Quadrivalent Human Papillomavirus (HPV) Vaccine in Cancer Survivors

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年轻癌症幸存者人口迅速增长，其中相当多的人是青少年/年轻成年人-性传播感染风险最高的年龄组。人乳头瘤病毒（HPV）是当今美国最常见的性传播感染，在年轻的性活跃个体中的患病率从女性的44.8%到男性的51.2%不等。HPV致癌株的持续感染（例如，16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HPV感染的持续性和HPV相关恶性肿瘤的风险。全身性癌症治疗可能导致免疫抑制持续时间延长，使癌症幸存者处于HPV相关发病率的较高风险中。四价HPV（qHPV）疫苗适用于预防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年轻个体中得到证实;然而，迄今为止，一般人群的疫苗摄取率较低，迄今为止尚无研究确定癌症幸存者的疫苗摄取率，或qHPV疫苗在该易感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HPV疫苗的最佳摄取和利用。该提案旨在（1）估计9-26岁癌症幸存者中HPV疫苗启动的流行率，并检查未启动的社会人口统计学、行为和医学决定因素;（2）在未免疫的幸存者中，评价3剂qHPV疫苗系列，以确定以下内容：第三剂和最后一剂疫苗接种后的免疫原性;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。评价疫苗接种后1年和2年的抗体应答持续性以及临床/宿主影响因素 将探索响应持续性。如果癌症幸存者的HPV疫苗启动率较低，这项研究将为开发基于理论的干预措施提供信息，以提高疫苗的吸收，并确定可能从有针对性的干预措施中获益最多的亚组。本研究还将确定与疫苗免疫原性应答不足相关的临床因素以及体液免疫能力对应答的影响，为未来在无法对标准3剂系列产生充分应答的亚组中开发替代疫苗接种策略提供基础。拟议的研究涉及健康促进，癌症预防和癌症生存的高度优先领域。重要的是，男性--一个在HPV疫苗接种方面研究严重不足的人群--将被包括在内;该研究将在四个地理位置不同的机构进行，以确保来自种族和种族多样化的癌症幸存者队列的代表性。 公共卫生相关性：人乳头瘤病毒（HPV）致癌株的持续感染与侵袭性HPV相关恶性肿瘤的发生密切相关;由于治疗相关的免疫抑制，年轻癌症幸存者持续HPV感染的风险可能会增加。四价HPV疫苗适用于预防9-26岁男性和女性的HPV相关癌症和癌前病变，但尚未确定癌症幸存者的疫苗摄取，免疫原性和安全性/耐受性。该提案将全面评估癌症幸存者的HPV疫苗（摄取，免疫原性和安全性/耐受性），确定疫苗接种的障碍/促进因素以及与免疫原性反应不足相关的因素，从而为疫苗推荐提供所需的证据基础，并促进HPV相关恶性肿瘤及其相关发病率和死亡率的一级预防。

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.