Discovery of Human Papilloma Virus in 1976: Leading to the Recent Development of an Anti-cancer Vaccine.

The first oncogenic virus (oncovirus) was discovered in chicken sarcoma by Peyton Rous (1879-1970) of Rockefeller Institute in 1911. This virus was later called Rous Sarcoma Virus (RSV). In an attempt to find its possible link to mammalian or human cancers, he tried to fish an oncovirus in mammalian tumors, but in vain. So he eventually left this oncovirus research field.

However, during 1950s-1960s, a few oncoviruses were found in mouse or rat tumors. Some of them carry oncogenic mutants of RAS genes called Ha-RAS and Ki-RAS. Because of these mammalian oncoviruses, Rous at age of 87 was awarded the 1966 Nobel prize, more than a half-century after his discovery of RSV. Yet human oncovirus still remained to be identified…

Since then many onco-virologists including Robert Gallo of NIH, who is an expert in HIV virus as well, raced to find the very first “human” oncovirus, in an attempt to prove that some of human cancers are caused by viruses.

Harald zur Hausen in Germany also joined this highly-heated human oncovirus hunting. In 1976, he published the hypothesis that human papilloma virus (HPV) plays an important role in the cause of cervical cancer. Interestingly, the first established human cell line known “HeLa” cells carries HPV, which was derived from cervical cancer of a black woman called “Henrietta Lacks”.

This pioneering research of zur Hausen’s eventually contributed to the development of a HPV vaccine which was introduced in 2006.

Rev Med Virol. 2006 May-Jun;16:139-49.

Human papilloma virus vaccines.

Stanley MA.

Department of Pathology, Cambridge, UK. mas@mole.bio.cam.ac.uk

A wealth of epidemiological and molecular evidence has led to the conclusion that virtually all cases of cervical cancer and its precursor intra-epithelial lesions are a result of infection with one or other of a subset of genital human papilloma viruses (HPVs) suggesting that prevention of infection by prophylactic vaccination would be an effective anti-cancer strategy.

The papilloma viruses cannot be grown in large amounts in culture in vitro, but the ability to generate HPV virus like particles (VLPs) by the synthesis and self-assembly in vitro of the major virus capsid protein L1 provides for a potentially effective sub unit vaccine. HPV L1 VLP vaccines are immunogenic and have a good safety profile.

Published data from proof of principle trials and preliminary reports from large Phase III efficacy trials suggest strongly that they will protect against persistent HPV infection and cervical intra epithelial neoplasia. However, the duration of protection provided by these vaccines is not known, the antibody responses induced are probably HPV type specific and immunisation should occur pre-exposure to the virus. Second generation vaccines could include an early antigen for protection post-exposure and alternative delivery systems may be needed for the developing world. Copyright (c) 2006 John Wiley & Sons, Ltd.