Liquid Biopsy Could Transform Diagnosis and Monitoring of Oropharyngeal (Mouth and Throat) Cancer

A new study supports liquid biopsy as an additional marker for diagnosing and monitoring human papillomavirus (HPV)-associated oropharyngeal cancer. In a retrospective observational study, a blood test used to assess tumor tissue showed 100% specificity for diagnosis and recurrence surveillance. Sensitivity for correctly identifying and monitoring disease was 91.5% and 88.4%, respectively.

Oropharyngeal cancer affects a particular area of the mouth and throat. The oropharynx is located behind the oral cavity, in the upper part of the throat involved in swallowing. It includes the tonsils and the base, or root, of the tongue. Oropharyngeal cancer therefore often begins in these areas and can be caused by viruses such as HPV. It is also commonly referred to as mouth and throat cancer.

HPV and Oropharyngeal Cancer

The rising incidence of oropharyngeal squamous cell carcinoma (OPSCC) is driven by an increasing proportion of high-risk HPV-associated disease. In fact, 80-90% of all newly diagnosed oropharyngeal cancers are associated with HPV. This virus-mediated cancer represents a distinct clinical condition with a better prognosis and treatment-response profile. These distinctive tumor characteristics have prompted various treatment modifications and multimodal protocols aimed at reducing treatment intensity. Despite the favorable prognosis, 15-25% of patients develop regional or distant metastatic disease recurrence after standard treatment.

Despite the growing role of HPV and advances in treatment, methods for diagnosing oropharyngeal squamous cell carcinoma (OPSCC) have remained relatively unchanged. Currently, diagnosis and treatment of HPV-associated oropharyngeal cancer rely on tissue-based diagnosis through biopsy of the primary tumor or fine-needle aspiration (FNA)/biopsy of a regional lymph node. Biopsies are guided by clinical examinations such as fiberoptic laryngoscopy and scans using computed tomography or positron emission tomography (PET). However, these detection methods have limitations in diagnostic accuracy, patient comfort and, most importantly, time.

Why Liquid Biopsy Is Important and Needed

In recent years, interest has grown in using circulating cell-free tumor DNA (ctDNA), known as liquid biopsy, to diagnose and monitor HPV-associated oropharyngeal cancer. Although several HPV biomarker assays are under investigation, a commercially available blood test measuring tumor tissue-modified viral (TTMV)-HPV DNA has shown considerable promise. This test is available in the US under the brand name NavDx®.

The test uses a distinct method to identify and quantify a DNA-fragment pattern, greatly improving specificity for detecting an HPV-associated cancerous tumor. However, evaluation has been limited to small cohort studies and clinical trials. This cohort study aimed to characterize the diagnostic performance of plasma TTMV-HPV DNA testing for diagnosing and monitoring HPV-associated oropharyngeal cancer.

TTMV-HPV DNA Testing

TTMV-HPV DNA testing is a liquid biopsy method used to diagnose and monitor HPV-associated oropharyngeal cancer. It combines detection of circulating HPV tumor DNA with analysis of tumor DNA fragments.

The study examined a cohort of 399 patients who underwent TTMV-HPV DNA testing. Test sensitivity and specificity were assessed. Sensitivity describes the ability to correctly detect the presence of disease, while specificity describes the ability to correctly identify its absence.

The study included patients with oropharyngeal cancer who underwent TTMV-HPV DNA testing during routine clinical care between April 2020 and September 2022.

The diagnostic cohort included patients with at least one TTMV-HPV DNA measurement before starting initial treatment. Patients were included in the surveillance cohort if they underwent at least one TTMV-HPV DNA test after completing primary treatment.

Study Results

New research published on July 9, 2023 in JAMA Otolaryngology Head and Neck Surgery supports liquid biopsy as an adjunct marker for diagnosing and monitoring HPV-associated oropharyngeal cancer. In a retrospective observational cohort study, a commercial blood test used to assess tumor tissue showed 100% specificity for diagnosis and recurrence surveillance. Sensitivity for correctly identifying and monitoring disease was 91.5% and 88.4%, respectively.

Specificity and Sensitivity of Liquid Biopsy

However, liquid biopsy testing can give misleading results in some situations. 

A positive test generally indicates that disease is present. In this study, however, approximately 10% of patients with HPV-associated oropharyngeal squamous cell carcinoma, the most common mouth and throat cancer, had a negative result. In other words, they had the disease, but the test failed to detect it correctly. This illustrates the potential for misleading or incorrect test results.

Patients with a negative test who nevertheless have a high likelihood of HPV-associated oropharyngeal cancer therefore require further medical assessment and testing. This provides a safeguard against misleading false-negative results.

Conclusion: The Future of Liquid Biopsy

These findings are exciting for head and neck cancer and suggest that circulating tumor DNA testing can assist diagnosis and surveillance. However, further prospective, multicenter studies are needed to confirm them. The technology shows considerable promise for transforming the detection and monitoring of HPV-associated disease. As the test is commercially available, its use in routine clinical care is expected to increase. Providing people diagnosed with cancer with clear, detailed instructions for monitoring their disease, and keeping those instructions updated, remains a priority area of oncology research.