Circulating Tumor HPV DNA in Patients With Stage I and II HPV-Associated Head and Neck Cancer After Surgery.

This cohort study examines the association of posttreatment circulating tumor human papillomavirus DNA (ctHPVDNA) with residual disease and 2-year overall survival and recurrence-free survival in patients with HPV-associated head and neck cancer.

Fenestration of the facial nerve by the stylomastoid artery.

BACKGROUND: Anatomic landmarks such as the tympanomastoid suture line, posterior belly of the digastric muscle, tragal pointer, and styloid process can assist the parotid surgeon in identifying and preserving the facial nerve. Vascular structures such as the posterior auricular artery and its branch, the stylomastoid artery, lay in close proximity to the facial nerve and have been proposed as landmarks for the identification of the facial nerve. In this case report, we describe an anatomic variation in which the stylomastoid artery has fenestrated the main trunk of the facial nerve, dividing it in two. METHODS: Two patients underwent parotidectomy (one for a pleomorphic adenoma, the second for a parotid cyst) through a standard anterograde approach with identification of the usual facial nerve landmarks. RESULTS: The appearance of the main trunk of the facial nerve was unusual in both patients due to its being fenestrated by the stylomastoid artery. The stylomastoid artery was divided, and the remainder of the facial nerve dissection was performed uneventfully with subsequent resection of the parotid mass in both patients. CONCLUSIONS: In rare instances, the stylomastoid artery can penetrate through the common trunk of the facial nerve. This is an important anatomic variant for the parotid surgeon to be aware of, as it can increase the difficulty of facial nerve dissection.

Use of the spider limb positioner for fibular free flap reconstruction of head and neck bony defects.

BACKGROUND: Osseous and osteocutaneous fibular free flaps are the workhorse of maxillomandibular reconstruction over 30 years after the initial description. Since 2019, we have routinely used the Spider Limb Positioner, adapted from its use in shoulder orthopedic procedures, for fibular free flap harvest. Herein, we describe this novel technique in our cohort. METHODS: We describe our intraoperative setup and endorse the versatility and utility of this technique in comparison to other reported fibular free flap harvest techniques. RESULTS: The Spider Limb Positioner was used 61 times in 60 different patients to harvest osseous or osteocutaneous fibular free flaps. Median (range) tourniquet time for flap harvest was 90 (40-124) minutes. No iatrogenic nerve compression injuries or complications related to lower extremity positioning occurred. CONCLUSION: We describe a novel approach to fibular free flap harvest utilizing the Spider Limb Positioner, which affords optimal ergonomics, visibility, and patient repositioning. There were no nerve injuries or complications related to positioning in our series.

Blood-based screening for HPV-associated cancers.

Background: HPV-associated oropharyngeal cancer (HPV+OPSCC) is the most common HPV-associated cancer in the United States yet unlike cervical cancer lacks a screening test. HPV+OPSCCs are presumed to start developing 10-15 years prior to clinical diagnosis. Circulating tumor HPV DNA (ctHPVDNA) is a sensitive and specific biomarker for HPV+OPSCC. Taken together, blood-based screening for HPV+OPSCC may be feasible years prior to diagnosis. Methods: We developed an HPV whole genome sequencing assay, HPV-DeepSeek, with 99% sensitivity and specificity at clinical diagnosis. 28 plasma samples from HPV+OPSCC patients collected 1.3-10.8 years prior to diagnosis along with 1:1 age and gender-matched controls were run on HPV-DeepSeek and an HPV serology assay. Results: 22/28 (79%) of cases and 0/28 controls screened positive for HPV+OPSCC with 100% detection within four years of diagnosis and a maximum lead time of 7.8 years. We next applied a machine learning model classifying 27/28 cases (96%) with 100% detection within 10 years. Plasma-based PIK3CA gene mutations, viral genome integration events and HPV serology were used to orthogonally validate cancer detection with 68% (19/28) of the cohort having multiple cancer signals detected. Molecular fingerprinting of HPV genomes was performed across patients demonstrating that each viral genome was unique, ruling out contamination. In patients with tumor blocks from diagnosis (15/28), molecular fingerprinting was performed within patients confirming the same viral genome across time. Conclusions: We demonstrate accurate blood-based detection of HPV-associated cancers with lead times up to 10 years before clinical cancer diagnosis and in doing so, highlight the enormous potential of ctDNA-based cancer screening.

