Carole Fakhry leads the Johns Hopkins Division of Head and Neck Surgery. Researchers on the team have recently gained new insights into circulating tumor DNA tests; incidence of human papilloma virus-associated squamous cell carcinoma; outcomes for laryngectomy; and more
Physicians in the Johns Hopkins Division of Head and Neck Surgery are advancing clinical research in their field. The following are just a few developments taking place.
Putting Circulating Tumor DNA Tests to the Test
Johns Hopkins continues to be at the forefront of elucidating HPV’s role in head and neck cancer. Circulating tumor DNA tests for human papillomavirus (HPV) are commercially available and are an active area of investigation at Johns Hopkins and nationally, offering the hope of earlier diagnosis of recurrent HPV oropharynx cancer (HPV-OPC) and potential applications for screening. Recently, Carole Fakhry and colleagues compared DNA detection results for HPV16 when collected orally or by blood and different testing modalities – droplet digital PCR (ddPCR), next generation sequencing (NGS), and quantitative real-time PCR (qPCR) — among patients with HPV-OPC. The team found that HPV DNA detection by NGS and ddPCR in plasma and oral samples both had higher sensitivity for HPV16-OPC than qPCR. In a limited cohort of follow-up patients, HPV levels detected in plasma by NGS but not ddPCR or qPCR reflected disease remission or progression.
“This study supports the potential role of HPV detection using circulating tumor DNA tests and helps to identify the pros and cons of each technology,” Fakhry says.
In another recent study examining PCR-based assays in an HPV screening cohort, the first to investigate this technology for HPV screening, Fakhry and her colleagues found that PCR had high specificity. The researchers also contextualized issues for physicians and patients in having these tests on the market for clinical care without guidelines, providing pros and cons of implementing circulating tumor DNA in practice.
Rising HPV-Associated Sinonasal Squamous Cell Carcinoma
In a recent study, Nyall London and his colleagues investigated whether the incidence and prevalence of human papillomavirus-associated sinonasal squamous cell carcinoma (SNSCC) were increasing. Using a national database and 25-year Johns Hopkins cohort, the researchers found a rise in both measures of HPV-associated SNSCC. The increase in prevalence in the Johns Hopkins cohort was 2.1% per year rising from around 15% of cases in 1995–1999 to around 50% of cases in more recent calendar periods. HPV16 was the most common serotype seen, affecting about 68.5 precent of individuals with HPV-positive SNSCC.
“This is the first demonstration of a rise in HPV-associated malignancy outside of the oropharynx and has important public health implications,” London says.
London and his colleagues also published a review of all known malignancies in the sinonasal tract for which the human papillomavirus has been implicated. This review highlighted the role of HPV as a potential oncogenic agent and clinically relevant factor for some of these sinonasal tumors.
Improving Outcomes of Laryngectomy and the Importance of Lymph Node Yield
In head and neck surgery, laryngectomy has become a high-risk, low-volume procedure due to shifts in primary management towards nonsurgical care, with surgery increasingly used for salvage after radiation, leading to a higher incidence of complications and need for specialized care. In a recent study, Christine Gourin and her colleagues retrospectively reviewed outcomes of 45,156 patients who underwent laryngectomy using a national database. The researchers found a strong volume-outcome relationship between hospital and surgeon laryngectomy volume and outcomes, with a minimum hospital volume threshold for laryngectomy associated with reduced postoperative morbidity and mortality.
Surgeon volume explained much of the association between hospital volume and laryngectomy outcomes, even at high-volume hospitals. These data suggest that regionalizing laryngectomy care to hospitals and surgeons with higher volumes will improve outcomes, even within high-volume centers.
“This approach is controversial and will require a cultural shift,” acknowledged Gourin, “but as hospitals increasingly consolidate within healthcare organizations, it just makes sense not to duplicate services when there is a minimum volume threshold that is associated with better outcomes.”
The number of lymph nodes removed during neck dissection has been established as a quality metric that correlates with long-term survival. A yield of at least 18 nodes in previously untreated patients is associated with improved survival and has been endorsed by the American Society of Clinical Oncology and the American Head and Neck Society. Recently, Gourin and her colleagues retrospectively reviewed 412 neck dissections over a four-year period to determine factors associated with neck dissection yield.
The researchers found that the extent of neck dissection and time frame were associated with specimens containing less than 18 nodes. Specifically, increased awareness and education of the importance of node count by the multidisciplinary head and neck cancer team since 2016 was associated with fewer specimens with less than 18 nodes and fewer neck dissections removing less than three levels.
“Node count is a viable and responsive quality indicator of the adequacy of neck dissection that identifies performance gaps and provides a target for quality improvement that addresses variability in practice patterns,” says Gourin, “and we plan to monitor this as a quality improvement measure for our team.”