2006: Gardasil: First Cancer Prevention Vaccine (2006)

The FDA approval of Gardasil (Merck) in June 2006 for prevention of human papillomavirus (HPV)
infection in females aged 9–26 marked the first time a vaccine had been explicitly licensed for
cancer prevention. The scientific groundwork was laid in the 1970s and 1980s by Harald zur Hausen,
who demonstrated that specific HPV genotypes—particularly HPV 16 and 18—integrate into host
cervical epithelial cells and drive malignant transformation through the E6 and E7 oncoproteins,
which inactivate p53 and pRb respectively. His work earned the 2008 Nobel Prize in Physiology or
Medicine.

The technological key to the vaccine was the self-assembly of HPV L1 major capsid protein into
virus-like particles (VLPs) that present the native capsid conformation to the immune system but
contain no viral DNA and therefore pose no infection risk. Research groups at the University of
Queensland (Ian Frazer and Jian Zhou) and at Georgetown University (John Schiller and Douglas
Lowy at the NIH) independently developed VLP-based HPV vaccines in the early 1990s. Merck
licensed the technology and engineered Gardasil as a quadrivalent vaccine targeting HPV 6, 11,
16, and 18—types responsible for approximately 70 % of cervical cancers and 90 % of genital warts.

Phase III trials demonstrated near-100 % efficacy against cervical intraepithelial neoplasia grades
2 and 3—precursors to invasive cervical cancer—caused by HPV 16 and 18 in HPV-naive women.
GlaxoSmithKline's bivalent Cervarix followed in 2007. Merck later developed Gardasil 9, covering
nine HPV genotypes and protecting against approximately 90 % of cervical cancers.

Population-level surveillance in countries with high vaccination coverage has since documented
dramatic declines in HPV 16/18 prevalence, precancerous cervical lesions, and—in long-term data
from Australia and Scotland—incidence of invasive cervical cancer itself, validating the vaccine's
cancer-prevention promise at national scale.