Main Session

Sep 29

PQA 07 - Head and Neck Cancer, Lung Cancer/Thoracic Malignancies, and Nursing and Supportive Care

3699 - Comparative Analysis of Intratumoral Microbiomes in HPV-Associated Oropharyngeal and Cervical Cancers

03:45pm - 05:00pm ET

Poster Hall - Exhibit Hall A

Screen: 15

POSTER

Presenter(s)

Helen Zhang, MD - Memorial Sloan Kettering Cancer Center, New York, NY

Y. Zhu¹, H. Y. Zhang¹, A. Momeni-Boroujeni², N. Katabi², A. Novaj¹, S. Sinha¹, A. de Gradisimo³, Y. Yu¹, N. Y. Lee¹, V. M. Williams¹, and N. Riaz¹; ¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ²Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, ³Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): Human papillomavirus (HPV) associated oropharyngeal (OPC) and cervical cancers (CC) share viral etiology, similar genomic features, and are commonly treated with definitive chemoradiation for locally advanced disease. However, outcomes after treatment vary dramatically with cervical cancers showing worse overall survival. Emerging evidence suggests that the intratumoral microbiome may influence the tumor microenvironment and response to therapy. However, whether tumor-associated microbial communities differ across HPV-driven cancers arising from distinct anatomical sites remains unclear. We sought to define and compare the intratumoral microbiome between HPV-associated OPC and CC.

Materials/Methods: We performed comparative analyses of intratumoral bacterial communities using 16S rRNA sequencing from institutional cohorts of OPC (n = 48) and CC (n = 21) tumors. Amplicon sequence variants were inferred using QIIME2 and DADA2, followed by rigorous contaminant filtering. Alpha and beta diversity metrics, taxonomic composition, and differential abundance analyses were conducted at the genus level. Findings were validated against independent public 16S datasets (OPC n = 74; CC n = 176), as well as MSK-IMPACT cohorts (OPC n = 42; CC n = 341) leveraging off-target sequencing for microbial detection.

Results: OPC tumors exhibited significantly higher microbial richness compared to CC tumors across institutional, public, and MSK-IMPACT cohorts. Beta diversity analyses demonstrated clear separation of microbial communities by cancer type (PERMANOVA, F = 9.51, p < 0.01). Although OPC and CC tumors shared broad phylum-level composition, marked and reproducible differences emerged at the genus level. Among the 269 genera in OPC and CC tumors, 14% of genera were identified as differentially abundant. OPC tumors were enriched for oral-associated taxa, including Fusobacterium, Prevotella, and Treponema, whereas CC tumors demonstrated enrichment of taxa associated with the gastrointestinal and genitourinary tracts, including Peptoniphilus, Bacteroides, and Blautia. These distinct, site-specific intratumoral microbial signatures showed robust reproducibility in the public validation datasets.

Conclusion: Despite shared viral etiology, genetic features, and treatment paradigms, HPV-associated OPC and CC harbor distinct and reproducible intratumoral microbiomes that their reflect tissue of origin. These findings suggest that the intratumoral microbiome may be a potential contributor of differences in treatment response observed among these HPV-associated cancers.