BETHESDA, MarylandTwo phase III studies involving tens of thousands of women should indicate before this decade’s end whether a vaccine aimed at preventing infection by two cancer-causing strains of human papillo-mavirus (HPV) will likely reduce the incidence and mortality of cervical cancer, and perhaps several other cancers as well.
Merck & Co. has accrued more than 20,000 young women for its phase III study and continues to enroll participants in the United States, Latin America, and Asia. The study, which began late in 2001, is open to females age 16 to 26 who have not had an abnormal Pap smear and are HPV negative. The two principal investigators are Laura A. Koutsky, PhD, of the University of Washington, and Eliav Barr, MD, of Merck. The company also plans another phase III study of premenopausal women age 25 and older.
GlaxoSmithKline expects to begin a phase III trial of its HPV vaccine later this year, which will also take several years and involve thousands of women.
"What is actually being done is to try to prevent persistent infection by the virus that causes cervical cancer," said Douglas R. Lowy, MD, chief of the National Cancer Institute’s Laboratories of Basic Research and Cellular Oncology, addressing an institute-sponsored science writer’s symposium. "A reduction in cervical cancer will take many years. A reduction in incidence based on infection and abnormal cytology, however, will occur sooner. The younger the age of the population targeted for vaccination, the longer the interval before the effects on HPV infection will be seen."
Both the ongoing Merck study and the forthcoming GlaxoSmithKline trial have the same two primary endpoints, Dr. Lowy said: a reduced incidence of persistent HPV infection and a reduced incidence of moderate- and high-grade dysplasia.
The key to developing HPV vaccines came with the discovery that a structural protein of the virus, called L1, can self-assemble to form virus-like particles (VLPs) when its gene is expressed in a cell. "They look very similar morphologically to infectious particles, but they don’t contain DNA. L1 is also highly immunogenic," Dr. Lowy said.
During the early 1990s, there was an intense research effort focusing on HPV. Several institutions, including the NCI and the laboratories of the University of Queensland in Australia, made notable discoveries that opened up new areas of research and development.