One Vaccine-Schedule Change That Actually Makes Sense
Developing an HPV vaccine was particularly difficult. One reason was that cancers caused by HPV usually occur several years after the initial infection. A vaccine trial may need to last decades, and such a delay could cost human lives and prove impractical.
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 received three doses of vaccine or an equivalent placebo and then were screened every six months – not for cancer but simply for HPV-16 infection. (HPV-16 is the most common cancer strain.) An initial report, published a little more than a year later, showed no HPV-16 infections in the vaccinated group. Even ten years later, vaccinated women remained protected. “It was absolutely breathtaking,” Stanley said. In terms of prolonging life, getting vaccinated against HPV 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 physician. “They maybe weren’t as organized as they could have been, so I was going to the hospital with my mom on the weekends,” she said. She also spent many afternoons in her father’s laboratory, drawing botanical specimens. His medical training, which coincided with the start of the AIDS epidemic, focused on infectious diseases, and she later continued her training with a Ph.D. in Medicine and Clinical Epidemiology at Oxford. For her thesis, she built mathematical models using clinical trials of the first HPV vaccines approved for use in England and the United States. The vaccine was capable of saving lives; the pressing question was how to increase access and reduce costs. Cervical cancer is currently the fourth most common cancer among women worldwide, but in countries like India and Kenya, its prevalence is second only to breast cancer. Although the cost of HPV vaccines is affordable for wealthy countries, it remains prohibitive for most low- and middle-income countries.
Initially, it seemed pretty clear that HPV vaccines would require a three-dose regimen. They are made of virus-like particles, rather than parts of the virus itself, and these vaccines (called protein-based vaccines) usually cause only a weak immune response after the first dose. Follow-up doses reinforce this response. But getting people to come three times is a tricky proposition. This difficulty is amplified not only by the prevailing skepticism towards vaccines, but also by the fact that HPV is sexually transmitted and that vaccines against this virus are ideally administered to girls and young women. In Japan, in 2013, unfounded reports that the HPV vaccine caused chronic pain or other neurological side effects spread in the media, leading the government to temporarily suspend its recommendation against HPV. Vaccination rates have fallen from seventy percent to less than one percent. In 2014, in northern Colombia, hundreds of school-aged girls who had received the HPV vaccine went to medical centers complaining of a rapid heartbeat, shortness of breath, and numbness in their arms and legs; a medical investigation concluded that vaccines were not the cause, but this conclusion was poorly received.
During an HPV vaccine trial that began in 2004 in Costa Rica, one of the most important discoveries was made by chance. Some seventy-five hundred women aged eighteen to twenty-five were enrolled. However, for various reasons, with pregnancy being a major problem, about twenty percent of them received less than three doses. But even women who received just one developed antibody levels nine times higher than those found in naturally infected people. Vaccine effectiveness between groups remained essentially the same, even years later. Aimée Kreimer, the lead author of this finding, suggested that perhaps a single dose was enough. “Kreimer was subjected to God knows how much skepticism,” said Stanley, who counted herself among the disbelievers at the time. “It was heresy that a protein-based vaccine worked with just one dose. »
Then a trial in India, started in 2009, turned even worse. The trial examined the effectiveness of switching from three doses of HPV to two. Led by the International Agency for Research on Cancer, the trial recruited twenty thousand girls and women. A few months later, seven girls participating in another HPV vaccine study — a demonstration study conducted by the nonprofit Program for Appropriate Technology in Health — died. PATH the trials were stopped. (An investigation found that one girl had drowned, another had died of a snake bite, two had swallowed toxic pesticides, one had died of malaria, another of what was suspected to be a brain hemorrhage, and another 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 others two or three, but those who had received one dose seemed be as protected as those who had received more.
