; Descamps, Dominique; Dubin, Gary

2011-12-01

In this observer-blind study (NCT00423046), women (N=1,106), stratified by age (18-26, 27-35, 36-45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck & Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5-100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0-100% (HPV-16/18 vaccine) and 72.3-84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4-5.8-fold higher for HPV-16 and 7.7-9.4-fold higher for HPV-18 with the HPV-16/18 vaccine versus the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p< 0.0001) in the total vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4⁺ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection.

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine

PubMed Central

Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Meric, Dorothée; Dessy, Francis J; Datta, Sanjoy K; Descamps, Dominique; Dubin, Gary

2011-01-01

In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18–26, 27–35, 36–45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck and Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5–100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0–100% (HPV-16/18 vaccine) and 72.3–84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4–5.8-fold higher for HPV-16 and 7.7–9.4-fold higher for HPV-18 with the HPV-16/18 vaccine vs. the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p < 0.0001) in the total vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4+ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection. PMID:22048173

Prevention of HPV-related cancers in Norway: cost-effectiveness of expanding the HPV vaccination program to include pre-adolescent boys.

PubMed

Burger, Emily A; Sy, Stephen; Nygård, Mari; Kristiansen, Ivar S; Kim, Jane J

2014-01-01

Increasingly, countries have introduced female vaccination against human papillomavirus (HPV), causally linked to several cancers and genital warts, but few have recommended vaccination of boys. Declining vaccine prices and strong evidence of vaccine impact on reducing HPV-related conditions in both women and men prompt countries to reevaluate whether HPV vaccination of boys is warranted. A previously-published dynamic model of HPV transmission was empirically calibrated to Norway. Reductions in the incidence of HPV, including both direct and indirect benefits, were applied to a natural history model of cervical cancer, and to incidence-based models for other non-cervical HPV-related diseases. We calculated the health outcomes and costs of the different HPV-related conditions under a gender-neutral vaccination program compared to a female-only program. Vaccine price had a decisive impact on results. For example, assuming 71% coverage, high vaccine efficacy and a reasonable vaccine tender price of $75 per dose, we found vaccinating both girls and boys fell below a commonly cited cost-effectiveness threshold in Norway ($83,000/quality-adjusted life year (QALY) gained) when including vaccine benefit for all HPV-related diseases. However, at the current market price, including boys would not be considered 'good value for money.' For settings with a lower cost-effectiveness threshold ($30,000/QALY), it would not be considered cost-effective to expand the current program to include boys, unless the vaccine price was less than $36/dose. Increasing vaccination coverage to 90% among girls was more effective and less costly than the benefits achieved by vaccinating both genders with 71% coverage. At the anticipated tender price, expanding the HPV vaccination program to boys may be cost-effective and may warrant a change in the current female-only vaccination policy in Norway. However, increasing coverage in girls is uniformly more effective and cost-effective than expanding vaccination coverage to boys and should be considered a priority.

Exploring reasons for non-vaccination against human papillomavirus in Italy.

PubMed

Giambi, Cristina; D'Ancona, Fortunato; Del Manso, Martina; De Mei, Barbara; Giovannelli, Ilaria; Cattaneo, Chiara; Possenti, Valentina; Declich, Silvia

2014-11-11

In Italy, free-of-charge HPV vaccination is offered to 11-year-old girls since 2007. The National Immunization Plan established the target coverage at a minimum of 70%; it should increase to 95% within 3-year time frame. In 2012, four year after the introduction of HPV vaccination, coverage was stable at 69%. We conducted a national cross-sectional study to explore barriers to vaccination in Italy. Vaccination services selected, through the immunization registries, a sample of unvaccinated girls born in 1997 or 1998 and posted to their families a 23-items questionnaire inquiring barriers to vaccination, HPV knowledge, source of information on HPV, perception of risk of contracting HPV, advice from consulted health professionals on HPV vaccination. We analysed 1,738 questionnaires. Main barriers were fear of adverse events (reported by 80% of families), lack of trust in a new vaccine (76%), discordant information received by health professionals (65%) and scarce information on HPV vaccination (54%). Overall, 54% of families replied correctly to more than half of 10 questions exploring knowledge on HPV vaccination. Families with a high knowledge score were more likely to live in Northern and Central Italy, be Italian, have a high educational level, include a mother who attended cervical screening regularly and consult more information sources. Although paediatricians/general practitioners and gynaecologists were considered the most trusted source of information by 79% and 61% of respondents, they were consulted only by 49% and 31%. Among parents who discussed vaccination with a physician, 28% received discordant advices and 31% received the recommendation of accepting vaccination. Fear of adverse events, discordance of information and advices from physicians, and scarce information were the more commonly reported barriers to HPV vaccination. Health professionals played a key role as information providers, thus they must be better trained to provide clear notions. Training needs to include the development of communication skills; transparent discussion about the pros and cons of vaccination may reduce fear of adverse events and increase trust in vaccination. The creation of a public health network around vaccination would allow sharing information and attitudes on vaccinations, so that homogeneous messages could reach the target population.

Depletion of HPV16 early genes induces autophagy and senescence in a cervical carcinogenesis model, regardless of viral physical state.

PubMed

Hanning, Jennifer E; Saini, Harpreet K; Murray, Matthew J; Caffarel, Maria M; van Dongen, Stijn; Ward, Dawn; Barker, Emily M; Scarpini, Cinzia G; Groves, Ian J; Stanley, Margaret A; Enright, Anton J; Pett, Mark R; Coleman, Nicholas

2013-11-01

In cervical carcinomas, high-risk human papillomavirus (HR-HPV) may be integrated into host chromosomes or remain extra-chromosomal (episomal). We used the W12 cervical keratinocyte model to investigate the effects of HPV16 early gene depletion on in vitro cervical carcinogenesis pathways, particularly effects shared by cells with episomal versus integrated HPV16 DNA. Importantly, we were able to study the specific cellular consequences of viral gene depletion by using short interfering RNAs known not to cause phenotypic or transcriptional off-target effects in keratinocytes. We found that while cervical neoplastic progression in vitro was characterized by dynamic changes in HPV16 transcript levels, viral early gene expression was required for cell survival at all stages of carcinogenesis, regardless of viral physical state, levels of early gene expression or histology in organotypic tissue culture. Moreover, HPV16 early gene depletion induced changes in host gene expression that were common to both episome-containing and integrant-containing cells. In particular, we observed up-regulation of autophagy genes, associated with enrichment of senescence and innate immune-response pathways, including the senescence-associated secretory phenotype (SASP). In keeping with these observations, HPV16 early gene depletion induced autophagy in both episome-containing and integrant-containing W12 cells, as evidenced by the appearance of autophagosomes, punctate expression of the autophagy marker LC3, conversion of LC3B-I to LC3B-II, and reduced levels of the autophagy substrate p62. Consistent with the reported association between autophagy and senescence pathways, HPV16 early gene depletion induced expression of the senescence marker beta-galactosidase and increased secretion of the SASP-related protein IGFBP3. Together, these data indicate that depleting HR-HPV early genes would be of potential therapeutic benefit in all cervical carcinogenesis pathways, regardless of viral physical state. In addition, the senescence/SASP response associated with autophagy induction may promote beneficial immune effects in bystander cells. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Mapping the interactome of HPV E6 and E7 oncoproteins with the ubiquitin-proteasome system.

PubMed

Poirson, Juline; Biquand, Elise; Straub, Marie-Laure; Cassonnet, Patricia; Nominé, Yves; Jones, Louis; van der Werf, Sylvie; Travé, Gilles; Zanier, Katia; Jacob, Yves; Demeret, Caroline; Masson, Murielle

2017-10-01

Protein ubiquitination and its reverse reaction, deubiquitination, regulate protein stability, protein binding activity, and their subcellular localization. These reactions are catalyzed by the enzymes E1, E2, and E3 ubiquitin (Ub) ligases and deubiquitinases (DUBs). The Ub-proteasome system (UPS) is targeted by viruses for the sake of their replication and to escape host immune response. To identify novel partners of human papillomavirus 16 (HPV16) E6 and E7 proteins, we assembled and screened a library of 590 cDNAs related to the UPS by using the Gaussia princeps luciferase protein complementation assay. HPV16 E6 was found to bind to the homology to E6AP C terminus-type Ub ligase (E6AP), three really interesting new gene (RING)-type Ub ligases (MGRN1, LNX3, LNX4), and the DUB Ub-specific protease 15 (USP15). Except for E6AP, the binding of UPS factors did not require the LxxLL-binding pocket of HPV16 E6. LNX3 bound preferentially to all high-risk mucosal HPV E6 tested, whereas LNX4 bound specifically to HPV16 E6. HPV16 E7 was found to bind to several broad-complex tramtrack and bric-a-brac domain-containing proteins (such as TNFAIP1/KCTD13) that are potential substrate adaptors of Cullin 3-RING Ub ligases, to RING-type Ub ligases implicated in innate immunity (RNF135, TRIM32, TRAF2, TRAF5), to the substrate adaptor DCAF15 of Cullin 4-RING Ub ligase and to some DUBs (USP29, USP33). The binding to UPS factors did not require the LxCxE motif but rather the C-terminal region of HPV16 E7 protein. The identified UPS factors interacted with most of E7 proteins across different HPV types. This study establishes a strategy for the rapid identification of interactions between host or pathogen proteins and the human ubiquitination system. © 2017 Federation of European Biochemical Societies.

Risk of Human Papillomavirus Infection in Cancer-Prone Individuals: What We Know

PubMed Central

Khoury, Ruby; Sauter, Sharon; Butsch Kovacic, Melinda; Nelson, Adam S.; Myers, Kasiani C.; Mehta, Parinda A.; Davies, Stella M.; Wells, Susanne I.

2018-01-01

Human papillomavirus (HPV) infections cause a significant proportion of cancers worldwide, predominantly squamous cell carcinomas (SCC) of the mucosas and skin. High-risk HPV types are associated with SCCs of the anogenital and oropharyngeal tract. HPV oncogene activities and the biology of SCCs have been intensely studied in laboratory models and humans. What remains largely unknown are host tissue and immune-related factors that determine an individual’s susceptibility to infection and/or carcinogenesis. Such susceptibility factors could serve to identify those at greatest risk and spark individually tailored HPV and SCC prevention efforts. Fanconi anemia (FA) is an inherited DNA repair disorder that is in part characterized by extreme susceptibility to SCCs. An increased prevalence of HPV has been reported in affected individuals, and molecular and functional connections between FA, SCC, and HPV were established in laboratory models. However, the presence of HPV in some human FA tumors is controversial, and the extent of the etiological connections remains to be established. Herein, we discuss cellular, immunological, and phenotypic features of FA, placed into the context of HPV pathogenesis. The goal is to highlight this orphan disease as a unique model system to uncover host genetic and molecular HPV features, as well as SCC susceptibility factors. PMID:29361695

The most important questions in cancer research and clinical oncology : Question 1. Could the vertical transmission of human papilloma virus (HPV) infection account for the cause, characteristics, and epidemiology of HPV-positive oropharyngeal carcinoma, non-smoking East Asian female lung adenocarcinoma, and/or East Asian triple-negative breast carcinoma?

PubMed

Wee, Joseph T S; Poh, Sharon Shuxian

2017-01-16

Specific research foci: (1) Mouse models of gamma-herpes virus-68 (γHV-68) and polyomavirus (PyV) infections during neonatal versus adult life. (2) For human papilloma virus (HPV)-positive oropharyngeal carcinoma (OPC)-(a) Asking the question: Is oral sex a powerful carcinogen? (b) Examining the evidence for the vertical transmission of HPV infection. (c) Examining the relationship between HPV and Epstein-Barr virus (EBV) infections and nasopharyngeal cancer (NPC) in West European, East European, and East Asian countries. (d) Examining the association between HPV-positive OPC and human leukocyte antigen (HLA). (3) For non-smoking East Asian female lung adenocarcinoma-(a) Examining the incidence trends of HPV-positive OPC and female lung adenocarcinoma according to birth cohorts. (b) Examining the association between female lung adenocarcinoma and HPV. (c) Examining the associations of lung adenocarcinoma with immune modulating factors. (4) For triple-negative breast carcinoma (TNBC) in East Asians-(a) Examining the association between TNBC and HPV. (b) Examining the unique epidemiological characteristics of patients with TNBC. A summary "epidemiological" model tying some of these findings together.

Are state laws granting pharmacists authority to vaccinate associated with HPV vaccination rates among adolescents?

PubMed

Trogdon, Justin G; Shafer, Paul R; Shah, Parth D; Calo, William A

2016-08-31

We explored whether state laws allowing pharmacists to administer human papillomavirus (HPV) vaccinations to adolescents are associated with a higher likelihood of HPV vaccine uptake. We examined provider-reported HPV vaccination among 13-17year olds in the National Immunization Survey-Teen: 2008-2014 for girls (N=48,754) and 2010-2014 for boys (N=31,802). Outcome variables were HPV vaccine initiation (⩾1 dose) and completion (⩾3 doses). The explanatory variable of interest was a categorical variable for the type of pharmacist authority regarding HPV vaccination for adolescents (<18years) in the state: not permitted (reference), by prescription, by collaborative practice protocol, or independent authority. We ran separate difference-in-difference regression models by sex. During 2008-2014, 15 states passed laws allowing pharmacists to administer HPV vaccine to adolescents. Pharmacist authority laws were not statistically significantly associated with increased HPV vaccine initiation or completion. As currently implemented, state laws allowing pharmacists to administer HPV vaccine to adolescents were not associated with uptake. Possible explanations that need further research include restrictions on pharmacists' third-party billing ability and the lack of promotion of pharmacy vaccination services to age-eligible adolescents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lack of differences in radiation-induced immunogenicity parameters between HPV-positive and HPV-negative human HNSCC cell lines.

PubMed

Schneider, Karolin; Bol, Vanesa; Grégoire, Vincent

2017-09-01

Clinical studies indicate that patients with HPV/p16-associated head & neck squamous cell carcinoma (HNSCC) represent a subgroup with a better prognosis and improved response to conventional radiotherapy. Involvement of immune-based factors has been hypothesized. In the present study, we investigated radiation-induced differences in release of damage associated molecular patterns (DAMPs), cytokines and activation of dendritic cells (DCs) in HPV-positive and negative HNSCC cancer cell lines. Calreticulin (CRT) exposure was detected on cancer cell surface. ATP, HMGB1 and cytokines were measured in culture supernatants. Maturation marker CD83 surface exposure was determined on DCs after co-incubation with irradiated tumor cells. There was no increase in DAMPs and cytokine profiles after radiation treatment and no difference between HPV+ and HPV- cell lines. The HPV/p16-positive SCC90 cells showed a trend for increased total CRT, HMGB1, and number of cytokines compared to all other cell lines. None of the irradiated cancer cell lines could affect DC maturation. Radiation treatment did not increase immunogenicity of HNSCC cell lines assessed by membrane CRT, ATP, HMGB1, cytokines production, and by activation of immature DCs. There was no difference between HPV-positive and HPV-negative cell lines. Copyright © 2017 Elsevier B.V. All rights reserved.

The politics of HPV vaccination policy formation in the United States.

PubMed

Abiola, Sara E; Colgrove, James; Mello, Michelle M

2013-08-01

This article explores the political dimensions of policy formation for the human papillomavirus (HPV) vaccine through case studies of six states: California, Indiana, New Hampshire, New York, Texas, and Virginia. Using thematic content analysis of semistructured key informant interviews with policy stakeholders, newspaper articles, and archival materials, we describe the trajectory of public health policy developments for HPV immunization and analyze key influences on policy outcomes through the theoretical lens of the Multiple Streams framework. Specifically, we examine factors influencing the extent to which HPV was perceived as a problem meriting policy action; political forces that facilitated and impeded policy adoption, including interest-group opposition and structural and ideological features of the states' political environments; and factors affecting which policy alternatives received consideration. We find that effective policy entrepreneurship played a critical role in determining policy outcomes. We conclude by discussing lessons from the case of HPV vaccination for future efforts to craft vaccination policies.

Human Papillomavirus Community in Healthy Persons, Defined by Metagenomics Analysis of Human Microbiome Project Shotgun Sequencing Data Sets

PubMed Central

Ma, Yingfei; Madupu, Ramana; Karaoz, Ulas; Nossa, Carlos W.; Yang, Liying; Yooseph, Shibu; Yachimski, Patrick S.; Brodie, Eoin L.; Nelson, Karen E.

2014-01-01

ABSTRACT Human papillomavirus (HPV) causes a number of neoplastic diseases in humans. Here, we show a complex normal HPV community in a cohort of 103 healthy human subjects, by metagenomics analysis of the shotgun sequencing data generated from the NIH Human Microbiome Project. The overall HPV prevalence was 68.9% and was highest in the skin (61.3%), followed by the vagina (41.5%), mouth (30%), and gut (17.3%). Of the 109 HPV types as well as additional unclassified types detected, most were undetectable by the widely used commercial kits targeting the vaginal/cervical HPV types. These HPVs likely represent true HPV infections rather than transitory exposure because of strong organ tropism and persistence of the same HPV types in repeat samples. Coexistence of multiple HPV types was found in 48.1% of the HPV-positive samples. Networking between HPV types, cooccurrence or exclusion, was detected in vaginal and skin samples. Large contigs assembled from short HPV reads were obtained from several samples, confirming their genuine HPV origin. This first large-scale survey of HPV using a shotgun sequencing approach yielded a comprehensive map of HPV infections among different body sites of healthy human subjects. IMPORTANCE This nonbiased survey indicates that the HPV community in healthy humans is much more complex than previously defined by widely used kits that are target selective for only a few high- and low-risk HPV types for cervical cancer. The importance of nononcogenic viruses in a mixed HPV infection could be for stimulating or inhibiting a coexisting oncogenic virus via viral interference or immune cross-reaction. Knowledge gained from this study will be helpful to guide the designing of epidemiological and clinical studies in the future to determine the impact of nononcogenic HPV types on the outcome of HPV infections. PMID:24522917

Impact of introduction of the 9-valent human papillomavirus vaccine on vaccination coverage of youth in North Carolina.

PubMed

Trogdon, Justin G; Shafer, Paul; Lindsay, Brianna; Coyne-Beasley, Tamera

2018-02-28

The objective of this study was to evaluate the impact of introduction of 9vHPV vaccine on HPV vaccination uptake (doses per capita) and initiation (≥1 doses), completion (≥3 doses) and compliance (≥3 doses within 12 months) by adolescents. We used a retrospective cohort analysis using North Carolina Immunization Registry (NCIR) data from January 2008 through October 2016. The sample included Vaccines for Children eligible adolescents aged 9 to 17 years in 2016, for whom the NCIR contains complete vaccination history. We applied an interrupted time series design to measure associations between ZIP Code Tabulation Area (ZCTA)-level HPV vaccination outcomes over time with the introduction of 9vHPV in North Carolina (NC) in July 2015. Each outcome displayed a linear upward trend over time with large seasonal spikes near August of each year, corresponding to the time when adolescents often receive other vaccines required for school entry. After accounting for these underlying trends, introduction of 9vHPV was not associated with a change in publicly funded HPV vaccination rates in NC. Our results indicate that 9vHPV substituted for 4vHPV in the first year after release in NC, but the release of 9vHPV was not associated with an overall change in HPV vaccination. Copyright © 2018 Elsevier Ltd. All rights reserved.

Partnering with middle school students to design text messages about HPV vaccination.

PubMed

Cates, Joan R; Ortiz, Rebecca R; North, Steve; Martin, Amanda; Smith, Richalle; Coyne-Beasley, Tamera

2015-03-01

Human papillomavirus (HPV) vaccination is routinely recommended for U.S. adolescents ages 11 to 12 years, yet vaccine coverage remains low. Text message HPV immunization reminders to parents have been effective with increasing uptake, but text messages directly to adolescents in order to increase HPV vaccination uptake are unknown. The purpose of this study was to examine the acceptability of text messages about HPV vaccination and message preferences among adolescents. Middle school students (n = 43) assisted in designing text messages to promote HPV vaccine among their peers. Through seven focus groups and two in-class surveys, we assessed students' knowledge of HPV vaccine, use of texting, and preferences for text messages and sources. The average age of participants was 13 years, and all were White (17 males, 26 females) in this rural setting. More than 70% used text messaging with a cell phone. The text message with the best composite score (M = 2.33, SD = 0.72) for likeability, trustworthiness, and motivation to seek more information was a gain frame emphasizing reduction in HPV infection if vaccinated against HPV. Text messages with lower scores emphasized threats of disease if not vaccinated. Participants (68%) preferred doctors as their information source. Text messaging to adolescents may be a strategy to improve HPV knowledge and vaccination. © 2014 Society for Public Health Education.

A cost comparison of introducing and delivering pneumococcal, rotavirus and human papillomavirus vaccines in Rwanda.

PubMed

Ngabo, Fidèle; Levin, Ann; Wang, Susan A; Gatera, Maurice; Rugambwa, Celse; Kayonga, Celestin; Donnen, Philippe; Lepage, Philippe; Hutubessy, Raymond

2015-12-16

Detailed cost evaluations of delivery of new vaccines such as pneumococcal conjugate, human papillomavirus (HPV), and rotavirus vaccines in low and middle-income countries are scarce. This paper differs from others by comparing the costs of introducing multiple vaccines in a single country and then assessing the financial and economic impact at the time and implications for the future. The objective of the analysis was to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda to inform domestic and external financial resource mobilization. Start-up, recurrent, and capital costs from a government perspective were collected in 2012. Since pneumococcal conjugate and HPV vaccines had already been introduced, cost data for those vaccines were collected retrospectively while prospective (projected) costing was done for rotavirus vaccine. The financial unit cost per fully immunized child (or girl for HPV vaccine) of delivering 3 doses of each vaccine (without costs related to vaccine procurement) was $0.37 for rotavirus (RotaTeq(®)) vaccine, $0.54 for pneumococcal (Prevnar(®)) vaccine in pre-filled syringes, and $10.23 for HPV (Gardasil (®)) vaccine. The financial delivery costs of Prevnar(®) and RotaTeq(®) were similar since both were delivered using existing health system infrastructure to deliver infant vaccines at health centers. The total financial cost of delivering Gardasil(®) was higher than those of the two infant vaccines due to greater resource requirements associated with creating a new vaccine delivery system in for a new target population of 12-year-old girls who have not previously been served by the existing routine infant immunization program. The analysis indicates that service delivery strategies have an important influence on costs of introducing new vaccines and costs per girl reached with HPV vaccine are higher than the other two vaccines because of its delivery strategy. Documented information on financial commitments for new vaccines, particularly from government sources, is a useful input into country policy dialogue on sustainable financing and co-financing of new vaccines, as well as for policy decisions by donors such as Gavi, the Vaccine Alliance. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Human Papillomavirus (HPV)

MedlinePlus

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An Examination of HPV16 Natural Immunity in Men Who Have Sex with Men (MSM) in the HPV in Men (HIM) Study.

PubMed

Beachler, Daniel C; Pinto, Ligia A; Kemp, Troy J; Nyitray, Alan G; Hildesheim, Allan; Viscidi, Raphael; Schussler, John; Kreimer, Aimée R; Giuliano, Anna R

2018-04-01

Background: Evidence suggests that natural antibodies developed after HPV16 infection may protect some women but not men against subsequent HPV16 reacquisition. Less is known whether antibodies developed following HPV16 infection are protective among men who have sex with men (MSM). Methods: Four hundred seventy-five MSM from the Human Papillomavirus Infection in Men (HIM) study were tested for serum antibodies to HPV16 L1 using enzyme-linked immunosorbent assays, and for anal and genital HPV16 DNA using PCR consensus primer system (PGMY 09/11). Adjusted Cox regression was used to evaluate whether baseline HPV16 seropositivity impacts subsequent genital or anal HPV16 DNA. Results: The risk of subsequent genital HPV16 [aHR = 1.05, 95% confidence interval (CI) = 0.66-1.68] and anal HPV16 infections among MSM (aHR = 2.34, 95% CI = 0.92-5.98) was similar or nonsignificantly higher in HPV16-seropositive than HPV16-seronegative MSM. The risk of genital HPV16 was also similar between HPV16-seronegative and HPV16-seropositive MSM in the highest tertile of HPV16 antibody levels and when restricting to those with new sex partners during follow-up ( P > 0.20). Among the 118 MSM who were HPV16 seropositive, 90% remained HPV16 seropositive up to 4 years later. When tested together, MSM with the highest antibody titers (top tertile) had similar levels to females (mean = 130.3 vs. 134.5 EU/mL, P = 0.84). Conclusions: Despite years of HPV16 seropositivity persistence and antibody titers comparable with females, this study suggested no evidence of HPV16 natural antibodies protecting against subsequent genital or anal HPV16 infection in MSM. Impact: This could help partially explain the high incidence of genital and anal HPV16 infection and related anal cancer seen in middle-aged and older MSM. Cancer Epidemiol Biomarkers Prev; 27(4); 496-502. ©2018 AACR . ©2018 American Association for Cancer Research.

A robust response to combination immune checkpoint inhibitor therapy in HPV-related small cell cancer: a case report.

PubMed

Ho, Won Jin; Rooper, Lisa; Sagorsky, Sarah; Kang, Hyunseok

2018-05-09

Human papillomavirus-related small cell carcinoma of the head and neck is an extremely rare, aggressive subtype with poor outcomes. Therapeutic options are limited and are largely adopted from small cell lung cancer treatment paradigms. This report describes a 69-year old male who was diagnosed of HPV-related oropharyngeal cancer with mixed small cell and squamous cell pathology which was clinically aggressive and progressed through multimodal platinum-based therapies. Upon manifestation of worsening metastatic disease, the patient was initiated on a combination of ipilimumab and nivolumab. Within 2 months of starting immunotherapy, a robust partial response was observed. During the treatment course, the patient developed immune-related adverse effects including new diabetes mellitus, colitis, and hypothyroidism. The disease-specific survival was 26 months. Combination immunotherapy may be an attractive option for HPV-related small cell head and neck cancers resistant to other treatment modalities and thus warrants further evaluation.

Attitudes towards Human Papilloma Virus Vaccination in the Latin American Andean Region.

PubMed

Nwanodi, Oroma

2017-09-08

This commentary explores the distribution of human papilloma virus (HPV) and HPV-related diseases, and factors affecting attitudes towards HPV, HPV-related diseases, and HPV vaccination in the Latin American Andean region. Lack of knowledge of HPV, known negative attitudes or incorrect assumptions about HPV, HPV-related diseases, and HPV vaccination provide a basis upon which to develop targeted HPV awareness and preventive health media campaigns. For maximal effect, media campaigns should use the internet, radio, and television to address health care providers, parents, and students. Additional programming can be developed for clinics to use in-house with their clients. Ministries of Education, Finance, and Health all have roles to play to increase national HPV, HPV-related diseases, and HPV vaccination awareness.

Final analysis of a study assessing genital human papillomavirus genoprevalence in young Australian women, following eight years of a national vaccination program.

PubMed

Garland, Suzanne M; Cornall, Alyssa M; Brotherton, Julia M L; Wark, John D; Malloy, Michael J; Tabrizi, Sepehr N

2018-05-31

The VACCINE [Vaccine Against Cervical Cancer Impact and Effectiveness] study evaluated the prevalence of quadrivalent vaccine-targeted human papillomavirus (HPV) genotypes (HPV 6, 11, 16, 18) amongst young women of vaccine-eligible age. Between October 2011 - June 2015, women aged 18-25 years from Victoria, Australia, were recruited through targeted advertising on the social networking website Facebook. Participants completed an online questionnaire and provided a self-collected vaginal swab for HPV DNA detection and genotyping (Linear Array HPV genotyping assay). Self-reported HPV vaccination details were verified with the National HPV Vaccination Program Register (NHVPR). Of 1223 who agreed to participate, 916 (74.9%) completed the survey and, for 1007 (82.3%) sexually-active participants, 744 (73.9%) returned the self-collected swab, of which 737 contained detectable DNA. 184/737 (25.0%) were positive for HPV. Vaccine-targeted HPV genotypes were detected in only 13 (1.7%) women: 11 HPV 16 (six vaccinated after sexual debut, five unvaccinated) and two HPV 6. Prevalence of any of HPV 31/33/45 collectively was 2.9%, varying significantly by vaccination status (fully 2.0%, unvaccinated 6.8%; p = 0.01). Vaccination rates among the sexually-active cohort were high, with 65.6%, 71.6% and 74.2% of participants having received three, at least two or at least one dose of vaccine, respectively. Of women self-reporting HPV vaccination, the NHVPR confirmed one or more doses were received in 90%. Strong associations were observed between vaccination status, age, language spoken at home and country of birth, as well as between HPV detection and the number of male sexual partners. Surveillance five to eight years' post-initiation of a national HPV vaccination program demonstrated a consistent and very low prevalence of vaccine-related HPV genotypes and some evidence of cross protection against related types amongst vaccine-eligible women from Victoria, Australia. Copyright © 2018. Published by Elsevier Ltd.

The Cervicovaginal Microbiota and Its Associations With Human Papillomavirus Detection in HIV-Infected and HIV-Uninfected Women.

PubMed

Reimers, Laura L; Mehta, Supriya D; Massad, L Stewart; Burk, Robert D; Xie, Xianhong; Ravel, Jacques; Cohen, Mardge H; Palefsky, Joel M; Weber, Kathleen M; Xue, Xiaonan; Anastos, Kathryn; Minkoff, Howard; Atrio, Jessica; D'Souza, Gypsyamber; Ye, Qian; Colie, Christine; Zolnik, Christine P; Spear, Gregory T; Strickler, Howard D

2016-11-01

 Bacterial vaginosis (BV) is characterized by low abundance of Lactobacillus species, high pH, and immune cell infiltration and has been associated with an increased risk of human papillomavirus (HPV) infection. We molecularly assessed the cervicovaginal microbiota over time in human immunodeficiency virus (HIV)-infected and HIV-uninfected women to more comprehensively study the HPV-microbiota relationship, controlling for immune status.  16S ribosomal RNA gene amplicon pyrosequencing and HPV DNA testing were conducted annually in serial cervicovaginal lavage specimens obtained over 8-10 years from African American women from Chicago, of whom 22 were HIV uninfected, 22 were HIV infected with a stable CD4 + T-cell count of > 500 cells/mm 3 , and 20 were HIV infected with progressive immunosuppression. Vaginal pH was serially measured.  The relative abundances of Lactobacillus crispatus and other Lactobacillus species were inversely associated with vaginal pH (all P < .001). High (vs low) L. crispatus relative abundance was associated with decreased HPV detection (odds ratio, 0.48; 95% confidence interval, .24-.96; P trend = .03) after adjustment for repeated observation and multiple covariates, including pH and study group. However, there were no associations between HPV and the relative abundance of Lactobacillus species as a group, nor with Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii individually.  L. crispatus may have a beneficial effect on the burden of HPV in both HIV-infected and HIV-uninfected women (independent of pH). © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine

PubMed Central

Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.

