Diagnostic Accuracy of Circulating Tumor HPV DNA Testing in Patients With a Lateral Neck Mass.

Importance: The most frequent presenting symptom for patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a lateral neck mass. Circulating tumor tissue-modified viral (TTMV)-HPV DNA is a unique biomarker produced by the fragmentation of HPV DNA during the degradation of HPV-associated tumors, and its detection and quantitation are currently being used as an adjunct to imaging in monitoring for disease recurrence and may have utility for diagnosis. Objective: To measure the diagnostic characteristics of TTMV-HPV DNA compared with gold standard tissue biopsy for diagnosing HPV-OPSCC in patients presenting with an indeterminate lateral neck mass. Design, Setting, and Participants: This prospective diagnostic test study enrolled patients 18 years or older who presented with a lateral neck mass to a large urban tertiary health care system from December 2021 to June 2023. Participants underwent standard-of-care testing to obtain a tissue diagnosis and a single TTMV-HPV DNA measurement. Main Outcomes and Measures: The primary outcome of interest was sensitivity, while specificity, positive predictive value, and negative predictive value were secondary end points. A subset analysis was performed comparing test performance metrics between TTMV-HPV DNA testing and fine-needle aspiration. Results: A total of 138 patients were included, of whom 80 (58.0%) were men, with median age of 57.5 years (IQR, 43.3-67.0 years). Of 138 patients, 87 (63.0%) had neck masses in level 2 and 47 (34.1%) had HPV-OPSCC. TTMV-HPV DNA testing exhibited a sensitivity of 95.7% (95% CI, 85.5%-99.5% [45 of 47 patients]), specificity of 97.8% (95% CI, 92.3%-99.7% [89 of 91 patients]), positive predictive value of 95.7% (95% CI, 85.5%-99.5% [45 of 47 patients]), and negative predictive value of 97.8% (95% CI, 92.3%-99.7% [89 of 91 patients]). Conclusions and Relevance: In this diagnostic study of patients presenting with a lateral neck mass, circulating TTMV-HPV DNA demonstrated excellent diagnostic test characteristics for the detection of HPV-OPSCC. Such testing may have particular utility for patients in whom obtaining adequate tissue is problematic, as is often the case with cystic neck masses and unknown primary tumors.

Improving Interdisciplinary Communication and Pathology Reporting for Head and Neck Cancer Resections: 3D Visualizations and Margin Reconciliation.

PURPOSE: Surgical pathology reports play an integral role in postoperative management of head and neck cancer patients. Pathology reports of complex head and neck resections must convey critical information to all involved clinicians. Previously, we demonstrated the utility of 3D specimen and defect scanning for communicating margin status and documenting the location of supplemental margins. We introduce a newly designed permanent pathology report which improves documentation of intraoperative margin mapping and extent of corresponding supplemental margins harvested. METHODS: We test the hypothesis that gaps in understanding exist for head and neck resection pathology reports across providers. A cross-sectional exploratory study using human-centered design was implemented to evaluate the existing permanent pathology report with respect to understanding margin status. Pathologists, surgeons, radiation oncologists, and medical oncologists from United States-based medical institutions were surveyed. The results supported a redesign of our surgical pathology template, incorporating 3D specimen / defect scans and annotated radiographic images indicating the location of inadequate margins requiring supplemental margins, or indicating frankly positive margins discovered on permanent section. RESULTS: Forty-seven physicians completed our survey. Analyzing surgical pathology reports, 28/47 (60%) respondents reported confusion whether re-excised supplemental margins reflected clear margins, 20/47 (43%) reported uncertainty regarding final margin status, and 20/47 (43%) reported the need for clarity regarding the extent of supplemental margins harvested intraoperatively. From this feedback, we designed a new pathology report template; 61 permanent pathology reports were compiled with this new template over a 12-month period. CONCLUSION: Feedback from survey respondents led to a redesigned permanent pathology report that offers detailed visual anatomic information regarding intraoperative margin findings and exact location/size of harvested supplemental margins. This newly designed report reconciles frozen and permanent section results and includes annotated radiographic images such that clinicians can discern precise actions taken by surgeons to address inadequate margins, as well as to understand the location of areas of concern that may influence adjuvant radiation planning.

