Lessons from the failure of human papillomavirus vaccine state requirements

The licensure in 2006 of a vaccine against the subtypes of human papillomavirus (HPV) responsible for the majority of cervical cancers and genital warts was heralded as a watershed moment for vaccination, cancer prevention, and global health. A safe and effective vaccine against HPV has long been viewed as an enormous asset to cervical cancer prevention efforts worldwide. This is particularly true for places lacking robust Pap screening programs where cervical cancer has the greatest prevalence and mortality. Well before its licensure, however, some observers noted significant obstacles that would need to be addressed in order for an HPV vaccination program to succeed. These included the vaccine's relatively high cost, availability, and opposition from socially conservative groups. Such concerns associated with the implementation of HPV vaccination were soon overwhelmed by the furor that followed the unexpectedly early efforts by the US state governments to require the vaccine as a condition of attendance in public schools, proposals imprecisely referred to as "mandates." In this study, we review the controversy surrounding this debate and its effects on important ethical and public health issues that still need to be addressed.     

Human papillomavirus infection: the role of vaccination in pediatric patients

Human papillomavirus (HPV) infection is the most common sexually transmitted infection among adolescents and adults in the United States. Given the prevalence of this infection and its relationship with the development of cervical cancer, HPV vaccine development has been a major public health initiative in the last decade. Despite extensive research in the development of these vaccines, there remain many unanswered questions in academic and public arenas regarding their administration and role in adolescent medicine.     

Human papillomavirus vaccines for cervical cancer.

Cervical cancer is one of the most common causes of cancer-related death in women. As a result of several recent advances in molecular biology, the association between human papillomavirus (HPV) infection and cervical cancer has been firmly established, and the oncogenic potential of certain HPV types has been clearly demonstrated. Several lines of evidence suggest the importance of the host's immune response, especially cellular immune response, in the pathogenesis of HPV-associated cervical lesions. These observations form a compelling rationale for the development of vaccine therapy to combat HPV infection. Both prophylactic and therapeutic HPV vaccine strategies are being developed. Prophylactic strategies currently under investigation focus on the induction of effective humoral immune responses against subsequent HPV infection. In this respect, impressive immunoprophylactic effects have been demonstrated in animals using papillomavirus-like particles (VLPs). VLPs are antigenic and protective, but are devoid of any viral DNA that may be carcinogenic to the host. For treatment of existing HPV infection, techniques to improve cellular immunity by enhancing viral antigen recognition are being studied. For this purpose, the oncogenic proteins E6 and E7 of HPV-16 and -18 are the focus of current clinical trials for cervical cancer patients. The development of successful HPV-specific vaccines may offer an attractive alternative to existing screening and treatment programs for cervical cancer.     

The known unknowns of HPV natural history

The discovery that certain high-risk strains of human papillomavirus (HR-HPV) cause nearly 100% of invasive cervical cancer has spurred a revolution in cervical cancer prevention by promoting the development of viral vaccines. Although the efficacy of these vaccines has already been demonstrated, a complete understanding of viral latency and natural immunity is lacking, and solving these mysteries could help guide policies of cervical cancer screening and vaccine use. Here, we examine the epidemiological and biological understanding of the natural history of HPV infection, with an eye toward using these studies to guide the implementation of cervical cancer prevention strategies.     

Introducing human papillomavirus vaccines - questions remain

Genital human papillomavirus (HPV) infection and HPV-associated cervical and other anogenital cancers are significant public health problems. HPV 16 and HPV 18 are responsible for approximately 70% of all invasive cervical cancers worldwide. The first prophylactic HPV virus-like particle (VLP) vaccine against HPV types 6/11/16/18 was licensed in 2006 for girls and women aged 9-26 years. The second prophylactic HPV vaccine against HPV types 16 and 18 has been licensed this year. These vaccines are almost 100% effective in preventing infection and high-grade precancer associated with the HPV types included in the vaccine. The vaccines are well tolerated, safe, and highly immunogenic when given in three doses within 6 months. Efficacy of the vaccine against external vulvar and HPV-related vaginal lesions is also high. Even though the vaccine is highly effective against high-grade cervical, vaginal, or vulvar precancers, this only applies to women unexposed to these HPV types and only to high-grade intraepithelial lesions caused by these HPV types. Therefore, it is important to understand that the population impact of the vaccines will be much lower than vaccinating naive populations. Implementing HPV vaccine is a great opportunity but also a great challenge. However, mandatory HPV vaccination may raise many questions, and more answers are needed.     