2012-01-01

Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic anti-tumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589

Immunization effects of a communication intervention to promote preteen HPV vaccination in primary care practices.

PubMed

Cates, Joan R; Crandell, Jamie L; Diehl, Sandra J; Coyne-Beasley, Tamera

2018-01-02

HPV vaccination at the recommended ages of 11-12 is highly effective yet has stalled well below the goal of 80% of the population. We evaluated a statewide practice-based communication intervention (tools: brochures, posters, online training for providers and resources for parents, video game for preteens) to persuade parents, preteens and providers to vaccinate against HPV. The 9-month intervention started May 1, 2015. We compared vaccine initiation and completion rates over three 9-month periods (baseline, intervention, post-intervention) between practices enrolled in the intervention and a comparable comparison group. All practices reported to the North Carolina Immunization Registry (NCIR) and had at least 100 11- and 12-year-olds who had not completed the HPV vaccine series. Of 175 eligible practices, the 14 intervention practices included 19,398 individuals and the 161 comparison practices included 127,896 individuals. An extended Cox model was used to test the intervention effect. The intervention had a significant effect on both initiation and completion during the intervention and post-intervention periods; the estimated hazard ratio (HR) for initiation was 1.17 (p = .004) during the intervention and 1.11 (p = .005) post-intervention. Likewise, completion during the intervention period was 17% higher in intervention practices, after controlling for baseline differences. This effect increased in the post-intervention period to 30% higher (p = .03). Individuals in the intervention practices were 17% more likely to initiate and complete HPV vaccination than in the comparison practices during the intervention period and the effect was sustained post-intervention. This intervention is promising for increasing rates of HPV vaccination at ages 11-12. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of school-entry and education mandates by states on HPV vaccination coverage: Analysis of the 2009–2013 National Immunization Survey-Teen

PubMed Central

Perkins, Rebecca B.; Lin, Mengyun; Wallington, Sherrie F.; Hanchate, Amresh D.

2016-01-01

ABSTRACT Objective: To determine the effectiveness of existing school entry and education mandates on HPV vaccination coverage, we compared coverage among girls residing in states and jurisdictions with and without education and school-entry mandates. Virginia and the District of Columbia enacted school entry mandates, though both laws included liberal opt-out provisions. Ten additional states had mandates requiring distribution of education to parents or provision of education within school curricula. Methods: Using data from the National Immunization Survey-Teen from 2009–2013, we estimated multilevel logistic regression models to compare coverage with HPV vaccines for girls ages 13–17 residing in states and jurisdictions with and without school entry and education mandates, adjusting for demographic factors, healthcare access, and provider recommendation. Results: Girls residing in states and jurisdictions with HPV vaccine school entry mandates (DC and VA) and education mandates (LA, MI, CO, IN, IA, IL, NJ, NC, TX, and WA) did not have higher HPV vaccine series initiation or completion than those living in states without mandates for any year (2009–2013). Similar results were seen when comparing girls ages 13–14 to those ages 15–17, and after adjustment for known covariates of vaccination. Conclusions: States and jurisdictions with school-entry and education mandates do not currently have higher HPV vaccination coverage than states without such legislation. Liberal opt-out language in existing school entry mandates may weaken their impact. Policy-makers contemplating legislation to improve vaccination coverage should be aware of the limitations of existing mandates. PMID:27152418

Upgrading public health programs for human papillomavirus prevention and control is possible in low- and middle-income countries.

PubMed

Steben, Marc; Jeronimo, Jose; Wittet, Scott; Lamontagne, D Scott; Ogilvie, Gina; Jensen, Christina; Smith, Jennifer; Franceschi, Silvia

2012-11-20

Cancer is an important cause of premature death in low- and middle-income countries (LMIC). Two preventive tools are available that have the potential together to sharply decrease the impact of cervical cancer in LMIC. The combination of human papillomavirus (HPV) vaccination and cervical cancer screening within existing programs is possible. Although there is a great deal of concern about introducing and strengthening HPV prevention efforts in LMIC, recent projects have demonstrated feasibility. Thus, with appropriate prioritization and resources, HPV prevention can be introduced and scaled up. Comprehensive HPV prevention strategies, mainly those geared at preventing cervical cancer, should include both vaccination and screening. The integration of both screening and vaccination will save the most lives, and such strategies are endorsed by many international organizations. However, some vaccine and screening programs are financed almost entirely by special externally-based programs. These more closely resemble demonstration exercises than sustainable national programs. In order for successful demonstration projects to have a broad impact on prevention, sustainable national funding based on strong commitments is essential. There may be challenges to implementing HPV prevention programs, but none should be considered insurmountable. Many LMIC have successfully adopted an HPV prevention agenda despite prevailing pessimism. Failure to act on this issue can perpetuate inequity in sexually transmitted infection and cancer prevention. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2012. Published by Elsevier Ltd.

Acceptance of the HPV vaccine among women, parents, community leaders, and healthcare providers in Ohio Appalachia.

PubMed

Katz, Mira L; Reiter, Paul L; Heaner, Sarah; Ruffin, Mack T; Post, Douglas M; Paskett, Electra D

2009-06-19

To assess HPV vaccine acceptability, focus groups of women (18-26 years), parents, community leaders, and healthcare providers were conducted throughout Ohio Appalachia. Themes that emerged among the 23 focus groups (n=114) about the HPV vaccine were: barriers (general health and vaccine specific), lack of knowledge (cervical cancer and HPV), cultural attitudes, and suggestions for educational materials and programs. Important Appalachian attitudes included strong family ties, privacy, conservative views, and lack of trust of outsiders to the region. There are differences in HPV vaccine acceptability among different types of community members highlighting the need for a range of HPV vaccine educational materials/programs to be developed that are inclusive of the Appalachian culture.

Development of a community pharmacy human papillomavirus vaccine program for underinsured university students along the United States/Mexico border.

PubMed

Navarrete, Jacquelyn P; Padilla, Margie E; Castro, Louise P; Rivera, José O

2014-01-01

To describe the development and implementation of a human papillomavirus (HPV) vaccine patient assistance program (PAP) for university students, and to acquire information on the number who accessed the program and completed the series. University of Texas at El Paso University Student Health Clinic Pharmacy, Fall 2011-Spring 2014. A community pharmacy located within the university student health clinic providing services to an underinsured student population. Existing evidence shows the benefit of using PAP in community pharmacies but is nonspecific regarding the use of PAP for vaccines in an uninsured and underinsured Hispanic student population. The implementation of this unique HPV vaccine program in a community setting aims to increase awareness, access, and rates. Primary measures included results from a needs-assessment questionnaire that were used to implement the HPV vaccine program. After implementation, utilization data were collected on the number of students who qualified and enrolled in the HPV PAP and the number of students who completed the HPV series. The preliminary data from a needs assessment indicated that a majority (72.1%, n = 80) of students did not understand how HPV is transmitted. A total of 89 students qualified for PAP. The majority were women (81%). A total of 71 students (79.8%) received their second dose and 43 (48.3%) completed the series. Although pharmacists continue to provide vaccine services, minorities such as the Hispanic population continue to be underimmunized. Students may not be taking the proper precautions to prevent the acquisition of HPV. For these reasons services such as this HPV vaccine program are warranted. Pharmacists need to continue to educate and advocate on the importance of vaccines and how they prevent disease.

The study of immunogenicity of the antigenic protein of high risk oncogenic type of the human papillomavirus HPV16 L1 produced in the plant expression system on the base of transgenic tomato.

PubMed

Salyaev, R K; Rekoslavskaya, N I; Stolbikov, A S; Tretyakova, A V

2017-05-01

The immunogenicity of plant-made peroral vaccine against cervical cancer was studied in mice during 342 days after vaccination with the material of tomato fruits genetically transformed with HPV16 L1 Ώ 5'UTR TMV. The immune response was found on day 4 after vaccination in blood serum of vaccinated mice. On days 90-100, the rise to maximum value of the level of antibodies to HPV16 L1 was in the range of 500 ng of the standard antibodies to HPV16 L1 (Santa Cruz Biotechnology, United States). This level of antibodies was retained until the end of the study.

The case for vaccinating boys against human papillomavirus.

PubMed

Hull, Sarah C; Caplan, Arthur L

2009-01-01

Vaccination policy in the case of human papillomavirus (HPV) has remained a constant source of controversy ever since Gardasil, Merck's vaccine against HPV, received US Food and Drug Administration approval in the summer of 2006. This controversy has centered on the risks and benefits of vaccinating girls and women in rich and poor nations alike. However, despite all of the attention created by this important policy question, relatively little has been focused on another key public health question: should boys be vaccinated against HPV as well? If herd immunity against the most carcinogenic strains of HPV could be more rapidly and efficiently achieved by vaccinating everyone at risk for being a carrier, it logically follows that vaccine policy should expand to include boys and men. Copyright 2009 S. Karger AG, Basel.

Communication skills in HPV prevention: an audit among Italian healthcare workers.

PubMed

Tafuri, S; Martinelli, D; Vece, M M; Quarto, M; Germinario, C; Prato, R

2010-08-02

This study aims to investigate the knowledge, the attitudes and practices on HPV vaccination of health professionals of Mother and Child Service of Puglia Region (Italy). The study was conducted through a standardized questionnaire. Of 455 respondents, 74.2% judged HPV vaccine very important for immunization calendar. 88.9% did not believe that the administration of HPV vaccine implies consent to the initiation of sexual activity but 34.2% sustained that vaccine can give a false sense of protection against sexually transmitted diseases. 62.2% believed that boys should also be vaccinated. Skills necessary in the implementation of strategies in the promotion of health are partially inadequate and appropriate ongoing education should be carried out for health care workers. Copyright 2010 Elsevier Ltd. All rights reserved.

C3-Luc Cells Are an Excellent Model for Evaluation of Cellular Immunity following HPV16L1 Vaccination.

PubMed

Li, Li-Li; Wang, He-Rong; Zhou, Zhi-Yi; Luo, Jing; Wang, Xiao-Li; Xiao, Xiang-Qian; Zhou, Yu-Bai; Zeng, Yi

2016-01-01

C3 and TC-1 are the two model cell lines most commonly used in studies of vaccines and drugs against human papillomavirus (HPV) infection. Because C3 cells contain both the HPV16 E and L genes, but TC-1 cells contain only the HPV16 E genes, C3 cells are usually used as the model cell line in studies targeting the HPV16 L protein. However, expression of the L1 protein is difficult to detect in C3 cells using common methods. In our study, Short tandem repeat analysis (STR) was used to demonstrate that C3 cells are indeed derived from mice, PCR results show that HPV16 L1, E6 and E7 genes were detected in C3 genomic DNA, and RT-PCR results demonstrated that L1 transcription had occurred in C3 cells. However, the expression of C3 protein was not found in the results of western blot and immunohistochemistry (IHC). Growth and proliferation of C3 were inhibited by mice spleen lymphocytes that had been immunized with a vaccine against HPV16L1. The luciferase gene was integrated into C3 cells, and it was confirmed that addition of the exogenous gene had no effect on C3 cells by comparing cell growth and tumor formation with untransformed cells. Cells stably expressing luciferase (C3-luc) were screened and subcutaneously injected into the mice. Tumors became established and were observed using a Spectrum Pre-clinical in Vivo Imaging System. Tumor size of mice in the different groups at various time points was calculated by counting photons. The sensitivity of the animals to the vaccine was quantified by statistical comparison. Ten or 30 days following injection of the C3-luc cells, tumor size differed significantly between the PBS and vaccine groups, indicating that C3 cells were susceptible to vaccination even after tumors were formed in vivo.

Health economic analysis of human papillomavirus vaccines in women of Chile: perspective of the health care payer using a Markov model.

PubMed

Gomez, Jorge Alberto; Lepetic, Alejandro; Demarteau, Nadia

2014-11-26

In Chile, significant reductions in cervical cancer incidence and mortality have been observed due to implementation of a well-organized screening program. However, it has been suggested that the inclusion of human papillomavirus (HPV) vaccination for young adolescent women may be the best prospect to further reduce the burden of cervical cancer. This cost-effectiveness study comparing two available HPV vaccines in Chile was performed to support decision making on the implementation of universal HPV vaccination. The present analysis used an existing static Markov model to assess the effect of screening and vaccination. This analysis includes the epidemiology of low-risk HPV types allowing for the comparison between the two vaccines (HPV-16/18 AS04-adjuvanted vaccine and the HPV-6/11/16/18 vaccine), latest cross-protection data on HPV vaccines, treatment costs for cervical cancer, vaccine costs and 6% discounting per the health economic guideline for Chile. Projected incremental cost-utility ratio (ICUR) and incremental cost-effectiveness ratio (ICERs) for the HPV-16/18 AS04-adjuvanted vaccine was 116 United States (US) dollars per quality-adjusted life years (QALY) gained or 147 US dollars per life-years (LY) saved, while the projected ICUR/ICER for the HPV-6/11/16/18 vaccine was 541 US dollars per QALY gained or 726 US dollars per LY saved. Introduction of any HPV vaccine to the present cervical cancer prevention program of Chile is estimated to be highly cost-effective (below 1X gross domestic product [GDP] per capita, 14278 US dollars). In Chile, the addition of HPV-16/18 AS04-adjuvanted vaccine to the existing screening program dominated the addition of HPV-6/11/16/18 vaccine. In the probabilistic sensitivity analysis results show that the HPV-16/18 AS04-adjuvanted vaccine is expected to be dominant and cost-saving in 69.3% and 77.6% of the replicates respectively. The findings indicate that the addition of any HPV vaccine to the current cervical screening program of Chile will be advantageous. However, this cost-effectiveness model shows that the HPV-16/18 AS04-adjuvanted vaccine dominated the HPV-6/11/16/18 vaccine. Beyond the context of Chile, the data from this modelling exercise may support healthcare policy and decision-making pertaining to introduction of HPV vaccination in similar resource settings in the region.

Cost-effectiveness analysis of HPV vaccination: comparing the general population with socially vulnerable individuals.

PubMed

Han, Kyu-Tae; Kim, Sun Jung; Lee, Seo Yoon; Park, Eun-Cheol

2014-01-01

After the WHO recommended HPV vaccination of the general population in 2009, government support of HPV vaccination programs was increased in many countries. However, this policy was not implemented in Korea due to perceived low cost-effectiveness. Thus, the aim of this study was to analyze the cost-utility of HPV vaccination programs targeted to high risk populations as compared to vaccination programs for the general population. Each study population was set to 100,000 people in a simulation study to determine the incremental cost-utility ratio (ICUR), then standard prevalence rates, cost, vaccination rates, vaccine efficacy, and the Quality-Adjusted Life-Years (QALYs) were applied to the analysis. In addition, sensitivity analysis was performed by assuming discounted vaccination cost. In the socially vulnerable population, QALYs gained through HPV vaccination were higher than that of the general population (General population: 1,019, Socially vulnerable population: 5,582). The results of ICUR showed that the cost of HPV vaccination was higher for the general population than the socially vulnerable population. (General population: 52,279,255 KRW, Socially vulnerable population: 9,547,347 KRW). Compared with 24 million KRW/QALYs as the social threshold, vaccination of the general population was not cost-effective. In contrast, vaccination of the socially vulnerable population was strongly cost-effective. The results suggest the importance and necessity of government support of HPV vaccination programs targeted to socially vulnerable populations because a targeted approach is much more cost-effective. The implementation of government support for such vaccination programs is a critical strategy for decreasing the burden of HPV infection in Korea.

Attitudes towards Human Papilloma Virus Vaccination in the Latin American Andean Region

PubMed Central

2017-01-01

This commentary explores the distribution of human papilloma virus (HPV) and HPV-related diseases, and factors affecting attitudes towards HPV, HPV-related diseases, and HPV vaccination in the Latin American Andean region. Lack of knowledge of HPV, known negative attitudes or incorrect assumptions about HPV, HPV-related diseases, and HPV vaccination provide a basis upon which to develop targeted HPV awareness and preventive health media campaigns. For maximal effect, media campaigns should use the internet, radio, and television to address health care providers, parents, and students. Additional programming can be developed for clinics to use in-house with their clients. Ministries of Education, Finance, and Health all have roles to play to increase national HPV, HPV-related diseases, and HPV vaccination awareness. PMID:28885601

HPV vaccination programs have not been shown to be cost-effective in countries with comprehensive Pap screening and surgery.

PubMed

Wilyman, Judy

2013-06-12

Pap screening combined with loop electrosurgical excision procedures (LEEP) is almost 100% effective in preventing cervical cancer mortality yet many countries with these procedures have now implemented broad HPV vaccination programs. HPV vaccines have not been demonstrated to be more effective or safer than Pap screening in the prevention of cervical cancer and Pap screening will still be required even in vaccinated women. The HPV vaccine costs Au$450 per person and it does not protect against ~30% of cancer. This investigation analyses the cost-effectiveness of using the HPV vaccine in countries where Pap screening and surgical procedures have already reduced cervical cancer mortality to very low rates. Cost-effectiveness of vaccination programs is being determined by mathematical models which are founded on many assumptions. It is necessary to examine the rigor of these assumptions to be certain of the health benefits that are predicted. In 2002 scientists concluded that HPV 16 and 18 were the central and independent cause of most cervical cancer. This conclusion was based on molecular technology. If HPV 16 and 18 infections are the central and independent cause of most cervical cancer then the incidence of HPV 16 and 18 should vary with the incidence and mortality of cervical cancer worldwide. This correlation does not exist. It is also observed that the majority of HPV 16/18 infections do not lead to cervical cancer. This indicates that other etiological or 'risk' factors are necessary for persistent HPV infection to progress to cancer. The benefits of HPV vaccines have been determined by using pre-cancerous lesions in young women as a surrogate for cervical cancer. This surrogate is found to be inadequate as an end-point for cervical cancer. Clinical trials have only provided speculative benefits for the efficacy of HPV vaccines against cancer and the long-term risks of the vaccine have not been established. Pap screening will still be required in vaccinated women hence HPV vaccination programs are not cost-effective, and may do more harm than good, in countries where regular Pap screening and surgery has already reduced the burden of this disease.

Human papillomavirus vaccine acceptability among parents of adolescent girls: obstacles and challenges in Mysore, India.

PubMed

Madhivanan, Purnima; Li, Tan; Srinivas, Vijaya; Marlow, Laura; Mukherjee, Soumyadeep; Krupp, Karl

2014-07-01

Worldwide, 530,000 women are diagnosed with cervical cancer and 275,000 die annually. India bears the greatest burden of the disease with 132,000 cases and 74,000 deaths yearly. Widespread uptake of human papillomavirus (HPV) vaccine could reduce incidence and mortality by two-thirds. This study explored obstacles and facilitators of parental acceptability of HPV vaccine. In 2010, questionnaires were sent home with a random sample of 800 girls attending 12 schools in Mysore city to be completed by a parent. Data were analyzed using multivariable logistic regression with generalized estimating equation to account for potential clustering by school. Of the 797 completed surveys; 71% reported willingness to accept HPV vaccine for their daughters. The adjusted odds of acceptance was higher among participants who received recommendation from their parents, perceived cervical cancer as a serious disease, believed that HPV vaccine was safe, or felt that vaccination was a good way to protect against cervical cancer. Parents who had concerns about vaccine side-effects or thought that it would cause pain had lower odds of acceptance. Future promotion of vaccine should emphasize safety of immunization and involve promotion to the extended family, so that they actively recommend immunization of young adolescent girls. Copyright © 2014. Published by Elsevier Inc.

Role of human papilloma virus-16 in the pathogenesis of oral lichen planus--an immunohistochemical study.

PubMed

Pol, Chetan A; Ghige, Suvarna K; Gosavi, Suchitra R

2015-02-01

Oral lichen planus (OLP) is a common chronic inflammatory immune-mediated disease with an aetiopathogenesis associated with cell-mediated immunological dysfunction. It is possible that oral mucosal viral infections, including human papilloma virus-16 (HPV-16) infection, may have a causative role in OLP pathogenesis. To assess the prevalence of HPV-16 in histopathologically diagnosed specimens of OLP and to evaluate whether any clinical features (such as the localisation of specimens) or the age or gender of patients, are correlated with the presence of this virus. This study was conducted on 30 specimens with a histopathological diagnosis of OLP, using the immunohistochemical marker HPV-16. Thirty normal oral mucosa specimens were also included as controls. Brown nuclear staining was accepted as positive for the HPV-16 antibody. The results were analysed using Fisher's exact test. P values<0.05 were considered to be significant. Significant correlation (P=0.0001) was observed between HPV-16 infection and samples with OLP. No statistical conclusions could be drawn regarding age, gender, localisation and HPV-16 positivity. Our study showed that HPV-16 may play a role in the pathogenesis of OLP. Taking into account the oncogenic potential of HPV-16, patients with OLP should be screened for the presence of this virus. © 2014 FDI World Dental Federation.

The Prevalence of Human Papillomavirus between the Neonates and Their Mothers

PubMed Central

Skoczyński, Mariusz; Goździcka-Józefiak, Anna; Kwaśniewska, Anna

2015-01-01

The impact of human papillomavirus (HPV) infection on pregnancy is a major problem of medicine. The transmission of the virus from mother to fetus is a process yet unresolved. The immune response and changed hormonal status of pregnant women might facilitate infection. A research on the prevalence of HPV infection was conducted at the Clinic of Obstetrics, Medical University of Lublin (Poland). The studied group included 152 randomly selected women. The material was tested for the presence of HPV DNA by means of polymerase chain reaction (PCR). The aim of the research was to assess the relation between HPV infections detected in the buccal smears of the neonates and the incidence of such infections in the cervical/buccal smears of their mothers. In the group of 152 infants HPV was found in 16 (10.53%). Among the cervical/buccal smears, HPV was isolated, respectively, in 24 (15.79%) and in 19 (12.5%) pregnant women. Statistically significant differences in the prevalence of HPV swabs from the newborns and the cervical/buccal smears of their mothers were found (p < 0.001). The identification of mothers in whose buccal smears HPV was detected can help develop a group of children who run a relatively significant risk of being infected. PMID:26713313

Definition of an HPV18/45 cross-reactive human T-cell epitope after DNA immunisation of HLA-A2/KB transgenic mice.

PubMed

McCarthy, Corinna; Youde, Sarah J; Man, Stephen

2006-05-15

Although human papillomavirus (HPV) types 16 and 18 are the most common types associated with cervical cancer worldwide, other related HPV types such as HPV 35, 45 and 58 have significant prevalence in geographically distinct populations. For development of global prophylactic and therapeutic vaccine strategies, it is important to study immune responses against these viruses and to define the degree of cross-reactivity between related HPV types. To investigate the potential for T cell cross-reactivity after vaccination, HLA-A2/Kb transgenic mice were immunised with DNA plasmid constructs containing HPV18 and 45 E6 and E7. Splenocytes from immunised mice were tested in direct ELIspot assays against overlapping pools of HPV 18 peptides. Immunisation with either HPV18 or HPV45 E6 DNA produced dominant T cell responses against an epitope (KCIDFYSRI) that was shared between HPV18 and HPV45. This peptide was shown to bind to HLA-A*0201 but not Db or Kb molecules on the cell surface. Furthermore this peptide was shown to be immunogenic in vitro to human T cells from 2 out of 3 HLA-A2+ healthy donors. Collectively, these results demonstrate that HPV 18 and 45 E6 DNA vaccines are immunogenic in mice and demonstrate that cross-reactive T cell responses against closely related HPV types can be induced in vivo. The use of the HLA-A2/Kb transgenic mice allowed definition of an HLA-A*0201 binding peptide epitope that would have been rejected on the basis of predicted major histocompatibility complex binding affinity. Copyright (c) 2005 Wiley-Liss, Inc.

Risk factors for infection by oncogenic human papillomaviruses in HIV-positive MSM patients in the ART era (2010-2016).

PubMed

Hidalgo-Tenorio, Carmen; Gil-Anguita, Concepción; Ramírez-Taboada, Jessica; Esquivias, Javier; López-Ruz, Miguel A; Balgahata, Omar Mohamed; Javier-Martinez, Rosario; Pasquau, Juan

2017-09-01

Squamous cell carcinoma of anus (SCCA) is one of the most frequent non-AIDS-defining diseases in HIV patients, mainly in men who have sex with men (MSM), and it is associated with human papillomavirus (HPV) infection.To determine the prevalence of high-risk HPV (HR-HPV) genotypes, premalignant lesions (HSIL) and SCCA in a cohort of HIV-positive MSM; to study the distribution of HPV genotypes according to anal histology results; and to analyze risk factors for this infection.This prospective single-center study was conducted between May 2010 and September 2016. At the study visit, cotton swabs were used to collect anal samples for cytology study in ThinPrep Pap Test liquid medium (Thin Prep Processor 2000, Hologic Corp, USA), and for HPV PCR (Linear Array HPV Genotyping Test). After, high-resolution anoscopy (HRA) (Zeiss 150 fc) was carried out. Logistic regression analysis was performed to identify risk factors for HR-HPV infection.The study included 319 patients, with mean age of 36.7 years; HR-HPV was detected in 81.3%. The prevalence of HSIL was 13.5% and SCCA was 0.3%. With regard to the distribution of HPV genotypes according to histology results, HPV 16 was the most frequent genotype in normal anal mucosa (26.7%), in LSILs (36.9%), and in HSILs (38%). In multivariate analysis, CD4 nadir < 200 cells/μL was the factor associated with infection by HR-HPV (OR 3.66, 95% CI 1.05%-12.75%).HIV-positive MSM showed a high prevalence of HSIL+ lesions and of infection by oncogenic HPV, which appears to be favored by a deficient immune system. HPV 16 was the most frequently isolated genotype in anal mucosa, regardless of lesion type.

Natural immune responses against eight oncogenic human papillomaviruses in the ASCUS-LSIL triage study

PubMed Central

Wilson, Lauren E.; Pawlita, Michael; Castle, Phillip E.; Waterboer, Tim; Sahasrabuddhe, Vikrant; Gravitt, Patti E.; Schiffman, Mark; Wentzensen, Nicolas

2014-01-01

Only a subset of women with human papillomavirus (HPV) infections will become seropositive, and the factors influencing seroconversion are not well-understood. We used a multiplex serology assay in women with mildly abnormal cytology results to examine seroreactivity to oncogenic HPV genotypes. An unbiased subset of women in the atypical squamous cell of undetermined significance /low-grade squamous intraepithelial lesion Triage Study (ALTS) provided blood samples at trial enrollment for serological testing. A Luminex assay based on GST-L1 fusion proteins as antigens was used to test seroreactivity against eight carcinogenic HPV genotypes (16, 18, 31, 33, 35, 45, 52, 58). We analyzed the relationship between seroprevalence in women free of precancer (N=2464) and HPV DNA status, age, sexual behavior, and other HPV-related risk factors. The overall seroprevalence was 24.5% for HPV16 L1 and ~ 20% for 18L1 and 31L1. Among women free of precancer, seroprevalence peaked in women less than 29 years and decreased with age. Type-specific seroprevalence was associated with baseline DNA detection for HPV16 (OR= 1.36, 95%CI: 1.04–1.79) and HPV18 (OR= 2.31, 95%CI: 1.61–3.32), as well as for HPV52 and HPV58. Correlates of sexual exposure were associated with increased seroprevalence across most genotypes. Women who were current or former smokers were less likely to be seropositive for all eight of the tested oncogenic genotypes. The multiplex assay showed associations between seroprevalence and known risk factors for HPV infection across nearly all tested HPV genotypes but associations between DNA- and serostatus were weak, suggesting possible misclassification of the participants’ HPV serostatus. PMID:23588935

The potential cost-effectiveness of prophylactic human papillomavirus vaccines in Canada.

PubMed

Brisson, Marc; Van de Velde, Nicolas; De Wals, Philippe; Boily, Marie-Claude

2007-07-20

Clinical trials have shown prophylactic human papillomavirus (HPV) vaccines to be effective against infection and disease. We examined whether HPV vaccination has the potential to be cost-effective. A cohort model of the natural history of HPV was developed, which fits simultaneously Canadian age and type-specific data for infection, cervical intraepithelial neoplasia, cervical cancer (CC) and genital warts (GW). Quality-Adjusted Life-Years (QALYs) lost and costs were estimated using data from the literature. Vaccinating 12-year-old girls (efficacy=95%, no waning, cost/course=CAN$ 400) against HPV-16/18 and HPV-6/11/16/18 is estimated to cost the health provider CAN$ 31,000 (80%CrI: 15,000-55,000) and CAN$ 21,000 (80%CrI: 11,000-33,000) per QALY-gained, respectively. Results were most sensitive to age at vaccination, duration of vaccine protection, vaccine cost and QALY-lost due to GW, and were least sensitive to the medical costs. Vaccinating adolescent girls against HPV is likely to be cost-effective. The main benefit of vaccination will be in reducing CC mortality. However, unless screening is modified, the treatment costs saved through vaccination will be insignificant compared to the cost of HPV immunization.

Human papillomavirus-related oropharyngeal cancer.

