Is a Comprehensive Approach Necessary for Preventing Cancers Caused by Infectious Agents?

In June 2012, Lancet Oncology published a review and analysis of the 2008 global burden of cancers attributable to infections, concluding that one in six cancers worldwide may be caused by preventable infections. The study estimated the population attributable fraction (PAF) of infectious agents for 27 cancers in 184 countries. Of the 12.7 million new cases of cancer that occurred, the PAF associated with an infectious etiology was 16.1 percent, which indicates about 2 million cancer cases were attributed to infection.

Epidemiologic research serves a critical role in increasing understanding of the natural history of infectious diseases involved in various cancers.

Four Culprit Infectious Agents

Four infections − human papillomavirus (HPV), Helicobacter pylori, and hepatitis B and C − account for about 1.9 million cancers globally.  Infection prevalence differs across countries and ages.  The PAF for less developed countries at 22.9% is almost three times higher than more developed countries at 7.4%.  Approximately 30 percent of the infection-based cancers were found in individuals younger than 50 years of age.  Hence, prevention of infection by vaccination, affordable antiviral therapy, or antimicrobial treatments would have a significant impact on the global cancer burden.  The 2012-2013 President’s Cancer Panel is holding four workshops to discuss how the HPV vaccine could serve as an example to accelerate progress in cancer prevention.

A pictorial depiction of immune cells from an individual vaccinated for HPV. Once vaccinated the body makes antibodies that recognize and attack the L1 protein on the surface of HPV viruses and prevent the virus from releasing its genetic material, thereby protecting the individual. National Cancer Institute’s Understanding Cancer Series: HPV Vaccine, Slide 9, image located at http://www.cancer.gov/cancertopics/understandingcancer/HPV-vaccine

Scientific Opportunities

Prevention of infection-related cancers would have a tremendous impact on reducing the global cancer burden. Scientific opportunities arising from some important observations include:

1. The scientific and public health questions do not end once a vaccine is available.The Food and Drug Administration (FDA) has approved two vaccines to prevent HPV infection. Both Gardasil® and Cervarix® are highly effective in preventing infections with HPV types 16 and 18, two high-risk HPVs that cause most cervical and anal cancers.  Gardasil® also prevents infection of two additional HPV types, 6 and 11, which cause approximately 90 percent of genital warts.  Neither of these HPV vaccines provides complete protection against infection with other HPV types.  Recent research suggests that both vaccines may provide partial protection against some additional HPV types that can cause cervical cancer.  Scientific challenges that remain include the need to better understand the mechanisms involved in HPV persistence and clearance, quantify the minimum doses required of the vaccines, determine whether alternate routes of administration are equally effective, and establish best practices for screening.
2. Certain cancers have been linked with infectious agents, but not all infected individuals develop cancer. Understanding what co-factors may be involved in the development of infection-related cancers is important.  Helicobacter and other infectious agents have been hypothesized to  be involved as co-factors in the development of certain cancers, such as gallbladder cancer and non-Hodgkin’s lymphoma, but to date, there have been insufficient data to firmly establish such connections.  Other co-factors that may increase cancer risk include but are not limited to: age, diet, impaired immunity, other health problems, environment, and genetics.
3. New methods and technologies have helped identify associations between previously unknown or unsuspected viruses and microorganisms and certain cancers. High-throughput sequencing of tumor tissue identified the Merkel cell polyomavirus associated with some, but not all, cases of Merkel cell carcinoma, and more recently, identified a potential link between Fusobacterium and colon cancer.  What steps are needed to apply a high-throughput sequencing approach to the study of other infectious agents?

Research Resources

NCI participates in several Funding Opportunity Announcements (FOA) to foster research related to infectious diseases. EGRP has a Web page with links to relevant funding opportunities, research resources, selected publications, and staff contact information. The Program also encourages investigator-initiated grant applications to study infectious diseases in relation to cancer risk.

What DoYOU Think?

Please tell us through the comment box below what you think are the most pressing, unanswered questions to tackle the global problem of cancer-causing infectious agents.

Vidya Vedham, Ph.D., M.S., is a Cancer Research Training Award (CRTA) fellow in EGRP’s Methods and Technologies Branch (MTB). She coordinates Program-level activities for existing projects focusing on multiple infections in cancer. Dr. Vedham obtained her Ph.D. from the University of Oklahoma Health and Sciences Center in Immunology. She has extensive research experience in cell biology, immunology, protein biochemistry, molecular biology, and biophysics. Prior to joining EGRP, Dr. Vedham served as a Special Volunteer in NCI’s Office of Science Planning and Assessment and as a CRTA fellow in NCI’s Laboratory of Cellular and Molecular Biology.