Naslov
Chromosomal copy number alterations in anal precancers from people with HIV

Autori
Mutetwa, Tinaye ; Karlić, Rosa ; Houldsworth, Jane ; Bowcock M., Anne ; Gaisa M., Michael ; Liu, Yuxin ; Polak, Paz ; Sigel, Kieth

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, pp prezentacija, znanstveni

Skup
CROI 2021, Conference on Retroviruses and Opportunistic Infections

Mjesto i datum
Online; konferencija, 06.03.2021. - 10.03.2021

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Anal cancer ; Copy number alteration ; FISH ; HPV ; HIV

Sažetak
Background: People living with HIV (PWH) are susceptible to high-risk human papillomavirus (HPV) infection of the anal canal owing to their immunocompromised status. The virus can transform anal squamous epithelia to low-grade squamous intraepithelial lesions (LSILs) and further to high-grade squamous intraepithelial lesions (HSILs). HSILs are well-defined cancer precursors that can progress to invasive cancer if left untreated. HPV-associated cancers commonly carry genomic abnormalities, specifically, a gain of chromosome 3q26 (PIK3CA), 20q13, 5p15 (TERT) and 7 centromere (cen7). We aimed to determine whether HPV-associated anal precancers carry similar genomic abnormalities and if so, to analyze their associations with histological severity and specific HPV types. Methods: Anal lesions from 63 unique patients (36 HSIL, 27 LSIL) were obtained via high-resolution anoscopy (HRA)-directed biopsy. Anal swabs were performed at the time of HRA to collect samples for cytological diagnosis and HPV DNA testing of HPV16, 18, and other (12) high-risk types. FISH-based HPV-associated Cancer Test (FHACT) was performed on the biopsy samples using four-color probes to detect any gain of chromosome 3q, 20q, 5p, and 7. The associations between genomic alterations, histological severity and HPV types were analyzed. Results: Our cohort had a median age of 50, was predominantly (70%) of Black and Hispanic race/ethnicity and 95% had suppressed HIV viral loads. Genomic abnormalities were detected in 47% of anal HSILs and 7% of LSILs (p=0.002). A gain of 3q, 20q, 5p, and cen7 was detected in 42%, 31%, 31%, and 19% of HSILs and 7%, 4%, 0%, and 0% of LSILs, respectively. Genomic abnormalities were more frequent in lesions associated with HPV16/18 infection, compared with those associated with non-16/18 types and negative HPV (42% vs. 24% vs. 9% ; p=0.06). 91% of lesions with 5p gain had gain in 20q. Cen7 gains were only detected in lesions with a gain of 20q13, suggesting a possible sequential order in development of chromosomal gains: 3q26 first, followed by 20q13 or 5p15, and then cen7. Conclusion: Anal precancers frequently demonstrate genomic abnormalities found in other HPV-associated cancers. The most common abnormality was the amplification of chromosome 3q, the location of PIK3CA gene. Our results suggest that PI3- kinase/AKT signaling pathway may play an important role in anal cancer development in PWH.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA