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Blood Test Spot On for HPV Cancer Recurrence

— Near-100% accuracy for ruling in or out recurrent oropharyngeal cancer

MedpageToday
A computer rendering of a DNA helix in the bloodstream

A blood test for tumor-associated human papillomavirus (HPV)-DNA had near-perfect accuracy for identifying oropharyngeal cancer patients at high risk of recurrence after treatment, a prospective study showed.

Overall, 28 patients tested positive for circulating tumor (ct) HPV-DNA, including 16 patients who had two consecutive positive tests. All but one of the 16 patients subsequently had biopsy-proven disease recurrence. No patient who had only negative tests developed recurrent disease.

The findings have clear and immediate implications for clinical practice, including earlier initiation of salvage therapy for patients with recurrent disease, reported Bhisham S. Chera, MD, of the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina, and colleagues in the .

"With regard to how this is applicable to clinical practice, I think it improves the effectiveness, it improves the efficiency, and it reduces the cost and financial toxicity to patients," Chera told 鶹ý. "This blood test's performance is really good: Negative predictive value (NPV) 100%, two consecutive positive tests, 94% positive predictive value (PPV). This performs better than any physical examination, PET/CT, or fiberoptic re-examination in identifying cancer recurrence. Right now, I think this is the best surveillance tool we have."

The findings extended those of a previous report, which showed that a persistently negative ctHPV-DNA test ruled out disease recurrence.

HPV infection accounts for a majority of new cases of oropharyngeal cancer in the U.S. After years of rapid increases in prevalence and incidence, oropharyngeal squamous cell carcinoma (OPSCC) has become the most common HPV-associated cancer, surpassing HPV-associated cervical cancer.

In general, HPV-positive OPSCC has a favorable prognosis as compared with HPV-negative disease, which has supported efforts to de-intensify treatment regimens to reduce exposure to potentially toxic therapies. Nonetheless, as many as a fourth of patiens will develop recurrences, the authors noted.

Most recurrences occur within the first 2 years after treatment, but some patients remain at risk of recurrence for as long as 5 years, or even longer in rare cases. Salvage therapy for recurrent HPV-positive OPSCC leads to better outcomes as compared with salvage therapy for recurrent HPV-negative disease.

PET/CT imaging 3 months after definitive treatment is standard for response assessment in many cases, the authors continued. National Comprehensive Cancer Network guidelines recommend surveillance visits at increasing time intervals through 5 years. During the visits, patients often undergo fiberoptic nasopharyngolaryngoscopy, although a recent report showed that routine surveillance rarely identifies recurrent disease.

A blood-based surveillance test based on detection of ctHPV-DNA offers potential for early detection of recurrent disease and has precedents in bladder, breast, and colorectal cancer. Chera and colleagues prospectively evaluated a ctHPV-DNA liquid biopsy in 115 patients who had completed definitive chemoradiotherapy for HPV-positive OPSCC. Each patient had PET/CT imaging 3 months after finishing treatment. Investigators tested patients for ctHPV-DNA at 6- to 9-month intervals.

During a median follow-up of 23 months, 28 patients tested positive for ctHPV-DNA, including 16 patients who had two consecutive positive tests. Also during follow-up, 15 patients developed biopsy-proven recurrence of OPSCC; all 15 had two consecutive positive tests for ctHPV-DNA. The median time from ctHPV-DNA positivity to recurrence was 3.9 months.

Consecutive positive tests had a PPV of 94%. The previous report from the study showed that a negative test had a NPV of 100%.

"The way I see this working in the clinic is that if you have a negative test, we don't do a fiberoptic exam, we don't order any imaging," said Chera. "If you have a patient whose surveillance test is positive, we would bring the patient back 2 or 3 months later and repeat the blood test. If it's positive again, then we would do an in-depth physical examination; we would do a fiberoptic exam and order a total-body PET/CT scan. This test can help us better identify which patients we can omit imaging in and those patients we can do imaging in."

The test very well could have value in the management of patients with other types of HPV-related cancers, he said. Investigators have already examined the rate of ctHPV-DNA clearance as a biomarker for response to treatment and a possible decision-making tool for treatment de-escalation.

The testing technology has been licensed to Naveris for commercial development, and multiple medical centers have already partnered with the company to conduct studies across a variety of HPV-related diseases, said Chera.

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    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined 鶹ý in 2007.

Disclosures

The study was supported by the University Cancer Research Fund, Burrows Wellcome Fund, NIH, University of North Carolina, and University of Florida.

Chera disclosed relevant relationships with Naveris and patent/royalty/intellectual property interests.

Primary Source

Journal of Clinical Oncology

Chera BS, et al "Plasma circulating tumor HPV DNA for the surveillance of cancer recurrence in HPV-associated oropharyngeal cancer" J Clin Oncol 2020; DOI: 10.1200/JCO.19.0244.