Study of natural history of infection to preventative vaccine
HPV Cervical Cancer Vaccine
With its flexible, international reach, LICR was able to access a large number of cancer samples in order to analyze the natural history or “epidemiology” of infection with human papillomavirus (HPV), the causative agent of genital cancers, with a view to preventing and/or treating these diseases.
LICR began studying the role of HPV in cancers of the cervix, penis and anus in the early 1980’s and found that DNA sequences from HPV were very often found in these genital tumors. This finding, along with others from around the world contributed to the confirmation that HPV is the causative agent of cervical cancer. Dr. Harald zur Hausen—a former member of the LICR Scientific Advisory Committee—was awarded the 2008 Nobel Prize for Medicine & Physiology for first postulating and then proving this theory.
However, the discovery of a high proportion of HPV infections in asymptomatic women led LICR to launch epidemiological studies aimed at understanding the risk correlates for HPV-associated cervical disease.
In 1993, the “Ludwig/McGill Cohort” was established by LICR investigators with a population of women from São Paulo, Brazil. This cohort formed one of the largest longitudinal studies of the natural history of HPV infection and risk of cervical cancer in the world. (The McGill part of the name pays tribute to the co-director of the cohort epidemiologist who worked at the LICR São Paulo Branch before moving to McGill University in Canada.)
LICR investigators found that most HPV infections are transient and of little clinical significance. However, the small proportion of women who harbor persistent HPV infections stand at a much greater risk of subsequent cervical neoplasia, indicating that persistent, not transient, HPV infections are the actual biologic precursor in cervical cancer onset. This and other findings on viral load (the amount of virus) and the integration of viral DNA into cervical cells were important for understanding the clinical significance of HPV DNA testing results and set policies for inclusion of some form of HPV testing in cervical cancer prevention internationally.
Results from LICR’s HPV natural history studies were seminal in facilitating the design and implementation of clinical trials of prophylactic vaccines against HPV. The LICR team was invited to lead a phase II trial of Merck & Co. Inc.’s prophylactic (preventative) HPV vaccine, which was the first study to demonstrate the safety, immunogenicity and efficacy of the vaccine. The vaccine—Gardasil®—was approved for licensing later that year (2005) and is now sold internationally.
