Are HBV and HPV infection only the tip of the iceberg?

Modern medicine has made most infectious diseases of bacterial origin easily managed. However, research has shown that chronic infections caused by a handful of viruses, bacteria, and parasites play a significant role in the development of certain cancers. Andrew Dannenberg, MD, is director of the Cancer Center at New York-Presbyterian Hospital/Weill Cornell Medical Center, and Henry R. Erle, M.D.–Roberts Family Professor of Medicine at Weill Cornell Medical College. He spoke on the subject at the recent AACR Frontiers in Cancer Prevention Research meeting and shared his thoughts with ONI about this important issue.

ONI: What role do infections play in the development of cancers?

DR. DANNENBERG: A widely held figure is that at least 15% to 20% of all cancer worldwide is caused by infections; however, the number could be larger. Estimates of infection-related cancers are, for a number of reasons, potentially conservative. For instance, infections may very well be involved in the etiology of cancers that haven't yet been confirmed as infection-related, such as skin (see page 53), prostate, colon, gallbladder, bladder, and certain types of lymphomas and leukemias. So the true number remains uncertain until more research is done.

ONI: Is infection-related cancer more prevalent in certain parts of the world?

DR. DANNENBERG: Clearly, the problem is much more severe in developing nations where, for example, chronic hepatitis B and H pylori are major causes of liver and gastric cancers, respectively.

ONI: What is the causal relationship between infections and cancer?

DR. DANNENBERG: Infectious organisms cause cancer by a variety of mechanisms including inactivation of tumor suppressor genes. The infection-inflammation connection is also important for understanding the pathogenesis of malignancy. Chronic inflammation predisposes to malignancy via multiple mechanisms. So, in addition to trying to prevent chronic infection with vaccines and anti-infectives, targeted therapies that disrupt chronic inflammatory processes may protect against cancer. Naturally, there's a lot of work and research needed in this area.

ONI: Should developing cancer-specific vaccines be a priority in US research efforts?

DR. DANNENBERG: Yes, but it's important to be specific when talking about vaccine therapy.

Obviously, there is tremendous interest in developing vaccines to treat cancer and this continues to be an important area of research. However, vaccines that protect against certain infections are already preventing the development of cancer and saving lives.

For example, in 1976, Baruch S. Blumberg, MD, PhD, won the Nobel Prize for discovering the hepatitis B virus and for developing the first vaccine against hepatitis B. As of 2000, in excess of 1 billion hepatitis B vaccinations have been carried out. The vaccine clearly leads to a reduction in the risk of developing liver cancer, so the benefits from this particular vaccine have been substantial.

Add to that the new vaccines we have against HPV [human papillomavirus]-related cervical cancer, and the cumulative accomplishments and promise in cancer prevention are nothing short of remarkable.

ONI: Where do we go from here?

DR. DANNENBERG: There's a real need to put this issue into proper perspective in the public forum. There are currently 350 million carriers of chronic hepatitis B, and more that 100 million infected with hepatitis C, many of whom are predisposed to preventable liver cancer. Gastric cancer, one of the most common forms of cancer worldwide, is caused, at least in part, by H pylori-associated infection. And HPV infection is the major cause of cervical cancer.

And that's just the tip of the iceberg. Thus, there needs to be a greater emphasis on understanding the mechanistic link between infection, inflammation, and the development of cancer.

We have unequivocal evidence that infection-related cancer can be prevented and that excellent science can provide the biological rationale for the development of therapies.

Preventing infection-related cancers represents a remarkable opportunity for improved public health.

ONI: Any closing thoughts on the topic?

DR. DANNENBERG: The reason I chose to speak about the link between chronic infection and cancer at the AACR Frontiers meeting was to enhance the visibility of this issue. I think it is grossly underappreciated by the general public, and, unfortunately, too many healthcare workers are unaware of the significance of chronic infection as a potentially preventable cause of cancer.

As I mentioned, the burden of preventable cancers related to chronic infection is much greater in the developing world, so perhaps that is one reason it's not on our number 1 or 2 "to-do" lists.

But given the success in developing vaccines that prevent infection and cancer, it's vital that we continue to focus on this issue as a tractable approach to reducing the cancer burden. A major challenge will be to develop vaccines that are less costly and more readily given so that great science translates to improved global health.