Biography

Dr. Schiffman received an M.D. from the University of Pennsylvania and an M.P.H. in epidemiology from The Johns Hopkins School of Hygiene and Public Health. He joined the NCI as a Staff Fellow in 1983 and, in 1996, was appointed Chief of the Interdisciplinary Studies Section in the Environmental Epidemiology Branch (which later became the HPV Research Group in the Hormonal and Reproductive Epidemiology Branch). He joined the Clinical Genetics Branch in October 2009 to study intensively why HPV is such a powerful carcinogenic exposure, akin to an acquired genetic trait with high penetrance for a cancer phenotype.

Dr. Schiffman received a Fulbright Scholarship in 1977 to carry out epidemiologic studies in Senegal. He has received numerous awards for his work in molecular epidemiology, including the ACS Medal of Honor and the AACR Prevent Cancer Foundation Award.

Research Interests

The main studies in which Dr. Schiffman played a major role in the past 5 years, listed chronologically, include: The Portland Kaiser Cohort; the Taiwan Cohort Study; the Guanacaste Natural History Study; the ASCUS-LSIL Triage Study (ALTS); the Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED/Biopsy); the Costa Rica Vaccine Trial (CVT); the Persistence and Progression (PaP) Study; and Nigeria Project Itoju. These studies overall have related HPV status to outcome for more than 100,000 women. Two were extremely large randomized trials. The two oldest cohorts have accrued more than 15 years of follow-up time. Through a natural progression of studies, he has pursued three main scientific themes: 1) HPV Natural History and Cervical Carcinogenesis; 2) Translational Studies of HPV Testing, Cytology, Colposcopy, and Vaccines; and 3) Risk Prediction and Cervical Cancer Prevention.

With regard to natural history, he has worked extensively with his major laboratory collaborator, Dr. Robert Burk (Albert Einstein, through a collaborative research agreement) on HPV phylogeny, investigating HPV at the levels of individual infections, women’s experience with HPV during their lifetimes, and populations. His work has helped promulgate a multi-stage causal model of HPV and cervical carcinogenesis based on a few distinct steps: acute infection with carcinogenic HPV type(s), detectable viral persistence (rather than clearance) linked to development of cervical precancer (CIN3), and invasion.

The natural history studies gave rise to translational research on HPV tests, serology, cytology, colposcopy, histology, and vaccines. He has helped to show that HPV testing is useful along the entire course of cervical cancer prevention, and must be integrated now with HPV vaccination. As co-Project Officer and Medical Monitor of the independent NCI Vaccine Trial, he has been heavily involved with virtually all aspects of that project.

The availability of improved cervical cancer risk tests and vaccines led to an active interest in risk prediction and cervical cancer prevention. These efforts rest on a universal base of quantifiable science (risk prediction) but reach into the realm of policy, which is deeply affected by setting. Thus, prevention work in the wealthy mainstream of the U.S. is much different than international work in low-resource settings; Dr. Schiffman has worked especially in Nigeria and Senegal. The high sensitivity of HPV DNA testing makes the test amenable to one or two screens in a lifetime.

In terms of HPV genomics, Dr. Schiffman and his laboratory and epidemiologist collaborators are using whole genome sequencing and genotype-phenotype analyses to understand the uniquely high carcinogenicity of HPV16 compared with closely related HPV types. Also, as a major new area, he is exploring the association between methylation of CpG sites in the HPV genome (particularly in L2 and L1) and diagnosis of CIN3, as compared with viral clearance. As part of the vaccine trial analysis, he and his collaborators will investigate whether HPV genetic variants explain partial cross-protection by comparing selected ?9- and ?7-containing samples from the Cervarix and Havrix (control) vaccine arms for variant status. Regarding clinical management, he and colleagues are conducting analyses of the impact of vaccination on frequency of cytologic abnormalities, colposcopic referrals, and biopsies.

Keywords

• Molecular epidemiology, human papillomaviruses (HPV), cervical cancer, multi-stage carcinogenesis, vaccination, prevention

Selected Publications

• Schiffman M, Wentzensen N, Wacholder S, Kinney W, Gage JC, Castle PE. Human papillomavirus testing in the prevention of cervical cancer. J Natl Cancer Inst 2011 Mar 2; 103(5):368-83. Epub 2011 Jan 31. Review. PubMed PMID: 21282563; PubMed Central PMCID: PMC3046952.
• Schiffman M, Rodriguez AC, Chen Z, Wacholder S, Herrero R, Hildesheim A, Desalle R, Befano B, Yu K, Safaeian M, Sherman ME, Morales J, Guillen D, Alfaro M, Hutchinson M, Solomon D, Castle PE, Burk RD. A population-based prospective study of carcinogenic human papillomavirus variant lineages, viral persistence, and cervical neoplasia. Cancer Res 2010 Apr 15; 70(8):3159-69. Epub 2010 Mar 30. PubMed PMID: 20354192; PubMed Central PMCID: PMC2855741.
• Rodríguez AC, Schiffman M, Herrero R, Hildesheim A, Bratti C, Sherman ME, Solomon D, Guillén D, Alfaro M, Morales J, Hutchinson M, Katki H, Cheung L, Wacholder S, Burk RD. Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection. J Natl Cancer Inst 2010 Mar 3; 102(5):315-24. Epub 2010 Feb 15. PubMed PMID: 20157096; PubMed Central PMCID: PMC2831050.
• Rodríguez AC, Schiffman M, Herrero R, Wacholder S, Hildesheim A, Castle PE, Solomon D, Burk R; Proyecto Epidemiológico Guanacaste Group. Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J Natl Cancer Inst 2008 Apr 2; 100(7):513-7. Epub 2008 Mar 25. PubMed PMID: 18364507.
• Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet 2007 Sep 8; 370(9590):890-907. Review. PubMed PMID: 17826171.

Collaborators

DCEG Collaborators

• Megan Clarke, M.H.S.; Julia Gage, Ph.D.; Arpita Ghosh, Ph.D.; Allan Hildesheim, Ph.D.; Hormuzd Katki, Ph.D.; Aimee Kreimer, Ph.D.; Lisa Mirabello, Ph.D.; Mahboobeh Safaeian, Ph.D.; Sholom Wacholder, Ph.D.; Nicolas Wentzensen, M.D., Ph.D.

Other NCI Collaborators

• Douglas Lowy, M.D.; John Schiller, M.D.; Diane Solomon, M.D.

Other ScientificCollaborators

• Kayode Ajenifuja, M.D., OAUTHC, Ile Ife, Nigeria Robert Burk, M.D., Albert Einstein College of Medicine, Bronx, NY Philip Castle, Ph.D., American Society Clinical Pathology, Washington, DC Gary Clifford, Ph.D., IARC, Lyon, France Michael Gold, M.D., Vanderbilt-Ingram, Nashville, TN Rolando Herrero, M.D., IARC, Lyon, France Rodney Long, M.A., National Library of Medicine, NIH Attila Lorincz, Ph.D., QMUC, London, England Walter Kinney, M.D., Kaiser Permanente Northern California, Oakland, CA Wim Quint, Ph.D., DDL, Delft, The Netherlands Ana Cecilia Rodriguez, M.D., Proyecto Epidemiologico Guanacaste, San Jose, Costa Rica Mark Stoler, M.D., University of Virginia, Charlottesville, VA Joan Walker, M.D., University of Oklahoma, Oklahoma City, OK Cosette Wheeler, Ph.D., University of New Mexico, Albuquerque, NM Rosemary Zuna, M.D., University of Oklahoma, Oklahoma City, OK