ctDNA predicts recurrence and survival in stage I and II HPV-associated head and neck cancer patients treated with surgery.

Human papillomavirus-associated oropharyngeal squamous cell carcinomas (HPV+OPSCC) release circulating tumor HPV DNA (ctHPVDNA) into the blood which we, and others, have shown is an accurate real-time biomarker of disease status. In a prior prospective observational trial of 34 patients with AJCC 8 stage I-II HPV+OPSCC treated with surgery, we reported that ctHPVDNA was rapidly cleared within hours of surgery in patients who underwent complete cancer extirpation, yet remained elevated in those with macroscopic residual disease. The primary outcomes of this study were to assess 2-year OS and RFS between patients with and without molecular residual disease (MRD) following completion of treatment in this prospective cohort. MRD was defined as persistent elevation of ctHPVDNA at two consecutive time points, without clinical evidence of disease. The secondary outcomes were 2-year OS and RFS between patients with and without detectable MRD after surgery. We observed that patients with MRD after treatment completion were more likely to recur compared to patients without MRD, while there was no difference in recurrence rates between patients with MRD and without MRD on postoperative day 1. OS did not significantly differ between patients with MRD after surgery or treatment completion compared to patients without MRD; however, time to death was significantly different between the groups in both settings, suggesting that with a larger sample size OS would differ significantly between the groups or that the impact of MRD detection on survival is time dependent.

Neck scar perception after neck dissection in HPV-associated oropharyngeal squamous cell carcinoma.

IMPORTANCE: While there has been an increased understanding of the impact of visible neck scars in some patients with certain diseases, this has not yet been explored in the HPV+ OPSCC population. OBJECTIVE: To understand patients' perception of their scar and the impact on their quality of life (QOL) at least 6 months after neck dissection (ND) for HPV+ oropharyngeal squamous cell carcinoma (OPSCC). DESIGN, SETTING, AND PARTICIPANTS: In this retrospective case-control study, patients who underwent primary transoral robotic surgery (TORS) and ND for HPV+ OPSCC between 2016 and 2021 at a single tertiary care center were identified. Data analysis was performed in January 2022. MAIN OUTCOMES AND MEASURES: Dermatology Life Quality Index was modified (mDLQI) to assess patients' perceptions of their scars. The primary outcome was the mean mDLQI survey score with higher scores corresponding to worse perceptions. Three questions adapted from the Self-Consciousness Scale (SCS) were also included to assess awareness of appearance. All questions were scaled on a 0-3 Likert Scale. Tweedie generalized linear model was used to understand the relationship between mDLQI score and patient- and procedure-specific factors (including the three SCS survey questions). An additional exploratory logistic regression was performed to understand the risk factors for clinically significant mDLQI score change. RESULTS: A total of 67 patients (response rate 57 %) completed the survey with a mean mDLQI survey score of 0.84 (max 30). Although there was a statistically significant negative association between private insurance and mDLQI survey score (95 % Confidence Interval [CI]: -2.72 - -0.38), and a positive association between the SCS score and mDLQI survey score (95 % CI: 0.23-0.81) (p < 0.05), these variables were not found to be risk factors for a clinically significant difference in mDLQI on multivariable analysis. CONCLUSION: The majority of patients felt their neck scars did not interfere with their daily lives. Patient perceptions of neck scars were consistent despite differing patient characteristics and treatment regimens.

