Opinion: ctHPVDNA Testing Could Improve Surveillance in Oropharyngeal Squamous Cell Carcinoma


Oncology nurses play a crucial role in educating patients regarding risks and benefits of circulating-tumor HPV DNA biomarker testing.

Amanda Brink, DNP, APRN, FNP-BC, AOCNP

Amanda Brink, DNP, APRN, FNP-BC, AOCNP

Oral and oropharyngeal squamous cell carcinoma (SCC) are prevalent malignancies, impacting approximately 1 in 60 men and 1 in 141 women in the United States. Nearly 55,000 new cases and 12,000 deaths were anticipated in relation to oral and oropharyngeal cancer in the United States in 2023. While other types of cancer, such as basal cell carcinoma, adenocarcinoma, and lymphoma, may affect the head and neck, 90% of head and neck cancers manifest as SCC.1

Oral SCC involves cancer affecting the lips, the front two-thirds of the tongue, the buccal mucosa, gingiva, hard palate, and the retromolar trigone (a small region behind the last molar), as well as the bottom row of teeth. On the other hand, oropharyngeal SCC (OPSCC) affects the back one-third of the tongue, tonsils, soft palate, nasopharynx, oropharynx, and hypopharynx.

Two primary risk factors for oral SCC are tobacco and alcohol consumption, whereas most oropharyngeal SCC is associated with human papillomavirus (HPV).1

Although vaccination for HPV is now widely available, its impact on rates of OPSCC in the short term is unlikely,2 as most cases of oral and oropharyngeal SCC are observed in patients between the ages of 50 and 70,1 who were likely exposed to HPV many years before the onset of OPSCC.

While HPV-positive OPSCC generally has a favorable prognosis compared to many other types of cancer, between 15 and 25% of patients will experience disease recurrence, putting them at risk for morbidity and mortality associated with OPSCC. After recurrence, the 2-year survival is estimated to be approximately 50%. Survival is better for patients who are found to have disease recurrence in only 1 location, suggesting that if recurrence could be identified earlier, survival rates may improve.2

For this reason, there is interest in enhancing the surveillance of patients treated for OPSCC by detecting circulating tumor DNA shed into the bloodstream from OPSCC.2

Circulating-Tumor HPV DNA Biomarker Testing

Lang Kuhs et al2 recently published a narrative review of the evidence regarding circulating tumor HPV DNA (ctHPVDNA) biomarker testing for surveillance in OPSCC. The review aims to assist clinicians in addressing questions about ctHPVDNA testing, including the accuracy of the test. Several studies utilizing the test demonstrated high positive predictive values (PPV) of approximately 95 to 100% for recurrence.2

PPV indicates the likelihood that a patient with a positive test truly has the disease, while negative predictive value (NPV) reflects the likelihood that a person with a negative test truly does not have the disease.3

For example, Hanna et al4 conducted a study involving 543 patients who completed treatment for HPV-associated OPSCC with curative intent. Among the 58 patients with any positive ctHPVDNA test, 55 developed recurrence (94.5% PPV), while 8 out of 495 with all-negative test results experienced recurrence (98.4% NPV). Seventy percent of patients had at least 2 tests, while 44% had at least 3 tests.

The review published by Lang Kuhs et al2 also examines how soon ctHPVDNA testing can detect recurrence, before it becomes evident on surveillance imaging or physical examination. In Hanna et al,4 the median lead time of positive ctHPVDNA testing before clinical or radiographic evidence of recurrence was 53 days (range, 7-610 days). Another study published by Chera et al demonstrated a median lead time of 3.9 months (range, 0.37-12.9 months).2

A common question in oncology is whether certain tests or interventions, while providing additional clinical and prognostic information, improve survival. Currently, the answer to this question is still unknown when it comes to ctHPVDNA testing in OPSCC. Further research will be needed to explore whether this testing improves patient outcomes when compared to the standard-of-care surveillance.

Nursing Considerations

Patients who are undergoing surveillance after being treated for cancer are often concerned about being off treatment and the risk for disease recurrence. Therefore, both patients and their oncology team members, including nurses, may be interested in taking a proactive role in surveillance, including participating in ctHPVDNA testing. Nurses can educate their patients regarding the potential benefits and risks of testing. Risks include the potential for increased patient anxiety with positive tests before any clinically evident disease. A falsely negative test may also lead clinicians and patients to dismiss imaging findings that would otherwise be concerning, such as an enlarged lymph node or a new lung nodule.

Cost of testing is often a consideration as well. The current list price of the commercially available tumor tissue-modified viral (TTMV)-HPV DNA test is $2,200 and is covered by Medicare, according to the manufacturer.5

In summary, OPSCC remains a significant health concern. The potential of ctHPVDNA testing for surveillance shows promise, with studies indicating high positive predictive values. However, its impact on survival outcomes and cost effectiveness necessitates further research. Nurses can encourage patients interested in contributing to surveillance research to participate in clinical trials.


  1. Pullen RL Jr. Oral and oropharyngeal cancer: An overview for nurses. Nursing. 2023;53(9):26-33. doi:10.1097/01.NURSE.0000946788.57053.35
  2. Lang Kuhs KA, Brenner JC, Holsinger FC, Rettig EM. Circulating Tumor HPV DNA for Surveillance of HPV-Positive Oropharyngeal Squamous Cell Carcinoma: A Narrative Review. JAMA Oncol. 2023;9(12):1716-1724. doi:10.1001/jamaoncol.2023.4042
  3. Department of Health. Disease Screening - Statistics Teaching Tools. Accessed January 14, 2024. https://www.health.ny.gov/diseases/chronic/discreen.htm
  4. Hanna GJ, Roof SA, Jabalee J, et al. Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance. Clin Cancer Res. 2023;29(20):4306-4313. doi:10.1158/1078-0432.CCR-23-1478
  5. Billing FAQs. NavDx. October 26, 2023. Accessed January 14, 2024. https://navdx.com/billing-faqs
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