In a NIH study, half of the women with genital chronic graft-versus-host-disease (cGVHD) had vaginal adhesions with one-third of these developing months after vulvar symptoms (Stratton, Obstet Gynecol, 2007;110:1041). Some with labial and vaginal adhesions have required surgery (Norian and Stratton, Obstet Gynecol, 2008;112:437). Furthermore, systemic immunosuppression is ineffective in preventing or treating genital cGVHD. An estrogen ring improved vaginal synechiae in all treated patients. Topical superpotent steroids and estrogen (with dilators for vaginal cGVHD) were effective in treating all vulvar and some vaginal cGVHD. Genital cGVHD should be considered and gynecologic assessment performed in women with cGVHD, even if they are asymptomatic (Shanis, 2012, Semin Hematol 49:83). Severe genital GVHD is associated with severe systemic GVHD and increased morbidity and mortality (Baird, Biol Blood Marrow Transplant 2013;19:632). Coincident genital GVHD and HPV disease can be difficult to manage (Sri, Transpl Infect Dis, in press). Squamous cell cancers, which include cervical cancer, are the most common second malignancy after HSCT. Preliminary reports indicate a loss of HPV seroreactivity among transplant recipients. In a recent NIH study, adult females were followed prospectively with cervical cytology testing long-term after HSCT for hematological malignancies (median: 7 years post-transplant;Savani and Stratton, Biol Blood Marrow Transplant. 2008 Sep;14:1072). One-third had HPV-related SIL (median time to SIL 51 months, range: 22-108) including high-grade SIL in 20%. Patients requiring continued ImmunoSuppressive Therapy (IST) had the highest risk (odds ratio OR 4.6, 95% confidence interval CI 1.1-16.4;P = .019). These abnormal cervical cytology results represent HPV disease that does not appear to be newly acquired HPV disease as many are not having intercourse. It is reasonable to hypothesize that a loss of antibody titers and/or T cell immunity to HPV can cause recurrence or reactivation of HPV disease. This high incidence of SIL in long-term HSCT survivors underscores the importance of gynecologic assessment after transplantation as well as the assessment of potential preventative strategies. In the next year, this clinical study will be conducted in women post stem cell transplantation. Genital cGVHD and its sequelae in women will also be further characterized.
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