The human papillomavirus (HPV) vaccine provides a safe, robust immune response against HPV in reproductive-aged women who have had a stem cell transplant. The results from the small study published in the Journal of the American Medical Association Oncology suggest that the vaccine may help prevent against new HPV infections, and associated cervical, vulvar, and other HPV-related cancers in women with a donor-acquired immune system.
“This is the first study demonstrating immune responses induced by HPV vaccination after allogeneic hematopoietic cell transplant,” said Richard Childs, M.D., clinical director of NHLBI’s Division of Intramural Research, and a study author. “This area is understudied and very important to investigate given the susceptibility to infection and increased risk of cancer in this population.”
The findings have implications for women who have had what is known as an allogeneic transplant to treat blood cancer, sickle cell disease, or other blood or immune-related conditions. After this type of transplant, which replaces abnormal blood-forming stem cells with healthy donor cells, doctors sometimes must prescribe drugs that suppress the immune system in order to prevent or treat rejection of the donor cells. However, these drugs may increase the risk of HPV infections, which have a seven-fold higher risk of the infection developing into cancer in post-transplant women than in healthy women.
While doctors have encouraged vaccinating post-transplant women, they have been unclear about whether these patients who were either on or off immunosuppressive therapy could produce an immune response following HPV vaccination. The researchers note that future investigations will explore viral and clinically efficacy, which would reveal more insight into protection against infection and associated lesions.
“Studies have shown that transplant recipients whose immune systems are suppressed have an increased presence of HPV disease that requires surgery,” said Pamela Stratton, M.D., lead study author and currently a scientist at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health. “Since HPV vaccination is considered the most effective intervention for controlling HPV infection and preventing HPV-related disease burden, the current study examined if the vaccine could evoke an immune response in patients who were on or off immunosuppressive therapy.”
From May 2010 to March 2016, the study enrolled 64 women participating in the Intramural Research Program at the National Heart, Lung, and Blood Institute, the National Cancer Institute, and other institutes at the National Institutes of Health Clinical Center. Forty-four of the women had received stem cell transplants, and of those, 23 were taking immunosuppressants, and 21 were off immunosuppressants. The remaining 20 were healthy volunteers.
The women received the first-generation FDA-approved quadrivalent HPV vaccine three times—on the first day, and at two and six months. The immune responses to vaccination were investigated in the laboratory of Ligia Pinto, Ph.D., at the Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute.
The quadrivalent HPV vaccine protects against infection with two high-risk HPV types, HPV-16 and HPV-18, that cause the majority of cervical cancers and pre-cancerous cervical lesions. This vaccine also protects against two low-risk HPV types, HPV-6 and HPV-11, that cause genital warts.
By the end of the study, the vast majority of the women had developed antibody responses to all four HPV vaccine types—that’s 78% of those receiving immunosuppressants, 95% of those off immunosuppression, and 100% of the healthy volunteers.
Five of the eight participants who had previous treatment with the drug rituximab, which researchers described as being known to hinder responses to vaccines, still mounted an immune response to the HPV vaccine. The side effects from the HPV vaccine were mild and did not differ across all groups of women.
Stratton notes that the study now presents data suggesting that current use of immunosuppression or prior use of rituximab after transplant should not preclude vaccination.
This study was funded as an Intramural Research Program Bench to Bedside Award sponsored by the Office of Research on Women’s Health, NHLBI, the National Cancer Institute (NCI), Frederick National Laboratory for Cancer Research, sponsored by NCI, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Study: Immune Response to Quadrivalent HPV Vaccine in Women after Hematopoietic Allogeneic Stem Cell Transplant: A Nonrandomized Controlled Trial. DOI: 10.1001/jamaoncol.2019.6722.
Clinical Trial Number: NCT01092195