Dr. Kreimer is a senior investigator in the Infections and Immunoepidemiology Branch (IIB). She focuses her research on the etiology and prevention of human papillomavirus (HPV) and cancers at multiple sites, including the head and neck and anogenital region. Dr. Kreimer has particular interests in translational research, cancer etiology related to the natural history of HPV infection at multiple anatomic sites, and cancer prevention. She received a Ph.D. in infectious disease epidemiology from the Johns Hopkins Bloomberg School of Public Health in 2003. Dr. Kreimer conducted postdoctoral research at the International Agency for Research on Cancer in Lyon, France and the National Cancer Institute, NIH.
Dr. Kreimer’s scientific interests lay in the evaluation of:
- The performance of prophylactic HPV vaccines, with a particular focus on the protection afforded by a single dose;
- Understanding the natural history of HPV infections at multiple anatomic sites; and,
- HPV 16-induced immunity, especially for the early antigens of the viral genome, as a possible biomarker for HPV-driven cancers.
HPV type 16 (HPV 16) infection is one of the most important human carcinogens, causing more than 500,000 cancer deaths per year worldwide, the majority of which are due to cervical cancer in low-income countries. It is well established that persistent infection with HPV 16, 18, or other carcinogenic HPV genotypes is the necessary, but not sufficient, cause of cervical cancer. Infection with HPV 16 is an established risk factor for some cancers at additional anatomic sites, including cancers of the anus, oropharynx, vagina, vulva, and penis. HPV type 16 causes about 50 percent of cervical cancers and upwards of 90 percent of the non-cervical HPV-driven cancers.
Dr. Kreimer is principal investigator of the Costa Rica HPV Vaccine Trial long-term follow-up study (CVT LTFU), a study that started as a randomized controlled trial of the bivalent HPV vaccine, in collaboration with Agencia Costarricense de Investigaciones Biomédicas (ACIB), and transitioned to an epidemiologic cohort study for the long-term follow-up phase. Using data from this study, Dr. Kreimer and colleagues were the first to demonstrate that the vaccine efficacy against incident persistent HPV 16/18 infection was comparably high among women who received three, two, or even a single dose of vaccine four years after HPV vaccination. They continue to evaluate this question and recently updated their findings to show that a single dose continues to provide robust protection a decade after HPV vaccination. Her team has also documented that the bivalent vaccine strongly protects against HPV infections at essentially all non-cervical anatomic sites where HPV causes cancer in a woman (i.e., the anus, vulva, and oral region), and that the level of protection was comparably high to that observed at the cervix among the same women. The CVT field effort is ongoing; a subset of women is expected to be followed for a median of 20 years following the initial vaccination. While the data on single-dose protection of the bivalent HPV are compelling, their post-hoc nature make the data inadequate to justify a formal change in current multi-dose HPV vaccine recommendations. Dr. Kreimer and her team developed additional trials to formally evaluate the efficacy, immune response, and potential public health impact of a single-dose strategy.
Dr. Kreimer and her NCI team, again in collaboration with ACIB, implemented the ESCUDDO study (Estudio de Comparacion de Una y Dos Dosis de Vacunas Contra el Virus de Papiloma Humano), a large, randomized, controlled, noninferiority efficacy trial designed to formally investigate the protection afforded by a single dose of the bivalent Cervarix® and nonavalent GARDASIL®9 HPV vaccines in Costa Rica. The main goals of the trial are to evaluate whether, in adolescent girls, one dose or two doses of these vaccines confers strong, durable protection against persistent HPV16/18 infections. Virologic endpoints are necessary in the evaluation of a one-dose schedule, as one-dose antibody levels are inferior to those of two doses, and presently, the minimum antibody level required for protection is unknown. Separately for each vaccine, one dose will be tested for noninferiority against the two-dose regimen. Analyses will also be conducted to estimate the vaccine efficacy versus no vaccination using a concurrent population survey of comparable, unvaccinated age-matched females in the same region, who will be tested for HPV DNA and then immediately vaccinated. Immunogenicity induced by these different vaccine dose schedules and vaccine products will be compared. Study results are expected in 2025 and are intended to provide definitive results for recommending bodies, if warranted.
The second trial implemented was PRIMAVERA (Puente de Respuesta Inmunológica para Mejorar el Acceso a Vacunas y ERrAdicar el cancer, Clinicaltrials.gov NCT03728881), a non-randomized, open-label, immunogenicity trial comparing one dose of the bivalent Cervarix® HPV vaccine in girls (9-14 years) to three doses of the quadrivalent Gardasil® HPV vaccine in women (18-25 years) in Costa Rica. PRIMAVERA aims to provide evidence that a single dose of the HPV vaccine will elicit an immune response sufficient to protect against targeted HPV infections and subsequent neoplasms.
Despite the great potential of HPV vaccination, the current birth cohorts (individuals in their 30s, 40s, 50s, etc.) will not experience the protection afforded by prophylactic HPV vaccines. Therefore, screening will remain an important tool in our fight against cancer for decades as these individuals age into cancer-susceptible phases of life. Thus, continued research into possible biomarkers of HPV-driven cancers is necessary. Dr. Kreimer and colleagues from the International Agency for Research on Cancer (IARC) and the German Cancer Research Center (DKFZ) discovered that the HPV 16 E6 antibody marker predicts risk of oropharyngeal cancer years before cancer development. They validated their discovery in an independent U.S.-based NCI cohort, the Prostate, Lung, Colon, and Ovary (PLCO) Screening Trial. Based on these findings, Dr. Kreimer and team formed the HPV Cancer Cohort Consortium (HPVC3) involving nine prospective cohort studies from Europe, North America and Australia. The main aim of HPVC3 is to evaluate HPV antibodies and risk of HPV-driven cancers, with a focus on oropharyngeal and anal cancer, but also including penile, cervical, vaginal, and vulvar cancer. Blood was collected up to 40 years prior to cancer diagnosis in this pooled effort. Dr. Kreimer also investigates HPV 16-E6 seroprevalence and kinetics in people without cancer.
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