Three Tenure-Track Investigators Join IIB

DCEG’s Infections and Immunoepidemiology Branch (IIB), formerly known as the Viral Epidemiology Branch, seeks to examine the important role of viral and bacterial infections as well as immunologic and inflammatory processes in cancer etiology. To expand IIB’s research portfolio in these areas, three new tenure-track investigators joined the Branch in 2008.

Anil K. Chaturvedi, D.V.M., Ph.D., came to IIB as a postdoctoral fellow in 2005. He received his D.V.M. in 1999 from Andhra Pradesh Agricultural University in India and his M.P.H. and Ph.D. in epidemiology from Tulane University. Dr. Chaturvedi focuses his research on elucidating the role of infectious agents and immunologic alterations in cancer etiology, with a particular concentration on cancers of the lung and of the head and neck as well as AIDS-related cancers.

Dr. Chaturvedi has sought to gain a better understanding of the proportion of head and neck cancers attributable to human papillomavirus (HPV) infection and of the interactive effects among HPV, alcohol consumption, tobacco use, and oral hygiene. To address these questions, Dr. Chaturvedi is focusing his studies on populations in India, which has a very high incidence of head and neck cancers. Dr. Chaturvedi hopes his work will help improve secondary preventive measures, including screening and early detection. He explained that “the oral cavity is very amenable to both visual inspection and specimen collection, providing a unique opportunity for early detection of disease.”

The research findings described in a paper by Dr. Chaturvedi and colleagues on HPV-associated head and neck cancers were selected as being among the Journal of Clinical Oncology’s major cancer research advances of 2008. The report showed a 0.8 percent increase in incidence per year from 1973 to 2004 for head and neck cancer sites related to HPV; conversely, the incidence of HPV-unrelated cancer sites was stable from 1973 to 1982 and decreased thereafter. Dr. Chaturvedi hypothesizes that changes in sexual behaviors among recent birth cohorts may explain the rising incidence of HPV-related head and neck cancers.

Dr. Chaturvedi is also investigating the role of infections and inflammation in lung cancer. His studies in high-risk populations, such as HIV-infected individuals and survivors of cervical cancer, have recorded an increased risk of lung cancer that is not fully explained by smoking. To pursue these hypotheses, he is using the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial cohort  to investigate the association between risk of lung cancer and chronic pulmonary infections, serum markers of inflammation, and genetic polymorphisms in the innate immunity and inflammation pathways. Dr. Chaturvedi is expanding his investigations by using a large multiplex panel of cytokines to better characterize the mechanisms involved.

His work also aims to characterize the relationship between HIV-induced immunosuppression and the increased risk of HPV-associated cancers. “Understanding this relationship is particularly relevant in the era of highly active antiretroviral therapies (HAART),” Dr. Chaturvedi stated. “As HIV-infected individuals live longer, the incidence of cancers that are not strongly related to immunosuppression may actually increase.” Using the HIV/AIDS-Cancer Match Study, he recently showed that the incidence of anal cancers has increased significantly in the United States since the introduction of HAART in 1996.

Dr. Chaturvedi noted that “the significant advances in molecular epidemiology over the past several years have greatly enabled the study of infections, inflammation, and immunity in cancer etiology.” Dr. Chaturvedi believes these studies have great relevance for prevention because the exposures are modifiable, as illustrated by the success of HPV vaccination programs.

Aimee R. Kreimer, Ph.D., joined IIB to pursue her interests in the epidemiology of HPV infection and cancers at cervical and non-cervical anatomic sites. She received her Ph.D. in infectious disease epidemiology from the Johns Hopkins Bloomberg School of Public Health in 2003, where she helped design and implement a case-control study that implicated HPV in the development of oropharyngeal cancer. An article about this study was recently published in the New England Journal of Medicine. For her postdoctoral research, Dr. Kreimer worked at NCI and the International Agency for Research on Cancer in Lyon, France, on studies of HPV-related cancers of the head and neck. When offered a tenure-track position within the Division, she knew it was a prime opportunity. “The resources, collaborations, and expertise across DCEG place it at the forefront of HPV-related cancer research,” Dr. Kreimer said.

At NCI, Dr. Kreimer has expanded her HPV research to include studies of esophageal, cervical, vulvar/vaginal, and anal cancers. Although HPV is generally linked to cervical cancer, there is mounting evidence that this virus may be associated with other cancers as well. “It was quite natural to begin studying HPV associated with cervical cancer because the model of HPV carcinogenesis at the cervix can be used to inform similar research at other sites in the body,” she remarked.

