Biography

Dr. Hildesheim received a Ph.D. in epidemiology from The Johns Hopkins School of Hygiene and Public Health in 1991. He has been at the NCI since 1987 and is currently the Chief of the Infections and Immunoepidemiology Branch. Dr. Hildesheim's research focuses on understanding host and viral factors involved in the pathogenesis of DNA virus-related tumors and in the evaluation of efficacy and underlying immunological mechanisms associated with the recently licensed prophylactic HPV vaccines.

Research Interests

We are conducting large-scale population studies to investigate exogenous and host factors involved in the pathogenesis of DNA virus-related tumors. Two groups of tumors are under investigation: female gynecological cancers linked to HPV and nasopharyngeal cancer linked to EBV. Non-viral factors involved in the pathogenesis of HPV and EBV-related cancers are also being examined, since infection alone is rarely sufficient for the development of cancer. We are also involved in the evaluation of the long-term impact of HPV vaccination and in elucidating immunological mechanisms involved in long-term vaccine efficacy. To this end, Dr. Hildesheim is the lead NCI investigator on a 7,465 women community-based HPV-16/18 Vaccine Trial in Costa Rica. .

Cervical Cancer

Our previous studies suggested that in addition to HPV infection, important determinants of cervical disease progression may include host immune response to HPV; exogenous and behavioral factors, such as parity, smoking and oral contraceptive use; and infection with sexually transmitted agents other than HPV. To further define the factors related to persistence of HPV infections and to the progression of these infections to high-grade cancer precursors, I have been involved in several U.S and international case-control and cohort studies, the largest of which is a population-based study of 10,000 women in Costa Rica who were enrolled and followed for 7 or more years. Within this large cohort, we have nested studies that have allowed us to evaluate immunological factors associated with HPV persistence, inherited genetic factors linked to persistence and progression of HPV infections, and other exogenous factors. We have also had the opportunity to explore mucosal immunological factors and their determinants.

HPV Vaccines Cancer

HPV vaccines designed to prevent infection and associated lesions associated with oncogenic HPV types 16 and 18 have been licensed in many countries. These vaccines have the potential to profoundly impact cervical cancer prevention strategies, and if applied wisely to reach underserved populations that have historically not benefited from secondary prevention programs based on Pap smears. Dr. Hildesheim is the lead NCI investigator on a 7,465 women community-based HPV-16/18 vaccine trial in Costa Rica. Initiated in 2004, this trial is designed to evaluate the safety and efficacy of the HPV-16/18 vaccine, to examine broader questions of long-term population impact of vaccination, and to explore cost-effective ways in which HPV-based vaccination and screening might be applied in the future. The trial involves active follow-up of participants and includes a rich biological specimen collection component that allows for the added evaluation of numerous scientific questions of etiological and immunological interest.

Nasophryngeal Cancer

Nasopharyngeal cancer has a very distinct geographic and ethnic distribution, occurring at high rates among ethnic Chinese from southeastern China and at much lower rates among Caucasians. While infection with EBV is believed to be necessary for development of the cancer, both genetic and exogenous factors are also thought to be important. Dr. Hildesheim has conducted several studies of NPC in Taiwan, including a case-control study of largely sporadic tumors (>1,000 participants) and a family-based study of multiplex NPC families (>3,000 participants from >350 families). These studies serve as the foundation from which numerous hypotheses related to genetic and environmental risk factors for NPC are being investigated.

Keywords

cervical cancer, human papillomaviruses, immune response, vaccines, nasopharyngeal carcinoma, Epstein-Barr virus, DNA tumor viruses, genetic susceptibility

