IN THIS ISSUE 2 Message from the Director 4 Our Supporters Science at the heart of medicine NEWS Einstein Cancer Center

century ago, cervical cancer was the leading cancer killer of Conquering American women, but today it’s not even in the top 10. This A great progress was due mainly to better prevention, screening Cervical Cancer and treatment—and Albert Einstein Cancer Center researchers have played active roles in all of these areas. The Vaccines Some 13 different types of human papillomavirus (HPV) cause cervical cancer, but just two are responsible for most cases: HPV16 (50 percent of cases) and HPV18 (10 percent). Today, two cervical cancer vaccines—Cervarix and Gardasil—protect against HPV16 and HPV18. How do they compare? “The College of Medicine was the lead site in a postmarketing clinical trial of these vaccines and found stronger immunity with Cervarix,” says Mark Einstein, M.D., M.S. ’05, associate professor of obstetrics & gynecology and women’s health. But Gardasil has an added virtue: It not only prevents cervical cancer; it also protects against genital warts by targeting two other viruses, HPV6 and HPV11. His conclusion: Both vaccines work and can spare women from potentially debilitating disease.

Newsletter of the Albert Einstein Cancer Center Above, from left: Mark H. Einstein, M.D., M.S. ’05; Robert D. Burk, M.D.; and ISSUE 6 • WINTER/SPRING 2013 Howard D. Strickler, M.D. (continued on page 2) Conquering Cervical Cancer (continued from page 1) MESSAGE FROM “My daughters will be getting the found that women infected with THE DIRECTOR vaccine when they come of age,” HIV—the human immunodeficiency says Dr. Einstein, also associate virus, which causes AIDS—are more professor of epidemiology & popula- likely to have high-risk, and multiple tion health and director of clinical types of, HPV infection and cervical I. DAVID GOLDMAN, M.D. research for women’s health and precancer. An organization that she Director, Albert Einstein gynecologic oncology at Montefiore, co-founded in 2004 in Rwanda, the Cancer Center the University Hospital and academic Women’s Equity in Access to Care Professor, Departments of medical center for Einstein. Medicine and Kathryn Anastos, M.D. Molecular Pharmacology Remaining Challenges Professor of Medicine (General Internal Medicine) Susan Resnick Fisher Much work remains to be done if we Professor of Epidemiology & Professor are to make cervical cancer a disease Population Health Professor of Obstetrics & of the past. Getting more girls vac- Gynecology and Women’s Health cinated should be a top priority. Co-director, Einstein Global stounding breakthroughs have Health Center occurred in our understanding The Centers for Disease Control Albert Einstein College of the genetic abnormalities that and Prevention recommends the of Medicine A Attending Physician in Medicine trigger cancer. Based on those insights, vaccine for all girls ages 11 and 12. Montefiore Medical Center researchers have developed powerful Yet only half of all American girls are new drugs to target genetic defects in getting it, many not early enough. and Treatment for HIV, brings antiretro- individual cancers. But these agents Einstein’s Nicolas F. Schlecht, Ph.D., viral drugs and cervical cancer screen- have had only limited impact in easing and colleagues detected HPV DNA in ing to HIV-positive women. cancer’s burden. Clearly, the best strat- 59 percent of cervical samples from Dr. Strickler heads HPV research in egy against cancer is to prevent it! 97 sexually active, inner-city adoles- the Women’s Interagency HIV Study One preventive-medicine success cent minority women who had not (WIHS). This study followed more than 3,000 HIV-infected and 1,000 unin- story is the decline in the incidence of Nicolas F. Schlecht, Ph.D. cervical cancer and the deaths it causes. Associate Professor of fected women for more than a decade. Epidemiology & It is the most comprehensive prospec- This issue of the newsletter describes Population Health the important role the Albert Einstein Associate Professor of Medicine tive investigation of the natural history Cancer Center (AECC) has played in this Albert Einstein College of of HPV infection and precancer/cancer Medicine achievement. development in HIV-positive women. The clear relationship between This study has played a major role in specific types of human papillomavi- been vaccinated, meaning the ado- defining cancer screening guidelines. rus (HPV) and cervical cancer has been lescents had already been exposed Dr. Strickler is also the Harold and established after decades of research. and infected. By contrast, in another Muriel Block Chair in Epidemiology & Vaccines to prevent HPV infection have study that included 327 fully vac- Population Health and co-leader of the been developed and are widely avail- cinated adolescents, the number of AECC’s Cancer Epidemiology Program. able. AECC scientists are now studying cervical samples positive for HPV was Dr. Einstein is the principal inves- the vaccines’ effectiveness in settings as much as 80 percent lower, depend- tigator of a National Cancer Institute where sexual activity occurs at an early ing on the type of HPV. These studies (NCI)-funded trial being carried out at age and where sexually transmitted dis- illustrate the urgency of the need for four large African hospitals. Women eases are prevalent. early vaccination, says Dr. Schlecht. with cervical cancer and HIV infection HPV infections are relatively common: Tackling the Problem will be treated with a combination of radiation and chemotherapy. And more than 40 percent of American of HIV and HPV women ages 14 to 59 are infected. through Dr. Anastos’ NCI-funded Kathryn Anastos, M.D., studies cervi- Fortunately, the cervical lesions caused education grant, African scientists cal cancer risk worldwide in women by such infections rarely progress to cer- and healthcare professionals come with HIV. In research conducted with vical cancer. AECC scientists are work- to Einstein for training in various Dr. Einstein, Robert D. Burk, M.D., ing to distinguish benign lesions from aspects of clinical and epidemio- and Howard D. Strickler, M.D., she ones destined to become cancerous. logical research. Their approach: analyze the molecular characteristics of HPV, and the cervical cells it infects, to identify infections that warrant aggressive—and curative—local CANCER Q&A treatment. AECC scientists are applying this Q: Who should get vaccinated against HPV infection? research in treating women with HIV/ AIDS and HPV infections of the cervix. A: The vaccines are not just for preventing cervical cancer in girls and women ages Their goal is a long life free of cervical 9 through 26. One of the two vaccines, Gardasil, also protects against genital warts cancer for all women infected with HPV. and anal cancer in men as well as women, and the U.S. Centers for Disease Control recommends that males be vaccinated with Gardasil at age 11 or 12. Einstein’s Early Contributions Screening and Treatment developed a way to avoid immune- system surveillance. The researchers Looking for changes in tumor cells. are looking for genetic and epigene- So-called epigenetic changes are “I came to Einstein in 1984 to work on tic (gene-expression) factors that give normal ways by which a cell’s gene the hepatitis B virus and liver cancer,” the virus this “invisibility cloak.” says Dr. Burk, “but I was intrigued by expression is controlled. The most the emerging evidence that cervical Molecular methods for cervical common epigenetic changes involve cancer was also caused by a virus.” molecules called methyl groups that cancer screening. A new four-year Dr. Burk and his Einstein colleagues attach to and silence genes. Cancer study led by Dr. Strickler and involv- went on to publish numerous papers can develop if methyl groups silence ing Drs. Burk, Einstein and Anastos on HPV. One of their most significant tumor-suppressor genes that help will examine the use of molecular contributions involved the natural history keep cancerous cells in check. Dr. methods to identify HPV and cellular of HPV infection and cervical disease in Einstein and his colleagues are study- factors that can improve the accuracy young women. ing patients at Montefiore and Jacobi of cervical cancer screening in HIV- “We showed that HPV infections and positive women. The NCI-supported the abnormal Pap smears that they cause study follows a 2012 paper pub- are usually transient,” says Dr. Burk. CERVICAL CANCER lished in the Journal of the American “Standard practice then was surgical removal of these lesions, on the assump- BY THE NUMBERS Medical Association by the team tion that they’d progress to cervical can- suggesting that HPV DNA testing cer. We found that 95 percent of these Projected new 12,340 can help reduce the frequency of Pap lesions disappear within two years on U.S. cases in 2013: testing in HIV-positive women. their own, which really changed the way HIV, aging and immune status. physicians treat young women with early Projected U.S. deaths: 4,030 Because antiretroviral therapy cervical disease.” Gloria Ho, Ph.D., joined Einstein’s has been so successful, more HIV- Source: American Cancer Society department of epidemiology & popula- positive women now live to the ages tion health in 1990 and, with Dr. Burk, Medical Centers who have persistent when cervical cancer rates peak. Dr. published important findings on the HPV infection and early precancerous Strickler recently received an NIH transmission of HPV and the viral types cervical lesions to see if methylation grant to explore: that pose the greatest risk of cervical patterns in the cervical cells predict • how menopause and HIV affect cancer. which lesions are likely to develop HPV infection and development into cancer. of early cervical lesions;

