HPV, cervical cancer link earns scientists Alpert Prize

Two scientists who discovered that specific types of human papillomavirus, or HPV, cause cancer of the cervix received the 20th annual Warren Alpert Foundation Scientific Prize on Sept. 15. As part of the day’s celebration, the prize winners Harald zur Hausen and Lutz Gissmann — both professors at the German Cancer Research Center in Heidelberg — delivered talks at a symposium in Harvard Medical School’s New Research Building (NRB).

The foundation recognized the two researchers for work in cloning and characterizing the most prevalent virus types in cervical cancer, HPV 16 and HPV 18. In 1983, Zur Hausen, Gissmann, and their colleagues identified HPV 16 in precursor lesions of genital cancer and, in 1985, revealed the genetic organization of HPV DNA in cervical cancer cells and the active transcription of HPV in these cells. The foundation will divide the $150,000 award between the winners.

“The discoveries of Harald zur Hausen, Lutz Gissmann, and their colleagues in the 1980s provided the first concrete evidence that specific HPV types were linked to cancer of the cervix in women. Their generosity in providing the molecular clones of these newly identified HPVs to others studying the papillomaviruses allowed research in this field to move forward rapidly, leading to an understanding of how HPV causes cancer, to the recognition of the large group of different HPV types associated with cancer, and to the development of the now FDA-approved HPV vaccine,” said Peter Howley, chair of the Harvard Medical School (HMS) Department of Pathology and an expert on the molecular biology of HPV infection and subsequent cancer development.

The scientists’ work on HPV began in 1972 after Zur Hausen and colleagues failed to find genetic sequences for herpes simplex virus 2 in human cervical cancer and started to analyze the possible role in the disease of genital tract HPV. The research was later bolstered by studies from cytologists providing evidence that an HPV was present in cervical dysplasia, a precursor lesion to cervical cancer and the basis of the Pap smear.

Two years later, in 1974, Lutz Gissmann joined the Zur Hausen group as a Ph.D. student. Together, the scientists helped establish the heterogeneity of the papillomavirus family. Based on the subsequent isolation of papillomavirus types in genital warts and laryngeal papillomatosis, two of Zur Hausen’s later students were able to clone and partially characterize HPV 16 and HPV 18. In these two seminal studies, Gissmann played a critical role in directing the molecular biological techniques that were central to the investigations. In 1983, the scientists identified HPV 16 in precursor lesions of genital cancer, and in 1985, they revealed the genetic organization and activity of HPV DNA in cervical cancer cells.

HPV16 and HPV18 are responsible for 70 percent of cervical cancer worldwide. From a global perspective, the disease ranks second in cancer incidence among women, responsible for approximately 270,000 deaths each year around the world. In many parts of Africa, Asia, and South America, it is the most frequent cancer among females. Zur Hausen and Gissmann’s findings paved the way for many subsequent groundbreaking studies, notably, the development of Gardasil, which in 2006 became the first preventive vaccine for cervical cancer to be approved by the U.S. Food and Drug Administration.

Each year the Warren Alpert Foundation receives 30 to 50 nominations for the Alpert Prize from scientific leaders around the world. Prize recipients are selected by the foundation’s scientific advisory board, made up of internationally recognized biomedical scientists and now chaired by Jeffrey Flier, dean of HMS.

Chelsea, Mass., native Warren Alpert first established the prize in 1987 after reading that Kenneth Murray of the University of Edinburgh had developed a successful vaccine for hepatitis B. Alpert decided immediately that he would like to reward such far-reaching breakthroughs, so he called Murray to tell him he had won a prize, and then set about creating the foundation.

To choose subsequent recipients of the prize, Alpert asked Caroline Shields Walker Distinguished Professor of Cell Biology Daniel Tosteson, then dean of HMS, to convene a panel of experts to select and honor renowned scientists from around the world whose research has had a direct impact on the treatment of disease.