PubMed

Taberna, M; Mena, M; Pavón, M A; Alemany, L; Gillison, M L; Mesía, R

2017-10-01

High-risk human papillomavirus (HPV) is now recognised as the principal cause of the increasing incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) in some parts of the world. The primary risk factor for developing HPV-related OPSCC is oral HPV-infection and the majority of oral HPV-infections are acquired by oral sex. Progression into an OPSCC includes persistent infection with evasion of immune response in the microenvironment, the activation of viral early genes (E6, E7) in basal epithelial cells, the deregulation of cell cycle and the accumulation of chromosomal instability. Patients affected by HPV-related OPSCC tend to be younger and have better outcomes. This observation has lead current research to evaluate treatment de-escalation options to reduce long-term associated morbidity. Moreover, a different molecular profile for HPV-related OPSCC has been described, opening new options for targeted therapy and immunotherapy approaches. This paper comprehensively reviews our accumulated knowledge regarding the role of HPV in OPSCC spanning from infection to cancer development, including its clinical diagnosis, management and preventive strategies. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

How Human Papillomavirus Replication and Immune Evasion Strategies Take Advantage of the Host DNA Damage Repair Machinery

PubMed Central

Bordignon, Valentina; Trento, Elisabetta; D’Agosto, Giovanna; Cavallo, Ilaria; Pontone, Martina; Pimpinelli, Fulvia; Mariani, Luciano; Ensoli, Fabrizio

2017-01-01

The DNA damage response (DDR) is a complex signalling network activated when DNA is altered by intrinsic or extrinsic agents. DDR plays important roles in genome stability and cell cycle regulation, as well as in tumour transformation. Viruses have evolved successful life cycle strategies in order to ensure a chronic persistence in the host, virtually avoiding systemic sequelae and death. This process promotes the periodic shedding of large amounts of infectious particles to maintain a virus reservoir in individual hosts, while allowing virus spreading within the community. To achieve such a successful lifestyle, the human papilloma virus (HPV) needs to escape the host defence systems. The key to understanding how this is achieved is in the virus replication process that provides by itself an evasion mechanism by inhibiting and delaying the host immune response against the viral infection. Numerous studies have demonstrated that HPV exploits both the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and rad3-related (ATR) DDR pathways to replicate its genome and maintain a persistent infection by downregulating the innate and cell-mediated immunity. This review outlines how HPV interacts with the ATM- and ATR-dependent DDR machinery during the viral life cycle to create an environment favourable to viral replication, and how the interaction with the signal transducers and activators of transcription (STAT) protein family and the deregulation of the Janus kinase (JAK)–STAT pathways may impact the expression of interferon-inducible genes and the innate immune responses. PMID:29257060

Vaccines for human papillomavirus infection: a critical analysis.

PubMed

Nath, Amiya Kumar; Thappa, Devinder Mohan

2009-01-01

This article takes a critical look at the pros and cons of human papillomavirus (HPV) vaccines. There is enough evidence to suggest that the prophylactic vaccines are efficacious in preventing various benign and malignant conditions (including cervical cancers) caused by HPV. Even though the vaccine is costly, hypothetical analysis has shown that HPV vaccination will be cost effective in the long run. Therapeutic HPV vaccines used to treat established disease are still undergoing evaluation in clinical studies, and results seem to be encouraging. Although several countries have started mandatory vaccination programs with the prophylactic HPV vaccines, conservatives have voiced concerns regarding the moral impact of such vaccination programs.

Awareness of HPV and Uptake of Vaccination in a High-Risk Population.

PubMed

Fishman, Jessica; Taylor, Lynne; Frank, Ian

2016-08-01

Immunization against the human papillomavirus (HPV) is effective at preventing HPV-related cancers, but vaccination rates have remained low. Levels of awareness could conceivably influence vaccination rates, but currently the relationship is unknown. This is the first study to test how strongly levels of awareness among parents and adolescents are related to subsequent HPV vaccination among a high-risk population of adolescents. This longitudinal cohort study measured baseline levels of awareness (about HPV, cervical cancer, HPV vaccination, and news or advertisements about HPV vaccination) among parents of adolescents and also a separate sample of adolescents. Participants resided in predominantly low-income, African American neighborhoods of a large American city. During a 12-month follow-up period, the outcome measures were defined as adolescent receipt of any HPV vaccination, as measured by clinic records. Within 1 year, <16% of adolescents received vaccination. The relationship between awareness and subsequent vaccination was either not statistically significant or not meaningful in magnitude, with R(2) = 0.004 to 0.02. The predicted probability of getting vaccination was <0.50 for all awareness levels and prediction accuracy was poor (area under the curve = 0.56-0.64). In this high-risk population, levels of awareness among parents and adolescents were not substantially related to subsequent adolescent HPV vaccination. Copyright © 2016 by the American Academy of Pediatrics.

Race-specific trends in HPV vaccinations and provider recommendations: persistent disparities or social progress?

PubMed

Burdette, Amy M; Webb, Noah S; Hill, Terrence D; Jokinen-Gordon, Hanna

2017-01-01

Although racial and ethnic differences in HPV vaccination initiation are well established, it is unclear whether these disparities have changed over time. The role of health provider recommendations in reducing any racial and ethnic inequalities is also uncertain. This study addresses these gaps in the literature. Repeated cross-sectional design. Using data from the National Immunization Survey-Teen (2008-2013), we estimated a series of binary logistic regressions to model race-specific trends in (1) provider recommendations to vaccinate against HPV and (2) HPV vaccine initiation for males (n = 56,632) and females (n = 77,389). Provider recommendations to vaccinate and HPV vaccination uptake have increased over time for adolescent males and females and across all racial and ethnic groups. Among girls, minority youths have seen a sharper increase in provider recommendations and HPV vaccination uptake than their White counterparts. Among boys, minority teens maintain higher overall rates of HPV vaccine uptake, however, Hispanics have lagged behind non-Hispanic Whites in the rate of increase in provider recommendations and HPV vaccinations. Our results suggest that racial and ethnic disparities in provider recommendations and HPV vaccinations have waned over time among males and females. While these trends are welcomed, additional interventions are warranted to increase overall rates of vaccination across race, ethnicity, and gender. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Prevention of HPV-Related Cancers in Norway: Cost-Effectiveness of Expanding the HPV Vaccination Program to Include Pre-Adolescent Boys

PubMed Central

Burger, Emily A.; Sy, Stephen; Nygård, Mari; Kristiansen, Ivar S.; Kim, Jane J.

2014-01-01

Background Increasingly, countries have introduced female vaccination against human papillomavirus (HPV), causally linked to several cancers and genital warts, but few have recommended vaccination of boys. Declining vaccine prices and strong evidence of vaccine impact on reducing HPV-related conditions in both women and men prompt countries to reevaluate whether HPV vaccination of boys is warranted. Methods A previously-published dynamic model of HPV transmission was empirically calibrated to Norway. Reductions in the incidence of HPV, including both direct and indirect benefits, were applied to a natural history model of cervical cancer, and to incidence-based models for other non-cervical HPV-related diseases. We calculated the health outcomes and costs of the different HPV-related conditions under a gender-neutral vaccination program compared to a female-only program. Results Vaccine price had a decisive impact on results. For example, assuming 71% coverage, high vaccine efficacy and a reasonable vaccine tender price of $75 per dose, we found vaccinating both girls and boys fell below a commonly cited cost-effectiveness threshold in Norway ($83,000/quality-adjusted life year (QALY) gained) when including vaccine benefit for all HPV-related diseases. However, at the current market price, including boys would not be considered ‘good value for money.’ For settings with a lower cost-effectiveness threshold ($30,000/QALY), it would not be considered cost-effective to expand the current program to include boys, unless the vaccine price was less than $36/dose. Increasing vaccination coverage to 90% among girls was more effective and less costly than the benefits achieved by vaccinating both genders with 71% coverage. Conclusions At the anticipated tender price, expanding the HPV vaccination program to boys may be cost-effective and may warrant a change in the current female-only vaccination policy in Norway. However, increasing coverage in girls is uniformly more effective and cost-effective than expanding vaccination coverage to boys and should be considered a priority. PMID:24651645

Exploring the role of ethnic identity on the attitudes towards HPV vaccine advertising among Puerto Ricans: A qualitative analysis

PubMed Central

Calo, William A.; Fernández, Maria E.; Fernández-Espada, Natalie; Colón-López, Vivian

2013-01-01

Despite the existence of guidelines recommending vaccination against the human papillomavirus (HPV) and widespread availability of the vaccine through the Vaccines for Children program, HPV vaccination rates among island Puerto Ricans are suboptimal. Advertising plays a central role in promoting HPV vaccination by increasing awareness of and knowledge about the vaccine; however, little is known about the influence of cultural factors on the impact of HPV messages delivered through the media. The aim of this qualitative study was to explore the role of ethnic identity on the attitudes towards HPV vaccine advertising among island Puerto Ricans. Five focus groups (n=23) were conducted with parents and non-vaccinated females. Our analysis found several themes that may influence attitudes towards HPV vaccine advertising among this population: physical ethnic similarity, relevance of information, and sociocultural congruence. Findings may assist in developing culturally appropriate health promotion programs and media to promote HPV vaccination among Puerto Ricans. PMID:24052477

Exploring the role of ethnic identity on the attitudes towards HPV vaccine advertising among Puerto Ricans: a qualitative analysis.

PubMed

Calo, William A; Fernández, Maria E; Fernández-Espada, Natalie; Colón-López, Vivian

2015-02-01

Despite the existence of guidelines recommending vaccination against the human papillomavirus (HPV) and widespread availability of the vaccine through the Vaccines for Children program, HPV vaccination rates among island Puerto Ricans are suboptimal. Advertising plays a central role in promoting HPV vaccination by increasing awareness of and knowledge about the vaccine; however, little is known about the influence of cultural factors on the impact of HPV messages delivered through the media. The aim of this qualitative study was to explore the role of ethnic identity on the attitudes towards HPV vaccine advertising among island Puerto Ricans. Five focus groups (n = 23) were conducted with parents and non-vaccinated females. Our analysis found several themes that may influence attitudes towards HPV vaccine advertising among this population: physical ethnic similarity, relevance of information, and sociocultural congruence. Findings may assist in developing culturally appropriate health promotion programs and media to promote HPV vaccination among Puerto Ricans.

Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like-particle vaccine in Latin American women.

PubMed

Perez, Gonzalo; Lazcano-Ponce, Eduardo; Hernandez-Avila, Mauricio; García, Patricia J; Muñoz, Nubia; Villa, Luisa L; Bryan, Janine; Taddeo, Frank J; Lu, Shuang; Esser, Mark T; Vuocolo, Scott; Sattler, Carlos; Barr, Eliav

2008-03-15

The prevalence of HPV infection in Latin America is among the highest in the world. A quadrivalent (types 6/11/16/18) human papillomavirus L1 virus-like-particle vaccine has been shown to be 95-100% effective in preventing HPV 6/11/16/18-related cervical and genital disease in women naive to vaccine HPV types. A total of 6,004 female subjects aged 9-24 were recruited from Brazil, Mexico, Colombia, Costa Rica, Guatemala and Peru. Subjects were randomized to immunization with intramuscular (deltoid) injections of HPV vaccine or placebo at enrollment (day 1), month 2 and month 6. Among vaccinated subjects in the per-protocol population from Latin America, quadrivalent HPV vaccine was 92.8 and 100% effective in preventing cervical intraepithelial neoplasia and external genital lesions related to vaccine HPV types, respectively. These data support vaccination of adolescents and young adults in the region, which is expected to greatly reduce the burden of cervical and genital cancers, precancers and genital warts. (c) 2007 Wiley-Liss, Inc.

Understanding genital warts: epidemiology, pathogenesis, and burden of disease of human papillomavirus.

PubMed

Bhatia, Neal; Lynde, Charles; Vender, Ronald; Bourcier, Marc

2013-12-01

As the most commonly sexually transmitted disease worldwide, human papillomavirus (HPV) infections are associated with significant morbidity and mortality. HPV infections most commonly affect young adults, women under 25 in particular. The most common risk factor for HPV infection in both sexes is a high number of lifetime sexual partners, whereas leading protective factors include circumcision, consistent condom use, and abstinence. Over 100 HPV types have been identified to date and are classified according to their level of oncogenic potential. HPV types 6 and 11 are responsible for approximately 90% of genital warts; HPV types 16 and 18 are responsible for 70% of invasive cervical cancers. External genital warts (EGWs) are the most common clinical manifestation of nononcogenic HPV infection. Coinfection with multiple HPV types is possible and may combine both low- and high-risk types, even in cases of genital warts. HPV infections are DNA viruses transmitted through skin-to-skin contact, invading the basal epithelial cells via microtears and evading the host immune response. Although non-life threatening, even low-risk HPV-type infections such as EGW carry a substantial psychosocial and economic burden. Stressors include the shame and embarrassment related to diagnosis, as well as the inconvenience and discomfort of treatment and the fear of recurrence, transmission, and the possible threat of cancer. Costs relate to routine screening for cervical cancer, treatment of genital warts, and the management and follow-up of malignancies.

Molecular tests potentially improving HPV screening and genotyping for cervical cancer prevention

PubMed Central

Gradíssimo, Ana

2018-01-01

INTRODUCTION Human papillomavirus (HPV)-related cancers can be averted by type-specific vaccination (primary prevention) and/or through detection and ablation of precancerous cervical lesions (secondary prevention). This review presents current challenges to cervical cancer screening programs, focusing on recent molecular advances in HPV testing and potential improvements on risk stratification. AREAS COVERED High-risk (HR)-HPV DNA detection has been progressively incorporated into cervix cancer prevention programs based on its increased sensitivity. Advances in next-generation sequencing (NGS) are being rapidly applied to HPV typing. However, current HPV DNA tests lack specificity for identification of cervical precancer (CIN3). HPV typing methods were reviewed based on published literature, with a focus on these applications for screening and risk stratification in the emerging complex clinical scenario post-vaccine introduction. In addition, the potential for NGS technologies to increase specificity is discussed in regards to reflex testing of specimens for emerging biomarkers for cervix precancer/cancer. EXPERT COMMENTARY Integrative multi-disciplinary molecular tests accurately triaging exfoliated cervical specimens will improve cervical cancer prevention programs while simplifying healthcare procedures in HPV-infected women. Hence, the concept of a “liquid-biopsy” (i.e., “molecular” Pap test) highly specific for early identification of cervical precancerous lesions is of critical importance in the years to come. PMID:28277144

Why are U.S. girls getting meningococcal but not human papilloma virus vaccines? Comparison of factors associated with human papilloma virus and meningococcal vaccination among adolescent girls 2008 to 2012.

PubMed

Perkins, Rebecca B; Lin, Mengyun; Silliman, Rebecca A; Clark, Jack A; Hanchate, Amresh

2015-01-01

Human papilloma virus (HPV) vaccination rates in the United States remain low, compared with other recommended adolescent vaccines. We compared factors associated with intention to receive and receipt of HPV and meningococcal vaccines and completion of the HPV vaccine series among U.S. adolescent girls. Secondary analysis of data from the National Immunization Survey-Teen for 2008 through 2012 was performed. Multivariable logistic modeling was used to determine factors associated with intent to receive and receipt of HPV and meningococcal vaccination, completion of the HPV vaccine series among girls who started the series, and receipt of HPV vaccination among girls who received meningococcal vaccination. Provider recommendation increased the odds of receipt and intention to receive both HPV and meningococcal vaccines. Provider recommendation was also associated with a three-fold increase in HPV vaccination among girls who received meningococcal vaccination (p<.001), indicating a relationship between provider recommendation and missed vaccine opportunities. However, White girls were 10% more likely to report provider recommendation than Black or Hispanic girls (p<.01), yet did not have higher vaccination rates, implying a role for parental refusal. No factors predicted consistently the completion of the HPV vaccine series among those who started. Improving provider recommendation for co-administration of HPV and meningococcal vaccines would reduce missed opportunities for initiating the HPV vaccine series. However, different interventions may be necessary to improve series completion. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Evaluation on the persistence of anti-HPV immune responses to the quadrivalent HPV vaccine in Chinese females and males: Up to 3.5 years of follow-up.

PubMed

Huang, Teng; Liu, Youping; Li, Yanping; Liao, Yuqin; Shou, Qiong; Zheng, Minghuan; Liao, Xueyan; Li, Rongcheng

2018-03-07

This was an extension study of a randomized, double-blind, placebo-controlled immunogenicity and safety study of the quadrivalent human papillomavirus (qHPV) (HPV 6, 11, 16, and 18) vaccine conducted in Chinese female subjects aged 9-45 years and male subjects aged 9-15 years. To investigate the persistence of anti-HPV 6, -11, -16, and -18 responses among Chinese subjects, subjects enrolled in the base study were followed up at around month 42 (approximately 3.5 years after vaccination). Among 600 subjects enrolled in the base study, a total of 468 subjects consented for participation in the extension study. Anti-HPV 6, -11, -16, and -18 antibodies were detected by the competitive Luminex immunoassay (cLIA) and total IgG Luminex immunoassay (IgG LIA). Among the female subjects who received the qHPV vaccine, the proportions of subjects remained seropositive were high with both the cLIA and IgG LIA for HPV type 6, 11, and 16 through approximately 42 months following the first dose vaccination. For HPV 18, the seropositivity rate remained high as 82.0% with the IgG LIA, while it decreased to 53.6% with the cLIA, which was similar to the findings observed in other studies. The seropositivity rates remained high at month 42 for all qHPV types with both the cLIA and IgG LIA among the male subjects. Administration of a 3-dose regimen of qHPV vaccine induces durable anti-HPV 6, anti-HPV 11, anti-HPV 16, and anti-HPV 18 responses among Chinese subjects for at least 3.5 years after vaccination. ClinicalTrials.gov registry:NCT01427777. Copyright © 2018. Published by Elsevier Ltd.

Human Papillomavirus Virus (HPV) Genotype- and Age-Specific Analyses of External Genital Lesions Among Men in the HPV Infection in Men (HIM) Study

PubMed Central

Ingles, Donna J.; Pierce Campbell, Christine M.; Messina, Jane A.; Stoler, Mark H.; Lin, Hui-Yi; Fulp, William J.; Abrahamsen, Martha; Sirak, Bradley A.; O'Keefe, Michael T.; Papenfuss, Mary; Gage, Christine; Carvalho da Silva, Roberto; Gonzalez Sosa, Rossana; Rojas Juarez, Oscar; Villa, Luisa L.; Lazcano Ponce, Eduardo; Giuliano, Anna R.

2015-01-01

Background. Human papillomavirus (HPV) causes external genital lesions (EGLs) in men, including condyloma and penile intraepithelial neoplasia (PeIN). We sought to determine the incidence of pathologically confirmed EGLs, by lesion type, among men in different age groups and to evaluate the HPV types that were associated with EGL development. Methods. HPV Infection in Men (HIM) study participants who contributed ≥2 visits from 2009–2013 were included in the biopsy cohort. Genotyping by an HPV line-probe assay was performed on all pathologically confirmed EGLs. Age-specific analyses were conducted for incident EGLs, with Kaplan–Meier estimation of cumulative incidence. Results. This biopsy cohort included 2754 men (median follow-up duration, 12.4 months [interquartile range, 6.9–19.2 months]). EGLs (n = 377) were pathologically confirmed in 228 men, 198 of whom had incident EGLs. The cumulative incidence of any EGL was highest among men <45 years old and, for condyloma, decreased significantly over time with age. The genotype-specific incidence of EGL varied by pathological diagnoses, with high- and low-risk genotypes found in 15.6% and 73.2% of EGLs, respectively. Condyloma primarily contained HPV 6 or 11. While PeIN lesions primarily contained HPV 16, 1 PeIN III lesion was positive for HPV 6 only. Conclusion. Low- and high-risk HPV genotypes contribute to the EGL burden. Men remain susceptible to HPV-related EGLs throughout the life span, making it necessary to ensure the longevity of immune protection against the most common causative HPV genotypes. PMID:25344518

Human papillomavirus virus (HPV) genotype- and age-specific analyses of external genital lesions among men in the HPV Infection in Men (HIM) Study.

PubMed

Ingles, Donna J; Pierce Campbell, Christine M; Messina, Jane A; Stoler, Mark H; Lin, Hui-Yi; Fulp, William J; Abrahamsen, Martha; Sirak, Bradley A; O'Keefe, Michael T; Papenfuss, Mary; Gage, Christine; Carvalho da Silva, Roberto; Gonzalez Sosa, Rossana; Rojas Juarez, Oscar; Villa, Luisa L; Lazcano Ponce, Eduardo; Giuliano, Anna R

2015-04-01

Human papillomavirus (HPV) causes external genital lesions (EGLs) in men, including condyloma and penile intraepithelial neoplasia (PeIN). We sought to determine the incidence of pathologically confirmed EGLs, by lesion type, among men in different age groups and to evaluate the HPV types that were associated with EGL development. HPV Infection in Men (HIM) study participants who contributed ≥2 visits from 2009-2013 were included in the biopsy cohort. Genotyping by an HPV line-probe assay was performed on all pathologically confirmed EGLs. Age-specific analyses were conducted for incident EGLs, with Kaplan-Meier estimation of cumulative incidence. This biopsy cohort included 2754 men (median follow-up duration, 12.4 months [interquartile range, 6.9-19.2 months]). EGLs (n = 377) were pathologically confirmed in 228 men, 198 of whom had incident EGLs. The cumulative incidence of any EGL was highest among men <45 years old and, for condyloma, decreased significantly over time with age. The genotype-specific incidence of EGL varied by pathological diagnoses, with high- and low-risk genotypes found in 15.6% and 73.2% of EGLs, respectively. Condyloma primarily contained HPV 6 or 11. While PeIN lesions primarily contained HPV 16, 1 PeIN III lesion was positive for HPV 6 only. Low- and high-risk HPV genotypes contribute to the EGL burden. Men remain susceptible to HPV-related EGLs throughout the life span, making it necessary to ensure the longevity of immune protection against the most common causative HPV genotypes. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Seroprevalence of Human Papillomavirus (HPV) Type 6, 11, 16, 18, by Anatomic Site of HPV Infection, in Women Aged 16-64 Years living in the Metropolitan Area of San Juan, Puerto Rico.

PubMed

Pérez-Caraballo, Aixa M; Suarez, Erick; Unger, Elizabeth R; Palefsky, Joel M; Panicker, Gitika; Ortiz, Ana Patricia

2018-03-01

It is unknown if human papillomavirus (HPV) serum antibody responses vary by anatomic site of infection. We aimed to assess the seroprevalence for HPV 6, 11, 16 and 18 in association with HPV DNA detection in different anatomic sites among women. This cross sectional population-based study analyzed data from 524 women aged 16-64 years living in the San Juan metropolitan area of Puerto Rico (PR). Questionnaires were used to assess demographic and lifestyle variables, while anogenital and blood samples were collected for HPV analysis. Logistic regression models were used to estimate the adjusted prevalence odds ratio (POR) in order to determine the association between HPV DNA infection status in the cervix and anus and serum antibody status, controlling for different potential confounders. Overall, 46.9% of women had detectable antibodies to one or more types whereas 8.7% had HPV DNA for one or more of these types detected in cervix (4.0%) or anus (6.5%). Women with cervical HPV detection tended to be more HPV seropositive than women without cervical detection (adjusted POR (95%CI): 2.41 (0.90, 6.47), p=0.078); however the type-specific association between cervical DNA and serum antibodies was only significant for HPV 18 (adjusted POR (95% CI): 5.9 (1.03, 33.98)). No significant association was detected between anal HPV and seropositivity (p>0.10). Differences in the anatomic site of infection could influence seroconversion, however, longitudinal studies will be required for further evaluation. This information will be instrumental in advancing knowledge of immune mechanisms involved in anatomic site response.

Altered Toll-like receptor expression and function in HPV-associated oropharyngeal carcinoma

PubMed Central

Tobouti, Priscila Lie; Bolt, Robert; Radhakrishnan, Raghu; de Sousa, Suzana Cantanhede Orsini Machado; Hunter, Keith D.

2018-01-01

Toll-like receptors (TLRs) have been widely investigated due to their importance in the inflammatory response and possible links to tumor promotion/regression and prognosis. In cancers with an infective etiology, such as human papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC), TLR responses may be activated and play a role in tumorigenesis. Our aim was to assess the expression of all TLRs in OPSCC cell lines (both HPV+ and HPV–) by qPCR, Western Blot and flow cytometry and assess their response to TLR ligands lipopolysaccharide (LPS), LPS ultra-pure (LPS-UP) and peptidoglycan (PGN) by analyzing IL-8 and IL-6 production. We also immunostained 61 OPSCC tissue samples with anti-TLR4. Results showed lower TLR1 and TLR6 mRNA expression and higher TLR9 protein expression in HPV+ when compared to HPV–OPSCC cells. TLR4 expression did not vary by HPV status in OPSCC cells, but TLR4 expression was significantly lower in HPV+OPSCC tissues. After stimulation with PGN, only one cell line (HPV+) did not secrete IL-6 or IL-8. Furthermore, HPV+OPSCC lines showed no IL-6 or IL-8 production on treatment with LPS/LPS-UP. The data suggest changes in TLR4 signaling in HPV+OPSCC, since we have shown lower tissue expression of TLR4 and no pro-inflammatory response after stimulation with LPS and LPS-UP. Also, it suggests that OPSCC may respond to HPV infection by increased expression of TLR9. This study demonstrates differences in expression and function of TLRs in OPSCC, which are dependent on HPV status, and may indicate subversion of the innate immune response by HPV infection. PMID:29416610

[What clinicians should know about human papilloma virus vaccines].

PubMed

Sanclemente, Gloria

2003-01-01

Human papillomaviruses (HPVs) are epitheliotropic viruses that infect the basal layer of mucosal and keratinizing epithelia. HPV viral genome is made up of an early transcription region (E) and a late region composed of genes L1, L2, and a long control region (LCR). Despite the benign character of most lesions, HPV oncogenicity has been demonstrated in anal cancer, epidermodysplasia verruciformis, and cervical cancer. Nearly 12% of worldwide cancer incidence is due to HPV infection and HPV-16 is the most prevalent genotype found. Therefore, efforts in vaccines against HPVs have been directed mainly toward this genotype to dramatically diminish worldwide anogenital cancer incidence. Therapeutic vaccines are based on induction of an immunologic response against infected cells that express modified viral antigens E6 and E7. Prophylactic vaccines are based on prevention of infection by means of induction of humoral immunity against capsid viral proteins L1 and L2. This article reviews basics of the design of HPV vaccines and the type of vaccines currently being evaluated in clinical studies.

E6 and E7 Gene Polymorphisms in Human Papillomavirus Types-58 and 33 Identified in Southwest China

PubMed Central

Wen, Qiang; Wang, Tao; Mu, Xuemei; Chenzhang, Yuwei; Cao, Man

2017-01-01

Cancer of the cervix is associated with infection by certain types of human papillomavirus (HPV). The gene variants differ in immune responses and oncogenic potential. The E6 and E7 proteins encoded by high-risk HPV play a key role in cellular transformation. HPV-33 and HPV-58 types are highly prevalent among Chinese women. To study the gene intratypic variations, polymorphisms and positive selections of HPV-33 and HPV-58 E6/E7 in southwest China, HPV-33 (E6, E7: n = 216) and HPV-58 (E6, E7: n = 405) E6 and E7 genes were sequenced and compared to others submitted to GenBank. Phylogenetic trees were constructed by Maximum-likelihood and the Kimura 2-parameters methods by MEGA 6 (Molecular Evolutionary Genetics Analysis version 6.0). The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by PAML 4.8 (Phylogenetic Analyses by Maximun Likelihood version4.8) software. The positive sites of HPV-33 and HPV-58 E6/E7 were contrasted by ClustalX 2.1. Among 216 HPV-33 E6 sequences, 8 single nucleotide mutations were observed with 6/8 non-synonymous and 2/8 synonymous mutations. The 216 HPV-33 E7 sequences showed 3 single nucleotide mutations that were non-synonymous. The 405 HPV-58 E6 sequences revealed 8 single nucleotide mutations with 4/8 non-synonymous and 4/8 synonymous mutations. Among 405 HPV-58 E7 sequences, 13 single nucleotide mutations were observed with 10/13 non-synonymous mutations and 3/13 synonymous mutations. The selective pressure analysis showed that all HPV-33 and 4/6 HPV-58 E6/E7 major non-synonymous mutations were sites of positive selection. All variations were observed in sites belonging to major histocompatibility complex and/or B-cell predicted epitopes. K93N and R145 (I/N) were observed in both HPV-33 and HPV-58 E6. PMID:28141822

The effect of a booster dose of quadrivalent or bivalent HPV vaccine when administered to girls previously vaccinated with two doses of quadrivalent HPV vaccine.

PubMed

Gilca, Vladimir; Sauvageau, Chantal; Boulianne, Nicole; De Serres, Gatson; Crajden, Mel; Ouakki, Manale; Trevisan, Andrea; Dionne, Marc

2015-01-01

This randomized, blinded study evaluated the immunogenicity and safety of a booster dose of Gardasil (qHPV) or Cervarix (bHPV) when administered to 12-13 year-old girls who were vaccinated at the age of 9-10 with 2 doses of qHPV (0-6 months). 366 out of 416 eligible girls participated in this follow-up study. Antibody titers were measured just before and one month post-booster. A Luminex Total IgG assay was used for antibody assessment and results are presented in Liminex Units (LU). Three years post-primary vaccination, 99-100% of subjects had detectable antibodies to 4HPV genotypes included in the qHPV with GMTs varying from 50 to 322 LU depending on genotype. After a booster dose of qHPV, a ≥4 fold increase of antibody titers to genotypes included in the vaccine was observed in 88-98% of subjects. Post-booster GMTs varied from 1666 to 4536 LU depending on genotype. These GMTs were 1.1 to 1.8-fold higher when compared to those observed one month post-second dose. After a booster of bHPV, a ≥4 fold increase of antibody titers to HPV16 and HPV18 was observed in 93-99% of subjects. The anti-HPV16 and HPV18 GMTs were 5458 and 2665 LU, respectively. These GMTs were 1.2 and 1.8 higher than those observed in the qHPV group (both P < 0.01). In bHPV group a 1.4-1.6-fold increase of antibody GMTs to HPV6 and HPV11was also observed (P < 0.001). The safety profile was acceptable for both vaccines. Both qHPV and bHPV increase antibody titers when given as a booster to girls previously vaccinated with 2 doses of qHPV. The magnitude of the immune response after booster is vaccine-dependent and has the same pattern as that reported after primary vaccination with qHPV or bHPV. When given as a booster, both vaccines have an acceptable safety profile. Longer follow-up studies are warranted to assess the need of booster doses.

