Over the years, DCEG research on the association between infectious agents and cancer has made a significant public health impact.
In 2016, the National Toxicology Program (NTP) released monographs on five viruses as part of its Report on Carcinogens:
The monographs outline current understandings of cancer hazards from particular viruses based on a large body of scientific research. Investigators in DCEG’s Infections and Immunoepidemiology Branch (IIB) produced a considerable portion of the evidence cited in the NTP reports. DCEG investigators study the role of viruses in cancer using techniques from molecular epidemiology to linkages of cancer and virus registries. Supported by DCEG research, the NTP’s results influence public health policies by regulatory bodies such as the CDC.
DCEG Publications on Epstein-Barr Virus
DCEG Publications on Kaposi Sarcoma-Associated Herpesvirus
DCEG Publications on Human Immunodeficiency Virus Type 1
DCEG Publications on Human T-Cell Lymphotrophic Virus Type 1
DCEG Publications on Merkel Cell Polyomavirus
Several DCEG investigators served in advisory and review roles in the monograph writing process. James Goedert, M.D., formerly a senior investigator in IIB, was a technical advisor for all five monographs. Charles S. Rabkin, M.D., M.Sc., senior investigator, IIB, served on the peer review panel for all five monographs. Sam M. Mbulaiteye, MBChB, M.Phil., M.Med., senior investigator, IIB, was a technical advisor for the KSHV monograph.
Human papillomavirus (HPV) is the cause of nearly all cervical cancers. Newer approaches to cervical cancer screening test for DNA (or RNA) of HPV at the cervix, whereas the Pap test detects abnormal cell changes associated with the development of cancer. Co-testing is now recommended for most women but clinicians were still unsure of the reassurance from a negative HPV test. Based on a study that included more than 1 million women, investigators at the National Cancer Institute, led by Julia C. Gage, Ph.D., M.P.H., determined that a negative test for HPV infection compared to a negative Pap test provides greater safety, or assurance, against future risk of cervical cancer. These findings provide evidence to support the currently recommended cotesting strategy with HPV and Pap, as well as the possibility of primary HPV testing as another alternative for cervical screening. Read more about this study. Reference: Gage JC, et al. Reassurance against future risk of precancer and cancer conferred by a negative HPV test. J Natl Cancer Inst 2014;106(8):pii:dju153.
Infection with Helicobacter pylori (H. pylori) —a bacterium found in the stomach—is a major cause of gastric cancer. Approximately two-thirds of the world’s population harbors the bacterium, with infection rates much higher in developing countries. Treatment of the infection with antibiotics had been shown in intervention trials to lower gastric cancer incidence when compared to placebo. Lowered gastric cancer mortality was also suggested. But benefits in older people and those with advanced precancerous lesions were unknown. NCI investigator Mitchell H. Gail, M.D., Ph.D., and collaborators found that a two-week course of H. pylori treatment given 15 years earlier was associated with lower gastric cancer incidence and mortality in older adults (aged 55 years and older at the beginning of the study). Incidence, but not mortality, was also statistically significantly reduced in subjects with advanced precancerous lesions initially. H. pylori treatment can benefit an entire population, not just the young or those with mild precancerous lesions in the stomach. Reference: Li WQ, et al. Effects of Helicobacter pylori treatment on gastric cancer incidence and mortality in subgroups. J Natl Cancer Inst 2014;106(7):pii:dju116.
Starting in the 1980s, DCEG investigators carried out landmark studies on the natural history of cervical cancer that firmly established HPV as the necessary cause of this malignancy (Schiffman et al., 1993, 2007). Their efforts laid the groundwork for vaccine development and improved strategies for screening.
The licensure of prophylactic HPV vaccines in the mid-2000s created the opportunity to reduce a large fraction of the disease burden of cervical cancer. However, the cost and logistical challenges of administering a three-dose regimen created a barrier to vaccinating adolescents. DCEG investigators reported that one or two doses of an HPV 16/18 vaccine may prevent cervical cancer just as effectively as three doses (Kreimer et al., 2011, 2015). Such an approach could lower the cost of vaccination and encourage the global dissemination of the vaccine.
In October 2016, the U.S. Food and Drug Administration (FDA) approved a two-dose regimen of the nonavalent HPV vaccine for adolescents ages 9 through 14. Shortly after, the Centers for Disease Control and Prevention (CDC) recommended a two dose regimen for all prophylactic HPV vaccines given to children ages 9 to 14, while keeping the 3 dose regimen for those 15 or older. This decision was based on a review of evidence from randomized clinical trials and other studies, including research conducted by DCEG investigators. Read more about the two-dose CDC recommendation at Cancer.gov.
DCEG investigators also reported that the HPV 16/18 vaccine provides strong protection against anal HPV infections that could eventually lead to anal cancer (Kreimer et al., 2011).
In 2012 the U.S. Preventive Services Task Force and a coalition of health organizations published new guidelines for cervical cancer screening. DCEG studies into the use of HPV DNA testing and cytology to stratify women into accurate and precise risk categories (Katki et al., 2011) have informed these revised guidelines. More information on HPV and cervical cancer.
DCEG research provided the initial assessment of the specificity, sensitivity, and appropriate applications of the first-generation HIV antibody testing system for diagnosis of HIV infection (Weiss et al., 1985). As a result of this work, those tests became standard care in the routine clinical practice of diagnosing individuals thought to have contracted HIV.
A prospective study of HIV infection and the development of AIDS in subjects with hemophilia showed that a much larger proportion of HIV-infected persons would develop AIDS than previously thought (Goedert et al., 1989), a finding with broad impact for public health prevention programs and clinical practice.
DCEG research led to the recognition that CD4 count and HIV viral load predict risk for the development of full-blown AIDS and death from AIDS (Goedert et al., 1987, 1989; Ehmann et al., 1994; O’Brien et al., 1996). These biomarkers are now the standard measures used to inform routine clinical care of HIV-positive patients, including counseling, screening, and medication management.
New worker safety recommendations for the handling of concentrated HIV samples in the laboratory were influenced by a DCEG study of HIV infection among laboratory workers (Weiss et al., 1988).
DCEG biostatisticians applied novel statistical methods to derive estimates of HIV prevalence in the U.S. population. Their findings revealed that prevalence was greatest among heterosexual individuals (Rosenberg et al., 1991; Rosenberg, 1995; Rosenberg and Biggar, 1998).
U.S. poliovirus vaccines were accidentally contaminated with simian virus 40 (SV40). These contaminated doses were widely administered from l955 through 1962. The public was alarmed by the possible risks from exposure to this oncogenic virus. DCEG investigators published results from after a study of newborns who received SV40-contaminated polio vaccine showing no increased risk of cancer (Fraumeni et al., 1963; Fraumeni et al., 1970; Mortimer et al., 1981).
The Food and Drug Administration (FDA) recommended screening all blood donations for human T-cell leukemia virus type I and II (HTLV-I/II) antibodies, based on DCEG research that demonstrated increased risks of HTLV-1 and associated complications following exposure to HTLV-I/II in contaminated blood (Blattner et al., 1982; Blayney et al., 1983).
The FDA decided not to screen the U.S. blood supply for human herpesvirus 8 (HHV-8) after DCEG research demonstrated that serological tests for HHV-8 had poor reproducibility (Rabkin et al., 1998).
DCEG studies linking Helicobacter pylori infection to the very high incidence of gastric cancer and precancerous lesions in Shandong province in China prompted a clinical trial that showed a sustained reduction in risk following a two-week course of antibiotics (You et al., 2006; Zhang et al., 2006; Ma et al., 2012; Li et. al., 2014).