Utility of TTMV-HPV DNA in resolving indeterminate findings during oropharyngeal cancer surveillance.

OBJECTIVES: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer. MATERIALS AND METHODS: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included. RESULTS: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence. CONCLUSION: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course.

The impact of distance to facility on treatment modality, short-term outcomes, and survival of patients with HPV-positive oropharyngeal squamous cell carcinoma.

PURPOSE: This study compared treatment and outcomes for patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) based on their travel distance to treatment facility. MATERIALS AND METHODS: Patients with cT1-4, N0-3, M0 HPV-positive OPSCC in the National Cancer Database from 2010 to 2019 were identified and split into four quartiles based on distance to facility, with quartile 4 representing patients with furthest travel distances. Multivariable-adjusted logistic regression and Cox proportional hazards modeling were used to analyze the primary outcome of treatment received, and secondary outcomes of clinical stage, overall survival, surgical approach (i.e., TORS versus other), and 30-day surgical readmissions. RESULTS: 17,207 patients with HPV-positive OPSCC were evenly distributed into four quartiles. Compared to patients in quartile 1, patients in quartile 4 were 40 % less likely to receive radiation versus surgery (OR = 0.60; 95 % CI = 0.54-0.66). Among the patients who received surgery, quartile 4 had a higher odds of receiving TORS treatment compared to quartile 1 (4v1: OR = 2.38; 95 % CI = 2.05-2.77), quartile 2 (4v2: OR = 2.31, 95 % CI = 2.00-2.66), and quartile 3 (4v3: OR = 1.75; 95 % CI = 1.54-1.99). Quartile 4 had a decreased odds of mortality compared to Quartile 1 (4v1: OR = 0.87; 95 % CI = 0.79-0.97). There were no differences among the quartiles in presenting stage and 30-day readmissions. CONCLUSIONS: This study found that patients with furthest travel distance to facility were more often treated surgically over non-surgical management, with TORS over open surgery, and had better overall survival. These findings highlight potential disparities in access to care for patients with HPV-positive OPSCC.

Evaluating human papillomavirus testing, prevalence, and association with prognosis in head and neck squamous cell carcinoma by subsite: A national cancer database study.

PURPOSE: To compare human papillomavirus (HPV) testing, prevalence, and association with prognosis between head and neck squamous cell carcinoma (HNSCC) subsites. MATERIALS AND METHODS: This study utilized the National Cancer Database (NCDB) to identify patients diagnosed with HNSCC between 2010 and 2017. Rates of HPV testing, HPV-positivity, and changes in these rates over time were measured by subsite. The impact of HPV-positivity on overall survival across six head and neck subsites was assessed using multivariable-adjusted Cox proportional hazards analysis. RESULTS: A total of 121,550 patients were included. Of this cohort, 87,575 (72.1%) were tested for HPV, with the oropharynx (55,049/64,158; 85.8%) displaying the highest rates of testing and the sinonasal tract (1519/2853; 53.2%) displaying the lowest testing rates. Of the 86,136 with a definitive result, 46,878 (54.4%) were HPV-positive, with the oropharynx (40,313/54,205; 74.4%) displaying the highest rates of HPV-positivity and the oral cavity (1818/11,505; 15.8%) displaying the lowest. HPV-positive malignancy was associated with significantly improved adjusted overall survival in the oropharynx (HR = 0.42 [95% CI: 0.43-0.47]), oral cavity (HR = 0.86 [95% CI: 0.79-0.95]), sinonasal tract (HR = 0.63 [95% CI: 0.48-0.83]), larynx (HR = 0.78 [95% CI: 0.71-0.87]), and hypopharynx (HR = 0.56 [95% CI: 0.48-0.66]), but not the nasopharynx (HR = 0.93 [95% CI: 0.77-1.14]). CONCLUSION: HPV testing rates were significantly lower in non-oropharyngeal subsites. This is relevant as HPV-associated disease displayed significantly improved overall survival in both the oropharynx and four of five non-oropharyngeal subsites. While validation with prospective studies is necessary, these findings may warrant HPV testing in all HNSCC subsites.