HPV vaccination with Gardasil: a breakthrough in women's health

Human papillomavirus (HPV) represents one of the most common sexually transmitted infections. Although infection is often self-limited, a percentage of women with HPV infection will go on to develop cervical precancerous or cancerous lesions. It is estimated that HPV16 is responsible for approximately half of all cervical cancers worldwide. Several studies have tested vaccines directed against specific HPV types, namely types 6, 11, 16 and 18. This paper reviews these studies, particularly focusing on a quadrivalent (type 6, 11, 16 and 18) HPV L1 virus-like particle vaccine under investigation in Phase III trials at present. Data indicate that this vaccine, referred to as Gardasil, can prevent precancerous cervical lesions and early in situ cervical cancers with few adverse effects, and the vaccine has been approved by the FDA for this indication. Another vaccine, HPV16 L1, directed solely against HPV16, has also been demonstrated to be effective (at present, follow-up has been for up to 48 months) in providing protection against persistent infection with this viral strain and preventing HPV16-related cervical intraepithelial neoplasia 2/3, while producing minimal adverse effects in recipients. Given the lack of a pharmacological intervention that can eradicate HPV in infected individuals and the prevalence of cervical cancer secondary to HPV infection across the world, the HPV vaccine represents a significant breakthrough in women's health.     

Therapeutic human papillomavirus vaccines: current clinical trials and future directions

Background: Cervical cancer is the second largest cause of cancer deaths in women worldwide. It is now evident that persistent infection with high-risk human papillomavirus (HPV) is necessary for the development and maintenance of cervical cancer. Thus, effective vaccination against HPV represents an opportunity to restrain cervical cancer and other important cancers. The FDA recently approved the HPV vaccine Gardasil for the preventive control of HPV, using HPV virus-like particles (VLP) to generate neutralizing antibodies against major capsid protein, L1. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and HPV-associated lesions. Furthermore, due to the considerable burden of HPV infections worldwide, it would take decades for preventive vaccines to affect the prevalence of cervical cancer. Thus, in order to speed up the control of cervical cancer and treat current infections, the continued development of therapeutic vaccines against HPV is critical. Therapeutic HPV vaccines can potentially eliminate pre-existing lesions and malignant tumors by generating cellular immunity against HPV-infected cells that express early viral proteins such as E6 and E7. Objective: This review discusses the future directions of therapeutic HPV vaccine approaches for the treatment of established HPV-associated malignancies, with emphasis on current progress of HPV vaccine clinical trials. Methods: Relevant literature is discussed. Results/conclusion: Though their development has been challenging, many therapeutic HPV vaccines have been shown to induce HPV-specific antitumor immune responses in preclinical animal models and several promising strategies have been applied in clinical trials. With continued progress in the field of vaccine development, HPV therapeutic vaccines may provide a potentially promising approach for the control of lethal HPV-associated malignancies.     

Human papillomavirus vaccines

OBJECTIVE: To review the pharmacology, efficacy, safety, tolerability, and pharmacoeconomics of Cervarix and Gardasil, 2 human papillomavirus (HPV) vaccines. DATA SOURCES: English-language articles were obtained by MEDLINE search (1966-February 2006) using the key words human papillomavirus vaccine, Cervarix, and Gardasil. Bibliographies of selected articles were used to identify additional sources. STUDY SELECTION AND DATA EXTRACTION: All available published articles or abstracts reporting the results of human studies of HPV vaccines were reviewed for inclusion in this article. Additional information about ongoing clinical trials was obtained from manufacturers' Web sites. DATA SYNTHESIS: Cervarix and Gardasil are recombinant vaccines against HPV. Cervarix targets HPV-16 and -18, which are responsible for 70% of cervical cancers. Gardasil also targets HPV-16 and -18, plus the HPV-6 and -11 types responsible for more than 80% of genital warts. Both vaccines have been effective in preventing persistent infection with targeted HPV types and in preventing cervical intraepithelial lesions, while Gardasil has also been effective in preventing vulvar and vaginal neoplasia and genital warts. Both vaccines have been well tolerated, with the most common adverse effects occurring at the injection site. Phase III trials are ongoing to further evaluate vaccine efficacy. CONCLUSIONS: Cervarix and Gardasil are effective for prevention of HPV infection and cervical lesions. Issues remaining to be addressed include duration of protection, efficacy for prevention of cervical cancer, optimal age for vaccination, feasibility of application to the developing world, the ideal combination of HPV subtypes, and the most efficient combination of vaccination and cervical cancer screening.     