Dr. Kreimer is actively involved in determining the efficacy of the HPV vaccine at both the cervix and non-cervical sites and in understanding the natural history of HPV infection through research conducted in NCI’s HPV vaccine trial in Costa Rica. To date, the trial has followed 7,500 women for four years; six years will be added to the trial to collect data on the longer-term efficacy and impact of the vaccine.

Dr. Kreimer is also collaborating with extramural investigators on a prospective study of HPV infection in a cohort of cancer-free men. The men will be followed for five years, and specimens will be collected every six months to test for HPV infections and outcomes, including infections of the oral cavity. “Currently, we do not have a clear understanding of HPV infections among healthy individuals,” Dr. Kreimer explained. “Obtaining data from multiple points in time will help to better understand the natural history of oral HPV infection.”

Dr. Kreimer believes that the discovery of virus-related cancers affords an important opportunity for cancer prevention. “HPV vaccination provides an incredible opportunity to protect against some cancers for which screening and treatment are not available in most of the world,” she said. “And if the vaccine is effective at protecting against extra-cervical infections, we may be able to further expand the scope of vaccination to protect against even more cancers.”

Mahboobeh Safaeian, Ph.D. (IIB), began her work in the Division as a Sallie Rosen Kaplan postdoctoral fellow in the Hormonal and Reproductive Epidemiology Branch. She received her Ph.D. in epidemiology in 2006 from the Johns Hopkins Bloomberg School of Public Health, where her doctoral dissertation focused on innovative methods of screening for cervical cancer in resource-poor communities and in communities that resist pelvic examination. She explained, “There is a huge disparity in cervical cancer incidence and mortality between developed and developing countries, which is mainly attributed to lack of resources for screening and, in some countries, reluctance among asymptomatic women to seek a pelvic exam. It was very exciting to have had the opportunity to validate HPV assessment in self-collected vaginal samples, which paves the way for much-needed research in countries and settings where cervical disease is a major public health problem.”

Researchers do not yet know why the majority of women with HPV infections eventually clear the infection while others go on to develop cervical cancer. To explore this issue, Dr. Safaeian is evaluating the role of cofactors in the progression of HPV infection through studies of inflammatory mechanisms, immune response, and genetic factors.

“The unique opportunity to partner with Dr. Ligia Pinto and her colleagues at the HPV Immunology Laboratory at NCI-Frederick, along with access to the HPV-related cohort studies in the Division, has allowed me to efficiently evaluate and utilize assays that measure the inflammatory and immunologic pathways attributable to HPV-related cancer,” Dr. Safaeian said.

To investigate the contribution of coinfection and inflammatory processes to the development of cervical cancer, Dr. Safaeian is studying the role of Chlamydia trachomatis in cervical carci-nogenesis among HPV-infected women in the HPV Natural History Study in Costa Rica. Because C. trachomatis and HPV infection have similar risk factors, special efforts are being made to determine whether C. trachomatis contributes independently to cervical carcinogenesis among HPV-positive women or whether the association is the result of residual confounding.

The progression of cervical cancer is affected by the type of HPV infection. To further investigate this association, Dr. Safaeian is comparing oncogenes in HPV types 16 (which accounts for nearly half of all cervical cancer), 31 (moderately associated with cervical cancer), and 73 (not associated with cervical cancer) to determine whether genetic and functional differences in HPV-16 may explain how it uniquely contributes to cervical cancer.

Dr. Safaeian is also studying differences in immune response to HPV infection and vaccination to determine whether the immune system’s reaction to HPV exposure contributes to the risk of subsequent HPV infections and cervical carcinogenesis. Within cohorts established by the Division, Dr. Safaeian is analyzing natural seropositivity to determine whether previous infections with an HPV type protect against future infections when a woman is re-exposed to the same or a similar HPV type. She is also investigating whether vaccinated women in the Costa Rica trial are partially protected against HPV infections of related types and the reasons for vaccine failure against these related types. In addition, she is evaluating host genetic markers associated with persistent infection and disease progression. Through these studies, Dr. Safaeian seeks to gain a deeper understanding of host factors that may help explain why some HPV-positive women develop cervical cancer while others do not. She hopes these studies will provide insights into the role of immune response in carcinogenesis at other sites.

—Jennifer Monti

Back to Top