In 1921, Albert Calmette and Camille Guérin began testing their new vaccine against tuberculosis. Their vaccine is called Bacillus Calmette-Guérin, or BCG, and it is still used in many countries around the world today. While it has limited effectiveness against the pulmonary form of tuberculosis — the most familiar form — is has shown effectiveness against tuberculous meningitis and miliary tuberculosis. Children are usually the recipients of the vaccine, especially if they are continously exposed to tuberculosis in their communities.
The BCG vaccine is not used in the United States today, however. This is because tuberculosis is not very prevalent in the US, and the BCG vaccine interferes with the tuberculin skin test, a test used to detect tuberculosis exposure. The immune response against the vaccine will many times give a false positive tuberculin test, requiring confirmatory testing at an additional cost. Because of this, immigrants from countries where the BCG vaccine is routinely given are tested for latent tuberculosis infection instead of the tuberculin skin test.
A recent article in the Journal of the American Medical Association (JAMA), by Usher et al,* is raising some eyebrows because of its findings regarding BCG and cancer. In it, researchers looked back at the results of a clinical trial that started 60 years ago. The clinical trial was done in order to look at the effects and side effects of the BCG vaccine. Half of the group was given the BCG vaccine, and the other was given a placebo. About 2,900 of the participants (from a total of about 3,200) were followed up for cancer diagnoses in their lifetime. The researchers found out that the rate of lung cancer in the vaccinated population was 18.2 cases per 100,000 person-years. In the population receiving the placebo, the rate of lung cancer was 45.4 cases per 100,000 person-years. (Person-years is a way of accounting for the fact that not all people were followed-up for the same amount of time because they entered and/or exited the study at different times.) This difference in rates was seen when taking into account the differences in sex, region, alcohol overuse, smoking, and tuberculosis.
It is important to note that most of the participants in this study were Native Americans given the BCG vaccine at around age 8. Lung cancer, like other cancers, tends to be associated with social determinants like poverty and poor housing. Native Americans tend to have higher rates of poverty and poor housing when compared to the general population of the United States. Nevertheless, within the study, these factors were accounted for, making the comparison between groups within the study population valid.
The authors discuss the different mechanisms by which the BCG vaccine could be preventing lung cancer in those who received it. It could be that the immune system is modulated in some form to eliminate cancerous cells. Or it could be that the vaccine prevented an infection with a pathogen — tuberculosis or otherwise — that would irritate the tissues and trigger cancer. Or the vaccine created some sort of change at the cellular level that made the cells resistant to mutations that would trigger cancer.
Whatever the mechanism is, this finding has big implications because the BCG vaccine is relatively cheap and easy to obtain and distribute. If there are populations deemed at increased risk of lung cancer, it might be worthwhile to consider administering the vaccine to reduce that risk. However, as is the case with all research, these findings need to be confirmed and studied further before a public health intervention should be planned and implemented.
*Usher NT, Chang S, Howard RS, et al. Association of BCG Vaccination in Childhood With Subsequent Cancer Diagnoses: A 60-Year Follow-up of a Clinical Trial. JAMA Netw Open. Published online September 25, 20192(9):e1912014. doi:10.1001/jamanetworkopen.2019.12014