The Global Fight Against Infection-Driven Cancers

Not long ago, I spoke with a friend who currently heads the Infectious Diseases and Oncology Research Institute (IDORI) at the University of the Witwatersrand in Johannesburg, South Africa. What a walk down memory lane. When we first met, I was a brand new attending, while Robert Breiman, MD, was an infectious diseases fellow who would soon join CDC and lead outbreak investigations of Streptococcus pneumoniae, Legionnaires disease, and hantavirus.

During the next stage of his 26-year career with CDC, Breiman directed the National Vaccine Program Office before moving overseas to hold senior posts in Bangladesh and Kenya, where he promoted immunization and continued to battle respiratory killers as well as diarrhea and emerging infections. He then ran Emory University’s Global Health Institute and oversaw what is now an eight-country, 19-site research network focused on targetable causes of death in neonates, infants, and children in Africa and Asia.

Breiman has now turned his attention to cancer. He believes that innovative, multi-disciplinary research around Africa’s rising burden of infection-driven cancers can ultimately save lives, not just there but worldwide. (In 2020 alone, the continent saw at least 800,000 new cancers and 500,000 cancer-related deaths.)

A Nascent Understanding

When Breiman and I first met 40 years ago, I wonder whether we discussed, or even grasped, the huge global nexus of cancer and infection. By that point, prominent scientists like Baruch Blumberg, MD, DPhil, had already argued that vaccinating against hepatitis B could massively reduce hepatoma’s global toll (as soon proved true), but in other respects, the world was still blindered.

For one thing, although evidence had just been published connecting human papillomavirus (HPV) with cervical cancer, the fact that an HPV vaccine might ultimately slash by nearly 90% that terrible, deadly disease — with its final, poignant hallmarks of hemorrhage, obstruction, and agonizing pain — was still unimagined.

Nor had we learned that Helicobacter pylori, a flagellated food- and water-borne bacillus now eradicated by multi-drug cocktails, was a major contributing factor in many people with gastric adenocarcinoma.

Finally, let’s consider colon cancer: an old enemy in new clothes currently killing people under 50. Take for example the actor Chadwick Boseman, who gained international fame as the Black Panther superhero. Remarkably, the talented Boseman was diagnosed at 39 and died 4 years later, but did much of his finest work while fighting an aggressive form of colon cancer that — according to data published this year — is often fueled by a distinct clade of Fusobacterium nucleatum that promotes rapid metastasis.

What if early detection and removal of this rogue anaerobe from human microbiomes could also save lives?

In short, Breiman and his colleagues at IDORI see many opportunities to address new questions and push back against 21st-century cancers linked to microbial culprits, including the world’s most common sexually transmitted virus whose (possible) role in prostate cancer is still coming into focus.

One More Reason to Vaccinate Boys Against HPV?

When I was a medical student, genital warts due to HPV were viewed as a superficial — albeit ugly — blight contracted through sex and other intimate skin-to-skin contact. Nonetheless, one far-sighted, tenacious scientist — the German virologist Harald zur Hausen, who later won a Nobel Prize — suspected that genital warts might also predispose women to cervical neoplasia. His suspicions grew stronger after zur Hausen failed to find genetic traces of herpes simplex virus in cervical samples from cancer-stricken women.

Then zur Hausen spent a dozen years confirming that HPV strains 16 and 18 were hidden agents that, in certain hosts, could remain dormant and acquire mutations that eventually triggered malignant transformation of cervical squamous epithelium. Thus, in 2006, the first HPV vaccine specifically targeting HPV 16 and 18 was marketed to young women to prevent cervical cancer.

Since then, we’ve also learned that HPV infections produce ano-genital and oral cancers in both women and men, and subsequent vaccines have expanded their artillery against additional oncogenic strains. Here in the U.S., a two-dose regimen of the nine-valent Gardasil vaccine is currently recommended for 11- and 12-year-olds of both sexes. Yet, its uptake is far from ideal — not only is the HPV vaccine reaching less than two-thirds of potential vaccinees, its usage varies widely from state to state.

In addition, perhaps not surprisingly, American males lag behind females in receiving Gardasil. Finally, as Breiman reminded me during our recent conversation, in much of the global south, including South Africa, public immunization programs do not offer the HPV vaccine to adolescent males.

This raises one more question ripe for further research and action. Since prostate cancer is now the most commonly diagnosed malignancy in men in 106 countries worldwide, and early evidence suggests that prostate cancer contains an “increased proportion of high-risk HPV types … compared to benign and healthy tissue,” might this fuel further uptake by males of a vaccine with already-proven anti-cancer benefits?

A Passion for Cutting-Edge Science and Equity

These days, Breiman spends a lot of time talking to potential investors, donors, and even people he casually meets on a plane. After all, one of his highest priorities is to raise funds to sustain IDORI and its new campus and staff. Along the way, he often shares surprising facts about his own turn from an eminent career in infectious diseases epidemiology to running a cancer research center in Africa.

One telling detail I never knew? Before deciding to attend medical school, Breiman majored in political science and thought he would study law in order to become “a modern-day Clarence Darrow fighting for social justice.” A few years later, he was drawn to infectious diseases because, at the time, it was a specialty where one could actually cure and prevent as opposed to palliating disease. Today, he finds that same excitement in oncology because of its modern surge in “cutting-edge therapeutics, diagnostics, and preventive tools.”

“But not in Africa,” he ruefully continued, revealing his deep love for the continent and his concern for its untapped human potential stemming from a lack of access to the modern healthcare we often take for granted.

Then again, he acknowledged, similar inequities exist right here at home with respect to the prevention of cancer as well as rates of early diagnosis and long-term survival among patients from diverse and marginalized groups.

My closing thought? Before long, perhaps we too can learn from the passionate vision for the future of reducing infection-driven cancers that is now unfolding in Johannesburg.

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