Human Papillomavirus 16 DNA and Epithelial Cell Immortalization

Abstract

Papillomaviruses have had a unique position in carcinogenesis studies. As early as 1907 Ciuffo¹ demonstrated that the infectious agent for the common wart persisted in filtered homogenates and thus was not due to a bacterial or protozean etiology. These findings raised the possibility that warts were caused by newly recognized submicroscopic entities that are now referred to as viruses. Shope and Hung² later isolated and characterized the first oncogenic DNA virus, referred to as cottontail rabbit papilloma. Subsequently, Rous and associates^3,4 demonstrated that when Shope papilloma virus was injected in rabbits, progression from papillomas to carcinomas would be accelerated by the application of either coal tar or a well characterized carcinogenic polycyclic hydrocarbon, 3-methylcholanthrene. This rabbit-virus model also responded to X-irradiation⁵ which was shown to contribute to progression of papillomas to carcinomas. A decade later, it was realized that X-irradiation of juvenile laryngeal papilloma (HPV 6/11) resulted in carcinomas⁶. Today, treatment is by surgery or laser. Human papilloma viruses (HPV) are strongly associated with anogenital cancer, including cervical cancer. HPV’s have been associated worldwide with 15% of the human cancers, most notably cancer of the uterine cervix, penis, vulva and anal region. HPV type 16, 18, 31, 33 and 39 have been identified in cervical cancer; over 90% of these neoplasias can be classified as positive. Current epidemiological evidence suggests that incidence of cervical cancer in women is greater in smokers than in non-smokers⁷.