HPV vaccination with Gardasil®: a breakthrough in women’s health

Human papillomavirus (HPV) represents one of the most common sexually transmitted infections. Although infection is often self-limited, a percentage of women with HPV infection will go on to develop cervical precancerous or cancerous lesions. It is estimated that HPV16 is responsible for approximately half of all cervical cancers worldwide. Several studies have tested vaccines directed against specific HPV types, namely types 6, 11, 16 and 18. This paper reviews these studies, particularly focusing on a quadrivalent (type 6, 11, 16 and 18) HPV L1 virus-like particle vaccine under investigation in Phase III trials at present. Data indicate that this vaccine, referred to as Gardasil^®, can prevent precancerous cervical lesions and early in situ cervical cancers with few adverse effects, and the vaccine has been approved by the FDA for this indication. Another vaccine, HPV16 L1, directed solely against HPV16, has also been demonstrated to be effective (at present, follow-up has been for up to 48 months) in providing protection against persistent infection with this viral strain and preventing HPV16-related cervical intraepithelial neoplasia 2/3, while producing minimal adverse effects in recipients. Given the lack of a pharmacological intervention that can eradicate HPV in infected individuals and the prevalence of cervical cancer secondary to HPV infection across the world, the HPV vaccine represents a significant breakthrough in women’s health.     

CA7-03: Adolescent and Adult Immunizations: Health Impact and Cost-Effectiveness

Background/Aims The scope of vaccines recommended for adolescents and adults by ACIP has grown in number of vaccines and populations covered. We estimated the relative health impact and cost-effectiveness of these vaccines to help guide quality improvement initiative decisions. Methods Markov deterministic and micro-simulation models were used to estimate the health impact and CE ratios for birth cohorts of four million using a societal perspective. All models used methods consistent with the 'reference case' of the Panel of Cost-Effectiveness in Health and Medicine, producing results that are comparable and suitable for ranking. The influenza model recognized the 2010 ACIP recommendation for universal vaccination. The pneumococcal model recognized the recent decline in adult incidence after introduction of the PCV7 childhood vaccine. The meningococcal model included the 2010 ACIP recommendation for a booster five years after an initial vaccination at age 11 or 12. The HPV model estimated the influence of vaccine on rates of cervical cancer with and without cancer screening. Parameter estimates were from published literature. Single- and multiple-variable sensitivity analyses were performed. Results Health impacts, measured as QALYs saved during the lifetime of the cohort, were greatest for influenza vaccine (283,300), followed by HPV vaccine with screening (221,100), pneumococcal vaccine (17,100) and meningococcal vaccine (2,900). CE ratios ranged from $9,300 for adult pneumococcal vaccination to over $640,000 for adolescent meningococcal vaccination. CE of influenza vaccination for ages 18 and older was $6,100, but the vaccine was most cost-effective for ages 65 and older ($4,000) and least cost-effective for ages 18 to 49 ($260,500). HPV vaccine CE was $15,100 without screening and $17,900 with screening. Results from micro-simulation of the zoster vaccine will also be presented. Discussion Priority among preventive health care services is important because of the limited time and resources of the health care delivery system and the need to focus on the most effective services. Our consistent methods allow for comparison of estimates across a number of services. Our updated models showed the greatest health impact from HPV vaccine in the presence of screening and influenza vaccination of adults ages 65 and older.     

Human papillomavirus, cervical cancer, and the vaccines

How are human papillomavirus (HPV), cervical cancer, and the recently developed HPV vaccines associated with each other? Human papillomavirus is a highly prevalent infection that is easily and unknowingly transmitted because of its asymptomatic nature and long incubation period. Infection requires skin-to-skin contact and is typically sexually transmitted. More than one-half of sexually active women acquire HPV, making it the most prevalent sexually transmitted disease. Cervical cancer ranks second in deaths from cancer among women in developing countries and kills nearly 4000 women in the United States annually. Several types of HPV have been strongly linked to causing cervical cancer and genital warts. Those causing cervical cancer are considered high-risk types and those causing genital warts are considered low-risk types. Until recently, prevention strategies included abstinence, condom usage, and early detection with a Papanicolaou test (Pap smear). New developments have led to 2 vaccines aimed at preventing the viral infection. One is a quadrivalent vaccine preventing infection from 4 HPV types (HPV types 6, 11, 16, and 18) (Gardasil). It is approved in the United States and Europe for the prevention of HPV-associated cervical cancers and genital warts in females between the ages of 9 and 26 years old. The second is a bivalent vaccine preventing infection from 2 high-risk oncogenic HPV types (HPV types 16 and 18) (Cervarix). It is currently under study and not yet available in the United States. Both vaccines have proven highly effective at preventing infection from their corresponding HPV types. Of importance, neither vaccine is to be used for treatment. Vaccination does not replace routine cervical cancer screening with Pap smears, as the vaccines do not protect against all HPV types.     

