Project Grant R01AI186576

EFFECTIVENESS OF THE HPV VACCINE IN IMMUNOCOMPROMISED POPULATIONS - PROJECT SUMMARY/ABSTRACT IMMUNOCOMPROMISED INDIVIDUALS-SUCH AS PEOPLE WITH HIV (PWH), AUTOIMMUNE CONDITIONS, AND A HISTORY OF SOLID ORGAN OR HEMATOPOIETIC STEM CELL TRANSPLANTATION-BEAR A SIGNIFICANTLY HIGHER BURDEN OF HUMAN PAPILLOMAVIRUS (HPV)-RELATED ANOGENITAL DISEASE COMPARED WITH IMMUNOCOMPETENT PEOPLE. WHILE HPV VACCINATION OFFERS A KEY OPPORTUNITY FOR PREVENTION, STUDIES IN IMMUNOCOMPROMISED POPULATIONS HAVE PRIMARILY EVALUATED VACCINE IMMUNOGENICITY AND SAFETY. MANY OF THESE PRIOR STUDIES DEMONSTRATED REDUCED ANTIBODY SEROCONVERSION RATES AND DURATION OF IMMUNE RESPONSES FOR IMMUNOCOMPROMISED POPULATIONS COMPARED WITH THE GENERAL POPULATION. WHILE THIS MAY TRANSLATE TO ATTENUATED PROTECTION AGAINST ANOGENITAL DISEASE, ADDITIONAL STUDIES THAT DIRECTLY EVALUATE VACCINE EFFECTIVENESS (VE) ARE WARRANTED TO INFORM OPTIMAL USE OF HPV VACCINE IN THESE HIGH-RISK INDIVIDUALS. TO DATE, THERE HAVE ONLY BEEN A FEW HPV VACCINE TRIALS IN PWH EVALUATING CLINICAL DISEASE (E.G., CONDYLOMA, CERVICAL DYSPLASIA/CANCER, AND ANAL DYSPLASIA/CANCER), BUT THESE WERE LIMITED BY SAMPLE SIZE, AND NONE WERE CONDUCTED IN PEOPLE WITH NON-HIV IMMUNOCOMPROMISING CONDITIONS. TO ADDRESS THESE MAJOR KNOWLEDGE GAPS, WE PROPOSE A COHORT STUDY IN TWO INTEGRATED HEALTH SYSTEMS TO EVALUATE HPV VE FOR PREVENTING ANOGENITAL DISEASE AMONG THREE DISTINCT GROUPS OF IMMUNOCOMPROMISED PEOPLE: (AIM 1) PWH; (AIM 2) PEOPLE WITH AUTOIMMUNE CONDITIONS (I.E., SYSTEMIC LUPUS ERYTHEMATOSUS [SLE], RHEUMATOID ARTHRITIS [RA], AND INFLAMMATORY BOWEL DISEASE [IBD], EACH EVALUATED SEPARATELY); AND (AIM 3) PEOPLE WITH A SOLID ORGAN OR HEMATOPOIETIC STEM CELL TRANSPLANT HISTORY. WE WILL EVALUATE VE FOR INCIDENT DISEASE AND RECURRENT DISEASE AMONG THOSE TREATED FOR PRIOR ANOGENITAL LESIONS. WE WILL ALSO PERFORM HPV GENOTYPING ON ARCHIVED ANOGENITAL CLINICAL SPECIMENS TO ESTIMATE VE FOR CERVICAL AND ANAL DYSPLASIA/CANCER ASSOCIATED WITH VACCINE-TARGETED HPV TYPES. FINALLY, WE WILL EVALUATE VE BY KEY VACCINATION CHARACTERISTICS, INCLUDING AGE AT VACCINATION, DOSES, TIME SINCE VACCINE, VACCINE TIMING (BEFORE/AFTER IMMUNOCOMPROMISING CONDITION), AND DISEASE-SPECIFIC FACTORS (E.G., CD4 COUNT FOR AIM 1, IMMUNOSUPPRESSIVE MEDICATION USE FOR AIM 2, AND TRANSPLANT TYPE FOR AIM 3). WE ANTICIPATE COHORTS OF ~35,000 PWH, ~15,800 WITH SLE, ~25,100 WITH RA, ~34,300 WITH IBD, AND ~21,300 WITH A TRANSPLANTATION HISTORY FROM YEARS 2006-2022. WE WILL ALSO ASSEMBLE COHORTS OF 20:1 DEMOGRAPHICALLY MATCHED IMMUNOCOMPETENT PEOPLE TO ENABLE COMPARISON OF VE ESTIMATES WITH THE CORRESPONDING IMMUNOCOMPROMISED GROUPS. WE ARE UNIQUELY POSITIONED TO ADDRESS THE AIMS GIVEN THE LARGE SAMPLES, LONG-TERM MEMBERSHIP RETENTION, DETAILED ELECTRONIC HEALTH RECORDS, AND ARCHIVED TISSUE SPECIMENS. WE ANTICIPATE OUR FINDINGS WILL INFORM TAILORED HPV VACCINATION STRATEGIES FOR DIVERSE IMMUNOCOMPROMISED POPULATIONS, INCLUDING CLARIFYING POTENTIAL BOOSTING OPTIONS AND BENEFITS OF EXTENDING CATCH-UP AGES, AND WILL THEREFORE BE OF GREAT INTEREST TO GUIDELINE GROUPS, CLINICIANS, AND PATIENTS.