Primary HPV testing versus cytology-based cervical screening in women in Australia vaccinated for HPV and unvaccinated: effectiveness and economic assessment for the National Cervical Screening Program.

PubMed

Lew, Jie-Bin; Simms, Kate T; Smith, Megan A; Hall, Michaela; Kang, Yoon-Jung; Xu, Xiang Ming; Caruana, Michael; Velentzis, Louiza Sofia; Bessell, Tracey; Saville, Marion; Hammond, Ian; Canfell, Karen

2017-02-01

Australia's National Cervical Screening Program currently recommends cytological screening every 2 years for women aged 18-69 years. Human papillomavirus (HPV) vaccination was implemented in 2007 with high population coverage, and falls in high-grade lesions in young women have been reported extensively. This decline prompted a major review of the National Cervical Screening Program and new clinical management guidelines, for which we undertook this analysis. We did effectiveness modelling and an economic assessment of potential new screening strategies, using a model of HPV transmission, vaccination, natural history, and cervical screening. First, we evaluated 132 screening strategies, including those based on cytology and primary HPV testing. Second, after a recommendation was made to adopt primary HPV screening with partial genotyping and direct referral to colposcopy of women positive for HPV16/18, we evaluated the final effect of HPV screening after incorporating new clinical guidelines for women positive for HPV. Both evaluations considered both unvaccinated and vaccinated cohorts. Strategies entailing HPV testing every 5 years and either partial genotyping for HPV16/18 or cytological co-testing were the most effective. One of the most effective and cost-effective strategies comprised primary HPV screening with referral of women positive for oncogenic HPV16/18 direct to colposcopy, with reflex cytological triage for women with other oncogenic types and direct referral for those in this group with high-grade cytological findings. After incorporating detailed clinical guidelines recommendations, this strategy is predicted to reduce cervical cancer incidence and mortality by 31% and 36%, respectively, in unvaccinated cohorts, and by 24% and 29%, respectively, in cohorts offered vaccination. Furthermore, this strategy is predicted to reduce costs by up to 19% for unvaccinated cohorts and 26% for cohorts offered vaccination, compared with the current programme. Primary HPV screening every 5 years with partial genotyping is predicted to be substantially more effective and potentially cost-saving compared with the current cytology-based screening programme undertaken every 2 years. These findings underpin the decision to transition to primary HPV screening with partial genotyping in the Australian National Cervical Screening Program, which will occur in May, 2017. Department of Health, Australia. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.

Optimal Management Strategies for Primary HPV Testing for Cervical Screening: Cost-Effectiveness Evaluation for the National Cervical Screening Program in Australia.

PubMed

Simms, Kate T; Hall, Michaela; Smith, Megan A; Lew, Jie-Bin; Hughes, Suzanne; Yuill, Susan; Hammond, Ian; Saville, Marion; Canfell, Karen

2017-01-01

Several countries are implementing a transition to HPV testing for cervical screening in response to the introduction of HPV vaccination and evidence indicating that HPV screening is more effective than cytology. In Australia, a 2017 transition from 2-yearly conventional cytology in 18-20 to 69 years to 5-yearly primary HPV screening in 25 to 74 years will involve partial genotyping for HPV 16/18 with direct referral to colposcopy for this higher risk group. The objective of this study was to determine the optimal management of women positive for other high-risk HPV types (not 16/18) ('OHR HPV'). We used a dynamic model of HPV transmission, vaccination, natural history and cervical screening to determine the optimal management of women positive for OHR HPV. We assumed cytology triage testing was used to inform management in this group and that those with high-grade cytology would be referred to colposcopy and those with negative cytology would receive 12-month surveillance. For those with OHR HPV and low-grade cytology (considered to be a single low-grade category in Australia incorporating ASC-US and LSIL), we evaluated (1) the 20-year risk of invasive cervical cancer assuming this group are referred for 12-month follow-up vs. colposcopy, and compared this to the risk in women with low-grade cytology under the current program (i.e. an accepted benchmark risk for 12-month follow-up in Australia); (2) the population-level impact of the whole program, assuming this group are referred to 12-month surveillance vs. colposcopy; and (3) the cost-effectiveness of immediate colposcopy compared to 12-month follow-up. Evaluation was performed both for HPV-unvaccinated cohorts and cohorts offered vaccination (coverage ~72%). The estimated 20-year risk of cervical cancer is ≤1.0% at all ages if this group are referred to colposcopy vs. ≤1.2% if followed-up in 12 months, both of which are lower than the ≤2.6% benchmark risk in women with low-grade cytology in the current program (who are returned for 12-month follow-up). At the population level, immediate colposcopy referral provides an incremental 1-3% reduction in cervical cancer incidence and mortality compared with 12-month follow-up, but this is in the context of a predicted 24-36% reduction associated with the new HPV screening program compared to the current cytology-based program. Furthermore, immediate colposcopy substantially increases the predicted number of colposcopies, with >650 additional colposcopies required to avert each additional case of cervical cancer compared to 12-month follow-up. Compared to 12-month follow-up, immediate colposcopy has an incremental cost-effectiveness ratio (ICER) of A$104,600/LYS (95%CrI:A$100,100-109,100) in unvaccinated women and A$117,100/LYS (95%CrI:A$112,300-122,000) in cohorts offered vaccination [Indicative willingness-to-pay threshold: A$50,000/LYS]. In primary HPV screening programs, partial genotyping for HPV16/18 or high-grade triage cytology in OHR HPV positive women can be used to refer the highest risk group to colposcopy, but 12-month follow-up for women with OHR HPV and low-grade cytology is associated with a low risk of developing cervical cancer. Direct referral to colposcopy for this group would be associated with a substantial increase in colposcopy referrals and the associated harms, and is also cost-ineffective; thus, 12-month surveillance for women with OHR HPV and low-grade cytology provides the best balance between benefits, harms and cost-effectiveness.

Optimal Management Strategies for Primary HPV Testing for Cervical Screening: Cost-Effectiveness Evaluation for the National Cervical Screening Program in Australia

PubMed Central

Hall, Michaela; Lew, Jie-Bin; Hughes, Suzanne; Yuill, Susan; Hammond, Ian; Saville, Marion; Canfell, Karen

2017-01-01

Background Several countries are implementing a transition to HPV testing for cervical screening in response to the introduction of HPV vaccination and evidence indicating that HPV screening is more effective than cytology. In Australia, a 2017 transition from 2-yearly conventional cytology in 18–20 to 69 years to 5-yearly primary HPV screening in 25 to 74 years will involve partial genotyping for HPV 16/18 with direct referral to colposcopy for this higher risk group. The objective of this study was to determine the optimal management of women positive for other high-risk HPV types (not 16/18) ('OHR HPV'). Methods We used a dynamic model of HPV transmission, vaccination, natural history and cervical screening to determine the optimal management of women positive for OHR HPV. We assumed cytology triage testing was used to inform management in this group and that those with high-grade cytology would be referred to colposcopy and those with negative cytology would receive 12-month surveillance. For those with OHR HPV and low-grade cytology (considered to be a single low-grade category in Australia incorporating ASC-US and LSIL), we evaluated (1) the 20-year risk of invasive cervical cancer assuming this group are referred for 12-month follow-up vs. colposcopy, and compared this to the risk in women with low-grade cytology under the current program (i.e. an accepted benchmark risk for 12-month follow-up in Australia); (2) the population-level impact of the whole program, assuming this group are referred to 12-month surveillance vs. colposcopy; and (3) the cost-effectiveness of immediate colposcopy compared to 12-month follow-up. Evaluation was performed both for HPV-unvaccinated cohorts and cohorts offered vaccination (coverage ~72%). Findings The estimated 20-year risk of cervical cancer is ≤1.0% at all ages if this group are referred to colposcopy vs. ≤1.2% if followed-up in 12 months, both of which are lower than the ≤2.6% benchmark risk in women with low-grade cytology in the current program (who are returned for 12-month follow-up). At the population level, immediate colposcopy referral provides an incremental 1–3% reduction in cervical cancer incidence and mortality compared with 12-month follow-up, but this is in the context of a predicted 24–36% reduction associated with the new HPV screening program compared to the current cytology-based program. Furthermore, immediate colposcopy substantially increases the predicted number of colposcopies, with >650 additional colposcopies required to avert each additional case of cervical cancer compared to 12-month follow-up. Compared to 12-month follow-up, immediate colposcopy has an incremental cost-effectiveness ratio (ICER) of A$104,600/LYS (95%CrI:A$100,100–109,100) in unvaccinated women and A$117,100/LYS (95%CrI:A$112,300–122,000) in cohorts offered vaccination [Indicative willingness-to-pay threshold: A$50,000/LYS]. Conclusions In primary HPV screening programs, partial genotyping for HPV16/18 or high-grade triage cytology in OHR HPV positive women can be used to refer the highest risk group to colposcopy, but 12-month follow-up for women with OHR HPV and low-grade cytology is associated with a low risk of developing cervical cancer. Direct referral to colposcopy for this group would be associated with a substantial increase in colposcopy referrals and the associated harms, and is also cost-ineffective; thus, 12-month surveillance for women with OHR HPV and low-grade cytology provides the best balance between benefits, harms and cost-effectiveness. PMID:28095411

Early Lessons Learned from Extramural School Programs That Offer HPV Vaccine

ERIC Educational Resources Information Center

Hayes, Kim A.; Entzel, Pamela; Berger, Wendy; Caskey, Rachel N.; Shlay, Judith C.; Stubbs, Brenda W.; Smith, Jennifer S.; Brewer, Noel T.

2013-01-01

Background: There has been little evaluation of school-located vaccination programs that offer human papillomavirus (HPV) vaccine in US schools without health centers (ie, extramural programs). This article summarizes lessons learned from such programs. Methods: In July to August 2010, 5 programs were identi?ed. Semistructured, in-depth telephone…

Comparative evaluation of the potential impact of rotavirus versus HPV vaccination in GAVI-eligible countries: a preliminary analysis focused on the relative disease burden.

PubMed

Kim, Sun-Young; Sweet, Steven; Chang, Joshua; Goldie, Sue J

2011-06-16

Immunization policymakers at global and local levels need to establish priorities among new vaccines competing for limited resources. However, comparison of the potential impact of single vaccination programs is challenging, primarily due to the limited number of vaccine analyses as well as their differing analytic approaches and reporting formats. The purpose of this study is to provide early insight into how the comparative impact of different new vaccines could be assessed in resource-poor settings with respect to affordability, cost-effectiveness, and distributional equity. We compared the health, economic, and financial consequences of introducing the two vaccines in 72 GAVI-eligible countries using a number of different outcome measures to evaluate affordability, cost-effectiveness, and distributional equity. We use simple static models to standardize the analytic framework and improve comparability between the two new vaccines. These simple models were validated by leveraging previously developed, more complex models for rotavirus and human papillomavirus (HPV). With 70% coverage of a single-age cohort of infants and pre-adolescent girls, the lives saved with rotavirus (~274,000) and HPV vaccines (~286,000) are similar, although the timing of averted mortality differs; rotavirus-attributable deaths occur in close proximity to infection, while HPV-related cancer deaths occur largely after age 30. Deaths averted per 1000 vaccinated are 5.2 (rotavirus) and 12.6 (HPV). Disability-adjusted life years (DALYs) averted were ~7.15 million (rotavirus) and ~1.30 million (HPV), reflecting the greater influence of discounting on the latter, given the lagtime between vaccination and averted cancer. In most countries (68 for rotavirus and 66 for HPV, at the cost of I$25 per vaccinated individual) the incremental cost per DALY averted was lower than each country's GDP per capita. Financial resources required for vaccination with rotavirus are higher than with HPV since both genders are vaccinated. While lifesaving benefits of rotavirus and HPV vaccines will be realized at different times, the number of lives saved over each target populations' lifetimes will be similar. Model-based analyses that use a standardized analytic approach and generate comparable outputs can enrich the priority-setting dialogue. Although new vaccines may be deemed cost-effective, other factors including affordability and distributional equity need to be considered in different settings. We caution that for priority setting in an individual country, more rigorous comparisons should be performed, using more comprehensive models and considering all relevant vaccines and delivery strategies.

Human papillomavirus vaccination: what is the best choice? A comparison of 16 strategies by means of a decisional model.

PubMed

Gasparini, R; Amicizia, D; Manfredi, P; Ansaldi, F; Lucioni, C; Gallelli, G; Panatto, D

2009-06-01

Some European countries decided to include human papillomavirus (HPV) vaccines in national immunization schedules. In order to help decision makers choose the best vaccination policy for females, a decisional model has been developed. The study was performed from the National Health Service perspective. Several hypotheses of multi-cohort vaccination policies were compared. 'Potentially avoidable infections' were chosen as the outcome. The model envisioned a short-term scenario (2008-2011). The best policy was that of vaccinating 12-year-olds and, a year later, those aged 14-16 years; the most expensive strategy was that of vaccinating 12-year-old females and, after 1 year, vaccinating those aged 15, 18 and 25 years. The sensitivity analysis showed that coverage rate has a great effect on the cost of avoidable infections. The study offers stake-holders an important datum-point for the choice of the best HPV policy vaccination in the short term. Indeed, it could generate interesting savings for the National Health Service and a rapid HPV immunization of young girls.

Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T Cell Mediated Tumor Control in the Genital Tract

PubMed Central

Sun, Yun-Yan; Peng, Shiwen; Han, Liping; Qiu, Jin; Song, Liwen; Tsai, Yachea; Yang, Benjamin; Roden, Richard B.S.; Trimble, Cornelia L.; Hung, Chien-Fu; Wu, T-C

2015-01-01

Purpose Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)-infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164). Experimental Design Here we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than IM delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16+ cervical cancer (TC-1 luc). Results We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8+ T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8+ T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8+ T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8+ T cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract. Conclusions Our results support future clinical translation using cervicovaginal TA-HPV vaccination. PMID:26420854

Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell-Mediated Tumor Control in the Genital Tract.

PubMed

Sun, Yun-Yan; Peng, Shiwen; Han, Liping; Qiu, Jin; Song, Liwen; Tsai, Yachea; Yang, Benjamin; Roden, Richard B S; Trimble, Cornelia L; Hung, Chien-Fu; Wu, T-C

2016-02-01

Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)-infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high-grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T-cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164). Here, we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than intramuscular (IM) delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16(+) cervical cancer (TC-1 luc). We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8(+) T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8(+) T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8(+) T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8(+) T-cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract. Our results support future clinical translation using cervicovaginal TA-HPV vaccination. ©2015 American Association for Cancer Research.

"Is It Like One of Those Infectious Kind of Things?" The Importance of Educating Young People about HPV and HPV Vaccination at School

ERIC Educational Resources Information Center

Davies, Cristyn; Skinner, Susan Rachel; Stoney, Tanya; Marshall, Helen Siobhan; Collins, Joanne; Jones, Jane; Hutton, Heidi; Parrella, Adriana; Cooper, Spring; McGeechan, Kevin; Zimet, Gregory

2017-01-01

The National Human Papillomavirus (HPV) Vaccination Program in Australia commenced in 2007 for girls and in 2013 for boys, using the quadrivalent HPV [4vHPV] vaccine. In Australia, students are primarily vaccinated en masse, on school grounds, after parental/ guardian consent is obtained. Students most often receive little, or no, education at…

A Multiple Streams analysis of the decisions to fund gender-neutral HPV vaccination in Canada.

PubMed

Shapiro, Gilla K; Guichon, Juliet; Prue, Gillian; Perez, Samara; Rosberger, Zeev

2017-07-01

In Canada, the human papillomavirus (HPV) vaccine is licensed and recommended for females and males. Although all Canadian jurisdictions fund school-based HPV vaccine programs for girls, only six jurisdictions fund school-based HPV vaccination for boys. The research aimed to analyze the factors that underpin government decisions to fund HPV vaccine for boys using a theoretical policy model, Kingdon's Multiple Streams framework. This approach assesses policy development by examining three concurrent, but independent, streams that guide analysis: Problem Stream, Policy Stream, and Politics Stream. Analysis from the Problem Stream highlights that males are affected by HPV-related diseases and are involved in transmitting HPV infection to their sexual partners. Policy Stream analysis makes clear that while the inclusion of males in HPV vaccine programs is suitable, equitable, and acceptable; there is debate regarding cost-effectiveness. Politics Stream analysis identifies the perspectives of six different stakeholder groups and highlights the contribution of government officials at the provincial and territorial level. Kingdon's Multiple Streams framework helps clarify the opportunities and barriers for HPV vaccine policy change. This analysis identified that the interpretation of cost-effectiveness models and advocacy of stakeholders such as citizen-advocates and HPV-affected politicians have been particularly important in galvanizing policy change. Copyright © 2017 Elsevier Inc. All rights reserved.

Can male vaccination reduce the burden of human papillomavirus-related disease in the United States?

PubMed

Low, Garren M I; Attiga, Yasser S; Garg, Gaurav; Schlegal, Richard; Gallicano, G Ian

2012-06-01

Human papillomavirus (HPV) can cause cervical cancer, as well as a number of other diseases in both men and women. Both sexes play a role in transmission of the disease, but the cost-effectiveness of HPV vaccination differs between them. It is necessary to determine the best allocation of limited resources between these two populations to produce the most effective strategy for reducing the burden from HPV-related disease. This literature review intends to elucidate the economic and social considerations that will lead to maximum utilization of vaccination programs, which in turn will reduce the burden of HPV-related disease. Current outreach in the United States is based on vaccination against HPV as a means for combating cervical cancer in women. If we are to include males, however, new marketing strategies must focus on educating patients about the full range of the vaccine's benefits. Men who have sex with men (MSM) are also unprotected against HPV in the current system. Social considerations alone may not be enough, however, as economic prediction models suggest that the associated costs outweigh the benefits in most circumstances. Taking this into account, our review also considers alternate methods of maximizing prevention of HPV-associated disease. The most prudent programs will include physician involvement in patient education and the implementation of structured vaccination and screening programs. Unfortunately, many countries do not have the necessary resources to undertake national vaccination programs. HPV testing and cytology screening for women and MSM may be the most financially reasonable option for many countries.

A randomized controlled trial of Human Papillomavirus (HPV) testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial)

PubMed Central

2010-01-01

Background In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome. Methods/Design HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases Discussion To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. Trial Registration International Standard Randomised Controlled Trial Number Register, ISRCTN79347302 PMID:20334685

Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection

PubMed Central

Gameiro, Steven F.; Zhang, Ali; Ghasemi, Farhad; Barrett, John W.; Mymryk, Joe S.

2017-01-01

Oncoproteins from high-risk human papillomaviruses (HPV) downregulate the transcription of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus in tissue culture model systems. This could allow infected or transformed cells to evade the adaptive immune response. Using data from over 800 human cervical and head & neck tumors from The Cancer Genome Atlas (TCGA), we determined the impact of HPV status on the mRNA expression of all six MHC-I heavy chain genes, and the β2 microglobulin light chain. Unexpectedly, these genes were all expressed at high levels in HPV positive (HPV+) cancers compared with normal control tissues. Indeed, many of these genes were expressed at significantly enhanced levels in HPV+ tumors. Similarly, the transcript levels of several other components of the MHC-I peptide-loading complex were also high in HPV+ cancers. The coordinated expression of high mRNA levels of the MHC-I antigen presentation apparatus could be a consequence of the higher intratumoral levels of interferon γ in HPV+ carcinomas, which correlate with signatures of increased infiltration by T- and NK-cells. These data, which were obtained from both cervical and oral tumors in large human cohorts, indicates that HPV oncoproteins do not efficiently suppress the transcription of the antigen presentation apparatus in human tumors. PMID:28891951

Cervical cancer cells suppress effector functions of cytotoxic T cells through the adenosinergic pathway.

PubMed

Mora-García, M L; Ávila-Ibarra, L R; García-Rocha, R; Weiss-Steider, B; Hernández-Montes, J; Don-López, C A; Gutiérrez-Serrano, V; Titla-Vilchis, I J; Fuentes-Castañeda, M C; Monroy-Mora, A; Jave-Suárez, L F; Chacón-Salinas, R; Vallejo-Castillo, L; Pérez-Tapia, S M; Monroy-García, A

2017-10-01

The expression of CD73 in tumor cells plays a significant role in the production of adenosine (Ado) that suppresses antitumor effector cells. In this study we analyzed the capability of HPV-positive (HPV+) cervical cancer (CeCa) cell lines CaSki, SiHa, HeLa, and RoVa; and HPV-negative (HPV-) cell lines C33A and ViBo to produce Ado and inhibit effector functions of CD8+ T cells. HPV+ CeCa cells expressed significantly higher levels of CD73 in the membrane (p<0.01) than HPV- CeCa cells and this expression was associated with the production of larger amounts of Ado (>400μM) compared to HPV-CeCa cells (<200μM) in the presence of AMP, as well asa stronger inhibition of (>50%) proliferation, activation, and cytotoxic activity of CD8+ T cells via interaction with A2A adenosine receptor. We also provide evidence that silenced E6/E7 expression in CeCa cells, strongly reduced its CD73 expression level and its capability to generate Ado. This results suggest that HPV infection, which is associated with more than 99% of CeCa cases, may present an increased constitutive expression of CD73 in cervical neoplasia to contribute to the suppression of the immune response mediated by the production of large amounts of Ado. Copyright © 2017 Elsevier Inc. All rights reserved.

Effectiveness Modelling and Economic Evaluation of Primary HPV Screening for Cervical Cancer Prevention in New Zealand

PubMed Central

Lew, Jie-Bin; Simms, Kate; Smith, Megan; Lewis, Hazel; Neal, Harold; Canfell, Karen

2016-01-01

Background New Zealand (NZ) is considering transitioning from 3-yearly cervical cytology screening in women 20–69 years (current practice) to primary HPV screening. We evaluated HPV-based screening in both HPV-unvaccinated women and cohorts offered HPV vaccination in New Zealand (vaccination coverage ~50%). Methods A complex model of HPV transmission, vaccination, cervical screening, and invasive cervical cancer was extensively validated against national population-based datasets. Sixteen potential strategies for HPV screening were considered. Results Most primary HPV strategies were more effective than current practice, for both unvaccinated women and cohorts offered vaccination. The optimal strategy for both groups was 5-yearly HPV screening in women aged 25–69 years with partial genotyping for HPV 16/18 and referral to colposcopy, and cytological triage of other oncogenic types. This is predicted to reduce cervical cancer incidence and mortality by a further 12–16% and to save 4–13% annually in program costs (excluding overheads). The findings are sensitive to assumptions about future adherence to initiating screening at 25 years. Conclusion Primary HPV screening with partial genotyping would be more effective and less costly than the current cytology-based screening program, in both unvaccinated women and cohorts offered vaccination. These findings have been considered in a review of cervical screening in NZ. PMID:27187495

Awareness, acceptability and uptake of human papilloma virus vaccine among Cameroonian school-attending female adolescents.

PubMed

Ayissi, Claudine Akono; Wamai, Richard G; Oduwo, Geofrey O; Perlman, Stacey; Welty, Edith; Welty, Thomas; Manga, Simon; Ogembo, Javier Gordon

2012-12-01

The purpose of this study is to assess awareness, knowledge and beliefs about HPV, cervical cancer HPV vaccine and willingness to vaccinate among adolescent females aged 12-26 years at clinics and schools in the North West Region of Cameroon where the Cameroon Baptist Convention Health Services (CBCHS) conducted a sensitization and education campaign. A questionnaire survey was administered among female adolescents in schools and clinics. Descriptive statistics including frequencies, percentages and proportions were generated for independent variables and bivariate analyses (Chi square test) were used to assess the relationship between independent and outcome variables. Data were analyzed using SAS Version 9.2. Out of a sample of 650 adolescent girls 553 willingly participated in this anonymous survey. Awareness of HPV (86.8%), cervical cancer (82.3%), and prevention of HPV infections through vaccination (75.9%) was significantly higher than in previous studies conducted in Cameroon and other developing countries. Higher perceptions of risk were associated with being sexually active (p = 0.0013), age (p = 0.0031) and level of education (p = 0.0274). Age and educational level were associated with HPV knowledge (p = 0.007 and p = 0.0008), respectively. The mean level of interest in HPV vaccination was 4.0 (SD = 1.27), which is above the mean. Our data indicate high awareness about HPV, cervical cancer and HPV vaccine among adolescents, and interest in receiving the vaccine and learning about the disease. CBCHS' community education strategy effectively raised acceptability and generated demand for HPV vaccine, making it a potential model for HPV immunization in Cameroon and other developing countries.

HLA-G and vertical mother-to-child transmission of human papillomavirus infection.

PubMed

Louvanto, Karolina; Roger, Michel; Faucher, Marie-Claude; Syrjänen, Kari; Grenman, Seija; Syrjänen, Stina

2018-06-01

Role of host factors in transmission of human papillomavirus (HPV)-infection from mother to her offspring is not known. Our aim was to study whether human leukocyte antigen (HLA)-G allele concordance among the mother-child pairs could facilitate vertical transmission of HPV, because HLA-G may contribute to immune tolerance in pregnancy. Altogether, 310 mother-child pairs were included from the Finnish Family HPV study. Overall, nine different HLA-G alleles were identified. The HLA-G genotype concordance of G ∗ 01:01:01/01:04:01 increased the risk of high risk (HR)-HPV genotype positivity in cord blood and infant's oral mucosa. The mother-child concordance of G ∗ 01:01:02/01:01:02 increased the risk of oral HPV positivity with HR-HPV genotypes both in the mother and offspring; OR 2.45 (95%CI 1.24-4.85). Discordant HLA-G allele for G ∗ 01:04:01 and for G ∗ 01:06 was significantly associated with infant's oral low risk (LR)-HPV at birth, OR 3.07 (95%CI 1.01-9.36) and OR 5.19 (95%CI 1.22-22.03), respectively. HLA-G had no association with HPV genotype-specific concordance between the mother and child at birth nor influence on perinatal HPV status of the child. Taken together, our results show that HLA-G molecules have a role in predicting the newborn's likelihood for oral HPV infection at birth. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Exploring the presentation of HPV information online: A semantic network analysis of websites.

PubMed

Ruiz, Jeanette B; Barnett, George A

2015-06-26

Negative vaccination-related information online leads some to opt out of recommended vaccinations. To determine how HPV vaccine information is presented online and what concepts co-occur. A semantic network analysis of the words in first-page Google search results was conducted using three negative, three neutral, and three positive search terms for 10 base concepts such as HPV vaccine, and HPV immunizations. In total, 223 of the 300 websites retrieved met inclusion requirements. Website information was analyzed using network statistics to determine what words most frequently appear, which words co-occur, and the sentiment of the words. High levels of word interconnectivity were found suggesting a rich set of semantic links and a very integrated set of concepts. Limited number of words held centrality indicating limited concept prominence. This dense network signifies concepts that are well connected. Negative words were most prevalent and were associated with describing the HPV vaccine's side-effects as well as the negative effects of HPV and cervical cancer. A smaller cluster focuses on reporting negative vaccine side-effects. Clustering shows the words women and girls closely located to the words sexually, virus, and infection. Information about the HPV vaccine online centered on a limited number of concepts. HPV vaccine benefits as well as the risks of HPV, including severity and susceptibility, were centrally presented. Word cluster results imply that HPV vaccine information for women and girls is discussed in more sexual terms than for men and boys. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Prospective Study of the Incidence of Juvenile-Onset Recurrent Respiratory Papillomatosis After Implementation of a National HPV Vaccination Program.

PubMed

Novakovic, Daniel; Cheng, Alan T L; Zurynski, Yvonne; Booy, Robert; Walker, Paul J; Berkowitz, Robert; Harrison, Henley; Black, Robert; Perry, Christopher; Vijayasekaran, Shyan; Wabnitz, David; Burns, Hannah; Tabrizi, Sepehr N; Garland, Suzanne M; Elliott, Elizabeth; Brotherton, Julia M L

2018-01-04

Recurrent respiratory papillomatosis is a rare but morbid disease caused by human papillomavirus (HPV) types 6 and 11. Infection is preventable through HPV vaccination. Following an extensive quadrivalent HPV vaccination program (females 12-26 years in 2007-2009) in Australia, we established a method to monitor incidence and demographics of juvenile-onset recurrent respiratory papillomatosis (JORRP) cases. The Australian Paediatric Surveillance Unit undertakes surveillance of rare pediatric diseases by contacting practitioners monthly. We enrolled pediatric otorhinolaryngologists and offered HPV typing. We report findings for 5 years to end 2016. The average annual incidence rate was 0.07 per 100000. The largest number of cases was reported in the first year, with decreasing annual frequency thereafter. Rates declined from 0.16 per 100000 in 2012 to 0.02 per 100000 in 2016 (P = .034). Among the 15 incident cases (60% male), no mothers were vaccinated prepregnancy, 20% had maternal history of genital warts, and 60% were first born; 13/15 were born vaginally. Genotyped cases were HPV-6 (n = 4) or HPV-11 (n = 3). To our knowledge, this is the first report internationally documenting decline in JORRP incidence in children following a quadrivalent HPV vaccination program. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

No evidence that HPV vaccination leads to sexual risk compensation.

PubMed

Hansen, Bo T

2016-06-02

Uptake of the HPV vaccine has been lower than the uptake of most other childhood vaccines offered in public programs. Since the HPV vaccine protects against a sexually transmitted virus, one barrier to uptake specific to the HPV vaccine may be the concern that vaccination may encourage risky sexual behaviour. Unanimous findings from recent studies show that HPV vaccination does not lead to sexual risk compensation, which is an important message to parents, clinicians and other decision-makers regarding HPV vaccination. Some issues remain to be investigated, like HPV vaccination and sexual risk compensation among boys.