Assessing Postoperative Phosphate and Calcium/Phosphate Ratio as Surrogates for Parathyroid Hormone Following Total Thyroidectomy.

OBJECTIVE: Evaluate utility of postoperative phosphate and calcium/phosphate ratio (Ca/P) as surrogates for parathyroid hormone (PTH) following total thyroidectomy. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital. METHODS: We retrospectively reviewed patients 18 years or older who underwent total thyroidectomy in a tertiary care hospital by a single surgeon from 2015 through 2021. Patients with incomplete data, pre-existing hypoparathyroidism, vitamin D deficiency, or renal failure were excluded. All patients had PTH drawn within 4 hours of surgery and serum calcium, albumin, and phosphate levels on postoperative Day 1. Corrected calcium was used to calculate a Ca/P. Receiver operating characteristic (ROC) curves were generated to compare phosphate level or Ca/P with PTH. Each possible surrogate was assessed relative to PTH cutoffs of less than 5, 10, 15, and 20 pg/mL. A good screening test was defined as having an area under the curve (AUC) greater than 0.8. RESULTS: A total of 185 patients underwent total thyroidectomy with 1 fellowship-trained otolaryngologist. Most patients were female (62%), median age 48 years. Most surgeries were performed for cancer (68%). Six (3.2%) patients required IV calcium supplementation and 2 (1.1%) required readmission for symptomatic hypocalcemia. ROC curves comparing phosphate and Ca/P to PTH at the listed cutoffs demonstrated AUC ranging from 0.55 to 0.66 and 0.61 to 0.79, respectively. None met the threshold for a good screening test. CONCLUSION: Postoperative phosphate and Ca/P ratio are not surrogates for PTH levels following total thyroidectomy. More research is needed to identify cost-effective strategies for postoperative calcium monitoring in patients undergoing total thyroidectomy. LEVEL OF EVIDENCE: Retrospective cohort study.

Thyroid Ethanol and Radiofrequency Ablation: A Call for Patient-Friendly Online Resources.

INTRODUCTION: The multiple treatment options available to patients with thyroid nodules can generate uncertainty and confusion. Radiofrequency ablation (RFA) and ethanol ablation (EA) are two alternative modalities to manage thyroid nodules. As patients more frequently utilize online resources to guide their decision-making, the quality of such resources must be evaluated. The goal of this study was to assess the quality of online patient materials relating to RFA and EA compared to standard thyroidectomy. METHODS: The terms "thyroidectomy," "thyroid radiofrequency ablation," and "thyroid ethanol ablation" were searched on Google. Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG), and Patient Education Materials Assessment Tool (PEMAT) understandability and actionability were calculated for each website. Statistical analysis was conducted on SPSS Statistics. Google trends were used to determine search interest for each term (May 2016 - May 2021). RESULTS: Of the 77 websites that met our inclusion criteria (30 thyroidectomy sites, 30 RFA sites, and 17 EA sites), the average FRE, FKGL, and SMOG scores of the RFA websites were significantly worse than those of the thyroidectomy websites (p < 0.05). The FKGL and SMOG scores of the EA websites were significantly worse than those of the thyroidectomy websites (p < 0.05). The average understandability and actionability scores for thyroidectomy websites were significantly higher than those of RFA and EA websites (p < 0.05). CONCLUSION: Ablation websites have lower search interest, readability, validity, understandability, and actionability scores in comparison to traditional thyroidectomy websites. Our findings emphasize the need to consider readability and PEMAT scores when developing online educational resources for ablative alternatives to thyroidectomy to allow for greater patient accessibility.

Diagnostic Difficulties of Plunging Ranula: A Review of 18 Cases.

