In healthy populations, the one month peak titers decline approximately 10-fold to a plateau level in the next 2 years and are maintained for more than 4 years thereafter [37]

In healthy populations, the one month peak titers decline approximately 10-fold to a plateau level in the next 2 years and are maintained for more than 4 years thereafter [37]. transplant (HSCT) participants A-966492 compared to those A-966492 who received the vaccine, but had not undergone HSCT (HPV6- p=0.030, HPV11-p=0.003, HPV16-p=0.018, HPV18-p= 0.001). It is unclear if these titers sufficiently protect from new infection since protective serologic cut offs have not yet been defined for the HPV vaccine. Individual immune functions were not associated with HPV seropositivity, however, underlying heterogeneous immune deficiency may explain higher rates of seropositivity in our younger unvaccinated participants (age 4C13 years). To better measure the efficacy of HPV vaccination in those with FA and other immune-compromised or cancer-prone disorders, future well-controlled vaccine studies are required. strong class=”kwd-title” Keywords: Human papillomavirus, Fanconi anemia, Serology, MGC20461 Vaccination Introduction Fanconi anemia (FA) is a genetic disorder that is characterized by genome instability, progressive bone marrow failure and predisposition to gynecological and head and neck squamous cell carcinomas (SCC) [1]. Reports by the International Fanconi Anemia Registry and the German FA registry estimated that the risk of head and neck SCC is over 500-fold higher among individuals with FA compared to the general population. The risk remains high even after hematopoietic stem cell transplantation (HSCT) and the tumors occur at strikingly early ages and carry dismal prognosis [2C4]. Additionally, individuals with FA treated with HSCT who develop graft vs host disease (GVHD) have a higher incidence of head and neck cancers in the ten years following treatment (28% vs 0% in those without GVHD); this finding points to the importance of minimizing the risk of GVHD [5]. Increased risk for GVHD observed in earlier FA studies is now reduced significantly by T-cell depletion of the donor graft [6, 7]. Chemotherapy and radiation are associated with high morbidity and mortality because of underlying DNA repair defects, making treatment of SCC difficult in this population [8C10]. Previous studies have found associations between human papillomavirus (HPV) infection, and cancers of anogenital and oropharyngeal regions in the general population [11C14]. Recent U.S. population-based studies conducted by the Centers for Disease Control and Prevention (CDC) show 62% of oropharyngeal cancers are attributable to HPV types 16 or 18 [15]. Studies of HPV in SCC tumors obtained from individuals with FA have shown contradictory findings [16C18]. The extent to which head and neck SCCs and anogenital cancers are associated with HPV in individuals with FA remains unanswered. However, these contradictory A-966492 reports have increased interest in studies addressing the role of HPV infection and vaccination in individuals with FA. In a study of individuals with FA living in Brazil, HPV positivity in oral samples was significantly higher than in non-FA controls [19]. Our group has also reported similar findings of higher HPV positivity in oral rinses of individuals with FA compared to their first-degree relatives [20]. Typically, an intact immune system recognizes, eliminates, and protects the body from viral and bacterial infections, as well as from transformed cells (pre-cancer cells) [21, 22]. Nevertheless, molecular and cellular mechanisms responsible for protection from and clearance of HPV infection are not completely understood [23]. Since our group and others have previously shown heterogeneous immune defects in those living with FA, a better understanding of the role of HPV and host immunity would allow for a more thoughtful approach towards prevention of HPV infection and risk reduction for SCC in this vulnerable population particularly as the HPV vaccine is available and recommended [24C27]. Data from clinical trials show that HPV vaccines, when given as a 3-dose series, have very high efficacy for prevention of vaccine typeCassociated cervical pre-cancers [28C30]. The prophylactic quadrivalent HPV vaccine has also been shown to prevent HPV16- A-966492 and HPV18-associated vaginal, vulvar, and anal pre-cancers and HPV6- and HPV11-associated anogenital warts [24, 31, 32]. No clinical trial data are currently available to demonstrate efficacy for prevention of oropharyngeal cancers. However, because many of these are attributable to HPV16, the HPV vaccine is likely to offer protection against these cancers as well. The current study sought to measure HPV antibody titers in vaccinated and naturally exposed, unvaccinated individuals with FA while simultaneously evaluating humoral immunity to provide insights into the prevalence of exposure to HPV and response to vaccination. Methods Informed Consent Child and adult participants with FA adopted in the Fanconi Anemia Comprehensive Care Center (FACCC) at Cincinnati Childrens Hospital Medical Center (CCHMC) were invited to participate in the study. Individuals with FA participating in the Fanconi Anemia Study Account (FARF) sponsored Adult or Family Meetings at Camp Sunshine were also offered the opportunity to participate. Informed consent was from participants at least 18 years of age. Parental permission was acquired for children less than 18 years of age. The study.