The cost-effectiveness of male HPV vaccination in the United States.

PubMed

Chesson, Harrell W; Ekwueme, Donatus U; Saraiya, Mona; Dunne, Eileen F; Markowitz, Lauri E

2011-10-26

The objective of this study was to estimate the cost-effectiveness of adding human papillomavirus (HPV) vaccination of 12-year-old males to a female-only vaccination program for ages 12-26 years in the United States. We used a simplified model of HPV transmission to estimate the reduction in the health and economic burden of HPV-associated diseases in males and females as a result of HPV vaccination. Estimates of the incidence, cost-per-case, and quality-of-life impact of HPV-associated health outcomes were based on the literature. The HPV-associated outcomes included were: cervical intraepithelial neoplasia (CIN); genital warts; juvenile-onset recurrent respiratory papillomatosis (RRP); and cervical, vaginal, vulvar, anal, oropharyngeal, and penile cancers. The cost-effectiveness of male vaccination depended on vaccine coverage of females. When including all HPV-associated outcomes in the analysis, the incremental cost per quality-adjusted life year (QALY) gained by adding male vaccination to a female-only vaccination program was $23,600 in the lower female coverage scenario (20% coverage at age 12 years) and $184,300 in the higher female coverage scenario (75% coverage at age 12 years). The cost-effectiveness of male vaccination appeared less favorable when compared to a strategy of increased female vaccination coverage. For example, we found that increasing coverage of 12-year-old girls would be more cost-effective than adding male vaccination even if the increased female vaccination strategy incurred program costs of $350 per additional girl vaccinated. HPV vaccination of 12-year-old males might potentially be cost-effective, particularly if female HPV vaccination coverage is low and if all potential health benefits of HPV vaccination are included in the analysis. However, increasing female coverage could be a more efficient strategy than male vaccination for reducing the overall health burden of HPV in the population. Published by Elsevier Ltd.

Nationwide prevalence of human papillomavirus infection and viral genotype distribution in 37 cities in China.

PubMed

Wang, Rong; Guo, Xiao-Lei; Wisman, G Bea A; Schuuring, Ed; Wang, Wen-Feng; Zeng, Zheng-Yu; Zhu, Hong; Wu, Shang-Wei

2015-07-04

Type-specific high-risk HPV (hrHPV) infection is related to cervical carcinogenesis. The prevalence of hrHPV infection varies geographically, which might reflect the epidemiological characteristics of cervical cancer among different populations. To establish a foundation for HPV-based screening and vaccination programs in China, we investigated the most recent HPV prevalence and genotypic distributions in different female age groups and geographical regions in China. In 2012, a total of 120,772 liquid-based cytological samples from women enrolled for population- or employee-based cervical screening in 37 Chinese cities were obtained by the Laboratory of Molecular Infectious Diseases of Guangzhou KingMed. A total of 111,131 samples were tested by Hybrid Capture II and the other 9,641 were genotyped using the Tellgenplex™ HPV DNA Assay. The total positive rate for hrHPV was 21.07 %, which ranged from 18.42 % (Nanchang) to 31.94 % (Haikou) and varied by region. The regions of Nanchang, Changsha, Hangzhou, Chengdu, Fuzhou, Guangdong, and Guiyang could be considered the low prevalence regions. Age-specific prevalence showed a "two-peak" pattern, with the youngest age group (15-19 years) presenting the highest hrHPV infection rate (30.55 %), followed by a second peak for the 50-60-year-old group. Overall, the most prevalent genotypes were HPV16 (4.82 %) and HPV52 (4.52 %), followed by HPV58 (2.74 %). Two genotypes HPV6 (4.01 %) and HPV11 (2.29 %) were predominant in the low-risk HPV (lrHPV) type, while the mixed genotypes HPV16 + 52 and HPV52 + 58 were most common in women with multiple infections. This study shows that HPV infection in China has increased to the level of an "HPV-heavy-burden" zone in certain regions, with prevalence varying significantly among different ages and regions. Data from this study represent the most current survey of the nationwide prevalence of HPV infection in China, and can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs.

4-Valent Human Papillomavirus (4vHPV) Vaccine in Preadolescents and Adolescents After 10 Years.

PubMed

Ferris, Daron G; Samakoses, Rudiwilai; Block, Stanley L; Lazcano-Ponce, Eduardo; Restrepo, Jaime Alberto; Mehlsen, Jesper; Chatterjee, Archana; Iversen, Ole-Erik; Joshi, Amita; Chu, Jian-Li; Krick, Andrea Likos; Saah, Alfred; Das, Rituparna

2017-12-01

We describe the final 10-year data for the long-term follow-up study of the 4-valent human papillomavirus (4vHPV) vaccine in preadolescents and adolescents. In the base study (V501-018), 1661 sexually inactive boys and girls received the 4vHPV vaccine (early vaccination group [EVG], managed for 9.9 years) or a placebo at day 1, month 2, and month 6. Thereafter, at month 30, the placebo group (catch-up vaccination group [CVG], managed for 7.4 years) received the 4vHPV vaccine by using the same dosing schedule. Long-term anti-HPV type 6, 11, 16, and 18 immune responses were assessed. Effectiveness was estimated by calculating the incidence rate of the primary endpoints (HPV types 6, 11, 16, and 18-related disease or persistent infection). For HPV types 6, 11, and 16, 89% to 96% of subjects remained seropositive through 10-years postvaccination. The preadolescents had 38% to 65% higher geometric mean titers at month 7, which remained 16% to 42% higher at 10 years compared with adolescents. No cases of HPV type 6, 11, 16, and 18-related diseases were observed. Ten subjects had a persistent infection of ≥6 months duration with vaccine-type HPV and 2 subjects had persistent infection for ≥12 months. No new serious adverse events were reported through 10 years. A 3-dose regimen of the 4vHPV vaccine was immunogenic, clinically effective, and generally well tolerated in preadolescents and adolescents during 10 years of follow-up. These long-term findings support efforts to vaccinate this population against HPV before exposure. Copyright © 2017 by the American Academy of Pediatrics.

Immune cell infiltration in head and neck squamous cell carcinoma and patient outcome: a retrospective study.

PubMed

Schneider, Karolin; Marbaix, Etienne; Bouzin, Caroline; Hamoir, Marc; Mahy, Pierre; Bol, Vanesa; Grégoire, Vincent

2018-03-01

Human papillomavirus (HPV) prevalence in oropharynx squamous cell carcinoma (OPSCC) is on the rise. HPV-linked OPSCCs represent a distinct clinical entity with a better treatment response and patient survival compared to tumors not linked to HPV. An emerging role in treatment response has been attributed to immune cell infiltration in human tumors. In this study, we investigated immune cell infiltration in human SCC of the head and neck region and its relation to overall survival after treatment with surgery (with or without radiotherapy) or concomitant chemo (or cetuximab)-radiotherapy. Paraffin-embedded tumor samples of 136 patients with SCC of the larynx, hypopharynx, oral cavity and oropharynx were processed for immunohistochemical detection of CD3 + T-cells, CD8 + cytotoxic T-cells, CD20 + B-cells and CD163 + M2 macrophages within the tumor infiltrated area. Clinico-pathological data were analyzed as a function of tumor location and p16-status. Immune cell infiltration was represented as stained area on the whole tumor infiltrated area, compared for the different tumor locations and correlated to patient survival. Patients with oropharynx tumors expressing significant p16 levels (p16-sg) had a 5-year overall survival of 85% compared to 43% for patients with no significant p16 (p16-ns) expression (HR: 0.3 - 95% CI: 0.1-0.6). Median immune cell infiltration (T- and B-lymphocytes) was significantly elevated in p16-sg oropharyngeal tumors, compared to p16-ns oropharyngeal tumors and to all other head and neck tumor locations. No difference in CD163 + macrophage infiltration was observed across the different patient groups. In the whole population, a high infiltration by CD3 + T-lymphocytes was associated to a significantly (p = .03; HR: 0.6, 95% CI: 0.4-0.97) better overall survival. Oropharynx cancer with significant p16 expression showed an increased overall survival and elevated T- and B-lymphocyte infiltration, which suggests a prognostic relevance of immune cell infiltration.

Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

PubMed Central

Egawa, Nagayasu; Egawa, Kiyofumi; Griffin, Heather; Doorbar, John

2015-01-01

Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted. PMID:26193301

Promising systemic immunotherapies in head and neck squamous cell carcinoma

PubMed Central

Gildener-Leapman, Neil; Ferris, Robert L.; Bauman, Julie E.

2016-01-01

SUMMARY Patients with head and neck squamous cell carcinoma (HNSCC) demonstrate poor survival and significant treatment morbidity with standard therapy. The immune profile in HNSCC, whether caused by carcinogen exposure or human papillomavirus (HPV), is notably immunosuppressive. Early clinical trials of immunotherapy in HNSCC were troubled by systemic toxicity or difficulties in local administration. Now, interest in immunotherapy has been revitalized by mechanistic insights into immune evasion by HNSCC, coupled to ongoing development of novel immunotherapies. This review will summarize immune escape mechanisms in HNSCC, namely downregulation of tumor antigen (TA) presentation, aberrant regulation of the signal transducer and activator of transcription (STAT) family, the immunosuppressive cytokine milieu, and dysregulation of immune effector cells. Therapeutic strategies hypothesized to specifically counter HNSCC immunosuppression will then be discussed. We will survey TA-targeted monoclonal antibodies (mAb), including the prototype cetuximab, as well as adjunctive strategies to enhance antibody-dependent cell-mediated cytotoxicity. We will review immunomodulation to restore STAT1/STAT3 activation balance. Examples of mAb therapy to block immunosuppressive cytokines, such as interleukin-6 or VEGF, will be provided. mAbs which release co-inhibitory T cell receptors such as CTLA-4 and PD-1, overexpressed in HNSCC, also hold therapeutic promise. Finally, we will describe principles for therapeutic vaccination in HPV-associated HNSCC, where non-host TAs such as viral oncoproteins represent ideal targets, and HPV-negative HNSCC, where p53 is a promising target. Insights into immunosuppression in HNSCC have elucidated mechanistic targets for immunotherapy. Rational clinical investigation may lead to effective stand alone or combinatorial treatment approaches. PMID:24126223

Human papillomavirus prevalence and type-distribution, cervical cancer screening practices and current status of vaccination implementation in Russian Federation, the Western countries of the former Soviet Union, Caucasus region and Central Asia.

PubMed

Rogovskaya, Svetlana I; Shabalova, Irina P; Mikheeva, Irina V; Minkina, Galina N; Podzolkova, Nataly M; Shipulina, Olga Y; Sultanov, Said N; Kosenko, Iren A; Brotons, Maria; Buttmann, Nina; Dartell, Myassa; Arbyn, Marc; Syrjänen, Stina; Poljak, Mario

2013-12-31

Limited data are available on the burden of human papillomavirus (HPV) and its associated diseases in the Russian Federation, the Western Countries of the former Soviet Union (Belarus, Republic of Moldova, Ukraine), the Caucasus region and Central Asia (Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan). Both the incidence and mortality rate of cervical cancer are higher in these countries than in most Western European countries. In this article, we review available data on HPV prevalence and type distribution in women with normal cytology, women from the general population, cervical precancerous lesions and cervical cancer, as well as data on national policies of cervical cancer screening and HPV vaccination initiatives in these countries. Based on scarce data from the 12 countries, the high-risk HPV (hrHPV) prevalence among 5226 women with normal cytology ranged from 0.0% to 48.4%. In women with low-grade cervical lesions, the hrHPV prevalence among 1062 women varied from 29.2% to 100%. HrHPV infection in 565 women with high-grade cervical lesions ranged from 77.2% to 100% and in 464 invasive cervical cancer samples from 89.8% to 100%. HPV16 was the most commonly detected hrHPV genotype in all categories. As the HPV genotype distribution in cervical diseases seems to be similar to that found in Western Europe the implementation of HPV testing in screening programs might be beneficial. Opportunistic screening programs, the lack of efficient call-recall systems, low coverage, and the absence of quality assured cytology with centralized screening registry are major reasons for low success rates of cervical cancer programs in many of the countries. Finally, HPV vaccination is currently not widely implemented in most of the twelve countries mainly due to pricing, availability, and limited awareness among public and health care providers. Country-specific research, organized nationwide screening programs, registries and well defined vaccination policies are needed. This article forms part of a Regional Report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Central and Eastern Europe and Central Asia Region" Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2013 Elsevier Ltd. All rights reserved.

Social representations of human papillomavirus in Bogotá, Colombia.

PubMed

Wiesner, Carolina; Acosta, Jesús; Díaz Del Castillo, Adriana; Tovar, Sandra

2012-01-01

Identifying DNA of Human papillomavirus (HPV) has been proposed as a new screening method for cervical cancer control. Conventionally, health education for screening programs is based on scientific information without considering any community cognitive processes. We examine HPV social representations of 124 men and women from diverse educational status living in Bogotá, Colombia. The social representation of HPV involves a series of figurative nuclei derived from meanings linked to scientific information. While women focused on symbols associated to contagion, men focused on its venereal character. Figurative nuclei also included long-term uncertainty, need or urgent treatment, and feelings of imminent death associated with cancer and chronic sexually transmitted infections. The social representation of HPV impeded many participants from clearly understanding written information about HPV transmission, clearance, and cancer risk; they are built into a framework of values, which must be deconstructed to allow women full participation in HPV screening programs.

Comparison between Urine and Cervical Samples for HPV DNA Detection and Typing in Young Women in Colombia.

PubMed

Cómbita, Alba Lucía; Gheit, Tarik; González, Paula; Puerto, Devi; Murillo, Raúl Hernando; Montoya, Luisa; Vorsters, Alex; Van Keer, Severien; Van Damme, Pierre; Tommasino, Massimo; Hernández-Suárez, Gustavo; Sánchez, Laura; Herrero, Rolando; Wiesner, Carolina

2016-09-01

Urine sampling for HPV DNA detection has been proposed as an effective method for monitoring the impact of HPV vaccination programs; however, conflicting results have been reported. The goal of this study was to evaluate the performance of optimized urine HPV DNA testing in women aged 19 to 25 years. Optimization process included the use of first void urine, immediate mixing of urine with DNA preservative, and the concentration of all HPV DNA, including cell-free DNA fragments. Urine and cervical samples were collected from 535 young women attending cervical screening at health centers from two Colombian cities. HPV DNA detection and genotyping was performed using an HPV type-specific multiplex genotyping assay, which combines multiplex polymerase chain reaction with bead-based Luminex technology. Concordance between HPV DNA detection in urine and cervical samples was determined using kappa statistics and McNemar tests. The accuracy of HPV DNA testing in urine samples was evaluated measuring sensitivity and specificity using as reference the results obtained from cervical samples. Statistical analysis was performed using STATA11.2 software. The findings revealed an overall HPV prevalence of 60.00% in cervical samples and 64.72% in urine samples, HPV-16 being the most frequent HPV type detected in both specimens. Moreover, our results indicate that detection of HPV DNA in first void urine provides similar results to those obtained with cervical samples and can be used to monitor HPV vaccination trials and programs as evidenced by the substantial concordance found for the detection of the four vaccine types. Cancer Prev Res; 9(9); 766-71. ©2016 AACR. ©2016 American Association for Cancer Research.

Cost-effectiveness of human papillomavirus vaccination in the United States.

PubMed

Chesson, Harrell W; Ekwueme, Donatus U; Saraiya, Mona; Markowitz, Lauri E

2008-02-01

We describe a simplified model, based on the current economic and health effects of human papillomavirus (HPV), to estimate the cost-effectiveness of HPV vaccination of 12-year-old girls in the United States. Under base-case parameter values, the estimated cost per quality-adjusted life year gained by vaccination in the context of current cervical cancer screening practices in the United States ranged from $3,906 to $14,723 (2005 US dollars), depending on factors such as whether herd immunity effects were assumed; the types of HPV targeted by the vaccine; and whether the benefits of preventing anal, vaginal, vulvar, and oropharyngeal cancers were included. The results of our simplified model were consistent with published studies based on more complex models when key assumptions were similar. This consistency is reassuring because models of varying complexity will be essential tools for policy makers in the development of optimal HPV vaccination strategies.

Dynamics of high-risk nonvaccine human papillomavirus types after actual vaccination scheme.

PubMed

Peralta, Raúl; Vargas-De-León, Cruz; Cabrera, Augusto; Miramontes, Pedro

2014-01-01

Human papillomavirus (HPV) has been identified as the main etiological factor in the developing of cervical cancer (CC). This finding has propitiated the development of vaccines that help to prevent the HPVs 16 and 18 infection. Both genotypes are associated with 70% of CC worldwide. In the present study, we aimed to determine the emergence of high-risk nonvaccine HPV after actual vaccination scheme to estimate the impact of the current HPV vaccines. A SIR-type model was used to study the HPV dynamics after vaccination. According to the results, our model indicates that the application of the vaccine reduces infection by target or vaccine genotypes as expected. However, numerical simulations of the model suggest the presence of the phenomenon called vaccine-induced pathogen strain replacement. Here, we report the following replacement mechanism: if the effectiveness of cross-protective immunity is not larger than the effectiveness of the vaccine, then the high-risk nonvaccine genotypes emerge. In this scenario, further studies of infection dispersion by HPV are necessary to ascertain the real impact of the current vaccines, primarily because of the different high-risk HPV types that are found in CC.

Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: a partially-blind randomised placebo-controlled study.

PubMed

Denny, Lynette; Hendricks, Bronwyn; Gordon, Chivaugn; Thomas, Florence; Hezareh, Marjan; Dobbelaere, Kurt; Durand, Christelle; Hervé, Caroline; Descamps, Dominique

2013-11-19

In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18-25 years (N=120) were stratified by CD4⁺ T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix®; GlaxoSmithKline Vaccines) or placebo (Al[OH]3) at 0, 1 and 6 months (double-blind). HIV-negative women (N=30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4⁺ T-cell responses, CD4⁺ T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4⁺ T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4⁺ T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4⁺ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection. Study ID: 107863/NCT00586339. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Women with HIV are more commonly infected with non-16 and -18 high-risk HPV types.

PubMed

McKenzie, Nathalie Dauphin; Kobetz, Erin N; Hnatyszyn, James; Twiggs, Leo B; Lucci, Joseph A

2010-03-01

To review and summarize evidence from clinical, translational and epidemiologic studies which have examined the clinically relevant aspects of HPV type prevalence and cervical dysplasia in HIV-infected women. Relevant studies were identified through a MEDLINE search. References of identified reports were also used to identify additional published articles for review. HIV-infected women in different geographic regions (such as Zambia, Brazil, Rochester NY) appear to be infected with less prevalent types of HR-HPV as compared to the general population who, across all continents, are more commonly infected with types 16 and 18. Secondly, integration of HPV DNA into the host genome is no longer thought to be a necessary cause of malignant transformation of cervical cells. However, rate of integration appears to differ by the type of HPV. In fact, the types of HPV which appear to be more common in cervical dysplasia of HIV-infected women are the same types which are more likely to require integration for malignant transformation. Finally, HPV types found in HIV-infected women are relatively common and likely to persist. The most common among these types belong to the alpha-9 and -7 species which are the most carcinogenic species. Given that current vaccines target HR-HPV-16/18, the findings from the above mentioned studies may have important implications for the design of HPV vaccines that target the types of HPV associated with disease risk in HIV-infected women. HPV typing and assessment of the physical state (whether it is integrated or episomal) appear to be two valuable parameters for the prognostic evaluation of dysplastic lesions of the uterine cervix. This, however, has not yet been assessed in HIV-infected women. Recent data about the immune response in HPV/HIV co-infection may lead to understanding potential mechanisms for less virulent HPV causing malignant transformation in HIV-infected women.

Feasibility of community-based careHPV for cervical cancer prevention in rural Thailand.

PubMed

Trope, Lee A; Chumworathayi, Bandit; Blumenthal, Paul D

2013-07-01

This study aimed to assess the safety, acceptability and feasibility of primary human papillomavirus (HPV) testing for cervical cancer prevention at the community level in a low-resource setting. After training a technician to run specimens on the careHPV unit, the study team traveled to a different village each day in rural Roi-et Province, Thailand. Women were tested for HPV using self-swab, followed by careHPV testing. Those with positive result were assessed immediately by visual inspection with acetic acid. Women positive for HPV and visual inspection with acetic acid were offered cryotherapy. Safety was determined by monitoring adverse events. Exit surveys assessed acceptability and feasibility. Feasibility was also assessed by measuring testing and triage throughputs. Technician training required 2.5 days to achieve competency. A total of 431 women were screened in 14 days, with an average of 31 women screened daily. No adverse events were reported. Women deemed the program overwhelmingly acceptable: 90.5% reported that they would take the self-swab again, 71.3% preferred the self-swab to a clinician swab. The program was also feasible: 99.8% of eligible women agreed to testing, 94.8% returned for same-day follow-up, and women only spent 30 to 50 minutes of their total time with the program from screening to results. Cervical cancer prevention programs based on self-swab HPV testing could be safe, acceptable, feasible, and effective at the community level in low-resource settings.

Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes

PubMed Central

Soldan, Kate; Lehtinen, Matti; Beddows, Simon; Brisson, Marc; Brotherton, Julia M.L.; Chow, Eric P.F.; Cummings, Teresa; Drolet, Mélanie; Fairley, Christopher K.; Garland, Suzanne M.; Kahn, Jessica A.; Kavanagh, Kimberley; Markowitz, Lauri; Pollock, Kevin G.; Söderlund-Strand, Anna; Sonnenberg, Pam; Tabrizi, Sepehr N.; Tanton, Clare; Unger, Elizabeth; Thomas, Sara L.

2016-01-01

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important. PMID:27648688

Genital Warts

MedlinePlus

... that they can't be seen with the naked eye. Sometimes, however, genital warts may multiply into ... on Immunization Practices recommends routine HPV vaccination for girls and boys ages 11 and 12. If not ...

Commercially available molecular tests for human papillomaviruses (HPV): 2015 update.

PubMed

Poljak, Mario; Kocjan, Boštjan J; Oštrbenk, Anja; Seme, Katja

2016-03-01

Commercial molecular tests for human papillomaviruses (HPV) are invaluable diagnostic tools in cervical carcinoma screening and management of women with cervical precancerous lesions as well as important research tools for epidemiological studies, vaccine development, and implementation and monitoring of vaccination programs. In this third inventory of commercial HPV tests, we identified 193 distinct commercial HPV tests and at least 127 test variants available on the market in 2015, which represents a 54% and 79% increase in the number of distinct HPV tests and variants, respectively, in comparison to our last inventory performed in 2012. Identified HPV tests were provisionally divided into eight main groups and several subgroups. Among the 193 commercial HPV tests, all but two target alpha-HPV types only. Although the number of commercial HPV tests with at least one published study in peer-reviewed literature has increased significantly in the last three years, several published performance evaluations are still not in line with agreed-upon standards in the HPV community. Manufacturers should invest greater effort into evaluating their products and publishing validation/evaluation results in peer-reviewed journals. To achieve this, more clinically oriented external quality-control panels and initiatives are required. For evaluating the analytical performance of the entire range of HPV tests currently on the market, more diverse and reliable external quality-control programs based on international standards for all important HPV types are indispensable. The performance of a wider range of HPV tests must be promptly evaluated on a variety of alternative clinical specimens. In addition, more complete HPV assays containing validated sample-extraction protocols and appropriate internal controls are urgently needed. Provision of a broader range of automated systems allowing large-scale HPV testing as well as the development of reliable, rapid, and affordable molecular point-of-care tests are priorities for the further improvement of HPV tests. Copyright © 2015 Elsevier B.V. All rights reserved.

Knowledge and awareness of HPV vaccine and acceptability to vaccinate in sub-Saharan Africa: a systematic review.

PubMed

Perlman, Stacey; Wamai, Richard G; Bain, Paul A; Welty, Thomas; Welty, Edith; Ogembo, Javier Gordon

2014-01-01

We assessed the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate in sub-Saharan African (SSA) countries. We further identified countries that fulfill the two GAVI Alliance eligibility criteria to support nationwide HPV vaccination. We conducted a systematic review of peer-reviewed studies on the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate. Trends in Diphtheria-tetanus-pertussis (DTP3) vaccine coverage in SSA countries from 1990-2011 were extracted from the World Health Organization database. The review revealed high levels of willingness and acceptability of HPV vaccine but low levels of knowledge and awareness of cervical cancer, HPV or HPV vaccine. We identified only six countries to have met the two GAVI Alliance requirements for supporting introduction of HPV vaccine: 1) the ability to deliver multi-dose vaccines for no less than 50% of the target vaccination cohort in an average size district, and 2) achieving over 70% coverage of DTP3 vaccine nationally. From 2008 through 2011 all SSA countries, with the exception of Mauritania and Nigeria, have reached or maintained DTP3 coverage at 70% or above. There is an urgent need for more education to inform the public about HPV, HPV vaccine, and cervical cancer, particularly to key demographics, (adolescents, parents and healthcare professionals), to leverage high levels of willingness and acceptability of HPV vaccine towards successful implementation of HPV vaccination programs. There is unpreparedness in most SSA countries to roll out national HPV vaccination as per the GAVI Alliance eligibility criteria for supporting introduction of the vaccine. In countries that have met 70% DTP3 coverage, pilot programs need to be rolled out to identify the best practice and strategies for delivering HPV vaccines to adolescents and also to qualify for GAVI Alliance support.

Knowledge and Awareness of HPV Vaccine and Acceptability to Vaccinate in Sub-Saharan Africa: A Systematic Review

PubMed Central

Perlman, Stacey; Wamai, Richard G.; Bain, Paul A.; Welty, Thomas; Welty, Edith; Ogembo, Javier Gordon

2014-01-01

Objectives We assessed the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate in sub-Saharan African (SSA) countries. We further identified countries that fulfill the two GAVI Alliance eligibility criteria to support nationwide HPV vaccination. Methods We conducted a systematic review of peer-reviewed studies on the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate. Trends in Diphtheria-tetanus-pertussis (DTP3) vaccine coverage in SSA countries from 1990–2011 were extracted from the World Health Organization database. Findings The review revealed high levels of willingness and acceptability of HPV vaccine but low levels of knowledge and awareness of cervical cancer, HPV or HPV vaccine. We identified only six countries to have met the two GAVI Alliance requirements for supporting introduction of HPV vaccine: 1) the ability to deliver multi-dose vaccines for no less than 50% of the target vaccination cohort in an average size district, and 2) achieving over 70% coverage of DTP3 vaccine nationally. From 2008 through 2011 all SSA countries, with the exception of Mauritania and Nigeria, have reached or maintained DTP3 coverage at 70% or above. Conclusion There is an urgent need for more education to inform the public about HPV, HPV vaccine, and cervical cancer, particularly to key demographics, (adolescents, parents and healthcare professionals), to leverage high levels of willingness and acceptability of HPV vaccine towards successful implementation of HPV vaccination programs. There is unpreparedness in most SSA countries to roll out national HPV vaccination as per the GAVI Alliance eligibility criteria for supporting introduction of the vaccine. In countries that have met 70% DTP3 coverage, pilot programs need to be rolled out to identify the best practice and strategies for delivering HPV vaccines to adolescents and also to qualify for GAVI Alliance support. PMID:24618636

Implementation of HPV-testing for cervical cancer screening in programmatic contexts: The Jujuy demonstration project in Argentina.

PubMed

Arrossi, Silvina; Thouyaret, Laura; Laudi, Rosa; Marín, Oscar; Ramírez, Josefina; Paolino, Melisa; Herrero, Rolando; Campanera, Alicia

2015-10-01

The aim of this article is to present results of programmatic introduction of HPV testing with cytologic triage among women 30 years and older in the province of Jujuy, Argentina, including description of the planning phase and results of program performance during the first year. We describe the project implementation process, and calculate key performance indicators using SITAM, the national screening information system. We also compare disease detection rates of HPV testing in 2012 with cytology as performed during the previous year. HPV testing with cytology triage was introduced through a consensus-building process. Key activities included establishment of algorithms and guidelines, creating the HPV laboratory, training of health professionals, information campaigns for women and designing the referral network. By the end of 2012, 100% (n = 270) of public health care centers were offering HPV testing and 22,834 women had been HPV tested, 98.5% (n = 22,515) were 30+. HPV positivity among women over 30 was 12.7%, 807 women were HPV+ and had abnormal cytology, and 281 CIN2+ were identified. CIN2+ detection rates was 1.25 in 2012 and 0.62 in 2011 when the program was cytology based (p = 0.0002). This project showed that effective introduction of HPV testing in programmatic contexts of low-middle income settings is feasible and detects more disease than cytology. © 2015 UICC.

Assessing cost-effectiveness of HPV vaccines with decision analytic models: what are the distinct challenges of low- and middle-income countries? A protocol for a systematic review.

PubMed

Ekwunife, Obinna I; Grote, Andreas Gerber; Mosch, Christoph; O'Mahony, James F; Lhachimi, Stefan K

2015-05-12

Cervical cancer poses a huge health burden, both to developed and developing nations, making prevention and control strategies necessary. However, the challenges of designing and implementing prevention strategies differ for low- and middle-income countries (LMICs) as compared to countries with fully developed health care systems. Moreover, for many LMICs, much of the data needed for decision analytic modelling, such as prevalence, will most likely only be partly available or measured with much larger uncertainty. Lastly, imperfect implementation of human papillomavirus (HPV) vaccination may influence the effectiveness of cervical cancer prevention in unpredictable ways. This systematic review aims to assess how decision analytic modelling studies of HPV cost-effectiveness in LMICs accounted for the particular challenges faced in such countries. Specifically, the study will assess the following: (1) whether the existing literature on cost-effectiveness modelling of HPV vaccines acknowledges the distinct challenges of LMICs, (2) how these challenges were accommodated in the models, (3) whether certain parameters systemically exhibited large degrees of uncertainty due to lack of data and how influential were these parameters on model-based recommendations, and (4) whether the choice of modelling herd immunity influences model-based recommendations, especially when coverage of a HPV vaccination program is not optimal. We will conduct a systematic review to identify suitable studies from MEDLINE (via PubMed), EMBASE, NHS Economic Evaluation Database (NHS EED), EconLit, Web of Science, and CEA Registry. Searches will be conducted for studies of interest published since 2006. The searches will be supplemented by hand searching of the most relevant papers found in the search. Studies will be critically appraised using Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement checklist. We will undertake a descriptive, narrative, and interpretative synthesis of data to address the study objectives. The proposed systematic review will assess how the cost-effectiveness studies of HPV vaccines accounted for the distinct challenges of LMICs. The gaps identified will expose areas for additional research as well as challenges that need to be accounted for in future modelling studies. PROSPERO CRD42015017870.