OBJECTIVE(S): Despite advancements in imaging techniques and cytological analysis, plunging ranula remains a challenging surgical, radiologic, and pathologic phenomenon. Of the 18 patients we evaluated at our institution, we highlight three cases that illustrate the high rate of misleading imaging and cytological results when assessing plunging ranula. METHODS: Imaging results, biopsy findings, operative techniques, and pathological reports were reviewed from patients who had either a preoperative or postoperative diagnosis of ranula and underwent surgery by a single head and neck surgeon at a tertiary care center. RESULTS: Of the 18 identified patients, computed tomography was correct on preoperative imaging 73% of the time and magnetic resonance imaging was correct on preoperative imaging 71% of the time. Two patients underwent preoperative ultrasound and their ultrasound reports did not accurately diagnose the presence of a ranula. Two patients underwent preoperative fine needle aspiration biopsy due to inconclusive preoperative imaging, in which results suggested either a ranula or epidermal cyst. Both ultimately did not match the final pathology. Three of eighteen patients (17%) underwent an inappropriate initial surgery due to incorrect imaging diagnoses and/or biopsy findings. CONCLUSION: Despite use of preoperative modalities to distinguish plunging ranula from other cystic floor of mouth lesions, surgeons must be aware that no workup modality is fully precise. The potential for revision surgery must be included in all preoperative discussions for presumed plunging ranula. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2689-2696, 2024.

Outcomes of Supracricoid Partial Laryngectomy Performed in the United States: A Systematic Review.

OBJECTIVE: The primary objective of this study was to evaluate oncologic outcomes of all published cases of supracricoid partial laryngectomy (SCPL) performed in the United States. The secondary objective was to assess the functional outcomes associated with this procedure. REVIEW METHODS: A systematic review of PubMed, SCOPUS, and Embase for all English-language studies pertaining to SCPL performed in the United States was conducted until August 2021. Primary outcomes included disease-specific survival (DSS), overall survival, and local recurrence rate. Secondary outcomes included larynx preservation rate, gastrostromy tube dependency, days to gastrostomy tube removal, decannulation rate, and days to decannulation. RESULTS: A total of six studies were included in the analysis. A total of 113 patients (58.5%) underwent SCPL surgery as a primary treatment method whereas 80 patients (41.5%) underwent SCPL as salvage surgery. The 5-year DSS rates were 87.8% and 100% for primary and salvage procedures, respectively. Approximately 10.3% of patients undergoing a salvage SCPL procedure experienced a local recurrence whereas only 1.85% of primary SCPL procedures resulted in local recurrence. The rates of decannulation following primary and salvage SCPL were 92.7% and 88.1%, respectively. With regard to swallowing, primary and salvage SCPL procedures demonstrated comparably low postoperative gastrostomy tube dependency rates of 3.66% and 4.76%, respectively. CONCLUSIONS: SCPL performed in the United States is an effective surgical technique that produces excellent outcomes in qualifying patients, thus validating its viability as an organ-preserving surgical alternative. Laryngoscope, 134:3003-3011, 2024.

The Impact of Hospital Safety-Net Burden Status on Patients with HPV-Positive Oropharyngeal Cancer.

OBJECTIVES: The objective of this study was to compare treatment characteristics and outcomes between patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) treated at hospitals of varying safety-net burden status. METHODS: Patients with cT1-4, N0-3, M0 HPV-positive OPSCC who underwent definitive surgery or radiation were included. Patients were grouped based on their treating hospital safety-net burden status, defined as the percentage of uninsured and Medicaid-insured patients with OPSCC treated at the facility and stratified as low burden (LBH: 0-25th percentile), medium burden (MBH: 25th-75th percentile), or high burden (HBH: 75th-100th percentile). The primary outcome was primary treatment with surgery versus radiation, evaluated with multivariable-adjusted logistic regression. Secondary outcomes included TORS versus open surgical approach, and overall survival evaluated with Cox proportional hazards analysis. RESULTS: Of the 19,810 patients with cT1-4, N0-3, M0 HPV-positive OPSCC included in this study, 4921 (24.8%) were treated at LBH, 12,201 (61.6%) were treated at MBH, and 2688 (13.6%) were treated at HBH. In multivariable-adjusted analysis, compared with treatment at LBH, treatment at HBH was associated with more frequent radiation over surgical treatment (OR: 1.26, 95% CI: 1.12-1.40, p < 0.001). For patients undergoing surgery, patients at HBH had less frequent transoral robotic surgery (OR: 0.30, 95% CI 0.24-0.38, p < 0.001) compared with patients treated at LBH. Overall survival of patients treated at HBH was worse than that of patients treated at LBH (HR: 1.27, 95% CI 1.13-1.43, p < 0.001). CONCLUSION: These findings highlight underlying disparities at higher safety-net burden facilities that impact patterns of care and outcomes for patients with OPSCC. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1733-1740, 2024.

