SAN DIEGO (FRONTLINE MEDICAL NEWS) – When genital warts return again and again in women no matter what’s tried, it’s time to think of GATA2 immunodeficiency, according to investigators from the National Institutes of Health, in Bethesda, Md.

A bone marrow transplant may prove curative, ending the cycle of vulvectomies and other surgeries, they said at the annual meeting of the Society of Gynecologic Oncology.

Surgery, at least before transplant, isn’t the answer because “the lesions are going to come right back.” When HPV is severe and persistent, “consider referral to an infectious disease immunologist who can work women up for GATA2 mutations, or you can just contact the NIH. Bone marrow transplantation is the only known curative treatment for HPV disease in GATA2 deficiency,” said lead investigator Ehren Dancy, a medical student in the Medical Research Scholars Program at the NIH.GATA2 [GATA binding protein 2] is a transcription factor key to the development and maintenance of hematopoiesis. Mutations in the GATA2 gene lead to a primary immunodeficiency marked by progressive monocytopenia, and B-cell and natural killer cell lymphopenia. Since 2011, GATA2 mutations have been linked to an ever increasing range of serious medical problems, including severe, persistent, and multifocal human papillomavirus (HPV) infections in women.

While 70% of healthy women clear HPV in 1 year, and more than 90% in 2 years, that wasn’t the case with the 35 women with GATA2 mutations at NIH. Twenty-seven (77%) reported abnormal Pap smears and/or genital and perigenital warts, generally diagnosed in the early to mid-20s. Twenty-one (78%) cases recurred despite treatment. About half the women had five or more surgeries, including cone biopsy, laser ablation, and vulvectomy. Seven women were diagnosed with HPV genital cancer before the age of 41; one has died.

Ten women have had bone marrow transplants, with a median follow-up of 16 months. HPV resolved in four and significantly improved in six. None of the patients in the review “demonstrated long-term HPV treatment response without bone marrow transplantation,” the investigators said.

Natural killer and monocyte cell counts were far below normal at the time of transplant.


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