There are several strong candidates for the first ever genetically engineered cervical cancer vaccine, according to scientists participating this week in a World Health Organization (WHO) meeting on the current status of development of prophylactic vaccines against human papillomavirus (HPV) infection. If successful, this vaccine will be the second vaccine against a major human cancer (the other being hepatitis B vaccine which prevents primary liver cancer).

Cervical cancer is the second most important cancer in women after breast cancer. Approximately 500,000 new cases are identified each year. Mortality is very high – nearly 300,000 deaths annually, with 80% of them in developing countries.

There is a huge discrepancy between incidence in developed and developing countries largely due to the availability of screening and treatment facilities in industrialized countries. The proportion of cancers in women attributable to HPV as a whole ranges from 3% to 5% in North America and Western Europe but in Latin America, South-west Asia and sub-Saharan Africa it reaches 20-24%.

Cervical cancer is a sexually transmitted disease caused by the human papillomavirus. Infection with HPV usually occurs in the early years of sexual activity but it takes up to twenty years for it to develop into a full blown malignant tumour. Scientists believe that essentially all cervical cancer is caused by infection with a few types of HPV.

HPV role in triggering off cervical cancer was discovered in 1983. WHO's International Agency for Research on Cancer (IARC) in Lyon, France, has been a leader in the epidemiological and laboratory studies needed to understand the disease. Ten years later, researchers in several countries are working on the prototype vaccine.

They have chosen different paths but most of them are based on genetically engineered VLP (Virus Like Particles) composed of the outer structural proteins of HPV. These VLPs are not infectious or carcinogenic because they contain no DNA. Some groups are trying to create a prophylactic vaccine, while others are developing a therapeutic vaccine for women who are already infected. Others are combining the two approaches. But all of them were confronted with huge obstacles. Human papillomavirus cannot be replicated in cell culture nor can it be transmitted to other animals, and human experimentation is limited given the carcinogenic nature of fully infectious HPVs.

"Because of the similarity of the genetic organization among papillomaviruses, animal models have provided knowledge of the human virus and natural host interaction", explains Dr Alfred Jenson of the Georgetown University, Washington, D.C., USA. "Experimental findings from the animal models and recent evidence from phase I trials strongly suggest that a prophylactic vaccine can interfere with the development of cervical cancer".

Participants of the WHO meeting agreed that in terms of public health prevention a prophylactic vaccine should be given priority. "The primary aim of an HPV vaccine would be prophylactic, although an effective therapeutic vaccine could also have considerable utility", explains Dr Theresa Aguado, Acting Team Leader, Vaccine Development, WHO Department of Vaccines and Other Biologicals. "A prophylactic vaccine would ideally be targeted to a young population that has not yet become sexually active, although older individuals may also benefit from such a vaccine".

Given the diversity of the population at risk from HPV infection, it is essential for the vaccine trials to include representative populations, to ensure global relevance. It is too early at this point to settle on a single vaccine formulation and WHO will encourage trials to evaluate several approaches. WHO was also asked to establish criteria for the standard evaluation of clinical outcomes in efficacy trials.

WHO will also support the groups conducting or planning epidemiological and economic studies required to implement vaccination trials and ultimately bring this vaccine into widespread public health use.

Development and introduction of HPV vaccines is an integral part of WHO's women's health policy.