Placental HPV Infection in HIV Positive and HIV Negative Zambian Women

Human papillomaviruses (HPVs) have been reported to infect epithelial trophoblastic cells of the placenta, induce cell death and even cause placental malfunction associated with spontaneous preterm delivery. To date, no study has been conducted to determine the role of HIV on HPV genotype distribution and pathogenesis in the placental compartment. This is despite the evidence that the human immunodeficiency virus (HIV) can decrease the cellular immune response and increase the incidence of malignant cancers in HPV patients. Therefore, in this study, we analyzed 200 genomic DNA (gDNA) samples extracted from paraffin embedded placental tissues of HIV positive and HIV negative Zambian women. The gDNA was PCR amplified using GP5+/GP6+ and CPI/CPII primers targeted to the L1 and E1regions of the HPV genome, respectively. We found the overall prevalence of HPV to be 85.0%. The prevalence of HPV in the HIV+ tissues was 84(80.8%), while that of the HIV-tissues was 86(89.6%). This difference in HPV prevalence between the HIV+ and HIV-placental tissues was not significant (p>0.05; p=0.112). Direct sequencing of the PCR products revealed 3 HPV genotypes namely: HPV6, 16 and 90.We observed a significant difference (p<0.05; p=0.0241) in the high risk (HR) HPV16 incidence between the HIV+ and HIV-tissue with an odds ratio of 2.1. Because p16 is a surrogate marker for HR-HPV infection, we analyzed the placental tissue sections by p16 immunohistochemistry (IHC). The relative p16 signal per tissue area was significantly different (p<0.05; p=0.0142) between the HIV+/HPV16+ and HIV-/HPV16+ groups. To confirm our L1 PCR findings, we also performed HPV16 L1 IHC and found that the relative L1signal per tissue area was significantly different (p<0.05; p=0.0132) between the HIV+/HPV16+ and HIV-/HPV16+ groups. To the best of our knowledge, we are the first group to study HPV in the context of HIV within the placental compartment. iii Acknowledgements I wish to express my heartfelt gratitude to my Advisor Dr. Peter C. Angeletti for his unwavering support, encouragement and guidance during my graduate training. I would also like to thank my Committee Members Dr. Charles Wood and Dr. Qing Sheng Li for their technical advice. Many thanks also go to Dr. Dawn Eggert for her technical assistance with Immunohistochemistry Staining and In Situ Hybridization and to Danielle Shea for her help with the purchase of some of the reagents. funding my graduate studies for the entire period. Last, but not the least, I am deeply indebted to my mother, brothers …