Immune Response Following Quadrivalent Human Papillomavirus Vaccination in Women After Hematopoietic Allogeneic Stem Cell Transplant: A Nonrandomized Clinical Trial

Question Is the quadrivalent human papillomavirus (HPV) vaccine immunogenic in reproductive-aged women after hematopoietic stem cell transplant? Findings In this open-label nonrandomized clinical trial that included 64 women, most of the clinically stable reproductive-aged women who underwent allogeneic hematopoietic cell transplant, including those receiving immunosuppression, developed robust anti-HPV neutralizing antibody responses after vaccination similar to those observed in healthy women. Meaning These findings suggest that the full HPV vaccine series might be administered to reproductive-aged women after allogeneic hematopoietic stem cell transplant and that the current use of immunosuppression or prior use of rituximab after transplant does not preclude vaccination. Importance Human papillomavirus (HPV) infection is found in about 40% of women who survive allogeneic hematopoietic stem cell transplant and can induce subsequent neoplasms. Objective To determine the safety and immunogenicity of the quadrivalent HPV vaccine (HPV-6, -11, -16, and -18) in clinically stable women post-allogeneic transplant compared with female healthy volunteers. Interventions Participants received the quadrivalent HPV vaccine in intramuscular injections on days 1 and 2 and then 6 months later. Design, Setting, and Participants This prospective, open-label phase-1 study was conducted in a government clinical research hospital and included clinically stable women posttransplant who were or were not receiving immunosuppressive therapy compared with healthy female volunteers age 18 to 50 years who were followed up or a year after first receiving quadrivalent HPV vaccination. The study was conducted from June 2, 2010, until July 19, 2016. After all of the results of the study assays were completed and available in early 2018, the analysis took place from February 2018 to May 2019. Main Outcomes and Measures Anti-HPV-6, -11, -16, and -18-specific antibody responses using L1 virus-like particle enzyme-linked immunosorbent assay were measured in serum before (day 1) and at months 7 and 12 postvaccination. Anti-HPV-16 and -18 neutralization titers were determined using a pseudovirion-based neutralization assay. Results Of 64 vaccinated women, 23 (35.9%) were receiving immunosuppressive therapy (median age, 34 years [range, 18-48 years]; median 1.2 years posttransplant), 21 (32.8%) were not receiving immunosuppression (median age, 32 years [range, 18-49 years]; median 2.5 years posttransplant), and 20 (31.3%) were healthy volunteers (median age, 32 years [range, 23-45 years]). After vaccine series completion, 18 of 23 patients receiving immunosuppression (78.3%), 20 of 21 not receiving immunosuppression (95.2%), and all 20 volunteers developed antibody responses to all quadrivalent HPV vaccine types (P = .04, comparing the 3 groups). Geometric mean antibody levels for each HPV type were higher at months 7 and 12 than at baseline in each group (all geometric mean ratios >1; P < .001) but not significantly different across groups. Antibody and neutralization titers for anti-HPV-16 and anti-HPV-18 correlated at month 7 (Spearman rho = 0.92; P < .001 for both). Adverse events were mild and not different across groups. Conclusions and Relevance Treatment with the HPV vaccination was followed by strong, functionally active antibody responses against vaccine-related HPV types and no serious adverse events. These findings suggest that HPV vaccination may be safely administered to women posttransplant to potentially reduce HPV infection and related neoplasia. This nonrandomized clinical trial examines the safety and immunogenicity of the quadrivalent human papillomavirus vaccine in clinically stable women post-allogeneic transplant compared with female healthy volunteers.

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