Association of Health Insurance Status and Vaccination Coverage among Adolescents 13-17 Years of Age.

PubMed

Lu, Peng-Jun; Yankey, David; Jeyarajah, Jenny; O'Halloran, Alissa; Fredua, Benjamin; Elam-Evans, Laurie D; Reagan-Steiner, Sarah

2018-04-01

To assess selected vaccination coverage among adolescents by health insurance status and other access-to-care characteristics. The 2015 National Immunization Survey-Teen data were used to assess vaccination coverage disparities among adolescents by health insurance status and other access-to-care variables. Multivariable logistic regression analysis and a predictive marginal modeling were conducted to evaluate associations between health insurance status and vaccination coverage. Overall, vaccination coverage was significantly lower among uninsured compared with insured adolescents for all vaccines assessed for except ≥3 doses of human papillomavirus vaccine (HPV) among male adolescents. Among adolescents 13-17 years of age, vaccination of uninsured compared with insured adolescents, respectively, for tetanus toxoid, reduced content diphtheria toxoid, and acellular pertussis vaccine was 77.4% vs 86.8%; for ≥1 dose of meningococcal conjugate vaccine was 72.9% vs 81.7%; for ≥1 dose of HPV was 38.8% vs 50.2% among male and 42.9% vs 63.8% among female adolescents; for 3 doses of HPV was 24.9% vs 42.8% among female adolescents. In addition, vaccination coverage differed by the following: type of insurance among insured adolescents, having a well-child visit at 11-12 years of age, and number of healthcare provider contacts in the past year. Uninsured were less likely than insured adolescents to be vaccinated for HPV (female: ≥1 dose and 3 doses; and male: ≥1 doses) after adjusting for confounding variables. Overall, vaccination coverage was lower among uninsured adolescents. HPV vaccination coverage was lower than tetanus toxoid, reduced content diphtheria toxoid, and acellular pertussis vaccine Tdap and meningococcal conjugate vaccine in both insured and uninsured adolescents. Wider implementation of effective evidence-based strategies is needed to help improve vaccination coverage among adolescents, particularly for those who are uninsured. Limitation of current federally funded vaccination programs or access to healthcare would be expected to erode vaccine coverage of adolescents. Published by Elsevier Inc.

HPV Immunization | Cancer Trends Progress Report

Cancer.gov

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

To Consent or Decline HPV Vaccination: A Pilot Study at the Start of the National School-Based Vaccination Program in Sweden

ERIC Educational Resources Information Center

Grandahl, Maria; Tydén, Tanja; Westerling, Ragnar; Nevéus, Tryggve; Rosenblad, Andreas; Hedin, Erik; Oscarsson, Marie

2017-01-01

Background: Parents' beliefs about human papillomavirus (HPV) vaccination influence whether they allow their daughters to be vaccinated. We examined the association between parents' refusal and sociodemographic background, knowledge and beliefs about HPV, and the HPV vaccination in relation to the Health Belief Model. Methods: The sample consisted…

A pilot study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16+ cervical intraepithelial neoplasia 2/3 (CIN2/3).

PubMed

Alvarez, Ronald D; Huh, Warner K; Bae, Sejong; Lamb, Lawrence S; Conner, Michael G; Boyer, Jean; Wang, Chenguang; Hung, Chien-Fu; Sauter, Elizabeth; Paradis, Mihaela; Adams, Emily A; Hester, Shirley; Jackson, Bradford E; Wu, T C; Trimble, Cornelia L

2016-02-01

The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of a plasmid vaccine, pNGVL4a-CRT-E7(detox), administered either intradermally, intramuscularly, or directly into the cervical lesion, in patients with HPV16-associated CIN2/3. Eligible patients with HPV16(+) CIN2/3 were enrolled in treatment cohorts evaluating pNGVL4a-CRT-E7(detox), administered by either particle-mediated epidermal delivery (PMED), intramuscular injection (IM), or cervical intralesional injection, at study weeks 0, 4, and 8. Patients were monitored for local injection site and systemic toxicity. A standard therapeutic resection was performed at week 15. The primary endpoints were safety and tolerability. Secondary endpoints included histologic regression and change in cervical HPV viral load. Exploratory endpoints included immune responses in the blood and in the target tissue. Thirty-two patients with HPV16(+) CIN2/3 were enrolled onto the treatment phase of the study, and were vaccinated. Twenty-two of 32 patients (69%) experienced vaccine-specific related adverse events. The most frequent vaccine-related events were constitutional and local injection site in nature, and were grade 1 or less in severity. Histologic regression to CIN 1 or less occurred in 8 of 27 (30%) patients who received all vaccinations and underwent LEEP. In subject-matched comparisons, intraepithelial CD8+ T cell infiltrates increased after vaccination in subjects in the intralesional administration cohort. pNGVL4a-CRT-E7(detox) was well-tolerated, elicited the most robust immune response when administered intralesionally, and demonstrated preliminary evidence of potential clinical efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

A Pilot Study of pNGVL4a-CRT/E7(detox) for the Treatment of Patients with HPV16+ Cervical Intraepithelial Neoplasia 2/3 (CIN2/3)

PubMed Central

Alvarez, Ronald D.; Huh, Warner K.; Bae, Sejong; Lamb, Lawrence S.; Conner, Michael G.; Boyer, Jean; Wang, Chenguang; Hung, Chien-Fu; Sauter, Elizabeth; Paradis, Mihaela; Adams, Emily A.; Hester, Shirley; Jackson, Bradford E.; Wu, T.C.; Trimble, Cornelia

2015-01-01

Objective The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of a plasmid vaccine, pNGVL4a-CRT-E7(detox), administered either intradermally, intramuscularly, or directly into the cervical lesion, in patients with HPV16-associated CIN2/3. Methods Eligible patients with HPV16+ CIN2/3 were enrolled in treatment cohorts evaluating pNGVL4a-CRT-E7(detox), administered by either particle-mediated epidermal delivery (PMED), intramuscular injection (IM), or cervical intralesional injection, at study weeks 0, 4, and 8. Patients were monitored for local injection site and systemic toxicity. A standard therapeutic resection was performed at week 15. The primary endpoints were safety and tolerability. Secondary endpoints included histologic regression and change in cervical HPV viral load. Exploratory endpoints included immune responses in the blood and in the target tissue. Results Thirty-two patients with HPV16+ CIN2/3 were enrolled onto the treatment phase of the study, and were vaccinated. Twenty-two of 32 patients (69%) experienced vaccine-specific related adverse events. The most frequent vaccine-related events were constitutional and local injection site in nature, and were grade 1 or less in severity. Histologic regression to CIN 1 or less occurred in 8 of 27 (30%) patients who received all vaccinations and underwent LEEP. In subject-matched comparisons, intraepithelial CD8+ T cell infiltrates increased after vaccination in subjects in the intralesional administration cohort. Conclusion pNGVL4a-CRT-E7(detox) was well-tolerated, elicited the most robust immune response when administered intralesionally, and demonstrated preliminary evidence of potential clinical efficacy. PMID:26616223

Optimization and validation of a high throughput method for detecting neutralizing antibodies against human papillomavirus (HPV) based on pseudovirons.

PubMed

Nie, Jianhui; Huang, Weijin; Wu, Xueling; Wang, Youchun

2014-09-01

The pseudoviron-based neutralization assay is accepted as the gold standard to evaluate the functional humoral immune response against HPV. The goal of this study was to develop and optimize a human papillomavirus (HPV) neutralization assay using HPV pseudovirons with Gaussia luciferase (Gluc) as the reporter gene. For this purpose, high-titers Gluc pseudovirons were generated by cotransfecting 293TT cells with HPV structural genes and Gluc expressing plasmids. Six types of neutralizing monoclonal antibodies, vaccines immunized serum samples and WHO international antibody standard were used to validate the new developed assay. The ideal circumstances of the assay were identified for cell counts (30,000/well for 96-well plate), pseudoviron inoculating size (100 times RLU above background) and incubation time (72 hr). The sensitivity of the Gluc assay was comparable to secreted alkaline phosphatase (SEAP) assay and higher than the green florescent protein (GFP) assay. The non-specific background for different types of sample was significantly different (rabbit sera > human sera > mouse sera, P < 0.01). The non-specific neutralization effects were not attributed to IgG antibody. The cutoff value for this assay was determined as 50% inhibition at a dilution of 1:40. Without requirements of sample dilution and different incubation times at different temperature before processing, the detection time was shortened from more than 90 min to less than 5 min for a 96-well plate compared with the SEAP-based assay. With the advantages of short detection time and easy-to-use procedure, the newly developed assay is more suitable for large sero-epidemiological studies or clinical trials and more amenable to automation. © 2014 Wiley Periodicals, Inc.

Altered Expression of TAP-1 and Major Histocompatibility Complex Class I in Laryngeal Papillomatosis: Correlation of TAP-1 with Disease

PubMed Central

Vambutas, Andrea; Bonagura, Vincent R.; Steinberg, Bettie M.

2000-01-01

Recurrent respiratory papillomatosis (RRP) is an insidious disease caused by human papillomavirus (HPV) infection. It is characterized by a variable clinical course that can include frequent disease recurrence, significant morbidity, and occasional mortality. The mechanisms responsible for the variability in the clinical course and the persistence of latent HPV infection remain unknown. Effective T-cell-mediated clearance of HPV-infected cells may be defective in patients with RRP, leading to recurrent disease and failure to suppress latent HPV reactivation. This study describes the down-regulation of the transporter associated with antigen presentation (TAP-1) and the major histocompatibility complex (MHC) class I protein expression in laryngeal papilloma tissue biopsies and cell culture of primary explants. There was a statistically significant correlation between reduction of TAP-1 expression in biopsy tissues and rapid recurrence of disease. Patients with RRP had less frequent recurrence if their papillomas expressed TAP-1 at levels close to that of normal tissue, compared with those with very low expression of TAP-1, who had frequent recurrence (32 versus 5 weeks to the next surgical intervention). These findings suggest that HPV may evade immune recognition by down-regulating class I MHC cell surface expression via decreased TAP-1 levels. Expression of TAP-1 could be used for prognostic evaluation of disease severity. Gamma interferon was able to restore class I MHC expression at the surfaces of laryngeal papilloma cells in culture. This up-regulation of class I MHC antigen at the cell surface potentially allows the infected cell to become a target for the immune system again. This finding provides some promise for nonsurgical treatment of laryngeal papillomas. PMID:10618282

Factors Associated With Parents’ Intent to Vaccinate Adolescents for Human Papillomavirus: Findings From the 2014 National Immunization Survey–Teen

PubMed Central

Mohammed, Kahee A.; Vivian, Elaina; Loux, Travis M.

2017-01-01

Introduction While factors associated with receipt of human papillomavirus (HPV) vaccination have been well characterized, less is known about the characteristics associated with parents’ intent to have their adolescent children vaccinated. This study aimed to examine factors associated with parental intention toward HPV vaccination. Methods We analyzed data on 10,354 adolescents aged 13 to 17 years from the 2014 National Immunization Survey–Teen. Weighted multivariable logistic regression was used to examine associations between sociodemographic characteristics of mothers and adolescents, as well as a health care provider recommendation with parents’ intention to have their children receive HPV vaccine. Results Among unvaccinated adolescents, Hispanic ethnicity (boys adjusted odds ratio [AOR], 1.87, 95% confidence interval [CI], 1.34–2.61; and girls AOR, 1.57; 95% CI, 1.05–2.35), mothers with less than a high school diploma (boys AOR, 2.41; 95% CI, 1.58–3.67; and girls AOR, 1.86; 95% CI, 1.02–3.38), and having a health care provider recommend the vaccine (boys AOR, 1.87; 95% CI, 1.52–2.31; and girls AOR, 1.38; 95% CI, 1.05–1.82) were significantly associated with parents’ intention to have their adolescent child vaccinated within the next 12 months. In addition, non-Hispanic black race was a significant predictor of parents’ intent to vaccinate for boys (AOR, 1.89; 95% CI, 1.35–2.65). Conclusion Maternal education and Hispanic ethnicity were the strongest predictors of parental intent to vaccinate against HPV, followed by provider recommendation. As HPV vaccination rates in the United States remain below the Healthy People 2020 goal, messages may need to be targeted based on maternal education, race/ethnicity, and provider recommendation. PMID:28595031

Barriers to human papillomavirus vaccine acceptability in Israel.

PubMed

Fisher, William A; Laniado, Hila; Shoval, Hila; Hakim, Marwan; Bornstein, Jacob

2013-11-22

Barriers to human papillomavirus (HPV) vaccine acceptability in Israel include Israel's relatively low incidence of cervical cancer; the religiously-based 80% circumcision rate in Israel, which is regarded as contributing to the lower incidence of HPV infection in the country; the fact that HPV vaccine provides immunity against only few virus types; the vaccine's high cost; and the perception that HPV transmission is associated with unacceptable sexual relations. A recent survey has demonstrated that, following media two campaigns, Israeli's level of awareness of the vaccine increased but the actual vaccination rate remained low, at approximately 10%. Survey findings also indicated that an enduring barrier to HPV vaccination is the vaccine's high cost. Recent research on a convenience sample of Israeli undergraduate women 21 to 24 years of age showed that intentions to receive HPV vaccination in the coming year were a function of women's attitudes towards getting vaccinated and their perceptions of social support for doing so. Undergraduate women who intended to be vaccinated perceived the prevention of cervical cancer, avoidance of personal health threat, and avoidance of HPV infection per se to be the advantages of undergoing HPV vaccination. Disadvantages of getting vaccinated included fear of vaccine side effects, cost of the vaccine, and newness of the vaccine, doubts about vaccines, time required to undergo multiple vaccinations, and dislike of injections. Friends', mothers' and physicians' recommendations influenced women's intentions to be vaccinated in the coming year as well. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human papilloma virus vaccines: Current scenario

PubMed Central

Pandhi, Deepika; Sonthalia, Sidharth

2011-01-01

Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection with an estimated worldwide prevalence of 9–13% and approximately 6 million people being infected each year. Mostly acquired during adolescence or young adulthood, HPV presents clinically as anogenital warts and may progress to precancerous lesions and cancers of the cervix, vagina, vulva, penis and anus, and oropharynx. HPV infection is considered to contribute to almost 100% cervical cancers and at least 80% of anal and 40–60% of vulvar, vaginal, and penile cancers. At present, two prophylactic HPV vaccines are commercially available and both are prepared from purified L1 structural proteins. These proteins self-assemble to form virus-like particles that induce a protective immunity. Gardasil® is a quadrivalent vaccine against HPV types 6, 11, 16, and 18 and is recommended for use in females 9–26 years of age, for the prevention of cervical, vulvar, and vaginal cancers and intraepithelial neoplasia and condyloma acuminata and recently for vaccination in boys and men 9–26 years of age for the prevention of genital warts. Cervarix™ is a bivalent vaccine approved for the prevention of cervical cancer and precancerous lesions caused by HPV 16 and 18, in females 10–25 years. HPV vaccines are safe and efficacious against type-specific HPV-induced anogenital warts, precancerous lesions, and cervical cancer. The vaccines are most effective when given before the onset of sexual activity and provide long-term protection. Effective vaccination coverage in young adolescent females will substantially reduce the incidence of these anogenital malignancy-related morbidity and mortality. There is need to generate India-specific data on HPV epidemiology and HPV vaccination efficacy as well as continue worldwide surveillance and development of newer vaccines. PMID:22021967

Quality of physician communication about human papillomavirus vaccine: findings from a national survey.

PubMed

Gilkey, Melissa B; Malo, Teri L; Shah, Parth D; Hall, Megan E; Brewer, Noel T

2015-11-01

Improving the quality of physicians' recommendations for human papillomavirus (HPV) vaccination is critical to addressing low coverage. Thus, we sought to describe HPV vaccine communication practices among primary care physicians. Pediatricians and family physicians (n = 776) completed our national online survey in 2014. We assessed the quality of their HPV vaccine recommendations on strength of endorsement (i.e., saying the vaccine is important), timeliness (recommending it by ages 11-12), consistency (recommending it routinely vs. using a risk-based approach), and urgency (recommending same-day vaccination). A sizeable minority of physicians reported that they do not strongly endorse HPV vaccine (27%) or deliver timely recommendations for girls (26%) or boys (39%). Many physicians (59%) used a risk-based approach to recommending HPV vaccine, and only half (51%) usually recommended same-day vaccination. Overall recommendation quality was lower among physicians who were uncomfortable talking about HPV vaccine or who believed parents did not value it. Quality was higher among physicians who began discussions by saying the child was due for HPV vaccine versus giving information or eliciting questions. Many physicians in our national sample reported recommending HPV vaccine inconsistently, behind schedule, or without urgency. These practices likely contribute to under-immunization among adolescents, and may convey ambivalence to parents. As one of the first studies to assess multiple aspects of recommendation quality, these findings can inform the many state and national initiatives that aim to improve communication about HPV vaccine so as to address the persistent underuse of a powerful tool for cancer prevention. ©2015 American Association for Cancer Research.

Distribution of High Risk Human Papillomavirus Types in Western Kazakhstan - Retrospective Analysis of PCR Data.

PubMed

Bekmukhambetov, Yz; Balmagambetova, Sk; Jarkenov, Ta; Nurtayeva, Sm; Mukashev, Tz; Koyshybaev, Ak

2016-01-01

Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV). Cancer of the cervix is the third or even the second most common cancer in women worldwide, more than 85% of the cases occurring in developing countries, such as China and India, including the Republic of Kazakhstan. The purpose was to determine the HPV type distribution to evaluate efficacy of vaccination and adjust cancer prevention strategy in Western Kazakhstan in the future. A retrospective analysis was conducted of data obtained from PCR laboratories in 4 regional centers for the time period covering 12 months, 2013-2014, using AmpliSens® Real-Time PCR kits for HPV testing of 12 genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). A total of 1,661 persons were HPV tested within 2013-14, but a proprotion examined for 16 and 18 genotypes only (563) was not been included for statistic analysis of distribution and ratio of the most common genotypes. Males accounted for only a small number (N=90 in total). Total number of the HPV-positive appeared to be 26.0%, or 286 of N=1098. Types distribution was as follows: type 16 (10.7%), 39 (5.83%), 51 (5.27%), 31 (4.85%), 56 (4.58%), 18 (3.61%), 59 (2.64%), 58 (2.22%), 35 (1.94%), 33 (1.25%). Overall the HPV infection was highest in 16-29 years old (62.4%) and decreased with age. Total prevalence of the HR-HPVs amongst male population was 21.4% with top five types 16, 18, 39, 51, 31. Trends forcorrelations between Aktau site and type 33 (Cramer's V 0.2029), between Caucasian ethnicity and type 33 (Cramer's V .1716), and between European ethnicities in Uralsk and type 45 (Cramer's V .1752) were found. Of N 563 tested separately for 16 or 18 types, 13.6% were positive. As a whole, the distribution of 16/18 types had a ratio of 3.53:1. Given the vaccine-targeted type 16 is widely spread amongst this regional population, HPV immunization program of adolescent girls 10-13 years should be implemented appropriately.

Pros, cons, and ethics of HPV vaccine in teens-Why such controversy?

PubMed

White, Mark Donald

2014-12-01

Human papillomavirus (HPV) infection remains one of the most commonly sexually transmitted infections in both females and males. HPV viruses are associated with several manifestations including genital warts, but more importantly for urology practitioners, cervical and penile carcinomas and recurrent genital condylomata in both sexes. The incidence of HPV-related carcinomas has increased in cervical, oropharyngeal, vulvar, penile, and anal cancers. Effective vaccines have been available for almost a decade, but widespread adoption of vaccine administration has been problematic for multiple reasons. Many countries (over 100) have adopted vaccine programs for females and an increasing number of countries are extending the indications to include males between the ages of 9-26. There still seems to be controversy surrounding these universal vaccination programs as well as some ethical and practical concerns regarding the administration of a vaccine for diseases that are associated with sexual contact in both sexes, especially during the early adolescent years. The objective was to provide a review of the available literature so pediatric and adult urologists may be more aware of the issues related to HPV vaccination in order to more effectively counsel patients and parents regarding the risks, benefits, and public health issues regarding HPV vaccination. This topic is especially relevant to pediatric urologists who see patients in the target age group for the HPV vaccine. There has been an explosion of literature regarding HPV vaccination programs and the relative difficulty in adopting the vaccine series with a completion rate of under 50% of patients in the recommended age ranges for vaccination. Articles were obtained from an extensive Medline literature search (1998-present) to evaluate the current HPV vaccination regimens for teenagers with special emphasis on the urologically focused disease burden. The adoption of universal HPV vaccination has been difficult, but appears to be increasing over time as public education improves and governmentally- mandated vaccine programs increase. Despite the ethical concerns raised, the benefits of vaccination with regard to cancer prevention outweigh the risks and potential side effects related to the quadrivalent vaccine administration. Clearly, more follow-up over time is required to document these improvements in public health. Urologists need to remain aware of the prevention strategies for HPV infection and should help with counseling parents and patients in the appropriate age groups for HPV vaccination. Urology providers need to help engage and educate the parents and teenage patients to help promote broader adoption of the HPV vaccine regimen.

Human papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vandermark, Erik R.; Deluca, Krysta A.; Gardner, Courtney R.

2012-03-30

The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. In contrast, activation of NF-kB by constitutive expressionmore » of p65 inhibited proliferation and immortalization. Our results suggest that inhibition of NF-kB by HPV-16 E6/E7 contributes to immortalization of cells from the cervical transformation zone.« less

Rational Design of Peptide Vaccines Against Multiple Types of Human Papillomavirus

PubMed Central

Dey, Sumanta; De, Antara; Nandy, Ashesh

2016-01-01

Human papillomavirus (HPV) occurs in many types, some of which cause cervical, genital, and other cancers. While vaccination is available against the major cancer-causing HPV types, many others are not covered by these preventive measures. Herein, we present a bioinformatics study for the designing of multivalent peptide vaccines against multiple HPV types as an alternative strategy to the virus-like particle vaccines being used now. Our technique of rational design of peptide vaccines is expected to ensure stability of the vaccine against many cycles of mutational changes, elicit immune response, and negate autoimmune possibilities. Using the L1 capsid protein sequences, we identified several peptides for potential vaccine design for HPV 16, 18, 33, 35, 45, and 11 types. Although there are concerns about the epitope-binding affinities for the peptides identified in this process, the technique indicates possibilities of multivalent, adjuvanted, peptide vaccines against a wider range of HPV types, and tailor-made different combinations of the peptides to address frequency variations of types over different population groups as required for prophylaxis and at lower cost than are in use at the present time. PMID:27279731

T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation.

PubMed

Woodham, Andrew W; Yan, Lisa; Skeate, Joseph G; van der Veen, Daniel; Brand, Heike H; Wong, Michael K; Da Silva, Diane M; Kast, W Martin

2016-12-01

Human papillomavirus type 16 (HPV16) infections are intra-epithelial, and thus, HPV16 is known to interact with Langerhans cells (LCs), the resident epithelial antigen-presenting cells (APCs). The current paradigm for APC-mediated induction of T cell anergy is through delivery of T cell receptor signals via peptides on MHC molecules (signal 1), but without costimulation (signal 2). We previously demonstrated that LCs exposed to HPV16 in vitro present HPV antigens to T cells without costimulation, but it remained uncertain if such T cells would remain ignorant, become anergic, or in the case of CD4+ T cells, differentiate into Tregs. Here we demonstrate that Tregs were not induced by LCs presenting only signal 1, and through a series of in vitro immunizations show that CD8 + T cells receiving signal 1 + 2 from LCs weeks after consistently receiving signal 1 are capable of robust effector functions. Importantly, this indicates that T cells are not tolerized but instead remain ignorant to HPV, and are activated given the proper signals.

Sustained Antibody Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent Human Papillomavirus (HPV) Vaccine in Adolescent Fijian Girls, and Subsequent Responses to a Single Dose of Bivalent HPV Vaccine: A Prospective Cohort Study.

PubMed

Toh, Zheng Quan; Russell, Fiona M; Reyburn, Rita; Fong, James; Tuivaga, Evelyn; Ratu, Tupou; Nguyen, Cattram D; Devi, Rachel; Kama, Mike; Matanitobua, Silivia; Tabrizi, Sepehr N; Garland, Suzanne M; Sinha, Rohit; Frazer, Ian; Tikoduadua, Lisi; Kado, Joseph; Rafai, Eric; Mulholland, Edward K; Licciardi, Paul V

2017-04-01

The duration of antibody response following reduced human papillomavirus (HPV) vaccine doses has not been determined. We compared the antibody responses in girls previously vaccinated with zero, 1, 2, or 3 doses of quadrivalent HPV vaccine (4vHPV; Gardasil, Merck) 6 years previously. A prospective cohort study was undertaken in 200 Fijian girls 15-19 years of age. Approximately equal numbers of girls from 2 main ethnic groups (Fijians of Indian descent [FID] and Indigenous Fijians [iTaukei]) in Fiji were recruited for each dosage groups. Blood was drawn before and 28 days following a single dose of bivalent HPV vaccine (2vHPV; Cervarix, GlaxoSmithKline). We measured neutralizing antibodies (NAb) against HPV-6, -11, -16, and -18 using the pseudovirion-based neutralization assay. After 6 years (before a dose of 2vHPV was given), the geometric mean NAb titers for all 4 HPV types were not statistically different between 2-dose (2D) and 3-dose (3D) recipients: HPV-6 (3D: 2216 [95% confidence interval {CI},1695-2896]; 2D: 1476 [95% CI, 1019-2137]; P = .07), HPV-11 (3D: 4431 [95% CI, 3396-5783]; 2D: 2951 [95% CI, 1984-4390]; P = .09), HPV-16 (3D: 3373 [95% CI, 2511-4530]; 2D: 3275 [95% CI, 2452-4373]; P = .89); HPV-18 (3D: 628 [95% CI: 445-888]; 2D: 606 [95% CI, 462-862]; P = .89), and were higher in FID than iTaukei girls. Although 1-dose recipients had significantly lower NAb titers than 2-/3-dose recipients, their NAb titers were 5- to 30-fold higher than unvaccinated girls. Post-2vHPV NAb titers against HPV-16 and -18 were not statistically different between girls who received 1, 2, or 3 doses of 4vHPV previously. Two doses of 4vHPV provide similar NAb titers as 3 doses for 6 years, although the clinical significance is unknown. A single dose of 4vHPV elicits antibodies that persisted for at least 6 years, and induced immune memory, suggesting possible protection against HPV vaccine types after a single dose of 4vHPV. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Modeling of US Human Papillomavirus (HPV) Seroprevalence by Age and Sexual Behavior Indicates an Increasing Trend of HPV Infection Following the Sexual Revolution.

PubMed

Ryser, Marc D; Rositch, Anne; Gravitt, Patti E

2017-09-01

The United States has experienced an increase in the incidence of human papillomavirus (HPV)-related cancers that are not screen-detectable. It has been hypothesized, but not directly demonstrated, that this is due to increasing HPV prevalence in the unvaccinated population. Female self-reported numbers of lifetime sex partners and HPV serology from the National Health and Nutrition Examination Survey (NHANES) were used to develop mathematical models of sexual partner acquisition and antibody dynamics. Modeled trends in sexual behaviors were compared to incidence data for cervical adenocarcinoma, oropharyngeal cancer, and anal cancer. The age-specific HPV seroprevalence data were best explained by a partner acquisition model that explicitly accounted for cohort-dependent changes in sexual behavior. Estimates of the mean time to loss of natural antibodies varied by model, ranging from 49 to 145 years. Inferred trends in sexual behavior over the past decades paralleled the increasing incidence of HPV-related cancers in the United States. The findings suggest that lower HPV seroprevalence in older US women primarily reflects cohort-specific differences in sexual behaviors, and is only marginally attributable to immune waning with age. Our results emphasize the importance of continuing surveillance of sexual behaviors, alongside vaccine status, to predict future disease burden. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Impact of malaria and helminth infections on immunogenicity of the human papillomavirus-16/18 AS04-adjuvanted vaccine in Tanzania.

PubMed

Brown, Joelle; Baisley, Kathy; Kavishe, Bazil; Changalucha, John; Andreasen, Aura; Mayaud, Philippe; Gumodoka, Balthazar; Kapiga, Saidi; Hayes, Richard; Watson-Jones, Deborah

2014-01-23

Endemic malaria and helminth infections in sub-Saharan Africa can act as immunological modulators and impact responses to standard immunizations. We conducted a cohort study to measure the influence of malaria and helminth infections on the immunogenicity of the bivalent HPV-16/18 vaccine. We evaluated the association between malaria and helminth infections, and HPV-16/18 antibody responses among 298 Tanzanian females aged 10-25 years enrolled in a randomized controlled trial of the HPV-16/18 vaccine. Malaria parasitaemia was diagnosed by examination of blood smears, and helminth infections were diagnosed by examination of urine and stool samples, respectively. Geometric mean antibody titres (GMT) against HPV-16/18 antibodies were measured by enzyme-linked immunosorbent assay. Parasitic infections were common; one-third (30.4%) of participants had a helminth infection and 10.2% had malaria parasitaemia. Overall, the vaccine induced high HPV-16/18 GMTs, and there was no evidence of a reduction in HPV-16 or HPV-18 GMT at Month 7 or Month 12 follow-up visits among participants with helminths or malaria. There was some evidence that participants with malaria had increased GMTs compared to those without malaria. The data show high HPV immunogenicity regardless of the presence of malaria and helminth infections. The mechanism and significance for the increase in GMT in those with malaria is unknown. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mapping the B cell epitopes within the major capsid protein L1 of human papillomavirus type 16.