Looking for changes in viruses. • what immune deficits drive the Dr. Einstein Honored Dr. Burk and his colleagues examined relationship of HIV with cervical methylation patterns in the genomes cancer and thus can be targeted of HPV viral types that cause most in prevention and treatment; cases of cervical cancer. In a 2012 study in the Journal of the National • which genes govern the interac- Cancer Institute, the researchers re- tion between the immune system ported higher HPV DNA methylation and abnormal cervical cells. in women with precancerous cervical A better treatment regimen. lesions compared to women with the Cisplatin is an effective cancer che- same HPV type but no detectable motherapy drug. But if cervical cancer precancerous cells. The findings sug- recurs and cisplatin has already been gest that HPV viral methylation can be Mark H. Einstein, M.D., M.S. ’05, right, with used, only 13 percent of patients useful in identifying which HPV cervi- Kathy Weinberg, president, National respond to the drug. Dr. Einstein and cal infections may lead to cancer. Women’s Division, and Willie Geist of NBC’s Dennis Y. S. Kuo, M.D., professor Today and MSNBC, Spirit Luncheon emcee. Dr. Burk is professor of pediatrics of clinical obstetrics & gynecology (genetics), of microbiology & immu- and women’s health, found that the nology, of obstetrics & gynecology Dr. Einstein was honored at the 58th combination of paclitaxel and oxali- and women’s health, and of epidemi- annual “Spirit of Achievement” platin—two other anticancer agents— ology & population health. He is also Luncheon, hosted by the New York is effective in treating patients with vice chair for translational research chapter of Einstein’s National Women’s recurrent cervical cancer who have in pediatrics at Einstein and attend- Division in May 2012 at the Plaza Hotel. previously been exposed to cisplatin. ing physician in pediatrics at The The luncheon benefited the Women’s Children’s Hospital at Montefiore. Division’s current initiative to support cutting-edge basic and translational How viruses slip under the radar. research studies at the Albert Einstein Einstein scientists led by Dr. Strickler ON THE WEB Cancer Center targeting breast, ovarian, found that HIV-positive women have To learn more about the cervical and uterine cancers. This year’s a low immune-system response to Albert Einstein Cancer Center, please visit Spirit luncheon, held in April, also HPV16, suggesting that the virus has www.einstein.yu.edu/cancer. supported research on women’s cancers. our supporters