Predictors of multiple dilations and functional outcomes after total laryngectomy and laryngopharyngectomy.

BACKGROUND: Following total laryngectomy (TL) or laryngopharyngectomy (TLP), patients may develop strictures that require multiple dilations to treat. However, the risk factors associated with dysphagia refractory to a single dilation are unknown. METHODS: Single-institution retrospective review of patients who underwent at least one stricture dilation after TL/TLP between March 2013 and March 2022. RESULTS: A total of 49 patients underwent stricture dilation after TL/TLP. Thirty-five (71%) underwent multiple dilations. Pharyngocutaneous fistula, primary chemoradiation therapy, and a shorter time interval from TL/TLP to first dilation were independently associated with dysphagia requiring multiple dilations. Patients in the multiple dilations group had a higher rate of limited diet and G-tube dependence compared to patients in the single dilation group. CONCLUSIONS: Shorter time interval to stricture formation is a prognostic indicator of the need for multiple dilations following TL/TLP. Patients requiring multiple dilations are at increased risk of persistent dysphagia long-term.

Early Weight-Bearing After Fibula Free Flap Surgery.

Importance: Despite the widespread use of fibula free flap (FFF) surgery for head and neck reconstruction, there are no studies assessing if early weight-bearing (EWB) affects postoperative recovery, and the timing of weight-bearing initiation following FFF surgery varies considerably across institutions. Therefore, it is important to understand the effect of EWB in these patients and whether it could improve postoperative recovery. Objective: To assess the association of EWB after FFF surgery with donor-site complications, length of stay, and discharge to home status. Design, Setting, and Participants: This retrospective cohort study took place at Massachusetts Eye and Ear, a single tertiary care institution in Boston, Massachusetts. A total of 152 patients who received head and neck reconstruction with a fibula osteocutaneous free flap between January 11, 2010, and August 11, 2022, were included. Exposure: EWB on postoperative day 1 vs non-EWB on postoperative day 2 or later. Main Outcomes and Measures: Patient characteristics, including demographic characteristics and comorbidities, surgical characteristics, donor-site complications, length of stay, and discharge disposition, were recorded. Descriptive statistics and multivariate logistic regressions were used to compute effect sizes and 95% CIs to compare postoperative outcomes in EWB and non-EWB groups. Results: A total of 152 patients (median [IQR] age, 63 [55-70] years; 89 [58.6%] male) were included. The median (IQR) time to postoperative weight-bearing was 3 (1-5) days. Among all patients, 14 (9.2%) had donor-site complications. EWB on postoperative day 1 was associated with shorter length of stay (adjusted odds ratio [AOR], 0.10; 95% CI, 0.02-0.60), increased rate of discharge to home (AOR, 7.43; 95% CI, 2.23-24.80), and decreased donor-site complications (AOR, 0.11; 95% CI, 0.01-0.94). Conversely, weight-bearing 3 or more days postoperatively was associated with an increased risk of pneumonia (AOR, 6.82; 95% CI, 1.33-34.99). Conclusions and Relevance: In this cohort study, EWB after FFF surgery was associated with shorter length of stay, increased rate of discharge to home, and decreased donor-site complications. These findings support the role of early mobilization to optimize postoperative recovery after FFF surgery.

Robotic Thyroidectomy via Posterior Neck Approach Using the Da Vinci Single Port System.

We describe a remote access thyroidectomy technique: robotic thyroidectomy via posterior neck approach using the Da Vinci single port (Sp) robotic system. This approach is feasible and safe in the Western population. Laryngoscope, 2023.

Depth of resection predicts loss of tongue tip sensation after partial glossectomy in oral tongue cancer: A pilot study.

