50: Increased Risk of Cervical Dysplasia in Long Term Survivors of Allogeneic Stem Cell Transplantation – Implications for Screening and HPV Vaccination

Abstract

Cervical, skin and head-neck cancer are most common secondary solid cancers in long-term survivors after allogeneic stem cell transplantation (allo-SCT). Although these cancers are linked to human papillomavirus (HPV) infection, the relationship between HPV and cancers after allo-SCT is not defined. Furthermore, Pap smear screening after SCT is not practiced routinely. We carried out a cross-sectional study of 92 patients receiving allo-SCT for hematological malignancies, enrolled at a minimum of 3 years post-transplantation between 04/2005–06/2007 in an IRB-approved long-term evaluation protocol. Ninety (98%) patients are alive after a median follow-up of 77 months (range 38–167). Evaluation of the 38 female patients (median age at transplant 33, range 9–60 years) included annual gynecological examination. Thirty five received a fractionated total body irradiation (TBI) (12–13.6 Gy) based myeloablative SCT and 3 received a non-TBI non-myeloablative SCT. Acute graft versus host disease (GVHD) (grade II-IV) occurred in 9 (24%) patients and chronic GVHD in 34 (89%), extensive in 10 (26%). Six (16%) patients received immunosuppressive therapy (IST) for chronic GVHD beyond 3 years from SCT. Thirty-five (92%) adult patients had annual cervical smear examinations, 14 (40%) were abnormal. High grade dysplasia was seen in 8 (23%), low grade lesions in 4 (11%) and 2 patients had atypical cells of uncertain significance. Median time to an abnormal smear was 51 months (17–153) and median age of these 12 patients was 42 years (range 19–62). Extensive chronic GVHD requiring prolonged IST was the only factor associated with an increased risk of cervical dysplasia (p = 0.028). Our data shows that cervical dysplasia (often high grade) is common after allo-SCT. These patients may be at increased risk of developing invasive cervical cancer. Patients requiring prolonged immunosuppression for chronic GVHD treatment may be especially at risk for all forms of HPV-related malignancy. Aggressive screening and preventive strategies with HPV vaccine appear warranted.