Ectopic Cervical Thymoma in a Patient Diagnosed With Graves Disease: A Systematic Literature Review.

Thymomas are benign thymic epithelial neoplasms, rarely found outside the anterior mediastinum. Although hyperthyroid states have been associated with thymic hyperplasia, only 3 thymoma cases have been previously reported in patients with Graves disease (GD), all within the anterior mediastinum. Here, we report a case of ectopic cervical thymoma in a 22-year-old female patient previously treated for GD. The patient underwent ultrasonography, computed tomography, inconclusive fine-needle aspiration, and ultimately gross dissection for diagnostic workup and definitive treatment of an anterior neck mass, producing a 2.5 × 2.3 × 1.5-cm entity consistent with Masaoka stage I and type B2 thymoma per World Health Organization classification. The patient underwent an uncomplicated subsequent clinical course, with no adjuvant radiotherapy administered. After conducting a systematic literature review, we conclude that of the 109 cases of ectopic cervical thymoma reported, this is the first to describe a case of ectopic cervical thymoma in a patient with a past medical history of GD. For GD patients in stable euthyroid remission with the persistent or recurrent presence of an anterior neck mass, the extrathyroidal origin of the mass should always be considered, including the exceptional presence of a cervical ectopic thymoma.

Frozen Section Timeout: Pilot Study to Reconcile Margins Using 3D Resected Specimen and Defect Scans.

OBJECTIVE: Opportunities exist to improve intraoperative communication and documentation of resection margin details. We instituted a "frozen section timeout" that centers around visualization of the paired resection specimen and surgical defect-facilitating effective, bidirectional exchange of information. METHODS: We designed an interactive form for use during the "frozen section timeout" including annotated 3D virtual models of the resected specimen and surgical defect, plus a "line-item" table for primary and supplemental margin results. The "timeout" was conducted over a Zoom call between the operating room and frozen section laboratory. The form was simultaneously projected and discussed while all members of the surgical care team stopped activities. Nurses, co-surgeons, and all other members of the surgical team were encouraged to take part in this process. RESULTS: Twenty-six frozen section timeouts were conducted during head and neck surgeries in the Department of Otolaryngology at Mount Sinai West Hospital. These timeouts were facilitated by the lead surgeon, and all other activities were halted to ensure that critical information was shared, documented, and agreed upon. During the timeout, the annotated specimen and defect scans were displayed, clearly demonstrating the at-risk margins and the corresponding location and breadth of supplemental margins harvested. CONCLUSION: Incorporating a frozen section timeout can improve intraoperative communication, increase transparency, and potentially eliminate uncertainty regarding margin status and tumor clearance. Visualization of at-risk margins and the corresponding location and breadth of supplemental margins promises an unprecedented level of documentation and understanding. This novel technique can establish a new and improved standard of care. LEVEL OF EVIDENCE: NA Laryngoscope, 134:725-731, 2024.

Circulating Tumor HPV DNA in Patients With Head and Neck Carcinoma: Correlation With HPV Genotyping.

Circulating tumor human papillomavirus DNA (ctHPVDNA) testing using digital-droplet polymerase chain reaction (PCR) detects fragments of tumor-modified human papillomavirus (HPV) in the plasma of patients with HPV-associated head and neck squamous cell carcinomas (HNSCCs). Its impact on tumor surveillance and primary diagnosis is limited by unresolved issues relating to sensitivity and specificity. The study population consisted of patients with HNSCC who had undergone ctHPVDNA testing. HPV status was determined by p16 immunohistochemistry and PCR-HPV genotyping on the tumor samples. For discrepant cases (HPV-positive/ctHPVDNA-negative), HPV status was confirmed by RNA in situ hybridization and, when possible, targeted single-nucleotide polymorphisms genotyping. A total of 167 patients had ctHPVDNA testing, and 141 tumors were HPV positive by p16 immunohistochemistry and PCR genotyping. Genotypes included types 16 (91.5%), 33 (4.3%), 35 (2.1%), and 18 (2.1%). ctHPVDNA was detected in 133 (94.3%) of HPV-positive HNSCCs but in none of the HPV-negative HNSCCs. Four of the 5 p16-positive cases that were negative by PCR and ctHPVDNA were positive by RNA in situ hybridization, and in 2 of these cases, rare high-risk genotypes were identified. ctHPVDNA had a sensitivity of 91.7%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 63.6%. The likelihood that patients with HPV-positive HNSCC have detectable ctHPVDNA is high. Non-HPV16 genotypes contribute to discrepancies but only in a small subset of cases. This finding validates ongoing efforts to use ctHPVDNA as a surveillance tool, and even as a primary diagnostic assay in patients presenting with masses in the neck and/or oropharynx.

