Papillomavirus research has passed through several phases. The field began slowly with the experimental transmission of human and animal warts prior to 1930. Greater interest in these viruses was stimulated in the 1930s by the demonstration that filtered extracts from cutaneous papillomas of wild cottontail rabbits could induce lesions with malignant potential in cottontail and domestic rabbits. Although investigations in the 1930s and 1940s were limited to in vivo studies in outbred rabbits, many principles of papillomavirus biology were established by observations made during this period.
The availability of infectious extracts permitted the reproducible induction of lesions whose natural history could be followed or be experimentally modified. Interest in papillomaviruses diminished during the 1950s and 1960s. This change was attributable to several factors, including the inability of papillomaviruses to propagate in culture at a time when the life-cycle and transforming activity of other oncogenic viruses could be studied in vitro, permitting rapid advances in molecular understanding of these processes in the more tractable systems. In addition, human papillomaviruses (HPV) were believed to have limited medical importance because the conditions they induced were thought to be limited to benign lesions with little or no potential for malignant progression.
The advent of molecular cloning during the 1970s led to a resurgence in papillomavirus research. As in other areas of biology, this technical revolution was critical to progress in the investigation of papillomaviruses. The unlimited availability of wild-type and mutant viral genomes made it possible to study the function of viral genes and their products, to use viral sequences as molecular probes to detect papillomavirus sequences in tissue, and to identify and molecularly clone new viral genotypes. Application of these molecular techniques led to the identification of HPV as the necessary infectious cause of a major public health problem, cervical cancer. These studies also provided insight into the pathogenesis of HPV-induced disease, established new paradigms for cellular transformation by viral genes, and identified candidate antigens for protection against papillomavirus infection.
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