The human papillomavirus, or HPV, can lead to a number of malignancies, including anal and vulvar cancer. But can the HPV vaccine be used as a treatment for anogenital precancers?
Dr. Margaret Madeleine, an epidemiologist with Fred Hutchinson Cancer Research Center’s Public Health Sciences Division, just received a five-year, $2.5 million grant from the National Cancer Institute to find out. It is the first U.S.-based trial to test whether the preventive HPV vaccine could be also be used as a therapy for these precancers.
“The HPV vaccine is totally effective and safe and is most effective for preventing HPV infection,” she said. “That’s the primary way to use the vaccine. This is a therapeutic use in people who’ve already been infected [with HPV] and has not been tested yet. It’s a new way to use the vaccine.”
According to Madeleine, people diagnosed with anal or vulvar in situ disease (or precancer) often experience recurrence after their initial treatment and have to undergo “incredibly invasive” surgeries to remove the new lesions.
She and her team plan to test whether the Gardasil 9 HPV vaccine could eliminate these recurrences by removing the HPV infection that drives the precancers.
Research by Fred Hutch’s Dr. Denise Galloway and colleagues laid the groundwork for the creation of the HPV vaccines Gardasil and Cervarix, which prevent HPV infection. Gardasil, approved in 2006 for use in the U.S., prevents the types of HPV that account for 70 percent of cervical cancers and 90 percent of genital warts. Gardasil 9, approved in early 2015, protects against 90 percent of cervical cancers as well as many cancers of the anus, penis, vulva, vagina and throat. Recommended for girls and boys starting at age 11 or 12, the HPV vaccine is currently in use only as a preventive.
Madeleine will work with Dr. Anna Wald, an epidemiologist with the Hutch’s Vaccine and Infectious Disease Division and medical director of the University of Washington Virology Research Clinic, to determine if the vaccine could also be used as a therapy. Their study will be a randomized, double-blind, placebo-controlled trial with two groups of patients, both of whom have been treated for an anogenital precancer but neither of whom have been vaccinated for HPV. One group will receive the Gardasil 9 HPV vaccine; the other group will receive a placebo.
The HPV Vaccine to Interrupt Progression of Vulvar and Anal Lesions trial, dubbed VIVA, will be conducted at Seattle’s Harborview Medical Center. Participants will be followed for three years.
Madeleine said earlier studies have shown that people with these types of precancers recur less often if they’ve had HPV vaccination or have natural antibodies to the virus.
“We think it will keep new infections from growing into tumors,” she said. “The idea is to see within three years whether there’s a 50 percent decrease in recurrence.”
If there is, Madeleine said the trial will answer a key question.
“If we can rigorously test this idea,” she said. “It would be a really nice answer to a question that’s outstanding: whether the vaccine has a therapeutic benefit.”
— Diane Mapes / Fred Hutch News Service
Fred Hutch clinical researcher, epidemiologist and pediatric oncologist Dr. Eric Chow has received three new grants to help him continue research aimed at bettering the lives of childhood and adolescent cancer survivors.
In March, the National Cancer Institute approved a $3.7 million, five-year grant extending Chow’s research into improving treatment of cardiovascular risk factors in childhood cancer survivors. The NCI also awarded Chow a $2.7 million grant to extend, by four years, his research into determining the long-term efficacy of a drug to minimize or prevent heart injury in pediatric cancer patients.
Chow said the two NCI studies are designed to lessen the risk of heart disease later in life for those who were treated as children or adolescents. According to the National Institutes of Health, premature cardiovascular disease is the leading non-cancer cause of death in these survivors.
“We know these survivors have a higher risk as adults because of their treatment as children,” Chow said. “And this risk is probably under-recognized by both the survivors themselves and their primary care physicians.”
Doctors may not think of childhood cancer survivors as being susceptible to heart problems due to their young age, he said, but risk factors like high blood pressure, high cholesterol and diabetes are often more common in these patients compared with peers of the same age who’ve never had cancer.
“There’s a sense that people may not take these conditions as seriously as often they don’t cause symptoms,” he said. “There may also be a hesitancy to treat people for these problems when they’re so young.”
The new grant will fund research that will hopefully “move the needle as far as people having better control over these potentially modifiable conditions that we think will decrease the risk of heart problems later on.”
Chow and his team will apply a risk-prediction algorithm to the 24,500-plus Childhood Cancer Survivor Study cohort to suss out 800 survivors who are most at risk for serious heart disease (Fred Hutch is the Statistical Center for the CCSS). They will then monitor the survivors for high blood pressure, cholesterol issues and diabetes, via at-home visits and the patients’ medical records. Those who are found to be underdiagnosed or undertreated will be eligible to participate in a year-long, randomized, controlled trial designed to improve control of these cardiovascular-disease risk factors through better care coordination with the survivors’ primary-care providers (the control arm will receive the intervention on a delayed basis).
“We can’t undo their chest radiation or the chemotherapy exposure which affected their heart function,” he said. “But there’s good evidence in the general population that high blood pressure or diabetes further increases your risk. So if we can better control those things, maybe we can reduce overall heart-disease risk in these long-term survivors.”