PubMed

Wang, Aiping; Li, Ning; Zhou, Jingming; Chen, Yumei; Jiang, Min; Qi, Yanhua; Liu, Hongliang; Liu, Yankai; Liu, Dongmin; Zhao, Jianguo; Wang, Yanwei; Zhang, Gaiping

2018-06-26

Persistent infection with human papillomavirus type16 (HPV16) has much association with the development of cervical cancer. L1 is the major capsid protein of HPV, it has been well investigated as a potential vaccine candidate. However, B cell epitopes present on L1 have not been well characterized. To identify the potential B-cell antigenic epitopes within HPV16 L1 protein, sixteen serial overlapping truncations (H1-H16) covering the whole region were expressed in E. coli and used in mice immunization. The mice antisera were tested in ELISA binding, IFA and HI assays. Finally, four fragments (H2, H4, H11, H12) were found to contain B cell epitopes of HPV16 L1 protein in ELISA and IFA assays, three fragments (H2, H3, H9) might contain neutralizing epitopes of HPV16 L1 protein in HI assay. Among them, H11 and H12 fragments contain B cell epitopes have never been reported before, and H3 was found as hemagglutination inhibition epitope for the first time. This work provides new insights to B cell epitopes on HPV16 L1 protein. Several new epitopes were identified and may provide some guidance for HPV16 subunit vaccine design. The results of this study might open new perspectives on the antibody-antigen reaction and have important implications for the development of epitopes-based protective HPV16 vaccines. Copyright © 2018. Published by Elsevier B.V.

Human Papilloma Virus in Head and Neck Squamous Cell Cancer

PubMed Central

Asvadi Kermani, I; Seifi, SH; Dolatkhah, R; Sakhinia, E; Dastgiri, S; Ebrahimi, A; Lotfy, A; Esmaeili, HA; G, Mohammadi; M, Naderpour; SH, Hajalipour; Haggi A, Asghari; M, Nadri

2012-01-01

Background Epidemiologic and molecular evidences have established a strong link between high risk types of Human Papilloma Virus and a subgroup of Head and Neck Squamous Cell Carcinomas (HNSCC). We evaluated the frequency of HPV positivity in HNSCC and its relationship to demographic and some risk factor variables in an open case- control study. Methods Fourteen recently diagnosed patients with squamous cell cancer of oropharynx, hypopharynx and larynx aged 18-50 years were examined from 2008-2010 in Tabriz, Iran. HPV DNA was extracted from paraffin-embedded blocks of each patient's sample for PCR evaluation. Saliva samples of 94 control cancer-free subjects were collected for DNA analysis. Multivariable logistic regression method was used to calculate odds ratio for case-control comparisons. Results High risk HPV was detected in 6(42.8%) patients, and 6(5.3%) control subjects which was statistically significant (p<0.0001). HPV-18 was the most frequent type both in the cases and controls. HPV-16 DNA was detected in two patients of the case group, but it was not detected in any of the controls. The relation between demographic and risk factor variables was not statistically significant. Conclusion HPV infection has a significant impact on HNSCC. Despite HPV-16 stronger impact, HPV-18 is more likely to cause malignant degeneration in such cancers amongst some communities. It is vital to introduce and conduct immunization schedules in health care systems to protect communities to some extent. PMID:25780535

UV Radiation Activates Toll-Like Receptor 9 Expression in Primary Human Keratinocytes, an Event Inhibited by Human Papillomavirus 38 E6 and E7 Oncoproteins.

PubMed

Pacini, Laura; Ceraolo, Maria Grazia; Venuti, Assunta; Melita, Giusi; Hasan, Uzma A; Accardi, Rosita; Tommasino, Massimo

2017-10-01

Several lines of evidence indicate that cutaneous human papillomavirus (HPV) types belonging to the beta genus of the HPV phylogenetic tree synergize with UV radiation in the development of skin cancer. Accordingly, the E6 and E7 oncoproteins from some beta HPV types are able to deregulate pathways related to immune response and cellular transformation. Toll-like receptor 9 (TLR9), in addition to playing a role in innate immunity, has been shown to be involved in the cellular stress response. Using primary human keratinocytes as experimental models, we have shown that UV irradiation (and other cellular stresses) activates TLR9 expression. This event is closely linked to p53 activation. Silencing the expression of p53 or deleting its encoding gene affected the activation of TLR9 expression after UV irradiation. Using various strategies, we have also shown that the transcription factors p53 and c-Jun are recruited onto a specific region of the TLR9 promoter after UV irradiation. Importantly, the E6 and E7 oncoproteins from beta HPV38, by inducing the accumulation of the p53 antagonist ΔNp73α, prevent the UV-mediated recruitment of these transcription factors onto the TLR9 promoter, with subsequent impairment of TLR9 gene expression. This study provides new insight into the mechanism that mediates TLR9 upregulation in response to cellular stresses. In addition, we show that HPV38 E6 and E7 are able to interfere with this mechanism, providing another explanation for the possible cooperation of beta HPV types with UV radiation in skin carcinogenesis. IMPORTANCE Beta HPV types have been suggested to act as cofactors in UV-induced skin carcinogenesis by altering several cellular mechanisms activated by UV radiation. We show that the expression of TLR9, a sensor of damage-associated molecular patterns produced during cellular stress, is activated by UV radiation in primary human keratinocytes (PHKs). Two transcription factors known to be activated by UV radiation, p53 and c-Jun, play key roles in UV-activated TLR9 expression. The E6 and E7 oncoproteins from beta HPV38 strongly inhibit UV-activated TLR9 expression by preventing the recruitment of p53 and c-Jun to the TLR9 promoter. Our findings provide additional support for the role that beta HPV types play in skin carcinogenesis by preventing activation of specific pathways upon exposure of PHKs to UV radiation. Copyright © 2017 American Society for Microbiology.

Access and Attitudes to HPV Vaccination amongst Hard-To-Reach Populations in Kenya

PubMed Central

Watson-Jones, Deborah; Mugo, Nelly; Lees, Shelley; Mathai, Muthoni; Vusha, Sophie; Ndirangu, Gathari; Ross, David A.

2015-01-01

Background Sub-Saharan Africa bears the greatest burden of cervical cancer. Human papillomavirus (HPV) vaccination programmes to prevent the disease will need to reach vulnerable girls who may not be able access health and screening services in the future. We conducted formative research on facilitators and barriers to HPV vaccination and potential acceptability of a future HPV vaccination programme amongst girls living in hard-to-reach populations in Kenya. Methods Stakeholder interviews with Ministry of Health staff explored barriers to and support for the uptake of HPV vaccination. A situation assessment was conducted to assess community services in Maasai nomadic pastoralist communities in Kajiado County and in Korogocho informal settlement in Nairobi city, followed by focus group discussions (n=14) and semi-structured interviews (n=28) with health workers, parents, youth, and community and religious leaders. These covered marriage, knowledge of cervical cancer and HPV, factors that might inhibit or support HPV vaccine uptake and intention to accept HPV vaccine if a programme was in place. Results Reported challenges to an HPV vaccination programme included school absenteeism and drop-out, early age of sex and marriage, lack of parental support, population mobility and distance from services. Despite little prior knowledge of cervical cancer and HPV, communities were interested in receiving HPV vaccination. Adequate social mobilisation and school-based vaccination, supplemented by out-reach activities, were considered important facilitating factors to achieve high coverage. There was some support for a campaign approach to vaccine delivery. Conclusions Given the high level of support for a vaccine against cervical cancer and the experience of reaching pastoralist and slum-dwellers for other immunizations, implementing an HPV vaccine programme should be feasible in such hard-to-reach communities. This may require additional delivery strategies in addition to the standard school-based delivery, with vaccine offered at multiple venues, potentially through a campaign approach. PMID:26115523

Attitudes towards and knowledge about Human Papillomavirus (HPV) and the HPV vaccination in parents of teenage boys in the UK.

PubMed

Sherman, Susan Mary; Nailer, Emma

2018-01-01

The incidence of cancers attributable to Human Papillomavirus (HPV) that affect males is on the rise. Currently in the UK teenage boys are not vaccinated against HPV while teenage girls are. The rationale for not vaccinating boys is that vaccinating girls should provide herd immunity to boys, however this does not protect men who have sex with men or men who have sex with unvaccinated women. The issue of whether to vaccinate boys or not is a controversial one with considerable lobbying taking place to change the existing policy. On one side of the debate are financial considerations while on the other side health equality is important. One avenue that has not been presented is the parental perspective. The current study uses a self-report questionnaire to explore what parents of teenage boys know about HPV and the vaccine and whether they want the vaccine for their sons. Only half of the parents had heard of HPV prior to completing the survey. Of those who had heard of HPV, knowledge about the health sequelae of HPV for men was poor relative to their knowledge about its impact on female health. Parents who would be willing to vaccinate their sons had higher levels of knowledge about HPV than those parents who would be unwilling or unsure. Irrespective of whether they had previously heard of HPV or not, once provided with a brief description of HPV, the majority of parents thought that boys should be offered the vaccination. There is a pressing need for public education about the potential impact of HPV on male health in order to facilitate uptake of the vaccine in the event of the vaccination programme being extended to men or to facilitate informed decision making about seeking the vaccine privately in the event that it isn't.

Attitudes towards and knowledge about Human Papillomavirus (HPV) and the HPV vaccination in parents of teenage boys in the UK

PubMed Central

Nailer, Emma

2018-01-01

The incidence of cancers attributable to Human Papillomavirus (HPV) that affect males is on the rise. Currently in the UK teenage boys are not vaccinated against HPV while teenage girls are. The rationale for not vaccinating boys is that vaccinating girls should provide herd immunity to boys, however this does not protect men who have sex with men or men who have sex with unvaccinated women. The issue of whether to vaccinate boys or not is a controversial one with considerable lobbying taking place to change the existing policy. On one side of the debate are financial considerations while on the other side health equality is important. One avenue that has not been presented is the parental perspective. The current study uses a self-report questionnaire to explore what parents of teenage boys know about HPV and the vaccine and whether they want the vaccine for their sons. Only half of the parents had heard of HPV prior to completing the survey. Of those who had heard of HPV, knowledge about the health sequelae of HPV for men was poor relative to their knowledge about its impact on female health. Parents who would be willing to vaccinate their sons had higher levels of knowledge about HPV than those parents who would be unwilling or unsure. Irrespective of whether they had previously heard of HPV or not, once provided with a brief description of HPV, the majority of parents thought that boys should be offered the vaccination. There is a pressing need for public education about the potential impact of HPV on male health in order to facilitate uptake of the vaccine in the event of the vaccination programme being extended to men or to facilitate informed decision making about seeking the vaccine privately in the event that it isn’t. PMID:29641563

Associations among human papillomavirus, inflammation, and fatigue in patients with head and neck cancer.

PubMed

Xiao, Canhua; Beitler, Jonathan J; Higgins, Kristin A; Glazer, Toby; Huynh, Linh Kha; Paul, Sudeshna; Felger, Jennifer C; Wommack, Evanthia C; Saba, Nabil F; Shin, Dong M; Bruner, Deborah W; Miller, Andrew H

2018-05-09

Human papillomavirus (HPV) infection has contributed to an increased incidence of squamous cell carcinoma of the head and neck (SCCHN). Fatigue is a major side effect of SCCHN and its treatment. However, to the authors' knowledge, the association between HPV and fatigue has not been examined to date, nor is it known whether HPV influences biological mechanisms of fatigue, including inflammation. Patients with SCCHN who were without distant metastasis were assessed at baseline (pre-radiotherapy) and 1 month and 3 months postradiotherapy. Fatigue was measured using the Multidimensional Fatigue Inventory. Peripheral inflammation was assessed by plasma C-reactive protein (CRP), interleukin 1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor 2 (sTNFR2), and IL-6. Mixed effect models were used to examine associations. A total of 94 patients who were newly diagnosed were enrolled; 53% had HPV-related tumors. Patients with HPV-unrelated tumors had higher fatigue and higher plasma CRP, sTNFR2, and IL-6 over time, especially at baseline and 3 months after intensity-modulated radiotherapy compared with those with HPV-related tumors (all P < .05). However, fatigue and plasma sTNFR2 increased more significantly from baseline to 1 month after radiotherapy in the HPV-related group compared with the HPV-unrelated group (both P < .01). Controlling for significant covariates, HPV status and inflammation were found to be independent predictors of fatigue over time. HPV status is an important marker of vulnerability to the behavioral and immune consequences of SCCHN and its treatment, providing support for different symptom management strategies. Special emphasis should be placed on addressing marked persistent fatigue in patients with HPV-unrelated tumors, whereas attention should be paid to the large increases in fatigue during treatment among patients with HPV-related tumors. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

The head and neck cancer immune landscape and its immunotherapeutic implications

PubMed Central

Mandal, Rajarsi; Şenbabaoğlu, Yasin; Havel, Jonathan J.; Dalin, Martin G.; Riaz, Nadeem; Lee, Ken-Wing; Ganly, Ian; Hakimi, A. Ari; Chan, Timothy A.; Morris, Luc G.T.

2016-01-01

Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation. We find that both HPV+ and HPV– HNSCC tumors are among the most highly immune-infiltrated cancer types. Strikingly, HNSCC had the highest median Treg/CD8+ T cell ratio and the highest levels of CD56dim NK cell infiltration, in our pan-cancer analysis of the most immune-infiltrated tumors. CD8+ T cell infiltration and CD56dim NK cell infiltration each correlated with superior survival in HNSCC. Tumors harboring genetic smoking signatures had lower immune infiltration and were associated with poorer survival, suggesting these patients may benefit from immune agonist therapy. These findings illuminate the immune landscape of HPV+ and HPV– HNSCC. Additionally, this landscape provides a potentially novel rationale for investigation of agents targeting modulators of Tregs (e.g., CTLA-4, GITR, ICOS, IDO, and VEGFA) and NK cells (e.g., KIR, TIGIT, and 4-1BB) as adjuncts to anti–PD-1 in the treatment of advanced HNSCC. PMID:27777979

Impact of quadrivalent human papillomavirus vaccine on genital warts in an opportunistic vaccination structure.

PubMed

Lurie, Samuel; Mizrachi, Yossi; Chodick, Gabi; Katz, Rachel; Schejter, Eduardo

2017-08-01

Genital warts are the most common sexually transmitted disease and have a detrimental impact on quality of life. Genital warts could be prevented by prophylactic HPV vaccination. The objective was to study real-life benefit of opportunistic HPV vaccination on age and gender specific incidence of genital warts. We performed a register-based population cohort study from publicly funded health-care provider in Israel. The incidence of genital warts was assessed during three time frame intervals: 2006-2008 (pre-vaccination effect period) 2009-2012 (early post-vaccination effect period) and 2013-2015 (late post-vaccination effect period), with an average annual number of members of 1,765,481, 1,906,774 and 2,042,678 in the years 2006-2008, 2009-2012 and 2013-2015, respectively. Among females, annual incidence of genital warts per 100,000 women decreased from 210.43 to 161.71 (OR 0.76, 95%CI 0.71-0.82, p<0.001) and to 146.8 (OR 0.69, 95%CI 0.66-0.72, p<0.001) between pre-vaccination period and early and late post-vaccination periods, respectively. Among males, annual incidence of genital warts per 100,000 men decreased from 262.85 to 232.40 (OR 0.88, 95%CI 0.83-0.93, p<0.001) and to 234.01 (OR 0.88, 95%CI 0.86-0.91, p<0.001) between pre-vaccination period and early and late post-vaccination periods, respectively. There is a potential benefit in reducing incidence of genital warts even in opportunistic HPV vaccination structure. This information may be relevant for health-care providers in countries where national immunization programs do not include HPV vaccines. Copyright © 2017 Elsevier Inc. All rights reserved.

Microwave therapy for cutaneous human papilloma virus infection.

PubMed

Bristow, Ivan; Lim, Wen Chean; Lee, Alvin; Holbrook, Daniel; Savelyeva, Natalia; Thomson, Peter; Webb, Christopher; Polak, Marta; Ardern-Jones, Michael R

2017-10-01

Human papilloma virus (HPV) infects keratinocytes of the skin and mucous membranes, and is associated with the induction of cutaneous warts and malignancy. Warts can induce significant morbidity and disability but most therapies, including cryotherapy, laser, and radiofrequency devices show low efficacy and induce discomfort through tissue destruction. Microwaves are readily capable of passing through highly keratinised skin to deliver energy and induce heating of the tissue in a highly controllable, uniform manner. To determine the effects of microwave on cutaneous HPV infection. We undertook a pilot study of microwave therapy to the skin in 32 consecutive individuals with 52 recalcitrant long-lived viral cutaneous warts. Additionally, we undertook a molecular characterisation of the effects of microwaves on the skin. Tissue inflammation was minimal, but 75.9% of lesions cleared which compares favourably with previous studies showing a clearance rate of 23-33% for cryotherapy or salicylic acid. We show that microwaves specifically induce dendritic cell cross-presentation of HPV antigen to CD8+ T cells and suggest that IL-6 may be important for DC IRF1 and IRF4 modulation to enhance this process. Keratinocyte-skin dendritic cell cross-talk is integral to host defence against HPV infections, and this pilot study supports the concept of microwave induction of anti-HPV immunity which offers a promising approach for treatment of HPV-induced viral warts and potentially HPV-related cancers.

Promotora outreach, education and navigation support for HPV vaccination to Hispanic women with unvaccinated daughters

PubMed Central

Parra-Medina, Deborah; Morales-Campos, Daisy Y.; Mojica, Cynthia; Ramirez, Amelie G.

2015-01-01

Background Cervical cancer disparities persist in the predominantly Hispanic population of South Texas, and Hispanic girls are less likely to initiate and complete the three-dose HPV vaccine series. Culturally relevant interventions are needed to eliminate these disparities and improve HPV vaccine initiation and completion. Subjects We enrolled 372 Hispanic women from South Texas’ Cameron and Hidalgo counties with a daughter aged 11–17 who had not received HPV vaccine. Intervention All participants received an HPV vaccine educational brochure in their preferred language (English or Spanish) and were invited to participate in the Entre Madre e Hija (EMH) program, a culturally relevant cervical cancer prevention program. EMH participants (n= 257) received group health education, referral and navigation support from a promotora (a trained, culturally competent community health worker). Those who declined participation in EMH received the brochure only (n=115). Results Eighty-four percent of enrolled participants initiated the HPV vaccine, and no differences were observed between EMH program and brochure-only participants. Compared to brochure-only participants, EMH participants were more likely to complete the vaccine series [Adj. OR=2.24, 95% CI (1.25, 4.02)]. In addition, participants who were employed and insured had lower odds of completing the vaccine series [Adj. OR=.45, 95% CI (.21 – .96); Adj. OR=.36, 95% CI (.13 – .98), respectively]. Conclusion All enrolled participants had high vaccine initiation rates (>80%); however, EMH program participants were more likely to complete the vaccine series. HPV vaccine promotion efforts that include referral and navigation support in addition to education show promise. PMID:24898942

Self-Sampling for Human Papillomavirus Testing: Increased Cervical Cancer Screening Participation and Incorporation in International Screening Programs

PubMed Central

Gupta, Sarah; Palmer, Christina; Bik, Elisabeth M.; Cardenas, Juan P.; Nuñez, Harold; Kraal, Laurens; Bird, Sara W.; Bowers, Jennie; Smith, Alison; Walton, Nathaniel A.; Goddard, Audrey D.; Almonacid, Daniel E.; Zneimer, Susan; Richman, Jessica; Apte, Zachary S.

2018-01-01

In most industrialized countries, screening programs for cervical cancer have shifted from cytology (Pap smear or ThinPrep) alone on clinician-obtained samples to the addition of screening for human papillomavirus (HPV), its main causative agent. For HPV testing, self-sampling instead of clinician-sampling has proven to be equally accurate, in particular for assays that use nucleic acid amplification techniques. In addition, HPV testing of self-collected samples in combination with a follow-up Pap smear in case of a positive result is more effective in detecting precancerous lesions than a Pap smear alone. Self-sampling for HPV testing has already been adopted by some countries, while others have started trials to evaluate its incorporation into national cervical cancer screening programs. Self-sampling may result in more individuals willing to participate in cervical cancer screening, because it removes many of the barriers that prevent women, especially those in low socioeconomic and minority populations, from participating in regular screening programs. Several studies have shown that the majority of women who have been underscreened but who tested HPV-positive in a self-obtained sample will visit a clinic for follow-up diagnosis and management. In addition, a self-collected sample can also be used for vaginal microbiome analysis, which can provide additional information about HPV infection persistence as well as vaginal health in general. PMID:29686981

HPV: Molecular pathways and targets.

PubMed

Gupta, Shilpi; Kumar, Prabhat; Das, Bhudev C

2018-04-05

Infection of high-risk human papillomaviruses (HPVs) is a prerequisite for the development of cervical carcinoma. HPV infections are also implicated in the development of other types of carcinomas. Chronic or persistent infection of HPV is essential but HPV alone is inadequate, additional endogenous or exogenous cues are needed along with HPV to induce cervical carcinogenesis. The strategies that high-risk HPVs have developed in differentiating epithelial cells to reach a DNA-synthesis competent state leading to tumorigenic transformation are basically due to overexpression of the E6 and E7 oncoproteins and the activation of diverse cellular regulatory or signaling pathways that are targeted by them. Moreover, the Wnt/β-catenin/Notch and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathways are deregulated in various cancers, and have also been implicated in HPV-induced cancers. These are basically related to the "cancer hallmarks," and include sustaining proliferative signals, the evasion of growth suppression and immune destruction, replicative immortality, inflammation, invasion, metastasis and angiogenesis, as well as genome instability, resisting cell death, and deregulation of cellular energetics. These information could eventually aid in identifying or developing new diagnostic, prognostic biomarkers, and may contribute to design more effective targeted therapeutics and treatment strategies. Although surgery, chemotherapy and radiotherapy can cure more than 90% of women with early stage cervical cancer, the recurrent and metastatic disease remains a major cause of cancer mortality. Numerous efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent years, research on treatment strategies has proposed several options, including the role of HPV E5, E6, and E7 oncogenes, which are retained and overexpressed in most of the cervical cancers and whose respective oncoproteins are critical to the induction and maintenance of the malignant phenotype. Other efforts have been focused on antitumor immunotherapy strategies. It is known that during the development of cervical cancer, a cascade of abnormal events is induced, including disruption of cell cycle control, perturbation of antitumor immune response, alteration of gene expression, deregulation of microRNA and cancer stem cell and stemness related markers expression could serve as novel molecular targets for reliable diagnosis and treatment of HPV-positive cancers. However, the search for new proposals for disease control and prevention has brought new findings and approaches in the context of molecular biology indicating innovations and perspectives in the early detection and prevention of the disease. Thus, in this article, we discuss molecular signaling pathways activated by HPV and potential targets or biomarkers for early detection or prevention and the treatment of HPV-associated cancers. Copyright © 2018 Elsevier Inc. All rights reserved.

Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery

PubMed Central

Best, Simon R.; Peng, Shiwen; Juang, Chi-Mou; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.; Pai, Sara I.

2009-01-01

DNA vaccines are an attractive approach to eliciting antigen-specific immunity. Intracellular targeting of tumor antigens through its linkage to immunostimulatory molecules such as calreticulin (CRT) can improve antigen processing and presentation through the MHC Class I pathway and increase cytotoxic CD8+ T cell production. However, even with these enhancements, the efficacy of such immunotherapeutic strategies is dependent on the identification of an effective route and method of DNA administration. Electroporation and gene gun-mediated particle delivery are leading methods of DNA vaccine delivery that can generate protective and therapeutic levels of immune responses in experimental models. In this study, we perform a head-to-head comparison of three methods of vaccination – conventional intramuscular injection, electroporation mediated intramuscular delivery, and epidermal gene gun-mediated particle delivery - in the ability to generate antigen specific cytotoxic CD8+ T cell responses as well as anti-tumor immune responses against an HPV-16 E7 expressing tumor cell line using the pNGVL4a-CRT/E7(detox) DNA vaccine. Vaccination via electroporation generated the highest number of E7-specific cytotoxic CD8+ T cells, which correlated to improved outcomes in the treatment of growing tumors. In addition, we demonstrate that electroporation results in significantly higher levels of circulating protein compared to gene gun or intramuscular vaccination, which likely enhances calreticulin’s role as a local tumor anti-angiogenesis agent. We conclude that electroporation is a promising method for delivery of HPV DNA vaccines and should be considered for DNA vaccine delivery in human clinical trials. PMID:19622402

[Utilization of self-sampling kits for HPV testing in cervical cancer screening - pilot study].

PubMed

Ondryášová, H; Koudeláková, V; Drábek, J; Vaněk, P; Slavkovský, R; Hajdúch, M

2015-12-01

To get initial experience with alternative sampling (self-sampling) for HPV testing as the means of cervical cancer screening program. Original work. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc. Based on expression of interest, 215 self-sampling kits were posted to women. Evalyn(®) Brush Vaginal swabs obtained by self-sampling were analyzed for the presence of HPV infection by Cobas 4800 HPV (Roche) followed by genotyping using PapilloCheck(®) HPV-Screening (Greiner Bio-One). Sixty women randomly chosen from our sample were sent a questionnaire focused on their experience with self-sampling. One hundred seventy-four of 215 (81%) distributed self-sampling devices have been delivered to analysis. All cervicovaginal swabs were sampled correctly and it was possible to analyze them by Cobas 4800 HPV test. Similarly, 98% (171/174) samples were analyzable by PapilloCheck(®) HPV-Screening.One hundred twenty-five (72%) of 174 tested samples were HPV negative. Low risk HPV infection was detected only in 7 samples (4%), and high risk HPV (hrHPV) infection was present in 42 samples (24%). The most frequently detected hrHPV genotypes were HPV16 (11/42; 26%) and HPV53 (6/42; 14%). HrHPV co-infection was detected in 10 cases, in 5 of them lrHPV infection was find also.Of the 60 questionnaires, 48 (80%) were returned. From this group, 47 (98%) women rated their experience with self-sampling device as good to excellent. User manual of self-sampling device was considered good to excellent by all women (100%). All women also rated the convenience of self-sampling device using as good to excellent. As expected, most of the women (n = 42 [88%]) preferred self-sampling to physician sampling. Cervicovaginal self-sampling leads to valid results of HPV screening using two molecular genetics methods and was accepted by Czech women very well. The self-sampling as an opportunity to participate in cervical cancer screening could increase the attendance of the screening program and would help to reduce the incidence and mortality for this disease in the Czech population.

Investigating Stakeholder Attitudes and Opinions on School-Based Human Papillomavirus Vaccination Programs

ERIC Educational Resources Information Center

Nodulman, Jessica A.; Starling, Randall; Kong, Alberta S.; Buller, David B.; Wheeler, Cosette M.; Woodall, W. Gill

2015-01-01

Background: In several countries worldwide, school-based human papillomavirus (HPV) vaccination programs have been successful; however, little research has explored US stakeholders' acceptance toward school-based HPV vaccination programs. Methods: A total of 13 focus groups and 12 key informant interviews (N?=?117; 85% females; 66% racial/ethnic…

Epidemiology of HPV Genotypes among HIV Positive Women in Kenya: A Systematic Review and Meta-Analysis.

PubMed

Menon, Sonia; Wusiman, Aibibula; Boily, Marie Claude; Kariisa, Mbabazi; Mabeya, Hillary; Luchters, Stanley; Forland, Frode; Rossi, Rodolfo; Callens, Steven; Vanden Broeck, Davy

2016-01-01

There is a scarcity of data on the distribution of human papillomavirus (HPV) genotypes in the HIV positive population and in invasive cervical cancer (ICC) in Kenya. This may be different from genotypes found in abnormal cytology. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18, and the nonavalent vaccine targeting 90% of all ICC cases, such HPV genotype distribution data are indispensable for predicting the impact of vaccination and HPV screening on prevention. Even with a successful vaccination program, vaccinated women will still require screening to detect those who will develop ICC from other High risk (HR) HPV genotypes not prevented by current vaccines. The aim of this review is to report on the prevalence of pHR/HR HPV types and multiple pHR/HR HPV genotypes in Kenya among HIV positive women with normal, abnormal cytology and ICC. PUBMED, EMBASE, SCOPUS, and PROQUEST were searched for articles on HPV infection up to August 2nd 2016. Search terms were HIV, HPV, Cervical Cancer, Incidence or Prevalence, and Kenya. The 13 studies included yielded a total of 2116 HIV-infected women, of which 89 had ICC. The overall prevalence of pHR/HR HPV genotypes among HIV-infected women was 64% (95%CI: 50%-77%). There was a borderline significant difference in the prevalence of pHR/HR HPV genotypes between Female Sex workers (FSW) compared to non-FSW in women with both normal and abnormal cytology. Multiple pHR/HR HPV genotypes were highly prominent in both normal cytology/HSIL and ICC. The most prevalent HR HPV genotypes in women with abnormal cytology were HPV 16 with 26%, (95%CI: 23.0%-30.0%) followed by HPV 35 and 52, with 21% (95%CI: 18%-25%) and 18% (95%CI: 15%-21%), respectively. In women with ICC, the most prevalent HPV genotypes were HPV 16 (37%; 95%CI: 28%-47%) and HPV 18 (24%; 95%CI: 16%-33%). HPV 16/18 gains prominence as the severity of cervical disease increases, with HPV 16/18 accounting for 61% (95%CI: 50.0%-70.0%) of all ICC cases. A secondary prevention program will be necessary as this population harbors multiple pHR/HR HPV co-infections, which may not be covered by current vaccines. A triage based on FSW as an indicator may be warranted.

