The idea of a vaccine to prevent cancer has been the source of much debate. Dr Mbulaiteye and Dr Buonaguro describe the development of vaccines over the years, the reasons for controversy and the need for evidence-based discussion.
Introduction
Figure 1
In 2012, Infectious Agents and Cancer commissioned a thematic series collection of articles on Prevention of HPV-related cancer. The articles have attracted wide interest and stimulated debate, including about the utility of vaccines in cancer control. The application of vaccines to control cancer fulfills a promise envisioned at the turn of the 20th century when remarkable experiments showed that some cancers were caused by infections.
Vaccines represent one of the most successful medical advances of all time. They prevent suffering and death from many acute infectious diseases for which it is possible to develop a vaccine. The application of vaccines on a global scale has been dramatically expanded as modern knowledge, techniques, management and policy frameworks have led to more cost-effective production and delivery pipelines to populations who need them.
For example, vaccination programmes, mandated by law or applicable regulations, have diminished morbidity and mortality from many infectious diseases that previously were scourges and posed severe economic burdens (such as measles, polio, diphtheria, Haemophilus influenzae type b and pneumococcal infections).
Global vaccination programmes have eradicated smallpox and reduced poliomyelitis transmission to such low levels that eradication is feasible.1 With this success, the possibility to control highly variable pathogens (i.e. HIV, influenza virus, malaria etc.) through vaccines has emerged.
In the cancer field, the search for human cancer caused by infections, particularly viruses, is motivated, in part, by the possibility of preventing such cancers through vaccination. By the turn of the 21st century, eight human viruses, including Epstein-Barr virus, human papilloma viruses (HPV), hepatitis B and C virus (HBV and HCV), had been linked to cancer in humans.
Vaccines have been developed and are being delivered to populations against two of these viruses – HBV and HPV. These vaccines are dramatically reducing the incidence of new infections and they are expected to dramatically reduce the risk of associated cancers, namely, liver and cervical.
The science of vaccines and their application, however, has had a long history rooted in trial and error approaches, which may be relevant today. The ‘low dose’ smallpox inoculation practices reported by Wang Zhangren’s Douzhen jinjing lu in 1579,2 and the introduction of ‘attenuated’ cowpox vaccination to prevent small pox by Dr John Fewster in 1765,3 later standardised by Edward Jenner in 1798,4 would probably not stand scientific scrutiny in today’s world. However, even at this time, fear of ‘inoculations’ was already present, as noted in the cartoon from 1802 (Figure 1).
A similar fear of vaccines exists today in some populations. Notwithstanding those fears, those pioneering efforts led directly to advances in knowledge and improvement in techniques to study immunity and to the development of vaccines, including the elimination of the arm-to-arm vaccinia transfer (associated with the high risk of syphilis transmission) and the worldwide implementation of the calf lymph vaccine developed by Galbiati in 1810.5,6
Pasteur’s 1885 discovery of an attenuated Rabies vaccine7 was a triumph against a frightening disease. The development of attenuated or inactivated vaccines against yellow fever, measles, rubella, and mumps, as well as the bacterial disease typhoid, Mycobacterium tuberculosis (BCG) Yersinia pestis (EV) followed in rapid succession.
Attenuated vaccines induce transient growth of the virus in the host. This elicits durable immunity in the host and renders booster doses unnecessary. Attenuated vaccines, however, may cause harm when the attenuated viruses revert and become virulent again.
In response, development of vaccines from inactivated – or killed – viruses eliminated the risk of reversion. Examples of these include those used against influenza, cholera, bubonic plague, polio, hepatitis A, and rabies. Because transient growth does not occur with inactivated vaccines, booster doses are needed to elicit adequate immunity.
More recently, modern medicines have relied on only components of the pathogen – the so-called subunits or conjugate vaccines. In some cases, they target inactivated toxins, such as the vaccines against tetanus and diphtheria. The subunits used are generally from a part of the pathogen exposed to the outside environment. Examples of subunit vaccines include the first generation of HBV vaccine, the current anti-HPV vaccines and Haemophilus influenzae type B vaccine.
Since the ‘80s, innovation in vaccine technology has included production of subunit proteins synthetically by recombinant technology, which has replaced the crude method of extraction from the pathogen, and vastly improved the safety of modern vaccines.
Viewed in today’s terms, vaccines are distant from the blind ‘trial and error’ inoculations of the 17th or 18th century. Today, vaccines are synonymous with prevention of morbidity and death from terrible diseases. Scourges of the past, like small pox or polio, have been subdued through vaccines. They represent the hope to control more infections that still afflict millions, if not billions, worldwide. These include infections that cause human cancer, which are attributable to infections in 20-30 percent of cases. Vaccines have been developed against HBV and HPV, suggesting that cautious optimism may be warranted.
Nonetheless, as in the early days, the safety of vaccines remains a subject to intense debate. Caution is urged when deploying vaccines to identify and deal with life-threatening side effects that may emerge. Responsible discussion is also urged to tone down alarmist messages that may mislead the public to reject vaccines and increase their health risks.
