Quadrivalent Human Papillomavirus (HPV) Vaccine in Cancer Survivors

癌症幸存者的四价人乳头瘤病毒 (HPV) 疫苗

• 批准号: 8271277
• 负责人: James Klosky
• 金额: $ 66.84万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-07 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8271277
• 关键词: 17 year old; Accounting; Address; Adolescent; Advisory Committees; Affect; Age; Age-Years; Anogenital venereal warts; Antibody Formation; Area; Behavioral; Behavioral Sciences; Cancer Survivor; Cancer Survivorship; Cervical; Chemotherapy-Oncologic Procedure; Clinical; Clinical Trials Design; Commit; Competence; Cross-Sectional Studies; Data; Development; Discipline of Nursing; Dose; Dysplasia; Epidemiology; Evaluation; Female; Foundations; Future; General Population; Genital system; HPV-High Risk; Health Promotion; Hepatitis B; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 6; Immunization; Immunocompromised Host; Immunosuppression; Individual; Infection; Inferior; Institution; Integration Host Factors; Intervention; Laboratory Research; Lesion; Malignant Childhood Neoplasm; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measures; Medical; Morbidity - disease rate; Mucous Membrane; Oncogenic; Oropharyngeal; Parents; Patients; Pediatric Oncology; Phase; Population; Premalignant; Prevalence; Primary Prevention; Radiation; Recommendation; Recurrence; Reporting; Research; Research Infrastructure; Research Priority; Risk; Safety; Schedule; Series; Sexually Transmitted Diseases; Subgroup; Survivors; United States; United States Food and Drug Administration; Vaccination; Vaccines; Vulnerable Populations; age group; arm; base; cancer prevention; cancer risk; cancer therapy; childhood cancer survivor; cohort; evidence base; evidence based guidelines; hematopoietic cell transplantation; high risk; immunogenic; immunogenicity; improved; indicated prevention; male; malignant mouth neoplasm; mortality; non-oncogenic; oncology; open label; prospective; respiratory; response; routine practice; sex; sexually active; theories; uptake; vaccination strategy; virology; young adult

DESCRIPTION (provided by applicant): Advances in treatment for childhood cancer over the past five decades have resulted in a rapidly growing population of young cancer survivors, a substantial number of whom are adolescent/young adults - the age group at highest risk for sexually transmitted infection. Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States today, with prevalence in young, sexually active individuals ranging from 44.8% in females to 51.2% in males. Persistent infection with oncogenic strains of HPV (e.g., types 16 and 18) is associated with the development of cancers affecting the genital tract and oropharyngeal mucosa. Immunosuppression increases persistence of HPV infection and risk of HPV-related malignancies. Systemic cancer treatment may result in immunosuppression for prolonged periods, placing cancer survivors at higher risk for HPV-related morbidity. The quadrivalent HPV (qHPV) vaccine is indicated for prevention of HPV-related cancers and precancerous or dysplastic lesions in males and females between 9 and 26 years of age. The safety, tolerability, immunogenicity, and efficacy of the qHPV vaccine have been demonstrated in healthy young individuals; however, vaccine uptake to date has been low in the general population and no studies to date have determined vaccine uptake in cancer survivors, or the immunogenicity or safety/tolerability of the qHPV vaccine in this vulnerable population. Thus, there is a critical need to develop evidence to inform optimal uptake and utilization of the HPV vaccine in cancer survivors. This proposal aims to (1) estimate the prevalence of HPV vaccine initiation in cancer survivors 9-26 years of age and examine the sociodemographic, behavioral, and medical determinants of non-initiation; and (2) among non-immunized survivors, evaluate the 3-dose qHPV vaccine series to determine the following: Immunogenicity following the third and final vaccine dose; clinical/host factors influencing immunogenicity; and the safety/tolerability of the qHPV vaccine. Evaluation of the antibody response persistence at 1 and 2 years post-vaccine initiation and clinical/host factors influencing response persistence will be explored. If rates of HPV vaccine initiation are low among cancer survivors, this study will inform development of theory-based interventions to improve vaccine uptake, and identify subgroups likely to derive the most benefit from targeted interventions. This study will also identify clinical factors associated with inadequate immunogenic response to the vaccine and the impact of humoral competence on response, providing a foundation for future development of alternative vaccination strategies in subgroups unable to mount an adequate response to the standard 3-dose series. The proposed research addresses the high priority areas of health promotion, cancer prevention, and cancer survivorship. Importantly, males - a population that has been significantly understudied in regard to HPV vaccination - will be included; and the study will be conducted across four geographically distinct institutions to assure representation from an ethnically and racially diverse cohort of cancer survivors. PUBLIC HEALTH RELEVANCE: Persistent infection with oncogenic strains of the human papillomavirus (HPV) is strongly associated with development of invasive HPV-related malignancies; risk for persistent HPV infection may be increased in young cancer survivors due to treatment-related immunosuppression. The quadrivalent HPV vaccine is indicated for prevention of HPV-related cancers and precancerous lesions in males and females age 9-26, but vaccine uptake, immunogenicity and safety/tolerability have not been determined in cancer survivors. This proposal will comprehensively evaluate the HPV vaccine (uptake, immunogenicity, and safety/tolerability) in cancer survivors, identifying barriers/facilitators to vaccination and factors associated with inadequate immunogenic response, thus providing the needed evidence base for vaccine recommendations, and promoting primary prevention of HPV-related malignancies and their associated morbidity and mortality in this vulnerable population.