The Albert Einstein Cancer Center gratefully acknowledges the generosity of the following individuals and organizations whose support is critical to advancing its mission.

NOTABLE GIFTS AND GRANTS Two research teams at Einstein and Einstein Cancer Center, director of the invade blood vessels and are then Montefiore have been awarded special Montefiore Einstein Center for Cancer carried to distant sites. This award is grants from the National Cancer Institute Care, professor of surgery and of the direct result of a pilot study that was (NCI). The grants, two of only 57 given genetics at Einstein and vice chair of funded, in part, by a generous gift nationwide and only five in New York surgery at Einstein and Montefiore. from Jane A. and Myles P. Dempsey. City, total more than $3 million. Dr. Kitsis holds the Dr. Gerald and Myra Dr. Condeelis is leader of the Albert The first, a grant of $1.7 million over Dorros Chair in Cardiovascular Disease, Einstein Cancer Center Tumor five years as part of the NCI’s “provoca- and is professor of medicine (cardiol- Microenvironment and Metastasis tive questions” program, was awarded to ogy) and of cell biology and director of Program, the Judith and Burton P. Steven K. Libutti, M.D., and Richard N. the Wilf Family Cardiovascular Research Resnick Chair in Translational Research, Kitsis, M.D. Using a model called multiple Institute at Einstein. professor and co-chair of anatomy and endocrine neoplasia type 1 (MEN1), the The second team, consisting of structural biology and co-director of researchers will investigate why certain Maja H. Oktay, M.D., Ph.D., Sumanta the Gruss Lipper Biophotonics Center; mutations promote cancer in some Goswami, Ph.D., and John S. Condeelis, Dr. Oktay is associate professor of tissues of the body but not in others. Ph.D., has been awarded $1.4 mil- pathology; and Dr. Goswami is The preliminary work for this grant was lion over four years to explore a novel assistant professor of anatomy and funded by a generous gift from Linda approach to studying metastasis. The structural biology. and Earle Altman. Dr. Libutti is associate scientists will focus on the crucial step in director of clinical services at the Albert metastasis in which breast cancer cells

EVENTS: Lunch & Learn

new approaches to research on the Gloria S. Huang, prevention, screening and treatment of M.D.; Paul R. gynecologic cancers. Overseers Marilyn Marantz, M.D., and Stanley M. Katz generously hosted M.P.H.; Overseer the event. Overseers Linda Altman, Rita Marilyn Katz, chair and Philip Rosen, Roslyn Goldstein and of the AECC’s Sue-ann Friedman were among those Cancer Research who attended this most informative Advisory Board; and Overseer program. Stanley M. Katz.

To learn more about supporting the work of the AECC, please contact: Gloria S. Huang, M.D., and Paul R. Experimental Therapeutics Program; IRA LIPSON Marantz, M.D., M.P.H., were the guest Dr. Marantz is associate dean for clinical Director of Institutional Advancement speakers at a “Lunch & Learn” program research education, associate director Albert Einstein College of Medicine for Einstein supporters and friends of the Harold and Muriel Block Institute Jack and Pearl Resnick Campus in June 2012 at Brae Burn Country for Clinical and Translational Research 1300 Morris Park Avenue Club in Purchase, NY. Dr. Huang is a at Einstein and Montefiore and director Harold and Muriel Block Bldg., Rm. 725 gynecologic oncologist and a member of Einstein’s Center for Public Health Bronx, NY 10461 of the Albert Einstein Cancer Center’s Sciences. They updated guests on 718.430.2371, [email protected]

ALBERT EINSTEIN ADMINISTRATION Associate Directors ADVISORY BOARD Leonard Augenlicht, Ph.D. CANCER CENTER Director Chairperson Susan Horwitz, Ph.D. I. David Goldman, M.D. Marilyn R. Katz Our mission: to promote and conduct Steven Libutti, M.D. research that will elucidate the origins Deputy Director Michael Prystowsky, M.D., Ph.D. of cancer and lead to effective new Roman Perez-Soler, M.D. Thomas Rohan, M.D., Ph.D. approaches for the prevention, diagnosis Richard Seither, Ph.D., M.S., M.B.A. and treatment of malignant diseases Pamela Stanley, Ph.D.