Thyroid cancer necrosis not evident on imaging: A cautionary case series on poorly differentiated thyroid carcinoma diagnosed only on final pathology.

OBJECTIVE: Poorly-differentiated thyroid cancer (PDTC) is a highly aggressive malignancy which is recently defined and understudied in the radiologic literature. Necrosis is a key histopathologic criterion for the diagnosis of PDTC. We illustrate the current difficulty in accurate identification of histopathologic necrosis on preoperative imaging. METHODS: A series of seven patients with the final diagnosis of PDTC from our institution were identified. Multimodality preoperative imaging was analyzed by two head and neck radiologists. Final pathology reports were queried confirming histopathologic evidence of necrosis. RESULTS: Patients presented with a wide range of preoperative imaging features. A consistent imaging appearance confirming necrosis was not identified. All patients were subsequently upstaged to PDTC following final pathological analysis. CONCLUSION: A lack of definitive evidence of necrosis on preoperative imaging does not exclude the possibility of PDTC. We demonstrate the need for further research to establish a clear methodology for the preoperative diagnosis of PDTC.

iPad Annotation of 3D Surgical Models Using Procreate®: Novel Documentation of Supplemental Margins.

We present a novel, efficient approach to demonstrating supplemental margins during oncologic resection. Surgeons and pathologists annotated 10 virtual models of surgical defects and resection specimens in 3D using an iPad-based application, Procreate®. Incorporating this method into the surgical workflow can improve interdepartmental communication and provide visual documentation of surgical steps taken to address at-risk margins. Laryngoscope, 2023.

Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance.

PURPOSE: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance. EXPERIMENTAL DESIGN: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154). RESULTS: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5-97.5] and 87.3% (95% CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9-99.8) and 98.4% (95% CI: 97.3-99.5), respectively. CONCLUSIONS: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.

Intraoperative three-dimensional scanning of head and neck surgical defects: Enhanced communication and documentation of harvested supplemental margins.

BACKGROUND: We have demonstrated the effectiveness of 3D resection specimen scanning for communicating margin results. We now address the corresponding surgical defect by debuting 3D defect models, which allow for accurate annotations of harvested supplemental margins. METHODS: Surgical defects were rendered into 3D models, which were annotated to document the precise location of harvested supplemental margins. 3D defect scans were also compared with routine 2D photography and were analyzed for quality, clarity, and the time required to complete the scan. RESULTS: Forty defects were scanned from procedures including segmental mandibulectomy, maxillectomy, and laryngopharyngectomy. Average duration of defect scan was 6 min, 45 s. In six of ten 2D photographs, the surgeon was unable to precisely annotate the extent of at least one supplemental margin. CONCLUSION: 3D defect scanning offers advantages in that this technique enables documentation of the precise location and breadth of supplemental margins harvested to address margins at-risk.

Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus-Associated Oropharyngeal Cancer.