Selected Publications

• Safaeian M, Porras C, Schiffman M, Rodriguez AC, Wacholder S, Gonzalez P, et al. Epidemiological Study of Anti HPV 16/18 Seropositivity and Subsequent Risk of HPV 16 and 18 Infections. J Natl Cancer Inst, in press.
• Rodríguez AC, García-Piñeres AJ, Hildesheim A, Herrero R, Trivett M, Williams M, Atmella I, Ramírez M, Villegas M, Schiffman M, Burk R, Freer E, Bonilla J, Bratti C, Pinto LA. Alterations of T-cell surface markers in older women with persistent human papillomavirus infection. Int J Cancer 2010 Apr 7.
• Wacholder S, Chen BE, Wilcox A, Macones G, Gonzalez P, Befano B, Hildesheim A, Rodríguez AC, Solomon D, Herrero R, Schiffman M; CVT group. Risk of miscarriage with bivalent vaccine against human papillomavirus (HPV) types 16 and 18: pooled analysis of two randomised controlled trials. BMJ 2010 Mar 2;340:c712. doi: 10.1136/bmj.c712.
• Wang SS, Gonzalez P, Yu K, Porras C, Li Q, Safaeian M, Rodriguez AC, Sherman ME, Bratti C, Schiffman M, Wacholder S, Burk RD, Herrero R, Chanock SJ, Hildesheim A. Common genetic variants and risk for HPV persistence and progression to cervical cancer. PLoS One 2010 Jan 13;5(1):e8667.
• Yu KJ, Gao X, Chen CJ, Yang XR, Diehl SR, Goldstein A, Hsu WL, Liang XS, Marti D, Liu MY, Chen JY, Carrington M, Hildesheim A. Association of human leukocyte antigens with nasopharyngeal carcinoma in high-risk multiplex families in Taiwan. Hum Immunol 2009 Nov;70(11):910-4.
• Chang CM, Yu KJ, Mbulaiteye SM, Hildesheim A, Bhatia K. The extent of genetic diversity of Epstein-Barr virus and its geographic and disease patterns: a need for reappraisal. Virus Res 2009 Aug;143(2):209-21. Review.
• Yu KJ, Hsu WL, Chiang CJ, Cheng YJ, Pfeiffer RM, Diehl SR, Goldstein AM, Gravitt PE, Chen CJ, Hildesheim A. Cancer patterns in nasopharyngeal carcinoma multiplex families in Taiwan. Int J Cancer 2009 Apr 1;124(7):1622-5.
• Porras C, Rodríguez AC, Hildesheim A, Herrero R, González P, Wacholder S, Burk RD, Schiffman M. Human papillomavirus types by age in cervical cancer precursors: predominance of human papillomavirus 16 in young women. Cancer Epidemiol Biomarkers Prev 2009 Mar;18(3):863-5.
• García-Piñeres AJ, Hildesheim A, Dodd L, Kemp TJ, Yang J, Fullmer B, Harro C, Lowy DR, Lempicki RA, Pinto LA. Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes from vaccine recipients. J Immunol 2009 Feb 1;182(3):1706-29.
• International Collaboration of Epidemiological Studies of Cervical Cancer, Appleby P, Beral V, Berrington de González A, Colin D, Franceschi S, Goodhill A, Green J, Peto J, Plummer M, Sweetland S. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet 2007 Nov 10;370(9599):1609-21. Review.
• Hildesheim A, Herrero R, Wacholder S, Rodriguez AC, Solomon D, Bratti MC, Schiller JT, Gonzalez P, Dubin G, Porras C, Jimenez SE, Lowy DR; Costa Rican HPV Vaccine Trial Group. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial. JAMA 2007 Aug 15;298(7):743-53.

Collaborators

DCEG Collaborators

• Philip Castle, Ph.D.; Anil Chaturvedi, Ph.D.; Roni Falk, M.S.; Alisa Goldstein, Ph.D.; Hormuzd Katki, Ph.D.; Jill Koshiol, Ph..D.; Aimee Kreimer, Ph.D., Sharon Liang, Ph.D.; Nora Macklin, M,P.H.; Ligia Pinto, Ph.D.; Mahboobeh Safaeian, Ph.D. Mark Schiffman, M.D.; Sholom Wacholder, Ph.D.; Sophia Wang, Ph.D.; Mark Sherman, M.D.; Nicolas Wentzensen, M.D., Ph.D.; Rose Yang, Ph.D.; Meredith Yeager, Ph.D.; Kelly Yu, Ph.D.

Other NCI Collaborators

• Jay Berzofsky, M.D.; Mary Carrington, Ph.D.; Lori Dodd, Ph.D.; Doug Lowy, M.D.; John Schiller, Ph.D.; Diane Solomon, M.D.

Other Scientific Collaborators

• Paula Gonzalez, M.D.; Rolando Herrero, M.D.; Silvia Jimenez, M.P.H.; Carolina Porras, M.S.; Ana Cecilia Rodriguez, M.D., Proyecto Epidemiologico Guanacaste, San Jose, Costa Rica
• Robert Burk, M.D., Albert Einstein College of Medicine, Bronx, NY
• Chien-Jen Chen, Ph.D.; Alex Lou, M.D.; Wan-Lun Hsu, National Taiwan University and Academia Scinica, Taipei, Taiwan
• Patti Gravitt, M.S. Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health Baltimore, MD
• Leen-Jan van Doorn, Ph.D., Wim Quint, Ph.D., Delft Diagnostics Laboratory, The Netherlands
• Paul Ahlquist, M.D., Bill Sugden, Ph.D., University of Wisconsin, Madison, Wisconsin