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Chromogenic In Situ Hybridization as a Tool for HPV-Related Head and Neck Cancer Diagnosis

Chromogenic In Situ Hybridization as a Tool for HPV-Related Head and Neck Cancer Diagnosis

Published on: June 14, 2019

Blood-based screening for HPV-associated cancers.

Dipon Das^1,2, Shun Hirayama^1,2,3, Ling Aye¹

¹Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, Massachusetts.

Medrxiv : the Preprint Server for Health Sciences

|February 8, 2024

Summary

This summary is machine-generated.

Blood tests can detect human papillomavirus-associated oropharyngeal cancer (HPV+OPSCC) up to 10 years before diagnosis. This breakthrough offers potential for early screening of this common cancer.

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Area of Science:

Oncology
Virology
Genomics

Background:

HPV-associated oropharyngeal cancer (HPV+OPSCC) is a leading cancer in the US, lacking a screening test.
Early development of HPV+OPSCC is presumed to occur 10-15 years before clinical diagnosis.
Circulating tumor HPV DNA (ctHPVDNA) is a validated biomarker for HPV+OPSCC.

Approach:

Developed HPV-DeepSeek, a whole genome sequencing assay for HPV detection with 99% sensitivity and specificity.
Analyzed 28 plasma samples from HPV+OPSCC patients collected 1.3-10.8 years pre-diagnosis using HPV-DeepSeek and serology assays.
Utilized a machine learning model for classification and orthogonal validation with PIK3CA mutations and viral integration events.

Key Points:

The HPV-DeepSeek assay detected HPV+OPSCC in 79% of cases with a maximum lead time of 7.8 years.
A machine learning model achieved 96% classification accuracy, with 100% detection within 10 years.
Orthogonal validation confirmed cancer signals in 68% of patients; molecular fingerprinting ruled out contamination and confirmed viral genome stability over time.

Conclusions:

Demonstrated accurate blood-based detection of HPV-associated cancers up to 10 years prior to clinical diagnosis.
Highlighted the significant potential of circulating tumor DNA (ctDNA)-based screening for early cancer detection.
Established a foundation for developing a feasible blood-based screening test for HPV+OPSCC.