描述（由申请人提供）：过去五十年来儿童癌症治疗的进展导致了迅速增长的年轻癌症幸存者，其中大量是青少年/年轻人 - 性传播风险最高的年龄段感染。人类乳头瘤病毒（HPV）是当今美国最常见的性传播感染，年轻，性活跃的个体患病率从女性的44.8％到男性的51.2％。 HPV的致癌菌株（例如16和18）的持续感染与影响生殖道和口咽粘膜的癌症的发展有关。免疫抑制会增加HPV感染的持久性和与HPV相关的恶性肿瘤的风险。全身性癌症治疗可能会导致长时间的免疫抑制，从而使癌症幸存者面临与HPV相关的发病率更高的风险。在9至26岁之间的男性和女性中，指示了预防与HPV相关的癌症以及癌前或发育不良的癌症的四相HPV（QHPV）疫苗。在健康的年轻人中已经证明了QHPV疫苗的安全性，耐受性，免疫原性和功效。但是，迄今为止，普通人群的疫苗吸收量很低，迄今为止，尚无研究率在癌症幸存者中摄取疫苗，或者QHPV疫苗在这种脆弱人群中的免疫原性或安全性/耐受性。因此，迫切需要开发证据，以告知癌症幸存者中HPV疫苗的最佳吸收和利用。该提案旨在（1）估计癌症幸存者中HPV疫苗启动的患病率9-26岁，并检查了非生机的社会人口统计学，行为和医疗决定因素； （2）在非免疫的幸存者中，评估3剂量QHPV疫苗系列以确定以下内容：第三次和最终疫苗剂量之后的免疫原性；影响免疫原性的临床/宿主因素；以及QHPV疫苗的安全性/耐受性。评估疫苗开始后1和2年的抗体反应持续性以及影响的临床/宿主因素 响应持久性将被探讨。如果癌症幸存者的HPV疫苗起始率较低，则该研究将为基于理论的干预措施的发展提供信息，以改善疫苗的摄取，并确定可能从目标干预措施中获得最大收益的亚组。这项研究还将确定与对疫苗的免疫原性反应不足以及体液能力对反应的影响相关的临床因素，这为未来在无法对标准3剂量系列的亚组中开发的替代疫苗接种策略的基础为基础。拟议的研究涉及健康促进，预防癌症和癌症生存的高优先级领域。重要的是，将包括男性 - 在HPV疫苗接种方面已被大大研究的人群 - 将包括在内；这项研究将在四个地理上不同的机构中进行，以确保来自种族和种族多样化的癌症幸存者队列的代表。 公共卫生相关性：人类乳头瘤病毒（HPV）的持续感染与侵入性HPV相关的恶性肿瘤的发展密切相关；由于治疗相关的免疫抑制，年轻的癌症幸存者可能会增加持续性HPV感染的风险。在癌症幸存者中，尚未确定疫苗的摄取，免疫原性和安全性/耐受性，但在癌症幸存者中尚未确定疫苗的摄取，免疫原性和安全性/耐受性。该提案将全面评估癌症幸存者中的HPV疫苗（摄取，免疫原性和安全性/耐受性），确定障碍/促进因素以疫苗接种和免疫原性反应相关的因素，从而为疫苗建议提供了所需的证据基础，并促进了一级预防预防效果。与HPV相关的恶性肿瘤及其在这一脆弱人群中相关的发病率和死亡率的研究。