Human papillomavirus in cervical screening and vaccination

Recent decades have witnessed a reduction in the incidence of cervical cancer in countries where screening programmes have achieved broad coverage. The recognized importance of high-risk HPV (human papillomavirus) infection in the aetiology of cervical cancer may introduce a role for HPV DNA testing in cervical screening programmes. Positive HPV DNA tests indicate women at risk of cervical cancer with greater sensitivity, but reduced specificity, compared with exfoliative cytology. Combining HPV testing with cytology may be useful in the triage of minor cytological abnormalities into those requiring referral to colposcopy (HPV positive) compared with those who can be safely managed by cytological surveillance (HPV negative). With its high sensitivity and high-negative-predictive value, HPV testing may also be useful for predicting treatment failure, since residual disease is very unlikely in the event of a negative HPV test. Ultimately, prevention is better than cure, and the advent of HPV prophylactic vaccines may obviate the need for population-based cervical screening programmes in the future. A multivalent vaccine administered to adolescents prior to the onset of sexual activity and boosted at regular intervals throughout their sexually active life may provide protection against type-specific HPV infection, malignant precursors and invasive cervical disease. Several large randomized placebo-controlled trials have been conducted with promising results. For those generations of women already exposed to high-risk HPV infection, therapeutic vaccines may offer advantages over conventional treatment, although much work still needs to be done.     

Laboratory and clinical aspects of human papillomavirus testing

Human papillomavirus (HPV) infection is associated with a wide spectrum of disease that ranges from self-limited skin warts to life-threatening cancers. Since HPV plays a necessary etiological role in cervical cancer, it is logical to use HPV as a marker for early detection of cervical cancer and precancer. Recent advances in technology enable the development of high-throughput HPV assays of different formats, including DNA-based, mRNA-based, high-risk group-specific and type-specific methods. The ultimate goal of these assays is to improve the accuracy and cost-effectiveness of cervical screening programs. HPV testing has several potential advantages compared to cytology-based screening. However, since the cancer to transient infection ratio is always low in the general population, HPV test results are bound to have a low positive predictive value that may subject women to unnecessary follow-up investigations. The wide-spread administration of prophylactic HPV vaccine will substantially decrease the incidence of cancer and precancer. This poses a number of challenges to cytology-based screening, and the role of HPV testing is expected to increase. Finally, apart from technical and cost-effectiveness considerations, one should also keep in mind the psycho-social impact of using sexually-transmitted agents as a marker for cancer screening.     

HPV Vaccination: Does It Have a Role in Preventing Penile Cancer and Other Preneoplastic Lesions?

ObjectivesHuman papillomavirus (HPV) is the most common sexually transmitted infection globally, which causes nearly all cervix carcinomas and contributes to oropharyngeal, penile, vulva, vagina, and anal cancers. Despite the role of HPV in several preneoplastic and cancerous lesions in men, male vaccine coverage is low. This article aims to provide insights into the pathophysiology of HPV-related penile cancer and penile intraepithelial neoplasia (PeIN). Moreover, this review endeavors to outline the advantages of implementing HPV vaccination in male vaccination programs and the role of health care providers in this mission.Data SourcesThis is a narrative review of relevant literature. A search on PubMed and Cochrane database was conducted. The following search terms were used: HPV vaccination, gender-neutral vaccination, male, genital warts, penile cancer, vaccine recommendations.ConclusionHPV is responsible for 50.8% of penile cancers globally, 79.8% of PeIN, and 90% of genital warts. In 2009 the Food and Drug Administration licensed the quadrivalent HPV vaccine for use in males, with a potential efficacy of 90% and 77.5% to reduce genital warts and anal intraepithelial neoplasia, respectively. However, the uptake of HPV vaccination in men is low, and gender-neutral vaccination is estimated to be implemented only in 42 countries worldwide. Because data in penile cancer are lacking, further research is needed to study the efficacy of incorporation of HPV vaccines in male vaccination programs on preventing penile cancer and PeIN.Implications for Nursing PracticeNurses and other members of the multidisciplinary team should take every opportunity to recommend HPV vaccination in adolescent men. Moreover, they play an important role in raising community awareness about the incidence of HPV and the related range of diseases. A practical approach is needed to incorporate HPV vaccines in vaccination programs and to optimize vaccination coverage.     

