Immune Response Following Quadrivalent Human Papillomavirus Vaccination in Women After Hematopoietic Allogeneic Stem Cell Transplant

Abstract

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 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 PARTICIPANTSThis 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 MEASURESAnti-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 ρ = 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.

Human Papillomavirus, Herpes Zoster, and Hepatitis B Vaccinations in Immunocompromised Patients: An Update for Pharmacists

“…Additionally, adverse effects were mild and did not differ across groups. 37 Although above studies report mixed seroconversion rates, 4vHPV vaccine was well tolerated across all trials and did not worsen patients' autoimmune conditions or lead to new onset autoimmune disease, which is a concern clinicians may have in providing 9vHPV vaccine to immunocompromised individuals. 34,38 Furthermore, as 9vHPV is an inactivated subunit vaccine, it is not contraindicated in immunocompromised patients.…”

Infectious complications and vaccines

“…Stratton et al showed that strong immune responses can be elicited by the quad ri va lent human pap il lo ma vi rus (HPV) vac cine with out sig nifi cant side effects. 25 It would be log i cal to vac ci nate HPV-sero neg a tive individ u als to pre vent acqui si tion of HPV, but whether vac ci na tion of HCT recip i ents already infected with HPV would result in a clini cal ben e fit is unknown. This could be a topic for future stud ies.…”

Uso das vacinas de HPV em imunocomprometidos (não HIV/aids): revisão sistemática da literatura e metanálise

“…A maioria dos estudos teve recrutamento baseado em amostra de conveniência. Porém, cinco autores relataram que realizaram cálculo de tamanho de amostra.32; 69; 71; 72; 81 Todavia, apenas dois deles, Esposito et al 72 e Stratton et al81 , conseguiram alcançar a Com relação aos desfechos avaliados, 22 estudos avaliaram a imunogenicidade primária das vacinas HPV e 18 avaliaram a segurança. Dois estudos avaliaram a persistência de anticorpos cinco anos após a primeira dose da vacina[75][76] , e apenas um estudo envolvendo transplantados de órgãos sólidos, avaliou a proteção clínica em seguimento dos participantes por três anos, por prontuário e história clínica 68 .…”

“…Mehta et al78 realizaram um estudo transversal com portadores de anemia de Fanconi, com média de idade de 15 anos, porém não relata se foram recrutados ambos os gêneros ou Os autores encontraram menor resposta para os HPV-6 e 11 nas participantes mais velhas independente do grupo. O tempo de transplante no momento da vacinação não interferiu na resposta vacinal para os quatro tipos de HPV81 . Não houve diferença estatisticamente significativa entre os três grupos com relação aos títulos de anticorpos no sétimo mês ou no 12º mês após o recrutamento, contudo os GMT foram mais baixos nas receptoras de TCTH em uso de imunossupressores.…”

“…Não houve diferença estatisticamente significativa entre os três grupos com relação aos títulos de anticorpos no sétimo mês ou no 12º mês após o recrutamento, contudo os GMT foram mais baixos nas receptoras de TCTH em uso de imunossupressores. Os autores observaram que receptoras de TCTH com contagem de CD19 mais baixa tinham menor resposta à vacina, independentemente do uso ou não de imunossupressores81 . Nesse estudo, além do método cLIA, foi também realizado ELISA, tendo sido observada alta correlação dos títulos de anticorpos entre os dois testes no sétimo mês de análise (Spearman ρ=0.92; p< .001).…”