OBJECTIVE(S): To characterize the change in sensory function following partial glossectomy for oral tongue cancer (OTC) and to identify predictors of loss of tongue-tip sensation (LoTTS). MATERIALS AND METHODS: Patients with at least three months follow-up after partial glossectomy for primary OTC were included. All patients underwent a qualitative tongue sensation assessment and an objective tongue sensory exam of the native tongue tip. Additional details regarding the oncologic resection, surgical reconstruction, and pathological stage were collected. Multiple linear and logistic regressions were used for statistical analysis. RESULTS: Sixty-four patients were enrolled, including 34 (53%) men with a median age of 65 at enrollment. Ten (15%) patients reported LoTTS. Increased depth of resection (DOR) was an independent predictor of LoTTS on multivariate analysis, with an increased risk at a threshold of 1.3 cm. LoTTS was also associated with worse subjective quality of life and perceptive speech performance in our qualitative tongue assessment. CONCLUSIONS: In this pilot study, we found that DOR is a critical prognostic factor in predicting post treatment function. Patients with an increased DOR, particularly above 1.3 cm, are at greatest risk of LoTTS and associated morbidity. These findings may be used to predict post-operative sensory deficits, manage patients' expectations, and optimize the reconstructive approach. Future studies are needed to validate and replicate our results.

Comparison of patient-reported upper extremity disability following free flaps in head and neck reconstruction: A systematic review and meta-analysis.

BACKGROUND: Comparisons of patient-reported donor site morbidity based on the Disabilities in Arm, Shoulder, and Hand (DASH) instrument across upper trunk free flaps in head and neck surgery, including radial forearm (RFFF), osteocutaneous radial forearm (OCRFF), scapular tip (STFF), and serratus anterior (SAFF) free flaps, may help inform donor tissue selection. METHODS: In this meta-analysis, 12 studies were included and the primary outcome was average DASH score. RESULTS: The pooled DASH scores were 12.14 (95% CI: 7.40-16.88) for RFFF (5 studies), 17.99 (11.87-24.12) for OCRFF (2 studies), 12.19 (8.74-15.64) for STFF (3 studies), and 16.49 (5.92-27.05) for SAFF (2 studies) and were not significantly different. CONCLUSIONS: Results suggest that patients generally function well, with minimal to mild donor site morbidity, when assessed at an average of 20 months after flap harvest. These results are based on few effects from primarily retrospective studies of fair quality, and further research is needed.

Double trouble: Synchronous and metachronous primaries confound ctHPVDNA monitoring.

BACKGROUND: Human papillomavirus-associated head and neck squamous cell carcinoma (HPV + HNSCC) occurs in the oropharynx (HPV + OPSCC), sinonasal cavity (HPV + SNSCC), and nasopharynx (HPV + NPC). Circulating tumor HPV DNA (ctHPVDNA) is an accurate tool for diagnosis, treatment monitoring, and recurrence detection. An emerging challenge with ctHPVDNA is that ~7.4% of HPV + HNSCC patients develop synchronous or metachronous HPV+ primaries, which could confound ctHPVDNA monitoring. METHODS: We describe a 65-year-old patient with T2N1M0 HPV16 + OPSCC and a 55-year-old patient with T2N2M0 HPV16 + OPSCC. Both patients were enrolled in our prospective observational ctHPVDNA study with longitudinal blood collections throughout treatment. Both patients developed multiple HPV+ primaries. RESULTS: Detailed discussion of the patients' treatment courses, the subsequent diagnoses of their second HPV+ primaries, and their ctHPVDNA monitoring is presented. CONCLUSIONS: As ctHPVDNA use becomes more prevalent, it is important to recognize that an increase in ctHPVDNA can come not only from the primary tumor or metastatic clones, but also from synchronous or metachronous second primaries.

Online Searches Related to Total Laryngectomy.

