DCEG research on the association between infectious agents and cancer has made significant improvements to public health.
Human Papillomavirus (HPV)
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.
Negative HPV Test Result is Better Predictor of Low Cervical Cancer Risk than Negative Pap Test
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, DCEG investigators 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.
Gage JC, et al. Reassurance against future risk of precancer and cancer conferred by a negative HPV test. J Natl Cancer Inst 2014.
Efficacy of HPV Vaccines – Doses
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. Such an approach could lower the cost of vaccination and encourage the global dissemination of the vaccine.
In 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 three 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.
Kreimer AR, Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine. J Natl Cancer Inst 2011.
Efficacy of HPV Vaccines – Non-Cervical Sites
DCEG investigators also reported that the HPV 16/18 vaccine provides strong protection against HPV infections in every place in the body where HPV causes cancer.
Kreimer et al., Efficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among young women: a nested analysis within the Costa Rica Vaccine Trial. Lancet Oncology, 2011.
Beachler DC, et al. Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection. J Natl Cancer Inst. 2015.
HPV-based Screening for Cervical Cancer
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 have informed these revised guidelines.
Katki, H.A., et al., Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice. Lancet Oncology 2011.
Cervical Cancer Screening for Women with HIV
In 2021, findings from the HIV/AIDS Cancer Match Study were used to inform an important revision to cervical cancer screening guidelines among HIV+ women.
Stier EA, Engels E, Horner MJ, …, Shiels M. Cervical cancer incidence stratified by age in women living with HIV compared with the general population in the United States, 2002-2016. AIDS 2021.
Cervical Screening and Clinical Management Guidelines
In 2020-2021, new guidelines for screening and clinical management of cervical precancer from the American Cancer Society, a U.S. consensus committee, and the World Health Organization, are based on research by DCEG investigators.
The 2019 ASCCP Risk-Based Management Consensus Guidelines are presented in a series of eight papers in the Journal of Lower Genital Tract DiseasesExit Disclaimer and are available free on the web and as a downloadable application for smartphones.
These guidelines utilize a risk-based approach and focus on HPV testing for primary screening. Paired with vaccination against HPV, they support the global effort to accelerate cervical cancer control.
Helicobacter pylori (H. pylori)
Evidence H. pylori Treatment Reduces Gastric Cancer Incidence and Mortality
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, though benefits in older people and those with advanced precancerous lesions were unknown. DCEG investigators 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.
Li WQ, et al. Effects of Helicobacter pylori treatment on gastric cancer incidence and mortality in subgroups. J Natl Cancer Inst 2014.
Ma JL et al., Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. J Natl Cancer Inst 2012.
You WC, et al., Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst 2006.
Zhang et al., 2006
Human Immunodeficiency Virus (HIV)
DCEG research provided the initial assessment of the specificity, sensitivity, and appropriate applications of the first-generation Human Immunodeficiency Virus (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 Human Immunodeficiency Virus 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).
National Toxicology Program Cites DCEG Research in Evaluations of Cancer Impact from Viruses
In 2016, the National Toxicology Program (NTP) released monographs on five viruses as part of its Report on Carcinogens: Epstein-Barr Virus (EBV), Kaposi Sarcoma-Associated Herpesvirus (KSHV), Human Immunodeficiency Virus Type 1 (HIV), Human T-Cell Lymphotrophic Virus Type 1 (HTLV-1), Merkel Cell Polyomavirus (MCV).
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. Supported by DCEG research, the NTP’s results influence public health policies by regulatory bodies such as the CDC.
Find DCEG Publications on Viruses
Several DCEG investigators served in advisory and review roles in the monograph writing process: James Goedert, M.D., (retired), technical advisor for all five monographs. Charles S. Rabkin, M.D., M.Sc., peer review panel for all five monographs, Sam M. Mbulaiteye, MBChB, M.Phil., M.Med., technical advisor for the KSHV monograph.
Other Infectious Agents
U.S. poliovirus vaccines were accidentally contaminated with simian virus 40 (SV40). These contaminated doses were widely administered from 1955 through 1962. The public was alarmed by the possible risks from exposure to this oncogenic virus. DCEG investigators published results from 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).