Human Papillomaviruses Can Pervade the Human Body to Its Core and May Play a Role in the Pathogenesis of Hematological Malignancies
MF Evans, C Tape, MR Lewis, CS-C Adamson, V Rajendran, Z Peng, K Cooper. University of Vermont College of Medicine, Burlington, VT; Fletcher Allen Health Care, Burlington, VT
Background: High-risk (hr) human papillomavirus (HPV) types are recognized as the cause of cervical carcinoma and at least a subset of head and neck tumors. Tumors from numerous other anatomic locations including breast, colon, and ovary have also tested positive for HPV; a casual relationship has yet to be proven, however. HPV has been characterized as an epitheliotropic infection, and, as such, there have been few studies examining the association of HPV with hematological conditions.
Design: DNA was extracted from archival (2000-2008) formalin-fixed, paraffin-embedded specimens of plasma cell myeloma [PCM] (29 samples from 27 patients), follicular lymphoma [FL] (32 samples from 30 patients) and normal bone marrow [NBM] (56 samples from 29 patients). PCR was performed using GP5+/6+ primers (which detect at least 37 different alpha genus HPV types) and two alternative cycling strategies: a 'touchdown' protocol and a 'slow-ramping' method. Cycle sequencing of PCR products was performed to identify the specific HPV genotype.
Results: HrHPV types (HPV16, 18, 45) were detected in PCM samples from 21 (77.8%) patients; low-risk (lr) types HPV were not found. Eighteen (60.0%) FL patients tested HPV positive; 11 (36.7%) for hrHPV types (HPV16, 18) and 7 (23.3%) for lrHPV types (HPV11, 81). Of the NBM cohort, HPV was detected in 16 (55.2%) patients; 10 (34.5%) for hrHPV types (HPV16, 18, 45) and 6 (20.7%) for lrHPV types (HPV81). LrHPV types (6, 67 and 89) were also recorded as co-infections in 5 of the hrHPV positive NBM samples. HrHPV was significantly more common in PCM patients than among NBM (P<0.002) controls or FL patients (P<0.01); there was no significant difference comparing hrHPV in FL and NBM samples.
Conclusions: HPV genotypes are detectable in PCM, FL and NBM samples; this finding broadens the range of neoplasms in which HPV has been reported. The findings raise the possibility that hrHPV may have a role in hematological malignancies, especially PCM. Further studies are required, however, to ascertain whether the HPV detected is causally or incidentally associated with these conditions.
Monday, March 22, 2010 1:00 PM
Poster Session II # 143, Monday Afternoon