OBJECTIVE: To identify the most frequently asked questions regarding "laryngectomy" through an assessment of online search data. METHODS: Google Search data based on the search term "laryngectomy" were analyzed using Google Trends and Search Response. The most common People Also Ask (PAA) questions were identified and classified by the concept. Each website linked to its respective PAA question was rated for understandability, ease of reading, and reading grade level. RESULTS: Search popularity for the term "laryngectomy" remained stable between 2017 and 2022. The most popular PAA themes were post-laryngectomy speech, laryngectomy comparison to tracheostomy, stoma and stoma care, survival/recurrence, and post-laryngectomy eating. Of the 32 websites linked to the top 50 PAA's, eleven (34%) were at or below an 8th grade reading level. CONCLUSION: Post-laryngectomy speech, eating, survival, the stoma, and the difference between laryngectomy and tracheostomy are the most common topics searched online in relation to "laryngectomy." These are important areas for both patient and healthcare provider education. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:2971-2976, 2023.

Comparison of Preoperative DOI Estimation in Oral Tongue Cancer With cN0 Disease.

OBJECTIVE: To understand the accuracy of pre- and intraoperative estimation of tumor depth of invasion (DOI). STUDY DESIGN: A retrospective case-control study. SETTING: Patients who presented at 1 institution with oral tongue squamous cell carcinoma that underwent oncologic resection between 2017 and 2019 were identified. METHODS: Patients that met the inclusion criteria were included. Patients with nodal, distant, or recurrent disease, prior history of head and neck cancer, or preoperative tumor assessment and/or final histopathology that did not include DOI were excluded. Preoperative DOI estimation and technique and pathology reports were obtained. Our primary outcome was the sensitivity and specificity of DOI estimation modalities including full-thickness biopsy (FTB), manual palpation (MP), punch biopsy (PB), and intraoperative ultrasound (IOUS). RESULTS: Tumor DOI was assessed quantitatively preoperatively in 40 patients by FTB (n = 19, 48%), MP (n = 17, 42%), or PB (n = 4, 10%). Additionally, 19 patients underwent IOUS to assess DOI. The sensitivities of FTB, MP, and IOUS for DOI ≥ 4 mm were 83% (confidence interval [CI]: 44%-97%), 83% (CI: 55%-95%), and 90% (CI: 60%-98%), respectively, and the specificities were 85% (CI: 58%-96%), 60% (CI: 23%-88%), and 78% (CI: 45%-94%). CONCLUSION: Our study demonstrated that DOI assessment tools measured had similar sensitivity and specificity in stratifying patients with DOI ≥4 mm, with no statistically superior diagnostic test. Our results support the need for additional research into nodal disease prediction and continued refinement of ND decisions with respect to DOI.

Surgical factors affecting regionally metastatic cutaneous squamous cell carcinoma to the parotid gland.

BACKGROUND: Understanding the impact of surgical treatment on regionally metastatic cutaneous squamous cell carcinoma (cSCC). METHODS: Retrospective series of 145 patients undergoing parotidectomy and neck dissection for regionally metastatic cSCC to the parotid. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) analyzed over 3 years. Multivariate analysis was completed using Cox proportional hazard models. RESULTS: OS was 74.5%, DSS was 85.5% and DFS was 64.8%. On multivariate analysis, immune status (HR = 3.225[OS], 5.119[DSS], 2.071[DFS]) and lymphovascular invasion (HR = 2.380[OS], 5.237[DSS], 2.595[DFS]) were predictive for OS, DSS, and DFS. Margin status (HR = 2.296[OS], 2.499[DSS]) and ≥18 resected nodes (HR = 0.242[OS], 0.255[DSS]) were predictive of OS and DSS, while adjuvant therapy was predictive of DSS (p = 0.018). CONCLUSIONS: Immunosuppression and lymphovascular invasion portended worse outcomes in patients with metastatic cSCC to the parotid. Microscopically positive margins and <18 nodes resected are associated with worse OS and DSS, while patients receiving adjuvant therapy had improved DSS.

Practice patterns in transoral robotic surgery: results of an American head and neck society survey.

