Article

Kahn JA.. HPV vaccination for the prevention of cervical intraepithelial neoplasia. N Engl J Med 361: 271-278

Division of Adolescent Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
New England Journal of Medicine (Impact Factor: 55.87). 08/2009; 361(3):271-8. DOI: 10.1056/NEJMct0806938
Source: PubMed

ABSTRACT

A sexually active 18-year-old woman presents to her internist for an annual examina- tion. During the review of her family history, she notes that her mother recently re- ceived a diagnosis of "pre-cervical cancer" and underwent a loop electrosurgical exci- sion procedure. The patient's mother has advised her to get the "cervical-cancer shot." Should this patient receive a human papillomavirus (HPV) vaccine, and how effective would vaccination be in preventing cervical cancer? The Clinical Problem Genital HPV infection is usually acquired through sexual contact and is extremely common. In a nationally representative study of women in the United States, 25% of persons between the ages of 14 and 19 years and 45% of persons between the ages of 20 and 24 years were HPV-positive.1 It is estimated that more than 80% of both men and women in the United States will be infected with HPV at some point in their lives.2 HPV is often acquired within months after the first sexual intercourse: in a study of university women who had recently had sexual intercourse for the first time and reported having only one partner, almost 30% became HPV-positive within 1 year.3 Although HPV infection is usually asymptomatic, anogenital warts or can- cers or other HPV-associated cancers develop in a subgroup of infected women and men. The clinical outcome of greatest significance for public health is cervical cancer. Globally, cervical cancer is the second most frequent cancer among women; each year, approximately 490,000 women receive this diagnosis and 270,000 die from cervical cancer.4 In the United States, the implementation of cytologic screening programs with the Papanicolaou (Pap) test has led to a decrease in rates of cervical cancer, since screening identifies precancerous cervical lesions that can be treated before they prog- ress to cancer. Despite such screening, in 2008, approximately 11,000 women in the United States received a diagnosis of cervical cancer and 3900 died from the disease.5 The direct medical costs associated with the prevention and treatment of HPV- related anogenital warts and cervical disease in the United States are estimated to be $4.0 billion annually,6 and productivity losses due to deaths from cervical can- cer are estimated to be $1.3 billion annually.7

