Circulating tumor-tissue modified HPV DNA testing in the clinical evaluation of patients at risk for HPV-positive oropharynx cancer: The IDEA-HPV study

Sana Batool; Rosh K V Sethi; Annette Wang; Kirsten Dabekaussen; Ann Marie Egloff; Catherine Del Vecchio Fitz; Charlotte Kuperwasser; Ravindra Uppaluri; Jennifer Shin; Eleni M Rettig

doi:10.1016/j.oraloncology.2023.106584

Circulating tumor-tissue modified HPV DNA testing in the clinical evaluation of patients at risk for HPV-positive oropharynx cancer: The IDEA-HPV study

Oral Oncol. 2023 Dec:147:106584. doi: 10.1016/j.oraloncology.2023.106584. Epub 2023 Oct 12.

Authors

Affiliations

¹ Harvard Medical School, Boston, MA, USA; Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, MA, USA.
² Harvard Medical School, Boston, MA, USA; Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, MA, USA; Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA; Center for Head and Neck Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
³ Harvard Medical School, Boston, MA, USA.
⁴ Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA; Department of Surgery, Amsterdam Medical Center, Amsterdam University, the Netherlands.
⁵ Harvard Medical School, Boston, MA, USA; Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
⁶ Naveris, Inc., Natick, MA, USA.
⁷ Harvard Medical School, Boston, MA, USA; Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA; Center for Head and Neck Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸ Harvard Medical School, Boston, MA, USA; Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, MA, USA; Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA; Center for Head and Neck Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: emrettig@bwh.harvard.edu.

PMID: 37837735
DOI: 10.1016/j.oraloncology.2023.106584

Abstract

Objectives: While survival outcomes are favorable for Human Papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs), early diagnosis may minimize treatment-related morbidity and mortality. This study evaluated circulating tumor tissue-modified viral (TTMV)-HPV DNA plasma testing to facilitate early diagnosis of HPV-positive OPSCCs.

Methods: In this prospective exploratory cohort study, patients presenting to an Otolaryngology-Head and Neck Surgery clinic with unexplained signs or symptoms considered high-risk for HPV-positive OPSCC were recruited between March 2021-October 2022. Circulating TTMV-HPV DNA testing was performed, and results were shared with subjects and treating clinicians. Clinicians were surveyed regarding the perceived clinical utility of the test.

Results: Thirty-nine subjects were included. Most subjects were women (N = 23, 59 %), white (N = 32, 82 %) and never-smokers (N = 20, 51 %) with median age 60 years. Circulating TTMV-HPV DNA was detected in 2/39 subjects, both subsequently diagnosed with HPV-positive OPSCC. Both were white men aged 70-80 years with a neck mass. One subject with undetectable TTMV-HPV DNA was also diagnosed with HPV-positive OPSCC through excisional neck mass biopsy. Other eventual diagnoses included 3 HPV-negative head and neck squamous cell carcinomas and 4 other malignancies. Testing was perceived as helpful in clinical decision-making for 26/38 (68 %) subjects, and useful for similar future patients for 32/37 (86 %) subjects.

Conclusion: Circulating TTMV-HPV DNA testing is feasible and holds potential as a diagnostic aid for HPV-positive OPSCC alongside standard clinical workup. Clinicians should be cognizant of its limitations, as a negative test does not necessarily indicate the absence of disease. Further studies to evaluate its utility are warranted.

Keywords: Circulating tumor DNA; Early diagnosis; Head and Neck cancer; Human Papillomavirus; Oropharyngeal cancer; Tumor tissue-modified viral HPV DNA.

MeSH terms

Carcinoma, Squamous Cell* / genetics
Cohort Studies
DNA, Viral / genetics
Female
Head and Neck Neoplasms* / diagnosis
Humans
Male
Middle Aged
Oropharyngeal Neoplasms* / pathology
Papillomaviridae / genetics
Papillomavirus Infections* / complications
Papillomavirus Infections* / diagnosis
Prognosis
Prospective Studies
Squamous Cell Carcinoma of Head and Neck / diagnosis

Substances

DNA, Viral