To understand perioperative practices for transoral robotic surgery (TORS) among academic medical centers. An electronic cross-sectional survey was distributed to fellows and program directors participating in 49 American Head and Neck Society fellowships. Operative decisions, medical and swallowing management, and disposition planning were assessed. Thirty-eight responses were collected (77.6%). Twenty-three centers (60.5%) performed > 25 cases annually with the remainder performing fewer. The da Vinci Si was the most commonly used platform (n = 28, 73.7%). A majority of institutions advocated tailored resection to adequate margins (n = 27, 71.1%) over fixed subunit-based resection (n = 11, 28.9%). Most surgeons (n = 29, 76.3%) performed neck dissection concurrent with TORS, and 89.5% (n = 34) routinely ligated external carotid artery branches. A minority of institutions (n = 17, 45.9%) endorsed a standardized TORS care pathway. Antibiotic choices and duration varied, the most common choice being ampicillin/sulbactam (n = 21, 55.3%), and the most common duration being 24 h or less (n = 22, 57.9%). Multimodal analgesia was used at 36 centers (94.7%), steroids at 31 centers (81.6%), and pharmacologic venous thromboembolic prophylaxis at 29 centers (76.3%). Nasogastric feeding tubes were placed during surgery at 20 institutions (54.1%). Speech-language pathologists routinely performed postoperative swallow evaluations at 29 (78.4%) sites. Practice patterns are variable among institutions performing TORS. While certain surgical and postoperative practices were quite common, many institutions reported no standard TORS care pathway. Further understanding of the impact of individual practices on outcomes is necessary to develop evidence-based perioperative protocols for TORS.

Detection and Monitoring of Circulating Tumor HPV DNA in HPV-Associated Sinonasal and Nasopharyngeal Cancers.

This prospective observational study examines if circulating tumor human papillomavirus DNA can be used as an accurate measure of disease status at the time of diagnosis, throughout treatment, and during monitoring in human papillomavirus-associated sinonasal and nasopharyngeal squamous cell carcinomas.

Cross-legged modification for medial sural artery perforator flap harvest.

When thin and pliable free tissue is needed, the medial sural artery perforator (MSAP) flap provides an excellent option with minimal donor site morbidity. However, among its pitfalls include difficult patient positioning and surgeon ergonomics throughout the harvest. We describe a novel positioning technique that may significantly improve surgeon ergonomics and ease of MSAP flap harvest. A cross-legged modification may eliminate many of the issues associated with the classic frog-leg position. While the patient is cross-legged, the surgeon is afforded a normal field of view that is closer to their body, while simultaneously providing support to the lateral side of the gastrocnemius muscle. This pictorial essay describes this positioning technique and subsequent harvest. By incorporating a more ergonomic cross-legged position during flap elevation, many of thedrawbacks of the MSAP flap could be eliminated.

Rate of atypical nodal metastases in surgically treated HPV-associated oropharyngeal squamous cell carcinoma.

BACKGROUND: Understanding of nodal metastasis in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC) is warranted. METHODS: Patients with HPV+ OPSCC who underwent neck dissection (ND) between 2016 and 2021 were reviewed. Pathology reports were reviewed for lymph node (LN) metastases. Noncontiguous metastases were defined as pathologic evidence of level II disease with another involved LN in a noncontiguous neck level. Skip metastases were defined as pathologic lymph node(s) in the neck without disease in level II. RESULTS: One hundred and thirty-one patients underwent levels II-IV ND with a mean (SD) LN yield of 33.3 (±13.5). The rate of atypical metastases in both the therapeutic and elective ND cohort was 5%. The noncontiguous and skip metastases were in level IV (n = 2) and level III (n = 4), respectively. CONCLUSIONS: Skip and noncontiguous metastases were rare in patients with HPV+ OPSCC undergoing surgical treatment. Surgeons may consider a selective ND omitting Level IV in select patients with HPV+ OPSCC undergoing surgery.