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Host Nuclear Genome Copy Number Variations Identify High-Risk Anal Precancers in People Living With HIV.

Authors :
Mutetwa T
Liu Y
Silvera R
Evans M
Yurich M
Tripodi J
Leonard I
Houldsworth J
Gümüş Z
Bowcock AM
Sigel K
Gaisa M
Polak P
Source :
Journal of acquired immune deficiency syndromes (1999) [J Acquir Immune Defic Syndr] 2024 Jun 01; Vol. 96 (2), pp. 190-195.
Publication Year :
2024

Abstract

Background: People living with HIV (PLWH) have substantially increased incidence of anal precancer and cancer. There are very little data regarding genomic disturbances in anal precancers among PLWH. In this study, specific chromosomal variants were identified in anal squamous intraepithelial lesions.<br />Methods: Overall, 63 anal biopsy specimens (27 low-grade intraepithelial lesions [LSIL] and 36 high-grade intraepithelial lesions [HSIL]) were collected from PLWH obtained as part of anal cancer screening in our NYC-based health system. Data on patient demographics, anal cytological, and high-risk human papillomavirus (HR-HPV) diagnoses were collected. Specimens were tested for a panel of chromosomal alterations associated with HPV-induced oncogenesis using fluorescence in situ hybridization, and analyses compared the associations of these alterations with clinical characteristics.<br />Results: Gains of 3q26, 5p15, 20q13, and cen7 were detected in 42%, 31%, 31%, and 19% of HSIL compared with 7%, 0%, 4%, and 0% of LSIL, respectively. If at least 1 abnormality was observed, 89% had a 3q26 gain. In lesions with 5p15 gains, 20q13 gains co-occurred in 91% of cases, while cen7 gain only co-occurred with the other 3 alterations. The sensitivity and specificity of any alteration to predict HSIL were 47% (95% CI: 30%-65%) and 93% (95% CI: 76%-99%), respectively.<br />Conclusions: Genomic alterations seen in HPV-associated cancers may help distinguish anal LSIL from HSIL. 3q26 amplification may be an early component of anal carcinogenesis, preceding 5p16, 20q13, and/or chr7.<br />Impact: Insights into potential genomic biomarkers for discriminating high-risk anal precancers are shared.<br />Competing Interests: The authors have no funding or conflicts of interest to disclose.<br /> (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Details

Language :
English
ISSN :
1944-7884
Volume :
96
Issue :
2
Database :
MEDLINE
Journal :
Journal of acquired immune deficiency syndromes (1999)
Publication Type :
Academic Journal
Accession number :
38630441
Full Text :
https://doi.org/10.1097/QAI.0000000000003409