TY - JOUR
T1 - Gene expression profiling informs HPV cervical histopathology but not recurrence/relapse after LEEP in ART-suppressed HIV+HPV+ women
AU - Papasavvas, Emmanouil
AU - Kossenkov, Andrew V.
AU - Azzoni, Livio
AU - Zetola, Nicola M.
AU - Mackiewicz, Agnieszka
AU - Ross, Brian N.
AU - Fair, Matthew
AU - Vadrevu, Surya
AU - Ramogola-Masire, Doreen
AU - Sanne, Ian
AU - Firnhaber, Cynthia
AU - Montaner, Luis J.
N1 - Funding Information:
This work was partially supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases grant UO1AI51986 to L.J.M. Additional support was provided by The Philadelphia Foundation (Robert I. Jacobs Fund), Ken Nimblett and the Summerhill Trust, AIDS funds from the Commonwealth of Pennsylvania and from the Commonwealth Universal Research Enhancement Program, The Pennsylvania Department of Health, as well as by the Wistar Cancer Center Support Grant (CCSG) CA010815. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. There are no potential conflicts of interest. The content of this publication does not necessarily reflect the views or policies of NIAID, nor does mention of trade names, commercial projects or organizations imply endorsement by the US Government. We would like to thank subjects who participated in the study and their providers.
Publisher Copyright:
© The Author(s) 2018.
PY - 2019/4/29
Y1 - 2019/4/29
N2 - Identification of factors associated with human papillomavirus (HPV) cervical histopathology or recurrence/relapse following loop electrosurgical excision procedure (LEEP) would allow for better management of the disease. We investigated whether gene signatures could (i) associate with HPV cervical histopathology and (ii) identify women with post-LEEP disease recurrence/relapse. Gene array analysis was performed on paraffin-embedded cervical tissue-isolated RNA from two cross-sectional cohorts of antiretroviral therapy (ART)-suppressed HIV+HPV+ coinfected women: (i) 55 women in South Africa recruited into three groups: high risk (HR) (−) (n = 16) and HR (+) (n = 15) HPV without cervical histopathology and HR (+) HPV with cervical intraepithelial neoplasia (CIN) grade 1/2/3 (n = 24), (ii) 28 women in Botswana with CIN2/3 treated with LEEP 12-month prior to recruitment and presenting with (n = 13) and without (n = 15) lesion recurrence/relapse (tissue was analyzed at first LEEP). Three distinct gene expression signatures identified were able to segregate: (i) HR+ HPV and CIN1/2/3, (ii) HR HPV-free and cervical histopathology-free and (iii) HR+ HPV and cervical histopathology-free. Immune activation and neoplasia-associated genes (n = 272 genes; e.g. IL-1A, IL-8, TCAM1, POU4F1, MCM2, SMC1B, CXCL6, MMP12) were a feature of cancer precursor dysplasia within HR HPV infection. No difference in LEEP tissue gene expression was detected between women with or without recurrence/relapse. In conclusion, distinctive gene signatures were associated with presence of cervical histopathology in tissues from ART-suppressed HIV+/HPV+ coinfected women. Lack of detection of LEEP tissue gene signature able to segregate subsequent post-LEEP disease recurrence/relapse indicates additional factors independent of local gene expression as determinants of recurrence/relapse.
AB - Identification of factors associated with human papillomavirus (HPV) cervical histopathology or recurrence/relapse following loop electrosurgical excision procedure (LEEP) would allow for better management of the disease. We investigated whether gene signatures could (i) associate with HPV cervical histopathology and (ii) identify women with post-LEEP disease recurrence/relapse. Gene array analysis was performed on paraffin-embedded cervical tissue-isolated RNA from two cross-sectional cohorts of antiretroviral therapy (ART)-suppressed HIV+HPV+ coinfected women: (i) 55 women in South Africa recruited into three groups: high risk (HR) (−) (n = 16) and HR (+) (n = 15) HPV without cervical histopathology and HR (+) HPV with cervical intraepithelial neoplasia (CIN) grade 1/2/3 (n = 24), (ii) 28 women in Botswana with CIN2/3 treated with LEEP 12-month prior to recruitment and presenting with (n = 13) and without (n = 15) lesion recurrence/relapse (tissue was analyzed at first LEEP). Three distinct gene expression signatures identified were able to segregate: (i) HR+ HPV and CIN1/2/3, (ii) HR HPV-free and cervical histopathology-free and (iii) HR+ HPV and cervical histopathology-free. Immune activation and neoplasia-associated genes (n = 272 genes; e.g. IL-1A, IL-8, TCAM1, POU4F1, MCM2, SMC1B, CXCL6, MMP12) were a feature of cancer precursor dysplasia within HR HPV infection. No difference in LEEP tissue gene expression was detected between women with or without recurrence/relapse. In conclusion, distinctive gene signatures were associated with presence of cervical histopathology in tissues from ART-suppressed HIV+/HPV+ coinfected women. Lack of detection of LEEP tissue gene signature able to segregate subsequent post-LEEP disease recurrence/relapse indicates additional factors independent of local gene expression as determinants of recurrence/relapse.
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U2 - 10.1093/carcin/bgy149
DO - 10.1093/carcin/bgy149
M3 - Article
C2 - 30364933
AN - SCOPUS:85065476875
SN - 0143-3334
VL - 40
SP - 225
EP - 233
JO - Carcinogenesis
JF - Carcinogenesis
IS - 2
ER -