Quadrivalent Human Papillomavirus (HPV) Vaccine in Cancer Survivors

描述（由申请人提供）：在过去的五十年中，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，其中相当多的人是青少年/年轻人-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、性活跃的个体中患病率从女性的44.8%到男性的51.2%不等。HPV致瘤毒株（例如16型和18型）的持续感染与影响生殖道和口咽粘膜的癌症的发展有关。免疫抑制增加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长时间的免疫抑制，使癌症幸存者面临hpv相关疾病的更高风险。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人中得到证实；然而，迄今为止，疫苗在一般人群中的吸收率很低，迄今为止没有研究确定癌症幸存者的疫苗吸收率，或qHPV疫苗在这一易感人群中的免疫原性或安全性/耐受性。因此，迫切需要找到证据，为癌症幸存者最佳地接受和利用HPV疫苗提供信息。本提案旨在(1)估计9-26岁癌症幸存者开始接种HPV疫苗的患病率，并检查未开始接种的社会人口统计学、行为和医学决定因素；(2)在未接种疫苗的幸存者中，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年抗体反应持续性评估及临床/宿主因素的影响

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.