Increasing Cervical Cancer and Human Papillomavirus Prevention Knowledge and HPV Vaccine Uptake through Mother/Daughter Education

This evidence-based initiative assessed the impact of language-appropriate cervical cancer and human papillomavirus (HPV) prevention education on knowledge level and HPV vaccine uptake among mothers and their daughters. Forty-one mother/daughter dyads from a low-cost, faith-based clinic for the uninsured in southeastern Texas participated in the nurse practitioner-led cervical cancer prevention educational sessions. Spanish was the primary language for the majority of participating mothers. The project produced appreciable knowledge increase and HPV vaccine uptake intent. Aggregate HPV vaccine uptake numbers for the clinic increased considerably compared to HPV vaccine administration prior to educational intervention.     

Cervical cancer screening in Thailand: an overview

In Thailand, there have been no 'organized' programmes of screening for cervical cancer. For the most part, screening has been unsystematic or provided to women 'on demand'. In 2002, the Department of Medical Services of the Ministry of Public Health proposed the screening of the entire population of women in Thailand at 5-yearly intervals from the ages of 35 to 60 years. As a first step, measures to increase the capacity for obtaining and interpreting papanicolaou (Pap) smears have been put in place. Research studies have examined the effectiveness of screening with Pap smears in Thailand, and confirmed that, as elsewhere, protection is related to the number of previous tests and the time elapsed since the most recent one. Coverage of the population remains low. Other methods of screening are being investigated in Thailand, including visual inspection following acetic acid (VIA), followed by immediate treatment of observed lesions by cryotherapy ('see and treat'). Other research studies have examined the acceptability and performance of self-sampling as a means of obtaining Pap smears, and the use of mobile clinics to increase coverage of at-risk women in rural settings. Human papillomavirus (HPV) testing has been used to identify high-risk women, or to help decide which women with low-grade abnormality on cytology should undergo more intensive follow-up. Prevalence of HPV in normal women in Thailand is 9-20%, but HPV testing has not been used on any systematic basis to date. Current screening programmes in Thailand are not very effective. The national cancer control programme aims to increase the coverage of screening. The population-based cancer registry will provide an effective and economical method of evaluating the impact of early diagnosis and screening at community level.     

Using the new HPV vaccines in clinical practice

Gardasil, a vaccine against human papillomavirus (HPV), recently became available in the United States for use in girls and women 9 to 26 years of age. A second HPV vaccine, Cervarix, is under development. These vaccines constitute the most significant development in cervical cancer prevention in the last 60 years, having the potential to reduce the incidence of cervical cancer by up to 70%     

Increasing Knowledge of Human Papillomavirus Among Young Adults

HPV is the most common sexually transmitted infection, affecting more than 43 million Americans. HPV is a public health concern because it is the leading cause of cervical, oropharyngeal, vulvar, vaginal, and anal cancer. Despite a highly effective vaccine, the rate of HPV vaccine completion among young adults falls below the Healthy People goal. In efforts to combat this public health concern, an educational brochure was distributed as a quality improvement project in an urban primary care office. After this educational intervention was implemented, there was a significant increase in young adults who received the HPV vaccine from their primary care provider.     

Exploring the Need of HPV Education Programs in Korean American Communities

Given the significantly higher cervical cancer risks faced by Korea Americans (KA), the aim of this study was to explore cultural influences and barriers affecting human papillomavirus (HPV) vaccination decisions and preferred educational methods to effectively deliver HPV information. Focus groups included 20 KA parents. This study found a lack of knowledge about HPV and the vaccine, along with negative perceptions about the vaccine, affects HPV vaccination decision-making. Ineffective conversations and a lack of HPV vaccine recommendations by health care providers influenced by cultural beliefs were found to be another major barrier. These findings reveal new insights to guide the development of HPV education programs.     

HPV vaccine

The incidence and the mortality from the disease have decreased dramatically in developed countries with increased use of cytologic screening and treatment of preinvasive disease. However, in developed countries including Japan, cervical cancer tends to affect younger women who may be responsible for young children. Therefore, the social consequences of the disease can be still tremendous. For cervical cancer prevention, vaccination programs against the two major cancer-causing types (HPV16 and 18) started in the world. We all look with eager anticipation towards the prospects of HPV vaccines and the perspective of eradicating cervical cancer in the not too distant future.