Importance: There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue-modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, use of these newer techniques has been limited to small cohort studies and clinical trials. Objective: To establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary clinical setting. Design, Setting, and Participants: This retrospective observational cohort study included patients with OPSCC who underwent TTMV-HPV DNA testing between April 2020 and September 2022 during the course of routine clinical care. For the diagnosis cohort, patients with at least 1 TTMV-HPV DNA measurement prior to initiation of primary therapy were included. Patients were included in the surveillance cohort if they had at least 1 TTMV-HPV DNA test performed after completion of definitive or salvage therapy. Main Outcomes and Measures: Per-test performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, for TTMV-HPV DNA testing. Results: Of 399 patients included in the analysis, 163 were in the diagnostic cohort (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), and 290 were in the surveillance cohort (median [IQR] age, 63 [57-70] years; 237 [81.7%] male). Of the 163 patients in the diagnostic cohort, 152 (93.3%) had HPV-associated OPSCC while 11 (6.7%) had HPV-negative OPSCC. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (95% CI, 85.8%-95.4% [139 of 152 tests]), and the specificity was 100% (95% CI, 71.5%-100% [11 of 11 tests]). In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. A total of 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (95% CI, 74.9%-96.1% [38 of 43 tests]) and specificity of 100% (95% CI, 99.3%-100% [548 of 548 tests]) in detecting the recurrences. Positive predictive value was 100% (95% CI, 90.7%-100% [38 of 38 tests]), and negative predictive value was 99.1% (95% CI, 97.9%-99.7% [548 of 553 tests]). The median (range) lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 (0-507) days. Conclusions and Relevance: This cohort study demonstrated that when evaluated in a clinical setting, the TTMV-HPV DNA assay demonstrated 100% specificity in both diagnosis and surveillance. However, the sensitivity was 91.5% for the diagnosis cohort and 88.4% for the surveillance cohort, signifying that nearly 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative. Additional research is required to validate the assay's performance and, if validated, then further research into the implementation of this assay into standard clinical practice guidelines will be required.

Frozen Section Analysis in Head and Neck Surgical Pathology: A Narrative Review of the Past, Present, and Future of Intraoperative Pathologic Consultation.

Frozen section has remained the diagnostic gold standard for intraoperative pathological evaluation of surgical margins for head and neck specimens. While achieving tumor-free margins is of utmost importance to all head and neck surgeons, in practice, there are numerous debates and a lack of standardization for the role and method of intraoperative pathologic consultation. This review serves as a summary guide to the historical and contemporary practice of frozen section analysis and margin mapping in head and neck cancer. In addition, this review discusses current challenges in head and neck surgical pathology, and introduces 3D scanning as a groundbreaking technology to bypass many of the pitfalls in the current frozen section workflow. The ultimate goal for all head and neck pathologists and surgeons should be to modernize practices and take advantage of new technology, such as virtual 3D specimen mapping techniques, that improves the workflow for intraoperative frozen section analysis.

Impact of Sternothyroid Muscle Division on Patient-Reported Voice Outcomes After Thyroid Surgery: A Prospective Study.

OBJECTIVE: Division of the sternothyroid muscle during thyroidectomy is a widely accepted surgical technique to provide improved exposure of the thyroid gland, thus facilitating the ligation of superior pole vessels and identification of the laryngeal nerves. However, few have examined the impact on voice outcomes. We evaluate the impact of sternothyroid muscle division on patient-perceived voice outcomes after thyroidectomy. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary academic institution. METHODS: A prospective cohort study was conducted comparing pre- and postoperative voice outcome data after thyroidectomy, measured using Voice Handicap Index-10. The cohort of 109 patients underwent lobectomy or total thyroidectomy by a single surgeon at 1 institution. The sternothyroid muscle was fully divided in all surgeries. The integrity of the recurrent laryngeal and external branches of the superior laryngeal nerve was assessed using intraoperative nerve monitoring and postoperative laryngoscopy. Pre- and postoperative Voice Handicap Index-10 scores were compared. RESULTS: No statistically significant difference was found between total pre- and postoperative Voice Handicap Index-10 scores (µpreop = 1.92, µpostop = 1.83, p = .87). There were no questions yielding statistically significant responses between pre- and postoperative groups. This was consistent regardless of whether the sternothyroid muscle was cut unilaterally or bilaterally. Men showed a statistically significant improvement in score after surgery. CONCLUSION: These findings support no difference in postoperative voice outcomes after the intraoperative division of the sternothyroid muscle. This supports the usage of this technique as a safe means to facilitate exposure during thyroid surgery and will serve as important information to guide intraoperative surgical decision-making.