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Gene expression profiling informs HPV cervical histopathology but not recurrence/relapse after LEEP in ART-suppressed HIV+HPV+ women
- Source :
- Carcinogenesis. 40:225-233
- Publication Year :
- 2018
- Publisher :
- Oxford University Press (OUP), 2018.
-
Abstract
- 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.
- Subjects :
- Adult
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Gene Expression
Uterine Cervical Neoplasms
HIV Infections
Cervix Uteri
Disease
Cervical intraepithelial neoplasia
Lesion
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Humans
Papillomaviridae
Cancer Biomarkers and Molecular Epidemiology
business.industry
Gene Expression Profiling
Papillomavirus Infections
virus diseases
Cancer
General Medicine
Gene signature
Uterine Cervical Dysplasia
medicine.disease
Gene expression profiling
Cross-Sectional Studies
030104 developmental biology
Anti-Retroviral Agents
Dysplasia
030220 oncology & carcinogenesis
Female
Histopathology
Neoplasm Recurrence, Local
medicine.symptom
business
Subjects
Details
- ISSN :
- 14602180 and 01433334
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....f51a8b4c53f03cbd8069f70139a4d808