2352P - Sex-based differences in genomic alterations and biomarkers in anal squamous cell carcinoma (ASCC)

Background

ASCC is a relatively rare malignancy. Several studies reported favourable prognosis in Female to Male patients (pts).Our work aims to identify and quantify sex-based differences in cancer-associated genomic alterations to better inform future precision medicine initiatives and provide insights on potential different survival based on sex.

Methods

A cohort of 1,380 ASCC pts (952 F,428 M) underwent genomic profiling on tissue biopsies using FoundationOne®/FoundationOne®CDx assays, to examine key differences in mutational patterns based on sex and HPV status.

Results

HPV-16 was prevalent in F while HPV-6 in M. PD-L1 expression: over 70% positive (1%), ∼20% high (50%) with similar rates in HPV+ vs HPV- (74.5% vs 63.9%; p=0.16) and sex (F:74% vs M:70.4%; p=0.80). TMB-High (10+mutations/Mb) was found in ∼18% without significant differences by sex (p=0.80); a slightly elevated rate was seen in HPV+ vs HPV- (18.4% vs 14.0%; p=0.16); 34% had PIK3CA alterations (37.1% in HPV+ vs.16.8% in HPV- ; p<.01 with similar rates by sex F:37.1% vs 20.8%; M:37.1% vs 13.3%); in contrast higher prevalence in HPV- vs HPV+ resulted to TP53 (44.9% vs 5.6% p<.01), TERT(31.3% vs 2.7% p<.01), CDNK2A (29% vs 2.9%p<.01), CDNK2B (11.7% vs 1.6% p<.01) and NOTCH1 (14.5% vs 5.1% p<.01); F had higher rates of alterations in PTEN (15.3% vs 8.4%p<.01) ,KMT2D (21% vs 13.1%, p<.01), CBFB (3.3% vs 0.2%; p<.01) and CREBBP (5.4 vs 2.6%; p=0.06),whereas M showed higher rates of alterations in TERT(15.2 vs 3.5% p<.01), TP53 (20.3% vs 7.8% p<.01),CDKN2A (14% vs 3.8%p<.01),CDKN2B (5.4% vs 2.2% p=.02), MYC (4.2% vs 1.6% p=.03) as well as amplifications on 11q13 such as CCND1(7%vs3.2%p=0.02), FGF19 (7%vs3.3%p=0.02), FGF3(7.2%vs3.6%,p=0.02), FGF4 (7% vs 3.5% p=0.02). BRCA1 and BRCA2 mutations were in 5% pts with mild M predominance (7% vs 4%) regardless HPV expression.

Conclusions

The higher incidence of HPV positivity in F compared to M remains the main hypothesis to justify the better prognosis of ASCC in women. A large proportion of PD-L1+ and TMB-High (∼70%), PIK3CA alterations (∼30%) and BRCA1/2 gene alteration (5%) may predict response to possible new therapeutic approaches for pts with ASCC like immunotherapy, targeted tyrosine kinase inhibitors, platinum chemotherapy and PARP inhibitors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.