Epidemiology of HPV Genotypes among HIV Positive Women in Kenya: A Systematic Review and Meta-Analysis

PubMed Central

Menon, Sonia; Wusiman, Aibibula; Boily, Marie Claude; Kariisa, Mbabazi; Mabeya, Hillary; Luchters, Stanley; Forland, Frode; Rossi, Rodolfo; Callens, Steven; vanden Broeck, Davy

2016-01-01

Background There is a scarcity of data on the distribution of human papillomavirus (HPV) genotypes in the HIV positive population and in invasive cervical cancer (ICC) in Kenya. This may be different from genotypes found in abnormal cytology. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18, and the nonavalent vaccine targeting 90% of all ICC cases, such HPV genotype distribution data are indispensable for predicting the impact of vaccination and HPV screening on prevention. Even with a successful vaccination program, vaccinated women will still require screening to detect those who will develop ICC from other High risk (HR) HPV genotypes not prevented by current vaccines. The aim of this review is to report on the prevalence of pHR/HR HPV types and multiple pHR/HR HPV genotypes in Kenya among HIV positive women with normal, abnormal cytology and ICC. Methods PUBMED, EMBASE, SCOPUS, and PROQUEST were searched for articles on HPV infection up to August 2nd 2016. Search terms were HIV, HPV, Cervical Cancer, Incidence or Prevalence, and Kenya. Results The 13 studies included yielded a total of 2116 HIV-infected women, of which 89 had ICC. The overall prevalence of pHR/HR HPV genotypes among HIV-infected women was 64% (95%CI: 50%-77%). There was a borderline significant difference in the prevalence of pHR/HR HPV genotypes between Female Sex workers (FSW) compared to non-FSW in women with both normal and abnormal cytology. Multiple pHR/HR HPV genotypes were highly prominent in both normal cytology/HSIL and ICC. The most prevalent HR HPV genotypes in women with abnormal cytology were HPV 16 with 26%, (95%CI: 23.0%-30.0%) followed by HPV 35 and 52, with 21% (95%CI: 18%-25%) and 18% (95%CI: 15%-21%), respectively. In women with ICC, the most prevalent HPV genotypes were HPV 16 (37%; 95%CI: 28%-47%) and HPV 18 (24%; 95%CI: 16%-33%). Conclusion HPV 16/18 gains prominence as the severity of cervical disease increases, with HPV 16/18 accounting for 61% (95%CI: 50.0%-70.0%) of all ICC cases. A secondary prevention program will be necessary as this population harbors multiple pHR/HR HPV co-infections, which may not be covered by current vaccines. A triage based on FSW as an indicator may be warranted. PMID:27764092

Human Papillomavirus (HPV) Genotyping: Automation and Application in Routine Laboratory Testing

PubMed Central

Torres, M; Fraile, L; Echevarria, JM; Hernandez Novoa, B; Ortiz, M

2012-01-01

A large number of assays designed for genotyping human papillomaviruses (HPV) have been developed in the last years. They perform within a wide range of analytical sensitivity and specificity values for the different viral types, and are used either for diagnosis, epidemiological studies, evaluation of vaccines and implementing and monitoring of vaccination programs. Methods for specific genotyping of HPV-16 and HPV-18 are also useful for the prevention of cervical cancer in screening programs. Some commercial tests are, in addition, fully or partially automated. Automation of HPV genotyping presents advantages such as the simplicity of the testing procedure for the operator, the ability to process a large number of samples in a short time, and the reduction of human errors from manual operations, allowing a better quality assurance and a reduction of cost. The present review collects information about the current HPV genotyping tests, with special attention to practical aspects influencing their use in clinical laboratories. PMID:23248734

Vaccination uptake by vaccine-hesitant parents attending a specialist immunization clinic in Australia.

PubMed

Forbes, Thomas A; McMinn, Alissa; Crawford, Nigel; Leask, Julie; Danchin, Margie

2015-01-01

Vaccine hesitancy (VH) is an issue of global concern. The quality of communication between healthcare providers and parents can influence parental immunization acceptance. We aimed to describe immunization uptake following specialist immunization clinic (SIC) consultation for Australian children of VH parents as a cohort, and according to pre-clinic parental position on immunization. At a single tertiary pediatric SIC (RCH, Melbourne) a retrospective descriptive study classified VH families according to 3 proposed parental positions on immunization at initial clinic attendance. Immunization status at follow up was ascertained via the Australian Children's Immunization Register and National HPV Program Register and compared between groups. Of the VH cohort, 13/38 (34%) families were classified as hesitant, 21 (55%) as late/selective vaccinators and 4 (11%) as vaccine refusers. Mean follow up post-SIC attendance was 14.5 months. For the overall VH cohort, the majority chose selective immunization (42%) following SIC consultation. When analyzed by pre-clinic parental position on immunization, there was a trend for hesitant families to proceed with full immunization, selective families to continue selective immunization and refusing families to remain unimmunised (p < 0.0001). The most commonly omitted vaccines were hepatitis B (66%) and Haemophilus influenzae type B (55%), followed by the meningococcal C conjugate vaccine (53%) and measles, mumps and rubella vaccine (53%). Immunization outcome appears to correlate with pre-clinic parental position on immunization for the majority of families attending a SIC in Australia, with selective immunization the most common outcome. Tailored communication approaches based on parental position on immunization may optimise clinic resources and engagement of families, but require prospective research evaluation.

Vaccination uptake by vaccine-hesitant parents attending a specialist immunization clinic in Australia

PubMed Central

Forbes, Thomas A; McMinn, Alissa; Crawford, Nigel; Leask, Julie; Danchin, Margie

2015-01-01

Vaccine hesitancy (VH) is an issue of global concern. The quality of communication between healthcare providers and parents can influence parental immunization acceptance. We aimed to describe immunization uptake following specialist immunization clinic (SIC) consultation for Australian children of VH parents as a cohort, and according to pre-clinic parental position on immunization. At a single tertiary pediatric SIC (RCH, Melbourne) a retrospective descriptive study classified VH families according to 3 proposed parental positions on immunization at initial clinic attendance. Immunization status at follow up was ascertained via the Australian Children's Immunization Register and National HPV Program Register and compared between groups. Of the VH cohort, 13/38 (34%) families were classified as hesitant, 21 (55%) as late/selective vaccinators and 4 (11%) as vaccine refusers. Mean follow up post-SIC attendance was 14.5 months. For the overall VH cohort, the majority chose selective immunization (42%) following SIC consultation. When analyzed by pre-clinic parental position on immunization, there was a trend for hesitant families to proceed with full immunization, selective families to continue selective immunization and refusing families to remain unimmunised (p < 0.0001). The most commonly omitted vaccines were hepatitis B (66%) and Haemophilus influenzae type B (55%), followed by the meningococcal C conjugate vaccine (53%) and measles, mumps and rubella vaccine (53%). Immunization outcome appears to correlate with pre-clinic parental position on immunization for the majority of families attending a SIC in Australia, with selective immunization the most common outcome. Tailored communication approaches based on parental position on immunization may optimise clinic resources and engagement of families, but require prospective research evaluation. PMID:26366978

Assessment of eight HPV vaccination programs implemented in lowest income countries.

PubMed

Ladner, Joël; Besson, Marie-Hélène; Hampshire, Rachel; Tapert, Lisa; Chirenje, Mike; Saba, Joseph

2012-05-23

Cervix cancer, preventable, continues to be the third most common cancer in women worldwide, especially in lowest income countries. Prophylactic HPV vaccination should help to reduce the morbidity and mortality associated with cervical cancer. The purpose of the study was to describe the results of and key concerns in eight HPV vaccination programs conducted in seven lowest income countries through the Gardasil Access Program (GAP). The GAP provides free HPV vaccine to organizations and institutions in lowest income countries. The HPV vaccination programs were entirely developed, implemented and managed by local institutions. Institutions submitted application forms with institution characteristics, target population, communication delivery strategies. After completion of the vaccination campaign (3 doses), institutions provided a final project report with data on doses administered and vaccination models. Two indicators were calculated, the program vaccination coverage and adherence. Qualitative data were also collected in the following areas: government and community involvement; communication, and sensitization; training and logistics resources, and challenges. A total of eight programs were implemented in seven countries. The eight programs initially targeted a total of 87,580 girls, of which 76,983 received the full 3-dose vaccine course, with mean program vaccination coverage of 87.8%; the mean adherence between the first and third doses of vaccine was 90.9%. Three programs used school-based delivery models, 2 used health facility-based models, and 3 used mixed models that included schools and health facilities. Models that included school-based vaccination were most effective at reaching girls aged 9-13 years. Mixed models comprising school and health facility-based vaccination had better overall performance compared with models using just one of the methods. Increased rates of program coverage and adherence were positively correlated with the number of vaccination sites. Qualitative key insights from the school models showed a high level of coordination and logistics to facilitate vaccination administration, a lower risk of girls being lost to follow-up and vaccinations conducted within the academic year limit the number of girls lost to follow-up. Mixed models that incorporate both schools and health facilities appear to be the most effective at delivering HPV vaccine. This study provides lessons for development of public health programs and policies as countries go forward in national decision-making for HPV vaccination.

Assessment of eight HPV vaccination programs implemented in lowest income countries

PubMed Central

2012-01-01

Background Cervix cancer, preventable, continues to be the third most common cancer in women worldwide, especially in lowest income countries. Prophylactic HPV vaccination should help to reduce the morbidity and mortality associated with cervical cancer. The purpose of the study was to describe the results of and key concerns in eight HPV vaccination programs conducted in seven lowest income countries through the Gardasil Access Program (GAP). Methods The GAP provides free HPV vaccine to organizations and institutions in lowest income countries. The HPV vaccination programs were entirely developed, implemented and managed by local institutions. Institutions submitted application forms with institution characteristics, target population, communication delivery strategies. After completion of the vaccination campaign (3 doses), institutions provided a final project report with data on doses administered and vaccination models. Two indicators were calculated, the program vaccination coverage and adherence. Qualitative data were also collected in the following areas: government and community involvement; communication, and sensitization; training and logistics resources, and challenges. Results A total of eight programs were implemented in seven countries. The eight programs initially targeted a total of 87,580 girls, of which 76,983 received the full 3-dose vaccine course, with mean program vaccination coverage of 87.8%; the mean adherence between the first and third doses of vaccine was 90.9%. Three programs used school-based delivery models, 2 used health facility-based models, and 3 used mixed models that included schools and health facilities. Models that included school-based vaccination were most effective at reaching girls aged 9-13 years. Mixed models comprising school and health facility-based vaccination had better overall performance compared with models using just one of the methods. Increased rates of program coverage and adherence were positively correlated with the number of vaccination sites. Qualitative key insights from the school models showed a high level of coordination and logistics to facilitate vaccination administration, a lower risk of girls being lost to follow-up and vaccinations conducted within the academic year limit the number of girls lost to follow-up. Conclusion Mixed models that incorporate both schools and health facilities appear to be the most effective at delivering HPV vaccine. This study provides lessons for development of public health programs and policies as countries go forward in national decision-making for HPV vaccination. PMID:22621342

Factors that influence parental vaccination decisions for adolescents, 13 to 17 years old: National Immunization Survey-Teen, 2010.

PubMed

Dorell, Christina; Yankey, David; Kennedy, Allison; Stokley, Shannon

2013-02-01

We aim to describe factors that influence parental decisions to vaccinate their adolescents. Data from the July to December 2010 National Immunization Survey-Teen Parental Concerns Module were analyzed to determine factors that influence parental decisions to vaccinate their adolescents. Parents reported that their adolescent's health care provider recommended tetanus toxoid/tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Td/Tdap; 74.4%), meningococcal conjugate (MenACWY; 60.3%), and human papillomavirus (HPV; 71.3%). Vaccination coverage estimates were significantly higher among parents who reported receiving a provider recommendation: 85.2% versus 76.7% (Td/Tdap), 77.3% versus 49.7% (MenACWY), and 62.2% versus 21.5% (HPV). Compared with Td/Tdap and MenACWY, fewer HPV vaccination conversations included recommendations for vaccination. Other than health care providers, school requirements (46.1%), news coverage (31.2%), and family (31.0%) were most frequently reported influences on parental vaccination decisions. Many factors influence parental decisions to vaccinate their adolescents; one of the most important factors is the provider recommendation. Missed opportunities for vaccination persist when strong vaccination recommendations are not given or are delayed.

[HPV vaccine implementation in Chile: an appraisal from the social determinants of health model].

PubMed

Fernández González, Loreto

2017-12-01

Cervical cancer is the fourth most common neoplasm in women worldwide and its incidence is associated with profound social inequities. In Chile, it is the second cause of death in women of reproductive age. The Chilean clinical guideline identifies the vaccine against Human Papillomavirus (HPV) as the main preventive measure. Since 2014, the Ministry of Health has implemented free immunization against HPV for girls and female adolescents. This article critically analyzes this public policy from the viewpoint of health equity, using as framework the Social Determinants of Health Model. Specifically, we address the structural determinants of income and gender, which act as material and social barriers for achieving immunization, affecting protection against cervical cancer. These barriers correspond to the high cost of the vaccine, and social attitudes/cultural beliefs towards sexual behavior in Latin America and Chile that affect the acceptability of vaccination. The Social Determinants of Health Model constitutes a useful tool for identifying health inequities and understanding public policy from an equity viewpoint that complements the biomedical and epidemiological understanding of disease. In this topic, the initiative aims to strengthen the idea of health as a human right and health promotion as an essential function of public health policy.

Enhanced immunogenicity of HPV 16 E7 fusion proteins in DNA vaccination.

PubMed

Michel, Nico; Osen, Wolfram; Gissmann, Lutz; Schumacher, Ton N M; Zentgraf, Hanswalter; Müller, Martin

2002-03-01

DNA vaccination is a promising approach for inducing both humoral and cellular immune responses. For immunotherapy of HPV-16-associated diseases the E7 protein is considered a prime candidate, as it is expressed in all HPV-16-positive tumors. Unfortunately, the E7 protein is a very poor inducer of a cytotoxic T-cell response, when being used as antigen in DNA vaccination. Here we demonstrate that after fusion to protein export/import signals such as the herpes simplex virus ferry protein VP22, E7 can translocate in vitro from VP22-E7-expressing cells to neighboring cells that do not carry the VP22-E7 gene. In vivo, the VP22-E7 fusion shows significantly increased efficiency in inducing a cytotoxic T-cell response. Our data suggest that the export function of VP22 plays a major role in this phenomenon, since VP22 can be replaced by classical protein export signals, without impairing the induction of the E7-specific cellular immune response. However, all E7 fusion constructs showed significantly elevated protein steady-state levels, which might also account for the observed boost in immunogenicity. (C)2002 Elsevier Science (USA).

Expectation prior to human papilloma virus vaccination: 11 to 12-Year-old girls' written narratives.

PubMed

Forsner, M; Nilsson, S; Finnström, B; Mörelius, E

2016-09-01

Expectations prior to needle-related procedures can influence individuals' decision making and compliance with immunization programmes. To protect from human papilloma virus (HPV) and cervical cancer, the immunization needs to be given before sexual debut raising interest for this study's aim to investigate how 11 to 12-year-old girls narrate about their expectations prior to HPV vaccination. A total of 27 girls aged 11 to 12 years participated in this qualitative narrative study by writing short narratives describing their expectations. The requirement for inclusion was to have accepted HPV vaccination. Data were subjected to qualitative content analysis. Findings showed the following expectations: going to hurt, going to be scared and going to turn out fine. The expectations were based on the girls' previous experiences, knowledge and self-image. The latent content revealed that the girls tried to transform uneasiness to confidence. The conclusion drawn from this study is that most girls of this age seem confident about their ability to cope with possible unpleasantness related to vaccinations. However, nurses need to find strategies to help those children who feel uneasy about needle-related procedures. © The Author(s) 2015.

Long-Term Follow-up of HPV Infection Using Urine and Cervical Quantitative HPV DNA Testing

PubMed Central

Vorsters, Alex; Van Keer, Severien; Biesmans, Samantha; Hens, Annick; De Coster, Ilse; Goossens, Herman; Ieven, Margareta; Van Damme, Pierre

2016-01-01

The link between infection with high-risk human papillomavirus (hrHPV) and cervical cancer has been clearly demonstrated. Virological end-points showing the absence of persistent HPV infection are now accepted as a way of monitoring the impact of prophylactic vaccination programs and therapeutic vaccine trials. This study investigated the use of urine samples, which can be collected by self-sampling at home, instead of cervical samples for follow-up of an HPV intervention trial. Eighteen initially HPV DNA-positive women participating in an HPV therapeutic vaccine trial were monitored during a three-year follow-up period. A total of 172 urine samples and 85 cervical samples were collected. We obtained a paired urine sample for each of the 85 cervical samples by recovering urine samples from six monthly gynaecological examinations. We performed a small pilot study in which the participating women used a urine collection device at home and returned their urine sample to the laboratory by mail. All samples were analyzed using quantitative real-time HPV DNA PCR. A good association (κ value of 0.65) was found between the presence of HPV DNA in urine and a subsequent cervical sample. Comparisons of the number of HPV DNA copies in urine and paired cervical samples revealed a significant Spearman rho of 0.676. This correlation was superior in women with severe lesions. The HPV DNA results of the small pilot study based on self-collected urine samples at home are consistent with previous and subsequent urine and/or cervical results. We demonstrated that urine sampling may be a valid alternative to cervical samples for the follow-up of HPV intervention trials or programs. The potential clinical value of urine viral load monitoring should be further investigated. PMID:27196899

Long-Term Follow-up of HPV Infection Using Urine and Cervical Quantitative HPV DNA Testing.

PubMed

Vorsters, Alex; Van Keer, Severien; Biesmans, Samantha; Hens, Annick; De Coster, Ilse; Goossens, Herman; Ieven, Margareta; Van Damme, Pierre

2016-05-17

The link between infection with high-risk human papillomavirus (hrHPV) and cervical cancer has been clearly demonstrated. Virological end-points showing the absence of persistent HPV infection are now accepted as a way of monitoring the impact of prophylactic vaccination programs and therapeutic vaccine trials. This study investigated the use of urine samples, which can be collected by self-sampling at home, instead of cervical samples for follow-up of an HPV intervention trial. Eighteen initially HPV DNA-positive women participating in an HPV therapeutic vaccine trial were monitored during a three-year follow-up period. A total of 172 urine samples and 85 cervical samples were collected. We obtained a paired urine sample for each of the 85 cervical samples by recovering urine samples from six monthly gynaecological examinations. We performed a small pilot study in which the participating women used a urine collection device at home and returned their urine sample to the laboratory by mail. All samples were analyzed using quantitative real-time HPV DNA PCR. A good association (κ value of 0.65) was found between the presence of HPV DNA in urine and a subsequent cervical sample. Comparisons of the number of HPV DNA copies in urine and paired cervical samples revealed a significant Spearman rho of 0.676. This correlation was superior in women with severe lesions. The HPV DNA results of the small pilot study based on self-collected urine samples at home are consistent with previous and subsequent urine and/or cervical results. We demonstrated that urine sampling may be a valid alternative to cervical samples for the follow-up of HPV intervention trials or programs. The potential clinical value of urine viral load monitoring should be further investigated.

[CD4 and CD8 T lymphocytes and NK cells in the stroma of the uterine cervix of women infected with human papillomavirus].

PubMed

Alves, Daniella Borges; Tozetti, Inês Aparecida; Gatto, Flávia Almeida; Cassandri, Fernanda; Ferreira, Alda Maria Teixeira; Carlos Eurico Dos Santos, Fernandes; Falcão, Gustavo Ribeiro; Scapulatempo, Ilzia Doraci Lins; Padovani, Cacilda Tezelli Junqueira; Abdo, Maria Auxiliadora Gomes Sandim

2010-01-01

Immune response might be a key element regarding the progression or regression of human papillomavirus (HPV) infection in the stroma of the uterine cervix. This study aimed to quantify the presence of CD4 and CD8 T lymphocytes and NK cells in the cervical stroma, by means of immunohistochemistry, in high and low grade lesions in patients infected by HPV METHODS: Fifty-six biopsy samples from the uterine cervix were used. Forty-three samples were positive for oncogenic high-risk HPV DNA and had a histopathological diagnosis of high and low-grade cervical intraepithelial neoplasia (CIN) or negative for intraepithelial lesion and malignancy (NILM); while the other 13 samples were negative for HPV DNA with a histopathological diagnosis of NILM RESULTS: Higher quantities of CD4 T lymphocytes were observed in CIN II/III, carcinoma and NILM samples (p = 0.04) and in those in which the viral load was between 10 and 1.000 RLU/PCB. CD8 T lymphocytes were predominant in CIN II/III samples (p = 0.02) and also in samples with viral loads between 100 and 1,000 RLU/PCB. NK cells predominated in samples with low-grade lesions and low viral load This study proved that in the initial stages of the infection, in which no high-grade cell abnormalities have yet occurred, no cells that might trigger the effector phase of the immune response.

Factors Associated with HPV Vaccination among Cambodian American Teenagers.

PubMed

Lee, Haeok; Kim, Minjin; Kiang, Peter; Shi, Ling; Tan, Kevin; Chea, Phala; Peou, Sonith; Grigg-Saito, Dorcas C

2016-11-01

Parents have general influence over their children's health and health behavior. However, given the dearth of specific literature regarding knowledge level and social and cultural factors influencing HPV vaccination behaviors among Cambodian American (CA) parent, it is difficult to develop an effective, evidence-based public health HPV vaccination program. Therefore, the objectives of this study were to determine the HPV vaccine uptakes among CA teenagers and to examine factors influencing HPV vaccine uptakes. A descriptive, cross-sectional survey design and a combination of network and targeted sampling methods were used. CA mothers (n = 130) completed a health survey through face-to-face interviews in either English or Khmer language. Girls vaccination rates were 29% while that of boys was 16%. Awareness and knowledge of HPV among CA mothers was very low, and many believed that their daughters, who speak English and were educated in the U.S., had more knowledge about health than they did. Logistic regression analysis showed that CA girls had significantly higher odds of vaccination when their mothers possessed a higher level of English reading ability and had greater awareness and knowledge of HPV. The strikingly low rates of HPV vaccination among CA girls and boys underscore the need to improve vaccination outreach, education, and uptake. The findings can be used to develop targeted public health HPV vaccination programs for CAs, which will reduce cervical cancer disparities. © 2016 Wiley Periodicals, Inc.

To Consent or Decline HPV Vaccination: A Pilot Study at the Start of the National School-Based Vaccination Program in Sweden.

PubMed

Grandahl, Maria; Tydén, Tanja; Westerling, Ragnar; Nevéus, Tryggve; Rosenblad, Andreas; Hedin, Erik; Oscarsson, Marie

2017-01-01

Parents' beliefs about human papillomavirus (HPV) vaccination influence whether they allow their daughters to be vaccinated. We examined the association between parents' refusal and sociodemographic background, knowledge and beliefs about HPV, and the HPV vaccination in relation to the Health Belief Model. The sample consisted of 200 (55%) parents of children aged 11-12 years in the Swedish national vaccination program. Data were collected using a self-reported questionnaire. Most parents (N = 186) agreed to the vaccination. Pearson's chi-square, Fisher's exact test, and the Mann-Whitney U test were used to analyze data. Declining parents saw more risks and fewer benefits of HPV vaccination but no differences in beliefs regarding the severity or young girls' susceptibility to HPV were found. There was an association between refusing the HPV vaccine and lower acceptance of previous childhood vaccinations, and their main source of information was the Internet. Parents who declined the vaccine believed it could adversely affect condom use, the age of their daughter's sexual debut, and the number of sexual partners. Parents should have the possibility to discuss HPV and HPV vaccine with a school nurse or other health care professionals, and should have access to evidence-based information on the Internet. © 2016 The Authors. Journal of School Health published by Wiley Periodicals, Inc. on behalf of American School Health Association.

HPV Immunization - Prevention Summary Table | Cancer Trends Progress Report

Cancer.gov

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

[News items on human papillomavirus and its vaccine in the Valencian press (2006-2011)].

PubMed

Tuells, José; Duro Torrijos, José Luis; Chilet Rosell, Elisa; Pastor Villalba, Eliseo; Portero Alonso, Antonio; Navarro Ortiz, Carmen; Galiana de la Villa, Eva María

2013-01-01

The process of introducing the human papillomavirus (HPV) vaccine aimed at teenage girls has not been entirely without controversy in Spain. This vaccine was originally hyped as a preventive measure in the fight against cervical cancer but the resulting euphoria was tempered by a message calling for evidence. During administration of the second dose of the vaccine in February 2009, an unexpected turn of events attracted vast media coverage when two teenagers experienced adverse effects after immunization in Valencia (Spain). This study analyzes the scope and content of news items on HPV, immunization and cervical cancer published between 2006 and 2011 in two widely disseminated regional newspapers in Valencia. We also discuss the extent to which the messages transmitted may have influenced acceptability of the vaccine. Copyright © 2012 SESPAS. Published by Elsevier Espana. All rights reserved.

Concordance of adolescent human papillomavirus vaccination parental report with provider report in the National Immunization Survey-Teen (2008-2013).

PubMed

Hirth, Jacqueline; Kuo, Yong-Fang; Laz, Tabassum Haque; Starkey, Jonathan M; Rupp, Richard E; Rahman, Mahbubur; Berenson, Abbey B

2016-08-17

To examine the accuracy of parental report of HPV vaccination through examination of concordance, with healthcare provider vaccination report as the comparison. The 2008-2013 National Immunization Survey (NIS)-Teen was used to examine accuracy of parent reports of HPV vaccination for their female daughters aged 13-17years, as compared with provider report of initiation and number of doses. Multivariable logistic regression models were used to examine associations related to concordance of parent and provider report. Of 51,746 adolescents, 84% concordance for HPV vaccine initiation and 70% concordance for number of doses was observed. Accuracy varied by race/ethnicity, region, time, and income. The parent report of number of doses was more likely to be accurate among parents of 13 and 14year old females than 17year olds. Accuracy of initiation and number of doses were lower among Hispanic and black adolescents compared to white parents. The odds of over-report was higher among minorities compared to whites, but the odds of underreport was also markedly higher in these groups compared to parents of white teens. Accuracy of parental vaccine report decreased across time. These findings are important for healthcare providers who need to ascertain the vaccination status of young adults. Strengthening existing immunization registries to improve data sharing capabilities and record completeness could improve vaccination rates, while avoiding costs associated with over-vaccination. Copyright © 2016 Elsevier Ltd. All rights reserved.

A survey on the prevalence of high-risk subtypes of human papilloma virus among women with cervical neoplasia in Isfahan University of Medical Science.

PubMed

Allameh, Tajossadat; Moghim, Sharareh; Asadi-Zeidabadi, Maryam

2011-12-01

Given the importance of epidemiological studies on the prevalence of human papilloma virus (HPV) and its subtypes to plan more effective strategies for cervical cancer prevention, the aim of this study was to determine the prevalence of HPV in women with cervical intraepithelial neoplasia and cancer in Isfahan. In this descriptive cross-sectional study, women referred to oncology clinic of Shahid Beheshti Hospital because of abnormal cytology of their cervices within the last year were studied. The 2001 Bethesda system was used for histologic classification. The distribution of different pathologies was as follows: squamous cell carcinoma (SCC) 34.7%, low-grade squamous intraepithelial lesions (LSIL) 30.5%, high-grade squamous intraepithelial lesions (HSIL) 22.8%, atypical squamous cell of undetermined significance (ASCUS) 8.4%, and adenocarcinoma (AC) 3.3%. There was no case of atypical glandular of undetermined significance or cases of adenocarcinoma associated with an early lesion. The presence of HPV infection and its subtypes including HPV 16, 18, 6 and 11 was assessed in different cytological categories of cervical neoplasia, by using polymerase chain reaction method. During this study, 130 patients were studied. Their median age was 52 years (range 29-73 years). HPV was detected in 118/130 patients (90.8%) with abnormal cervical cytology. The prevalence of positive HPV samples was 97.6, 80, 93.1, 92.3, and 66.6% in cases with SCC, AC, HSIL, LSIL, and ASCUS, respectively (P < 0.05 between SCC and ASCUS, HSIL and ASCUS, and LSIL and ASCUS). Out of 118 cases with positive HPV, 98 (83.1%) were positive for multiple HPV types 16, 18, and 11 or 6. The distribution of studied HPV subtypes among women with positive HPV was as follows: 49.1% for both types 16 and 18, 10.1% for type 16, 1.69% for type 18 and 22% for type 11 or 6. The prevalence of HPV type 16 was not significantly different in various cytological categories of cervical neoplasia (P > 0.05). The prevalence of HPV type 16 and 18 was significantly higher than the HPV type 11 or 6 in cervical neoplastic lesions (P < 0.05). The results of this research indicated the high prevalence of HPV infection in all categories of cervical neoplasia. This emphasizes the importance of HPV screening and vaccination programs. In order to assess more effective screening programs in Isfahan and evaluate the cost-effectiveness of vaccination programs, further population-based prospective studies are required.

Does the vaginal microbiota play a role in the development of cervical cancer?

PubMed

Kyrgiou, Maria; Mitra, Anita; Moscicki, Anna-Barbara

2017-01-01

Persistent infection with oncogenic human papillomavirus (HPV) is necessary but not sufficient for the development of cervical cancer. The factors promoting persistence as well those triggering carcinogenetic pathways are incompletely understood. Rapidly evolving evidence indicates that the vaginal microbiome (VM) may play a functional role (both protective and harmful) in the acquisition and persistence of HPV, and subsequent development of cervical cancer. The first studies examining the VM and the presence of an HPV infection using next-generation sequencing techniques identified higher microbial diversity in HPV-positive as opposed to HPV-negative women. Furthermore, there appears to be a temporal relationship between the VM and HPV infection in that specific community state types may be correlated with a higher chance of progression or regression of the infection. Studies describing the VM in women with preinvasive disease (squamous intraepithelial neoplasia [SIL]) consistently demonstrate a dysbiosis in women with the more severe disease. Although it is plausible that the composition of the VM may influence the host's innate immune response, susceptibility to infection, and the development of cervical disease, the studies to date do not prove causality. Future studies should explore the causal link between the VM and the clinical outcome in longitudinal samples from existing biobanks. Copyright © 2016 Elsevier Inc. All rights reserved.