The other NCI grant will investigate whether a cardioprotectant known as dexrazoxane might be useful in curbing cardiomyopathy or heart failure brought on by a common class of chemotherapy drugs known as anthracyclines.
Chow said anthracyclines and related drugs are well-documented as the single most important risk factor associated with subsequent development of cardiomyopathy and heart failure among cancer survivors. The American Society of Clinical Oncology currently recommends dexrazoxane for all adults exposed to high doses of anthracyclines. Safety concerns have limited its use in children, however.
“Dexrazoxane is given at the time of cancer treatment as a primary prevention strategy,” Chow explained. “It’s to prevent subsequent treatment-related heart failure.”
Chow and co-principal investigator Dr. Steven Lipshultz, a pediatric cardiologist based at Wayne State University, will plumb data from a series of clinical trials conducted on 1,200 children with leukemia and lymphoma between 1995 and 2001 in which half of the children were randomly assigned to receive the cardioprotectant with their chemo and half were not. Initial three- to five-year follow-up data suggest that the children who were given dexrazoxane had less heart damage. Chow and his team will look at the heart health of 200 of these childhood cancer survivors, now 15 to 20 years older, and provide longer-term follow-up data on the effectiveness of dexrazoxane as a potential cardioprotectant for children.
“This is basically a test to determine the effectiveness of it as a primary heart-disease strategy,” Chow said. “If dexrazoxane is found to be effective in minimizing or preventing heart injury among these childhood cancer survivors 15 to 20 years after cancer diagnosis, this would have significant implications on current clinical practice and potentially drug regulatory policy.”
Chow’s third grant is a $100,000 award from the Rally Foundation to look at echocardiographic change in cancer survivors at risk for cardiomyopathy. This project will involve cardiologists and oncologists from Seattle Children’s and Fred Hutch as well as City of Hope, Emory University, Hospital for Sick Children in Toronto and the University of Minnesota.
“We are very excited and grateful for this second year of funding from the Rally Foundation,” Chow said. “This will help us carry our momentum from the first year, where we have been working with four other Children’s Oncology Group sites across the country to learn more about this complication of otherwise successful cancer treatment.”
— Diane Mapes / Fred Hutch News Service
For the sixth consecutive year, Fred Hutchinson Cancer Research Center and its cancer care partner, Seattle Cancer Care Alliance, each have earned CEO Cancer Gold Standard accreditation in recognition of their commitment to employee health.
The accreditation calls for companies to take concrete steps in the following five key areas to reduce the risk of cancer and other chronic disease in their workforces:
All of the requirements of the CEO Gold Standard are based on scientific evidence, and the program is carefully reviewed annually to ensure that it remains comprehensive and up to date.
The CEO Roundtable on Cancer Inc., a nonprofit organization of leading CEOs representing diverse industries, was founded in 2001 when President George H.W. Bush challenged a group of executives to “do something bold and venturesome about cancer within your own corporate families.” The CEOs responded to the president’s challenge by creating and encouraging the widespread adoption of the CEO Cancer Gold Standard, which has been adopted by nearly 200 U.S. employers. There are no membership costs or fees associated with being a Gold Standard employer.
In nominating the Hutch and SCCA for accreditation, benefits compensation manager Jonathan Sheppard said the commitment of both institutions to eliminating cancer doesn’t end in the laboratory or the clinic. “It extends to our culture as a workplace,” he said. “We actively encourage and empower employees and their family members in a myriad of ways to make healthy choices that reduce cancer risk, and we provide outstanding health insurance benefits.”
Among the attributes that make the Hutch a Gold Standard employer are its tobacco-free environment and its industry-leading tobacco-cessation program. Based on research showing that positive incentives are most successful, the Hutch implemented a cash-incentive plan for employees who enroll in a tobacco-cessation program and stay quit.
Other perks that make the Hutch and SCCA Gold Standard employers include:
An on-site employee health clinic. Slated to open this summer, The Health Clinic, operated by Premise Health, the nation’s leading manager of on-site health clinics, will be available for all employees who are enrolled in a Fred Hutch- or SCCA-sponsored medical plan. The clinic will provide, at no cost, a wide array of high-quality primary care and preventive services, wellness coaching and physical therapy.
A popular health and wellness program. Our Healthy Challenge attracts Hutch and SCCA employees each year to challenge themselves to develop better nutrition and exercise habits, and other healthy behaviors. Now in its 15th year, the Healthy Challenge also includes educational seminars and prize incentives to keep participants engaged.
A robust bike commuter-support program. Bus/transit subsidies, free shower and towel service, locked bike cages and on-site bike repair and maintenance facilities are available for regular bike commuters – more than 730 from the Hutch (over 25 percent) and more than 160 from SCCA (about 10 percent).
Excellent health insurance benefits. The Hutch and SCCA’s health benefits provide coverage for the highest quality cancer screening and treatment services, including clinical trials at SCCA, whose cancer survival rates are among the highest in the nation.
On-site cancer screening facilities. Mammography/breast imaging and colonoscopy screening are made easily available in the SCCA outpatient clinic on the Fred Hutch campus.
Other CEO Cancer Gold Standard-accredited organizations in the U.S. include the National Cancer Institute, the American Cancer Society and the Centers for Disease Control and Prevention.
— Kristen Woodward / Fred Hutch News Service