What question did this study set out to answer?

The aim is to improve risk stratification for HPV+ head and neck cancer by analyzing viral and host genomic diversity alongside social factors.

April 5, 2026

Abstract 3237: A multimodal sequencing framework to define viral and host genomic heterogeneity in HPV associated head and neck cancer

Q: What is the clinical evidence from this study?

Study design: Observational. Population: HPV-associated head and neck cancer (n=18). Intervention: Multimodal sequencing framework (short-read and long-read sequencing). Primary outcome: Viral and host genomic heterogeneity and associations with social determinants of health.

Key Result

Preliminary multimodal sequencing of 18 patients with HPV+ head and neck cancer revealed White patients predominantly had HPV16, while non-16 types were more prevalent among other racial groups.

Key Points

The aim is to improve risk stratification for HPV+ head and neck cancer by analyzing viral and host genomic diversity alongside social factors.
Enrolled patients with p16-positive HPV+ head and neck cancer.
Conducted DNA extraction and HPV genotyping using specific primers.
Performed short-read and long-read sequencing to characterize viral genotypes and host mutations.
Collected demographic and social determinants data to explore correlations with genomic findings.
Ten patients have been enrolled; eight tumor specimens analyzed.
Preliminary HPV genotyping shows a distribution of high-risk types including HPV16, HPV18, and others.
Findings suggest variation in HPV types across different racial and ethnic groups, with White patients more likely to have HPV16.

Study Design

Type

Observational (n=18)

Structured PICO

Population

18 patients (10 enrolled, 8 archived specimens) with biopsy-proven, p16-positive HPV-associated head and neck cancer

Intervention

Multimodal sequencing framework (short-read and long-read sequencing) integrated with social determinants of health (SDOH)

Outcome

Viral genotype characterization, host mutational profiling, and associations with demographic, clinical, and SDOH variablessurrogate

Early genomic profiling of HPV-associated head and neck cancer suggests racial and ethnic differences in high-risk HPV genotypes, highlighting the need for diverse cohorts in precision oncology.

Limitations

Early findings with a small preliminary sample size
Ongoing expansion of the cohort and completion of sequencing analyses are still required

Abstract

Abstract Background: This study aims to integrate viral and host genomic analyses with social determinants of health (SDOH) to improve biologic risk stratification in patients with human papillomavirus-associated head and neck cancer (HPV+ HNC). Methods: Patients with biopsy-proven, p16-positive HPV+ HNC were enrolled. Archived or fresh tumor tissue underwent DNA extraction followed by HPV consensus-primer genotyping targeted to the L1 locus (MY09/MY11 primer sequences) to determine viral type. Samples with confirmed HPV infection proceed to short-read sequencing for viral genotype characterization and host mutational profiling, and long-read sequencing to define HPV integration architecture, HPV-host fusion events, and larger structural variants. Demographic, clinical, and SDOH variables were collected to explore associations between patient context and genomic heterogeneity. Results: To date, 10 patients have provided informed consent and have been enrolled in this study. Additionally, eights archived tumor specimens have been analyzed. The cohort consists of seven White male, two Hispanic or Latino male, and one White female patients. Archived specimens were derived from three White, two Asian, two Black, and one Hispanic patient. Preliminary HPV genotyping demonstrates a distribution of high-risk HPV types, including HPV16, HPV18, HPV33, HPV35, and HPV59. These early results suggest a potential variation across ancestry and SDOH-defined clusters, with White patients predominantly demonstrating the HPV16 genotype, while there is a higher prevalence of non-16 types amongst other racial and ethnic groups. Conclusions: These early findings highlight the value of broadening HPV genotype characterization and capturing patient diversity to uncover the full spectrum of viral and host genomic variation in HPV+ HNC. Ongoing expansion of the cohort and completion of sequencing analyses will be critical next steps toward defining clinically meaningful genomic subgroups and developing future frameworks for precision risk stratification, surveillance, and treatment personalization in HPV-associated head and neck cancer. Citation Format: Ella P. Jackert, Shu-Yun Cheng, Swar Vimawala, Liyang Tang, Daniel Kwon, Niels C. Kokot, Uttam Sinha, Albert Y. Han. A multimodal sequencing framework to define viral and host genomic heterogeneity in HPV associated head and neck cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3237.

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