Developing an H.P.V. vaccine was distinctly challenging. One reason was that cancers from H.P.V. usually occur many years after the initial infection. A vaccine trial might need to run for decades, and such a delay could be life-costing, as well as impractical.
The epidemiologist Laura Koutsky, of the University of Washington, got around this problem by designing, with others, a double-blind study in which more than two thousand women were given three doses of the vaccine or an equivalent placebo and then screened every six months—not for cancer but, instead, simply for H.P.V.-16 infection. (H.P.V.-16 is the most common cancer-causing strain.) An early report, published a bit more than a year later, showed no H.P.V.-16 infections in the vaccinated group. Even ten years later, the women who had been immunized remained protected. “It was absolutely stunning,” Stanley said. In terms of extending life, getting an H.P.V. vaccine is as important for a woman as quitting smoking.
Ruanne Barnabas, a physician-scientist, grew up in South Africa, where her father worked as a botanist and her mother was a public-health doctor. “They weren’t maybe as organized as they could have been, so I would go to the hospital with my mom on the weekends,” she said. She also spent many afternoons in her dad’s laboratory, drawing botanical specimens. Her medical training, which coincided with the beginning of the AIDS epidemic, focussed on infectious disease, and she later continued her training with a Ph.D. in medicine and clinical epidemiology at Oxford. For her thesis, she constructed mathematical models using clinical trials of the first H.P.V. vaccines approved for use in England and in the U.S. The vaccine was capable of saving lives—the pressing question was how to increase access and lower costs. Cervical cancer is currently the fourth most common cancer in women globally, but in countries such as India and Kenya its prevalence is second only to breast cancer. Although the cost of H.P.V. vaccines is within reach for well-off countries, it is a stretch for most low- and middle-income ones.
It seemed pretty clear initially that H.P.V. vaccines would require a three-dose regimen. They are made of virus-like particles, rather than parts of the virus itself, and such vaccines (called protein-based vaccines) generally provoke only a weak immune response after the first dose. The follow-up doses boost that response. But getting people to turn up three times is an iffy proposition. This difficulty is amplified not only by ambient vaccine skepticism but also by the fact that H.P.V. is sexually transmitted and vaccines against it are ideally given to girls and young women. In Japan, in 2013, unfounded reports of the H.P.V. vaccine causing chronic pain or other neurological side effects spread in the media, leading the government temporarily to suspend its H.P.V. recommendation. Vaccination rates fell from seventy per cent to less than one per cent. In 2014, in northern Colombia, hundreds of school-age girls who had received the H.P.V. vaccine went to medical centers complaining of a racing heart, shortness of breath, and numbness in their arms and legs; a medical investigation concluded that the vaccines were not the cause, but the conclusion was poorly received.
In an H.P.V. vaccine trial that began in 2004 in Costa Rica, one of the most important findings came about by the by. Some seventy-five hundred women between the ages of eighteen and twenty-five were enrolled. However, for various reasons, pregnancy being a major one, about twenty per cent of them received fewer than three doses. But even the women who received only one developed antibody levels nine times higher than those found in naturally infected individuals. The vaccine efficacy among the groups remained essentially equal, even years down the line. Aimée Kreimer, the lead author on this discovery, suggested that maybe one dose was sufficient. “Kreimer was subjected to God knows how much skepticism,” Stanley, who counted herself among the disbelievers back then, said. “It was heresy for a protein-based vaccine to work with only one dose.”
Then a trial in India, begun in 2009, went even more wrong. The trial was looking at the efficacy of going from three H.P.V. doses to two. Led by the International Agency for Research Against Cancer, the trial enrolled twenty thousand girls and women. Before several months had passed, seven girls in a different H.P.V.-vaccine study—a demonstration study led by the nonprofit Program for Appropriate Technology in Health—died, and both the I.A.R.C. and PATH trials were stopped. (An investigation uncovered that one girl had drowned, another died from snake bite, two had swallowed poisonous pesticides, one died as a result of malaria, another of what was suspected to be a cerebral hemorrhage, and one of a high fever that Indian government investigators concluded was “very unlikely” to have resulted from the vaccine.) Some women had received one dose, and some two or three, but the women with one dose appeared to be as protected as those with more.