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    • "Since both cross-protection of the available HPV16/18 vaccines and its clinical relevance determined with the data available for vaccine efficacy have shown additional protection against HPVs -31, -33, -45, -51, -52, -56 andThe number HPV risk types may add up to more than the total number of cancer patients for each age group due to multiple-infection of some patients or may be less than reported in Table 2because some participants' age was not available. % are of the total number of HPV positive cases (presented as n) in each age range -58[27,28], the expected impact of HPV vaccination on cervical cancers in Ghana may be further increased. Specifically, if the infection by HPV59 depends on a prior infection by HPV18[24]since they most occurred together in this study, then a lower prevalence of both HPV18, HPV 59 and lower frequency of multiple infection may result after the introduction of the HPV16/18 vaccines. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Human Papillomavirus (HPV) infections have been shown to be a necessary risk factor for the development of cervical cancer. However, HPV genotype distribution varies geographically, both in type and relative prevalence. In order to ensure a successful introduction of available vaccines, there is the need to identify pre-vaccination HPV genotype prevalence in Ghana and the extent of single and multiple-infections. Methods Paraffin-embedded cervical tissues of 256 confirmed cervical cancer cases diagnosed at the Korle-Bu Teaching Hospital during the period January 2004 to December 2006 were selected after hematoxylin and eosin staining and confirmation. Following a heat-proteinase K-based tissue lysis, HPV was detected and typed by a nested-multiplex PCR assay using an E6/E7 consensus primer and type-specific primers. Results Of the 256 cases, 230 (89.8 %, 95 % CI 85.7–93.4 %) were positive for HPV DNA. HPV18 (47.4 %), HPV59 (42.2 %), HPV45 (37.4 %) and HPV16 (9.0 %) were the four common HPV genotypes detected. A total of 110 (47.8 %) of the 230 HPV DNA positive tissues, were infected by a single HPV genotype while the other 120 (52.2 %) were infected by multiple HPV genotypes. A significant association was determined between each of the following HPV genotypes and multiple-infection; HPV18 (OR = 6.97; 95 % CI, 3.89–12.50), HPV59 (OR = 9.56; 95 % CI, 5.57–20.02) and HPV45 (OR = 1.94; 95 % CI, 1.12–3.35). Conclusion The prevalence of the following high risk HPV genotypes (HPV18, HPV59, HPV45) were relatively high among the cases of cervical cancers reported at this hospital in Ghana during the study period. Additionally, there was a high frequency of HPV multiple-infections among these cases.
    Full-text · Article · Dec 2016 · Infectious Agents and Cancer
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    • "It simulates the natural history of cervix uteri carcinoma from infection to death. It concentrates on cancerous high-risk HPV types (Kahn 2009; Lowy and Schiller 2006), in particular type 16 and 18 as they are the main targets of HPV-vaccination programs. The model assumes that HPV is exclusively transferred by sexual intercourse, whether during stable partnership (in the following called ''stable partnership'') or short term (in the following called ''short-term relationship''). "
    [Show abstract] [Hide abstract] ABSTRACT: Health policy support in least developing countries is needed to allocate scarce resources most efficiently and produce the maximum health at given resources. However, planners frequently face severe uncertainty of biological, economic and health service structures and parameters. This paper presents a model of cervical cancer (CUC) in Cambodia as an example of health policy support under extreme uncertainty. The projections are based on a multi-compartment dynamic policy model, specifically developed for CUC in Cambodia. The model simulates the demographic system and infections through sexual intercourse for 100 years. Data were taken from the literature and adjusted for Cambodia through interviews. CUC is an increasing problem in Cambodia and the number of deaths due to cervical cancer growths faster than the population. On average, Cambodia will lose some 5159 years of life per year due to CUC. From the alternative interventions against CUC, a “see-and-treat” approach based on VIA screening of women 30–49 years every 3 years seems to be most efficient. The results of the simulation indicate that the “see-and-treat” approach should be implemented in Cambodia. Even under strong changes of parameters and assumptions, this finding is robust. The model is currently being used in development planning. The example shows that health policy support is possible even under extreme uncertainty if the model builder employs a sufficient number of sensitivity analyses and scenarios.
    Preview · Article · Oct 2015
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    • "It is estimated that more than 80% of both men and women in the United States will be infected with HPV at some point in their lives [20, 21]. Estimated yearly cervical cancer cases and deaths associated with HPV are 490,000 and 270,000, respectively [20, 21]. Sexually transmitted HPV is a necessary factor for the development of cervical cancer and its precursor lesions. "
    [Show abstract] [Hide abstract] ABSTRACT: Human Papillomaviruses (HPV) are a diverse group of small non-enveloped DNA viruses. Some HPVs are classified as low-risk as they are very rarely associated with neoplasia or cancer in the general population, and cause lenient warts. Other HPVs are considered as high-risk types because they are responsible for several important human cancers, including cervical cancer, a large proportion of other anogenital cancers, and a growing number of head and neck cancers. Transmission of HPV occurs primarily by skin-to-skin contact. The risk of contracting genital HPV infection and cervical cancer is influenced by sexual activity. Currently two prophylactic HPV vaccines, Gardasil® (Merck, USA) and Cervarix® (GlaxoSmithKline, UK), are available and recommended for mass immunization of adolescents. However, these vaccines have limitations as they are expensive and require cold chain storage and trained personnel to administer them by injection. The use of nano or micro particulate vaccines could address most of these limitations as they are stable at room temperature, inexpensive to produce and distribute to resource poor regions, and can be administered orally without the need for adjuvants in the formulation. Also it is possible to increase the efficiency of these particulate vaccines by decorating the surface of the nano or micro particulates with suitable ligands for targeted delivery. Oral vaccines, which can be delivered using particulate formulations, have the added potential to stimulate mucosa-associated lymphoid tissue located in the digestive tract and the gut-associated lymphoid tissue, both of which are important for the induction of effective mucosal response against many viruses. In addition, oral vaccines provide the opportunity to reduce production and administration costs and are very patient compliant. This review elaborately discusses different strategies that can be pursued to develop a nano or micro particulate oral vaccine for HPV induced cancers and other diseases. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
    Full-text · Article · Apr 2015 · Journal of Pharmacy and Pharmaceutical Sciences
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