Gravitt’s own push has been to prove the virus behaves differently than everybody has always assumed.
According to all the published literature, HPV clears completely in the overwhelming majority of individuals who never even know they were infected. After a year or two, the virus DNA is undetectable. The implication: It’s gone. Any subsequent HPV infections detected during a person’s lifetime are assumed to be newly acquired, and not reactivations of past infections.
Gravitt’s data tell a different story. She’s deconstructing what was a nice, clean, linear narrative, and mucking it up with a messy truth: HPV is controlled, not cleared. Though it may be completely undetectable, it’s not cleared.
If anyone can buck the scientific status quo, it’s Gravitt. Renowned for having developed the gold standard method for detecting and genotyping HPV, she learned firsthand from Shah that hard-won scientific truth trumps all.
Increasingly her studies reveal that latent but undetectable HPV is reactivating in the cohorts she’s studying: menopausal women who have been monogamous or sexually abstinent for decades, for instance. Menopause and aging may be vulnerable times, immunologically speaking, during which the probability of reactivation is increased, says Gravitt, “but we really need to do more research to confirm that.”
The issue is contentious. In addition to those in the clearance camp, there’s the dismissive camp: So what if one says controlled, and another says cleared? If one says reactivate, and another says reinfect? Isn’t this all just semantics, like one says po-tay-to, and another says po-tah-to?
“Well, no,” Gravitt insists. “It’s important to figure out whether the virus clears or is controlled. It makes a big difference in terms of disease risk in later life, and in terms of how you might prevent HPV-associated disease, particularly in older people.”
The distinction also carries psycho-social importance, explains Anne Rositch, PhD, MSPH, a postdoc working in Gravitt’s lab. Increasingly, clinicians are confronting middle-aged patients in long, monogamous marriages who, oddly enough, have acquired “new” HPV infections, she says. They’re asking her, How could that happen? What’s going on?
Plausible answers come from molecular epidemiology, a hybrid science involving population-based research at a molecular level. In the tradition of Shah, Gravitt and Rositch are bench scientists whose expertise is analyzing biological samples in the context of big and diverse cohorts of people.
If the accepted HPV story is accurate—that it’s acquired during sexual debut and clears within two years then the prevalence of HPV infection in populations should not be associated with individuals’ cumulative lifetime sexual behavior, Gravitt explains. Rather, only with their recent sexual behavior. But that’s not what she is finding.
Gravitt published dogma-defying findings in the Journal of Infectious Diseases in December 2012, under the title, “A Cohort Effect of the Sexual Revolution May Be Masking an Increase in Papillomavirus Detection at Menopause in the United States.” The study indicates a greater prevalence of HPV infection in the population of menopausal women whose sexual debut was post–sexual revolution than those whose debut was pre–sexual revolution. When her team looked at newly detected HPV in this cohort, only 13 percent of infection was attributed to new sex partners, whereas 72 percent was attributed to having a higher number of lifetime partners. The takeaway: These infections probably weren’t new.
“As long as you are controlling these infections, your immediate risk of [cancer] is going to be low,” Gravitt explains. “But if menopause, or just getting old, increases HPV reactivation, then we need to look at what this means for screening these older women who came of age during the sexual revolution and are much more likely to reach menopause with latent HPV than the postmenopausal women we have screened in the past.”
It will be important to determine if the historical low risk of cancer in postmenopausal women will continue to hold steady as the baby boomers age, she adds, and to reexamine questions like when and under what conditions is it safe to stop routine screening.
Helping Gravitt stay on track as she dogs the undetectable is decades-old advice from Shah: “One of the frustrating things about being a scientist is you work very hard and it seems no one is paying attention. [As a young investigator] I had been complaining to Keerti—kind of like, ‘Woe is me. How is it that no one sees what I do? Do I have it wrong?’ And Keerti just looked at me, with the sweetest face, and said, ‘Patti. You talk too much and write too little.’
“To this day, whenever I get into that anxious state, which can be paralyzing, I just shut up and sit down and write out what I’m thinking. Because nobody will pay attention until it’s down on paper.”
“It’s important to figure out whether the virus clears or is controlled."—Patti Gravitt
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