Quadrivalent Human Papillomavirus (HPV) Vaccine in Cancer Survivors

描述(申请人提供)：过去50年来，儿童癌症治疗的进步导致年轻癌症幸存者的人口迅速增长，其中相当一部分是青少年/年轻人--性传播感染风险最高的年龄段。人乳头瘤病毒(HPV)是当今美国最常见的性传播感染，在年轻的性行为活跃的人中的流行率从女性的44.8%到男性的51.2%不等。持续感染致癌HPV毒株(例如，16型和18型)与影响生殖道和口咽粘膜的癌症的发展有关。免疫抑制增加了HPV感染的持久性和HPV相关恶性肿瘤的风险。全身癌症治疗可能导致较长时间的免疫抑制，使癌症幸存者患HPV相关疾病的风险更高。四价HPV(QHPV)疫苗用于预防9至26岁男性和女性的HPV相关癌症和癌前病变或发育不良病变。QHPV疫苗的安全性、耐受性、免疫原性和有效性已在健康的年轻个体中得到证明；然而，到目前为止，普通人群的疫苗接种率很低，到目前为止还没有研究确定癌症幸存者的疫苗接种率，或者qHPV疫苗在这一脆弱人群中的免疫原性或安全性/耐受性。因此，迫切需要发展证据，告知癌症幸存者对HPV疫苗的最佳吸收和利用。这项建议旨在(1)评估9-26岁癌症幸存者中HPV疫苗启动的流行率，并检查不启动的社会人口学、行为和医学决定因素；(2)在未接种的幸存者中，评估3剂qHPV疫苗系列，以确定以下内容：第三剂和最后一剂疫苗后的免疫原性；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。疫苗接种后1年和2年抗体应答持久性及临床/宿主影响因素的评价 我们将探讨响应持久性。如果癌症幸存者的HPV疫苗启动率较低，这项研究将为基于理论的干预措施的发展提供信息，以提高疫苗接种率，并确定可能从有针对性的干预措施中获得最大好处的亚群。这项研究还将确定与疫苗免疫原性反应不足相关的临床因素以及体液能力对反应的影响，为未来为无法对标准三剂系列疫苗产生足够反应的亚组制定替代疫苗接种策略奠定基础。这项拟议的研究涉及健康促进、癌症预防和癌症存活率的高度优先领域。重要的是，男性--在HPV疫苗接种方面研究严重不足的人群--将被包括在内；这项研究将在四个不同地理位置的机构进行，以确保来自不同种族和种族的癌症幸存者队列的代表性。

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.