It is too early to judge the effectiveness of the first specific vaccine against human papillomavirus (HPV) for cervical cancer, but scientists should pursue the role of infectious agents in other potentially preventable cancers, said the two winners of the 2007 Warren Alpert Foundation Prize at a symposium they gave about their work on Sept. 15 at HMS.
The $150,000 Alpert Prize was awarded to Harald zur Hausen, professor emeritus, and Lutz Gissmann, professor—both at the German Cancer Research Center in Heidelberg—for their work in cloning and characterizing the most prevalent virus types in cervical cancer, HPV 16 and HPV 18, said HMS dean Jeffrey Flier in his introduction.
“Very importantly, they made their clones available to other scientists, accelerating studies that ultimately led to the development of effective vaccines against the disease,” Flier said. “This success holds enormous promise for world health since, on a global level, cervical cancer ranks No. 2 in cancer incidence among women and represents in many parts of Africa, Asia, and South America the most frequent cancer among females.”
The first generation of prophylactic vaccines against HPV are composed of an empty viral protein capsid, Gissmann said. The vaccines prime the immune system, which normally does not see the infectious agent because the virus is usually sequestered by tough outer skin cells known as keratinocytes. Scientific challenges remain in developing alternative vaccines that are affordable and practical, such as not needing refrigeration. Immune therapy for people already infected with HPV is the next step.
So far, the results are not very encouraging for immune therapy in people already infected, Gissmann said. “If it does not work with HPV, immune therapy will never work. Here we have a defined tumor antigen.” The potential benefits of HPV vaccines that reach more people include the reduction of other HPV related cancers, including those of the vulva, penis, and head and neck, he said.
Zur Hausen reviewed the history of papillomavirus research, beginning with recognition in 1933 by R.E. Shope that an agent caused “horned” papillomas in wild cotton tail rabbits. He suggested that infectious agents may underlie other malignant tumors, including certain skin cancers induced under immunosuppression or hematological malignancies. Such agents will be difficult to find, in part because they may originate in domestic animals and may not replicate in human cells.
The relationship between infections may be complicated and unexpected, zur Hausen said. In the case of leukemia, frequent childhood infections before age 1 seem to be protective in some way, he said. The link between colorectal and breast cancer and red meat may be due to rare or medium cooking temperatures, which do not kill infectious agents in the meat. “Research on infectious causes of human cancers has a great potential for future surprises,” he said.
